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Conserved domains on  [gi|1844139549|ref|NP_001369722|]
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receptor tyrosine-protein kinase erbB-2 isoform o precursor [Homo sapiens]

Protein Classification

receptor tyrosine-protein kinase erbB-3; receptor tyrosine-protein kinase erbB-4( domain architecture ID 12013639)

receptor tyrosine-protein kinase erbB-3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate; it binds the neuregulin ligands, NRG1 and NRG2, and relies on its heterodimerization partners (such as HER2) for activity following ligand binding; receptor tyrosine-protein kinase erbB-4 catalyzes the transfer of the gamma-phosphoryl group from ATP to tyrosine residues in protein substrates; it plays an essential role as cell surface receptor for neuregulins and EGF family proteins

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
712-976 0e+00

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05109:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 279  Bit Score: 587.76  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELRK--------------GIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05109      1 MRILKETELKKvkvlgsgafgtvykGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05109    161 IDETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 976
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
511-643 1.48e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


:

Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 200.29  E-value: 1.48e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 7.48e-41

Furin-like cysteine rich region;


:

Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 147.20  E-value: 7.48e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
52-173 2.47e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


:

Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.47e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
366-482 1.15e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


:

Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.15e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139549  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
641-684 3.42e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer.


:

Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.42e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
 
Name Accession Description Interval E-value
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
712-976 0e+00

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 587.76  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELRK--------------GIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05109      1 MRILKETELKKvkvlgsgafgtvykGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05109    161 IDETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 976
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
718-962 3.60e-116

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 361.81  E-value: 3.60e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  718 TELRKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHV 796
Cdd:pfam07714   13 GEVYKGTLKGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVTEYMPGGDLLDFL 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMA 876
Cdd:pfam07714   93 RKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMA 172
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:pfam07714  173 PESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFS 252

                   ....*.
gi 1844139549  957 ELVSEF 962
Cdd:pfam07714  253 ELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
719-962 6.93e-113

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 352.99  E-value: 6.93e-113
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   719 ELRKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR 797
Cdd:smart00219   14 EVYKGKLKGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEpLYIVMEYMEGGDLLSYLR 93
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKVPIKWMAL 877
Cdd:smart00219   94 KNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY-YRKRGGKLPIRWMAP 172
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   878 ESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRE 957
Cdd:smart00219  173 ESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSE 252

                    ....*
gi 1844139549   958 LVSEF 962
Cdd:smart00219  253 LVEIL 257
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
511-643 1.48e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 200.29  E-value: 1.48e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 7.48e-41

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 147.20  E-value: 7.48e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
52-173 2.47e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.47e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
735-1161 4.41e-29

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 122.81  E-value: 4.41e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPyGCLLDHVRENRGRLGSQDLLNW 811
Cdd:COG0515     34 PVALKVLRPElaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPyLVMEYVE-GESLADLLRRRGPLPPAEALRI 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE-TEYHADGGKVPikWMALESILRRRFTHQSD 890
Cdd:COG0515    113 LAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATlTQTGTVVGTPG--YMAPEQARGEPVDPRSD 190
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  891 VWSYGVTVWELMTfGAKPYDGIPAREipdLLEKGERLPQPPICTidvymimvkcwmIDSECRPRFRELVsefSRM-ARDP 969
Cdd:COG0515    191 VYSLGVTLYELLT-GRPPFDGDSPAE---LLRAHLREPPPPPSE------------LRPDLPPALDAIV---LRAlAKDP 251
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  970 -QRFvviQN-----EDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHR---HRSSSTRS 1040
Cdd:COG0515    252 eERY---QSaaelaAALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAaaaAAPAAAAA 328
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549 1041 GGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCS 1120
Cdd:COG0515    329 AAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAA 408
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|.
gi 1844139549 1121 PQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSP 1161
Cdd:COG0515    409 AAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAA 449
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
366-482 1.15e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.15e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139549  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
787-911 3.36e-10

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 64.05  E-value: 3.36e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  787 MPY--GCLL-DHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD---IDE 860
Cdd:NF033483    86 MEYvdGRTLkDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSsttMTQ 164
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  861 TE-------Y----HADGGKVpikwmalesilrrrfTHQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:NF033483   165 TNsvlgtvhYlspeQARGGTV---------------DARSDIYSLGIVLYEMLT-GRPPFDG 210
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
742-903 4.17e-10

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 63.48  E-value: 4.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  742 RENTSPKANKE--ILDEAYVMAGVGSPYVSRLLGiclTSTVQLVTQL-MP-YGCLLDHVRENRGRLGSQDLLNWCMQIAK 817
Cdd:PHA03212   117 CEHVVIKAGQRggTATEAHILRAINHPSIIQLKG---TFTYNKFTCLiLPrYKTDLYCYLAAKRNIAICDILAIERSVLR 193
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  818 GMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL-LDIDETEYHADGGKVPIKwmALESILRRRFTHQSDVWSYGV 896
Cdd:PHA03212   194 AIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGAACFpVDINANKYYGWAGTIATN--APELLARDPYGPAVDIWSAGI 271

                   ....*..
gi 1844139549  897 TVWELMT 903
Cdd:PHA03212   272 VLFEMAT 278
FU smart00261
Furin-like repeats;
557-603 7.37e-08

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 49.82  E-value: 7.37e-08
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1844139549   557 ARHCLPCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSG 603
Cdd:smart00261    1 DGECKPCHPECA------TCTGPGPDDCTSCKHgfFLDGGKCVSECPPG 43
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
641-684 3.42e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer.


Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.42e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
235-280 2.24e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 45.59  E-value: 2.24e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  235 CCHEQCAaGCTGPKHSDCLACLHFN--HSGICELHCPALVTYNTDTFE 280
Cdd:cd00064      1 PCHPSCA-TCTGPGPDQCTSCRHGFylDGGTCVSECPEGTYADTEGGV 47
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
562-607 4.97e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 44.82  E-value: 4.97e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  562 PCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSGVKPD 607
Cdd:cd00064      1 PCHPSCA------TCTGPGPDQCTSCRHgfYLDGGTCVSECPEGTYAD 42
FU smart00261
Furin-like repeats;
235-270 7.17e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 41.34  E-value: 7.17e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139549   235 CCHEQCAaGCTGPKHSDCLACLHFNH--SGICELHCPA 270
Cdd:smart00261    6 PCHPECA-TCTGPGPDDCTSCKHGFFldGGKCVSECPP 42
 
Name Accession Description Interval E-value
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
712-976 0e+00

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 587.76  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELRK--------------GIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05109      1 MRILKETELKKvkvlgsgafgtvykGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05109    161 IDETEYHADGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 976
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
712-976 0e+00

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 557.80  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELR--------------KGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05057      1 LRIVKETELEkgkvlgsgafgtvyKGVWIPEGEKVKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICLS 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05057     81 SQVQLITQLMPLGCLLDYVRNHRDNIGSQLLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLD 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05057    161 VDEKEYHAEGGKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDV 240
                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 976
Cdd:cd05057    241 YMVLVKCWMIDAESRPTFKELANEFSKMARDPQRYLVIQ 279
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
712-1009 0e+00

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 550.78  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELRK--------------GIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05108      1 LRILKETEFKKikvlgsgafgtvykGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLT 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05108     81 STVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05108    161 AEEKEYHAEGGKVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 240
                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ-NEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEY 1009
Cdd:cd05108    241 YMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQgDERMHLPSPTDSNFYRALMDEEDMDDVVDADEY 313
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
712-999 2.32e-153

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 462.23  E-value: 2.32e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  712 MRILKETELR--------------KGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 777
Cdd:cd05110      1 LRILKETELKrvkvlgsgafgtvyKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLS 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd05110     81 PTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDFGLARLLE 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  858 IDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 937
Cdd:cd05110    161 GDEKEYNADGGKMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDV 240
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  938 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNED-LGPASPLDSTFYRSLLEDDD 999
Cdd:cd05110    241 YMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDrMKLPSPNDSKFFQNLLDEED 303
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
713-976 2.82e-130

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 400.49  E-value: 2.82e-130
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  713 RILKETELR--------------KGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS 778
Cdd:cd05111      2 RIFKETELRklkvlgsgvfgtvhKGIWIPEGDSIKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGA 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI 858
Cdd:cd05111     82 SLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARNVLLKSPSQVQVADFGVADLLYP 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  859 DETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 938
Cdd:cd05111    162 DDKKYFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVY 241
                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1844139549  939 MIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 976
Cdd:cd05111    242 MVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIK 279
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
718-962 3.60e-116

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 361.81  E-value: 3.60e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  718 TELRKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHV 796
Cdd:pfam07714   13 GEVYKGTLKGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVTEYMPGGDLLDFL 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMA 876
Cdd:pfam07714   93 RKHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIKWMA 172
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:pfam07714  173 PESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQCWAYDPEDRPTFS 252

                   ....*.
gi 1844139549  957 ELVSEF 962
Cdd:pfam07714  253 ELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
719-962 6.93e-113

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 352.99  E-value: 6.93e-113
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   719 ELRKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR 797
Cdd:smart00219   14 EVYKGKLKGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEpLYIVMEYMEGGDLLSYLR 93
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKVPIKWMAL 877
Cdd:smart00219   94 KNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDY-YRKRGGKLPIRWMAP 172
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   878 ESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRE 957
Cdd:smart00219  173 ESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDRPTFSE 252

                    ....*
gi 1844139549   958 LVSEF 962
Cdd:smart00219  253 LVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
719-962 1.61e-111

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 349.54  E-value: 1.61e-111
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   719 ELRKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR 797
Cdd:smart00221   14 EVYKGTLKGKGDGKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEpLMIVMEYMPGGDLLDYLR 93
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   798 ENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIKWMA 876
Cdd:smart00221   94 KNRPKeLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLY-DDDYYKVKGGKLPIRWMA 172
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:smart00221  173 PESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQCWAEDPEDRPTFS 252

                    ....*.
gi 1844139549   957 ELVSEF 962
Cdd:smart00221  253 ELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
719-962 7.53e-105

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 331.81  E-value: 7.53e-105
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVR 797
Cdd:cd00192     10 EVYKGKLK-GGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEePLYLVMEYMEGGDLLDFLR 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENR--------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGK 869
Cdd:cd00192     89 KSRpvfpspepSTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYYRKKTGGK 168
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  870 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd00192    169 LPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELMLSCWQLDP 248
                          250
                   ....*....|...
gi 1844139549  950 ECRPRFRELVSEF 962
Cdd:cd00192    249 EDRPTFSELVERL 261
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
721-970 5.27e-85

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 277.31  E-value: 5.27e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  721 RKGIWIPDGeNVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENR 800
Cdd:cd05060     12 RKGVYLMKS-GKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGVCKGEPLMLVMELAPLGPLLKYLKKRR 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 gRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHAD-GGKVPIKWMALES 879
Cdd:cd05060     91 -EIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNRHQAKISDFGMSRALGAGSDYYRATtAGRWPLKWYAPEC 169
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  880 ILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05060    170 INYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPEDRPTFSELE 249
                          250
                   ....*....|.
gi 1844139549  960 sefSRMARDPQ 970
Cdd:cd05060    250 ---STFRRDPE 257
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
719-963 8.00e-78

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 257.74  E-value: 8.00e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRE 798
Cdd:cd05056     21 DVYQGVYM-SPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITENPVWIVMELAPLGELRSYLQV 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIKWMALE 878
Cdd:cd05056    100 NKYSLDLASLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYME-DESYYKASKGKLPIKWMAPE 178
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd05056    179 SINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPSKRPRFTEL 258

                   ....*
gi 1844139549  959 VSEFS 963
Cdd:cd05056    259 KAQLS 263
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
721-963 9.72e-75

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 248.41  E-value: 9.72e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  721 RKGIWI-PDGEnvKIPVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVR 797
Cdd:cd05040     12 RRGEWTtPSGK--VIQVAVKCLKSDvlSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSPLMMVTELAPLGSLLDRLR 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEY-HADGGKVPIKWMA 876
Cdd:cd05040     90 KDQGHFLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDHYvMQEHRKVPFAWCA 169
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEK-GERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05040    170 PESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKeGERLERPDDCPQDIYNVMLQCWAHKPADRPTF 249

                   ....*...
gi 1844139549  956 RELVSEFS 963
Cdd:cd05040    250 VALRDFLP 257
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
719-962 1.33e-69

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 233.71  E-value: 1.33e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHV 796
Cdd:cd05034     10 EVWMGVW-----NGTTKVAVKTLKPGTmSPEA---FLQEAQIMKKLRHDKLVQLYAVCSDEEpIYIVTELMSKGSLLDYL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKW 874
Cdd:cd05034     82 RTGEGRaLRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNVCKVADFGLARL--IEDDEYTArEGAKFPIKW 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd05034    160 TAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKKEPEERPT 239

                   ....*...
gi 1844139549  955 FRELVSEF 962
Cdd:cd05034    240 FEYLQSFL 247
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
726-965 7.91e-67

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 227.69  E-value: 7.91e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  726 IPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR--- 800
Cdd:cd05053     36 LDNKPNEVVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKhKNIINLLGACTQDgPLYVVVEYASKGNLREFLRARRppg 115
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 ------------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--AD 866
Cdd:cd05053    116 eeaspddprvpeEQLTQKDLVSFAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLAR--DIHHIDYYrkTT 193
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  867 GGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWM 946
Cdd:cd05053    194 NGRLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMEKPQNCTQELYMLMRDCWH 273
                          250
                   ....*....|....*....
gi 1844139549  947 IDSECRPRFRELVSEFSRM 965
Cdd:cd05053    274 EVPSQRPTFKQLVEDLDRI 292
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
734-965 2.36e-66

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 224.94  E-value: 2.36e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWC 812
Cdd:cd05033     33 IDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTkSRPVMIVTEYMENGSLDKFLRENDGKFTVTQLVGML 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05033    113 RGIASGMKYLSEMNYVHRDLAARNILVNSDLVCKVSDFGLSRRLEDSEATYTTKGGKIPIRWTAPEAIAYRKFTSASDVW 192
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05033    193 SFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQKDRNERPTFSQIVSTLDKM 265
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
725-966 1.84e-65

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 223.41  E-value: 1.84e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  725 WIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC---LTSTVQLVTQLMPYGCLLDHVRENRG 801
Cdd:cd05038     25 YDPLGDNTGEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCespGRRSLRLIMEYLPSGSLRDYLQRHRD 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALESI 880
Cdd:cd05038    105 QIDLKRLLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKEYYYVkEPGESPIFWYAPECL 184
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYD--GIPAREIP------------DLLEKGERLPQPPICTIDVYMIMVKCWM 946
Cdd:cd05038    185 RESRFSSASDVWSFGVTLYELFTYGDPSQSppALFLRMIGiaqgqmivtrllELLKSGERLPRPPSCPDEVYDLMKECWE 264
                          250       260
                   ....*....|....*....|
gi 1844139549  947 IDSECRPRFRELVSEFSRMA 966
Cdd:cd05038    265 YEPQDRPSFSDLILIIDRLR 284
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
736-964 1.00e-64

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 219.91  E-value: 1.00e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVReNRGR--LGSQDLLNWC 812
Cdd:cd05039     32 VAVKCLKDDS--TAAQAFLAEASVMTTLRHPNLVQLLGVVLEgNGLYIVTEYMAKGSLVDYLR-SRGRavITRKDQLGFA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidETEYHADGGKVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05039    109 LDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVSDFGLAK-----EASSNQDGGKLPIKWTAPEALREKKFSTKSDVW 183
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSR 964
Cdd:cd05039    184 SFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELDPAKRPTFKQLREKLEH 255
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
719-958 2.49e-64

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 219.20  E-value: 2.49e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKankEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHV 796
Cdd:cd05068     23 EVWEGLW-----NNTTPVAVKTLKPGTmDPE---DFLREAQIMKKLRHPKLIQLYAVCtLEEPIYIITELMKHGSLLEYL 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDEtEYHA-DGGKVPIKWM 875
Cdd:cd05068     95 QGKGRSLQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKVED-EYEArEGAKFPIKWT 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05068    174 APEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIMLECWKADPMERPTF 253

                   ...
gi 1844139549  956 REL 958
Cdd:cd05068    254 ETL 256
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
726-960 9.38e-64

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 217.98  E-value: 9.38e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  726 IPDGEnVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT-QLMPYGCLLDHVRENR---- 800
Cdd:cd05032     30 VVKGE-PETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTGQPTLVVmELMAKGDLKSYLRSRRpeae 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 -----GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIK 873
Cdd:cd05032    109 nnpglGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLAARNCMVAEDLTVKIGDFGMTR--DIYETDYYRKGGKglLPVR 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  874 WMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRP 953
Cdd:cd05032    187 WMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHLDLPENCPDKLLELMRMCWQYNPKMRP 266

                   ....*..
gi 1844139549  954 RFRELVS 960
Cdd:cd05032    267 TFLEIVS 273
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
733-956 1.27e-63

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 217.28  E-value: 1.27e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENR------GRLGS 805
Cdd:cd05044     26 ETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLdNDPQYIILELMEGGDLLSYLRAARptaftpPLLTL 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH----VKITDFGLARllDIDETEYH-ADG-GKVPIKWMALES 879
Cdd:cd05044    106 KDLLSICVDVAKGCVYLEDMHFVHRDLAARNCLVSSKDYrervVKIGDFGLAR--DIYKNDYYrKEGeGLLPVRWMAPES 183
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  880 ILRRRFTHQSDVWSYGVTVWELMTFGAKPYdgiPAR---EIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd05044    184 LVDGVFTTQSDVWAFGVLMWEILTLGQQPY---PARnnlEVLHFVRAGGRLDQPDNCPDDLYELMLRCWSTDPEERPSFA 260
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
733-960 2.83e-63

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 215.77  E-value: 2.83e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05059     28 KIDVAIKMIKEGS--MSEDDFIEEAKVMMKLSHPKLVQLYGVCTKqRPIFIVTEYMANGCLLNYLRERRGKFQTEQLLEM 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR-LLDideTEYHADGG-KVPIKWMALESILRRRFTHQS 889
Cdd:cd05059    106 CKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARyVLD---DEYTSSVGtKFPVKWSPPEVFMYSKFSSKS 182
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  890 DVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05059    183 DVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPEERPTFKILLS 253
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
736-965 6.94e-63

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 214.98  E-value: 6.94e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKanKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVRE-NRGRLGSQDLLNWCM 813
Cdd:cd05052     34 VAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCtREPPFYIITEFMPYGNLLDYLREcNREELNAVVLLYMAT 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHAdGGKVPIKWMALESILRRRFTHQSDVWS 893
Cdd:cd05052    112 QIASAMEYLEKKNFIHRDLAARNCLVGENHLVKVADFGLSRLMTGDTYTAHA-GAKFPIKWTAPESLAYNKFSIKSDVWA 190
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  894 YGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05052    191 FGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPSDRPSFAEIHQALETM 262
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
728-963 3.12e-61

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 210.41  E-value: 3.12e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS--TVQLVTQLMPYGCLLDHVRENRGRLGS 805
Cdd:cd05058     18 DSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSegSPLVVLPYMKHGDLRNFIRSETHNPTV 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHA----DGGKVPIKWMALESIL 881
Cdd:cd05058     98 KDLIGFGLQVAKGMEYLASKKFVHRDLAARNCMLDESFTVKVADFGLAR--DIYDKEYYSvhnhTGAKLPVKWMALESLQ 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd05058    176 TQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCWHPKPEMRPTFSELVSR 255

                   ..
gi 1844139549  962 FS 963
Cdd:cd05058    256 IS 257
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
511-643 1.48e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 200.29  E-value: 1.48e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
736-961 1.22e-58

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 202.29  E-value: 1.22e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd05041     23 VAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVqKQPIMIVMELVPGGSLLTFLRKKGARLTVKQLLQMCLD 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGG--KVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05041    103 AAAGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGMSR--EEEDGEYTVSDGlkQIPIKWTAPEALNYGRYTSESDVW 180
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd05041    181 SFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPENRPSFSEIYNE 249
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
735-955 3.05e-58

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 201.73  E-value: 3.05e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCM 813
Cdd:cd05116     24 TVAVKILKnEANDPALKDELLREANVMQQLDNPYIVRMIGICEAESWMLVMEMAELGPLNKFLQKNR-HVTEKNITELVH 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADG-GKVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05116    103 QVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGLSKALRADENYYKAQThGKWPVKWYAPECMNYYKFSSKSDVW 182
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05116    183 SFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDVDERPGF 245
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
733-965 3.41e-58

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 202.02  E-value: 3.41e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05065     32 EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRpVMIITEFMENGALDSFLRQNDGQFTVIQLVGM 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD---IDETEYHADGGKVPIKWMALESILRRRFTHQ 888
Cdd:cd05065    112 LRGIAAGMKYLSEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFLEddtSDPTYTSSLGGKIPIRWTAPEAIAYRKFTSA 191
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  889 SDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05065    192 SDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDCWQKDRNLRPKFGQIVNTLDKM 268
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
736-965 4.38e-58

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 202.50  E-value: 4.38e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR----GRLGS----- 805
Cdd:cd05045     33 VAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDgPLLLIVEYAKYGSLRSFLRESRkvgpSYLGSdgnrn 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 --------------QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVP 871
Cdd:cd05045    113 ssyldnpderaltmGDLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMKISDFGLSRDVYEEDSYVKRSKGRIP 192
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 IKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSEC 951
Cdd:cd05045    193 VKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTGYRMERPENCSEEMYNLMLTCWKQEPDK 272
                          250
                   ....*....|....
gi 1844139549  952 RPRFRELVSEFSRM 965
Cdd:cd05045    273 RPTFADISKELEKM 286
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
734-963 5.31e-58

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 201.12  E-value: 5.31e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVRENRGR-LGSQDLLNW 811
Cdd:cd05148     31 VRVAIKILKSDDLLKQ-QDFQKEVQALKRLRHKHLISLFAVCsVGEPVYIITELMEKGSLLAFLRSPEGQvLPVASLIDM 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd05148    110 ACQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARL--IKEDVYLSSDKKIPYKWTAPEAASHGTFSTKSDV 187
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  892 WSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:cd05148    188 WSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLECWAAEPEDRPSFKALREELD 259
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
720-955 9.18e-58

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 200.56  E-value: 9.18e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  720 LRKGIWipDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVREN 799
Cdd:cd05115     20 VKKGVY--KMRKKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALMLVMEMASGGPLNKFLSGK 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALE 878
Cdd:cd05115     98 KDEITVSNVVELMHQVSMGMKYLEEKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSYYKArSAGKWPLKWYAPE 177
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05115    178 CINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKWEDRPNF 254
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
719-965 3.61e-57

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 199.04  E-value: 3.61e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVR 797
Cdd:cd05063     20 EVFRGILKMPGRK-EVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKfKPAMIITEYMENGALDKYLR 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID-ETEYHADGGKVPIKWMA 876
Cdd:cd05063     99 DHDGEFSSYQLVGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDDpEGTYTTSGGKIPIRWTA 178
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd05063    179 PEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVYQLMLQCWQQDRARRPRFV 258

                   ....*....
gi 1844139549  957 ELVSEFSRM 965
Cdd:cd05063    259 DIVNLLDKL 267
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
734-965 4.23e-57

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 198.55  E-value: 4.23e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWC 812
Cdd:cd05066     33 IPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKpVMIVTEYMENGSLDAFLRKHDGQFTVIQLVGML 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID-ETEYHADGGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd05066    113 RGIASGMKYLSDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVLEDDpEAAYTTRGGKIPIRWTAPEAIAYRKFTSASDV 192
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  892 WSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05066    193 WSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQKDRNERPKFEQIVSILDKL 266
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
727-965 3.77e-56

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 197.88  E-value: 3.77e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR---- 800
Cdd:cd05099     38 KSRPDQTVTVAVKMLKDNATDKDLADLISEMELMKLIGKhKNIINLLGVCTQEgPLYVIVEYAAKGNLREFLRARRppgp 117
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 -----------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--ADG 867
Cdd:cd05099    118 dytfditkvpeEQLSFKDLVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLAR--GVHDIDYYkkTSN 195
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  868 GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 947
Cdd:cd05099    196 GRLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEELFKLLREGHRMDKPSNCTHELYMLMRECWHA 275
                          250
                   ....*....|....*...
gi 1844139549  948 DSECRPRFRELVSEFSRM 965
Cdd:cd05099    276 VPTQRPTFKQLVEALDKV 293
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
736-958 2.83e-54

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 191.78  E-value: 2.83e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYG----CLLDHVRE-------NRGRL 803
Cdd:cd05051     49 VAVKMLRPDASKNAREDFLKEVKIMSQLKDPNIVRLLGVCTRDePLCMIVEYMENGdlnqFLQKHEAEtqgasatNSKTL 128
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdideteYHADGGKV------PIKWMAL 877
Cdd:cd05051    129 SYGTLLYMATQIASGMKYLESLNFVHRDLATRNCLVGPNYTIKIADFGMSRNL------YSGDYYRIegravlPIRWMAW 202
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  878 ESILRRRFTHQSDVWSYGVTVWELMTFG-AKPYDGIPARE-IPDLLEK----GER--LPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd05051    203 ESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTDEQvIENAGEFfrddGMEvyLSRPPNCPKEIYELMLECWRRDE 282

                   ....*....
gi 1844139549  950 ECRPRFREL 958
Cdd:cd05051    283 EDRPTFREI 291
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
734-965 1.42e-53

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 190.23  E-value: 1.42e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR----------- 800
Cdd:cd05101     57 VTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKhKNIINLLGACTQDgPLYVIVEYASKGNLREYLRARRppgmeysydin 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 ----GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--ADGGKVPIKW 874
Cdd:cd05101    137 rvpeEQMTFKDLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLAR--DINNIDYYkkTTNGRLPVKW 214
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd05101    215 MAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQRPT 294
                          250
                   ....*....|.
gi 1844139549  955 FRELVSEFSRM 965
Cdd:cd05101    295 FKQLVEDLDRI 305
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
727-955 1.52e-53

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 188.75  E-value: 1.52e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQL-VTQLMPYGCLLDHVRENRGRLGS 805
Cdd:cd05036     30 MPGDPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQRLPRFiLLELMAGGDLKSFLRENRPRPEQ 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 ------QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARllDIDETEYHADGGK--VPIKW 874
Cdd:cd05036    110 pssltmLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKGPgrvAKIGDFGMAR--DIYRADYYRKGGKamLPVKW 187
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd05036    188 MPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRMDPPKNCPGPVYRIMTQCWQHIPEDRPN 267

                   .
gi 1844139549  955 F 955
Cdd:cd05036    268 F 268
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
722-963 1.80e-53

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 187.85  E-value: 1.80e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDGEnvkipVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENR 800
Cdd:cd05112     22 LGYWLNKDK-----VAIKTIREGA--MSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQApICLVFEFMEHGCLSDYLRTQR 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPIKWMALESI 880
Cdd:cd05112     95 GLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRFV-LDDQYTSSTGTKFPVKWSSPEVF 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05112    174 SFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERPEDRPSFSLLLR 253

                   ...
gi 1844139549  961 EFS 963
Cdd:cd05112    254 QLA 256
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
727-958 4.57e-53

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 187.58  E-value: 4.57e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYGCL------------- 792
Cdd:cd05048     29 PSSEESAISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKEQPQcMLFEYMAHGDLheflvrhsphsdv 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 --LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK- 869
Cdd:cd05048    109 gvSSDDDGTASSLDQSDFLHIAIQIAAGMEYLSSHHYVHRDLAARNCLVGDGLTVKISDFGLSR--DIYSSDYYRVQSKs 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  870 -VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 948
Cdd:cd05048    187 lLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQLLPCPEDCPARVYSLMVECWHEI 266
                          250
                   ....*....|
gi 1844139549  949 SECRPRFREL 958
Cdd:cd05048    267 PSRRPRFKEI 276
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
719-962 5.95e-53

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 185.82  E-value: 5.95e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIpdgenvKIPVAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHV 796
Cdd:cd13999      8 EVYKGKWR------GTDVAIKKLKVEDDNDELlKEFRREVSILSKLRHPNIVQFIGACLSpPPLCIVTEYMPGGSLYDLL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVpiKWMA 876
Cdd:cd13999     82 HKKKIPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTEKMTGVVGTP--RWMA 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLL-EKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd13999    160 PEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAVvQKGLRPPIPPDCPPELSKLIKRCWNEDPEKRPSF 238

                   ....*..
gi 1844139549  956 RELVSEF 962
Cdd:cd13999    239 SEIVKRL 245
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
729-958 7.21e-53

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 185.96  E-value: 7.21e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  729 GENVKIPVAIKVLRENTSPKAnkeILDEAYVMAGVGSPYVSRLLGICL--TSTVQLVTQLMPYGCLLDHVReNRGR--LG 804
Cdd:cd05082     25 GDYRGNKVAVKCIKNDATAQA---FLAEASVMTQLRHSNLVQLLGVIVeeKGGLYIVTEYMAKGSLVDYLR-SRGRsvLG 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  805 SQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidETEYHADGGKVPIKWMALESILRRR 884
Cdd:cd05082    101 GDCLLKFSLDVCEAMEYLEGNNFVHRDLAARNVLVSEDNVAKVSDFGLTK-----EASSTQDTGKLPVKWTAPEALREKK 175
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  885 FTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd05082    176 FSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLDAAMRPSFLQL 249
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
729-965 8.71e-53

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 185.85  E-value: 8.71e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  729 GENVKIPVAIKVLRENTSPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVReNRGR--LGSQ 806
Cdd:cd05083     25 GEYMGQKVAVKNIKCDVTAQA---FLEETAVMTKLQHKNLVRLLGVILHNGLYIVMELMSKGNLVNFLR-SRGRalVPVI 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 DLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldideTEYHADGGKVPIKWMALESILRRRFT 886
Cdd:cd05083    101 QLLQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFGLAKV-----GSMGVDNSRLPVKWTAPEALKNKKFS 175
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  887 HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05083    176 SKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAEPGKRPSFKKLREKLEKE 254
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
736-965 3.72e-52

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 185.60  E-value: 3.72e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR------------- 800
Cdd:cd05098     48 VAVKMLKSDATEKDLSDLISEMEMMKMIGKhKNIINLLGACTQDgPLYVIVEYASKGNLREYLQARRppgmeycynpshn 127
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 --GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--ADGGKVPIKWMA 876
Cdd:cd05098    128 peEQLSSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLAR--DIHHIDYYkkTTNGRLPVKWMA 205
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd05098    206 PEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDKPSNCTNELYMMMRDCWHAVPSQRPTFK 285

                   ....*....
gi 1844139549  957 ELVSEFSRM 965
Cdd:cd05098    286 QLVEDLDRI 294
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
719-960 8.57e-52

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 182.81  E-value: 8.57e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVR 797
Cdd:cd14203     10 EVWMGTW-----NGTTKVAIKTLKPGTmSPEA---FLEEAQIMKKLRHDKLVQLYAVVSEEPIYIVTEFMSKGSLLDFLK 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWM 875
Cdd:cd14203     82 DGEGKyLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARL--IEDNEYTArQGAKFPIKWT 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd14203    160 APEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKDPEERPTF 239

                   ....*
gi 1844139549  956 RELVS 960
Cdd:cd14203    240 EYLQS 244
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
736-960 2.03e-51

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 182.39  E-value: 2.03e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRG-RLGSQDLLNWCM 813
Cdd:cd05067     34 VAIKSLKQGSmSPDA---FLAEANLMKQLQHQRLVRLYAVVTQEPIYIITEYMENGSLVDFLKTPSGiKLTINKLLDMAA 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05067    111 QIAEGMAFIEERNYIHRDLRAANILVSDTLSCKIADFGLARL--IEDNEYTArEGAKFPIKWTAPEAINYGTFTIKSDVW 188
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05067    189 SFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLMRLCWKERPEDRPTFEYLRS 256
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
733-963 2.08e-51

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 181.74  E-value: 2.08e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05085     20 KTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQrQPIYIVMELVPGGDFLSFLRKKKDELKTKQLVKF 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK-VPIKWMALESILRRRFTHQSD 890
Cdd:cd05085    100 SLDAAAGMAYLESKNCIHRDLAARNCLVGENNALKISDFGMSR--QEDDGVYSSSGLKqIPIKWTAPEALNYGRYSSESD 177
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  891 VWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:cd05085    178 VWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENRPKFSELQKELA 250
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
730-966 2.54e-51

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 183.46  E-value: 2.54e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPY-VSRLLGIC-LTSTVQLVTQLMPYGCLLDHVRENRGR-LGSQ 806
Cdd:cd05055     62 SDAVMKVAVKMLKPTAHSSEREALMSELKIMSHLGNHEnIVNLLGACtIGGPILVITEYCCYGDLLNFLRRKRESfLTLE 141
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 DLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDI-DETEYHADG-GKVPIKWMALESILRRR 884
Cdd:cd05055    142 DLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKICDFGLAR--DImNDSNYVVKGnARLPVKWMAPESIFNCV 219
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  885 FTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:cd05055    220 YTFESDVWSYGILLWEIFSLGSNPYPGMPVDSkFYKLIKEGYRMAQPEHAPAEIYDIMKTCWDADPLKRPTFKQIVQLIG 299

                   ...
gi 1844139549  964 RMA 966
Cdd:cd05055    300 KQL 302
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
728-965 2.76e-51

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 184.45  E-value: 2.76e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR----- 800
Cdd:cd05100     39 DKPNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKhKNIINLLGACTQDgPLYVLVEYASKGNLREYLRARRppgmd 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 ----------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--ADGG 868
Cdd:cd05100    119 ysfdtcklpeEQLTFKDLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLAR--DVHNIDYYkkTTNG 196
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  869 KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 948
Cdd:cd05100    197 RLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAV 276
                          250
                   ....*....|....*..
gi 1844139549  949 SECRPRFRELVSEFSRM 965
Cdd:cd05100    277 PSQRPTFKQLVEDLDRV 293
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
733-959 4.42e-51

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 181.21  E-value: 4.42e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05114     28 QYKVAIKAIREGA--MSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKpIYIVTEFMENGCLLNYLRQRRGKLSRDMLLSM 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd05114    106 CQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYV-LDDQYTSSSGAKFPVKWSPPEVFNYSKFSSKSDV 184
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  892 WSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05114    185 WSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGRPTFADLL 252
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
728-965 4.60e-51

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 181.58  E-value: 4.60e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-------LVTQLMPYG-----CLLD 794
Cdd:cd05035     24 DGSQLK--VAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkppspmVILPFMKHGdlhsyLLYS 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  795 HVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADG--GKVPI 872
Cdd:cd05035    102 RLGGLPEKLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAARNCMLDENMTVCVADFGLSR--KIYSGDYYRQGriSKMPV 179
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd05035    180 KWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVYFLMYFCWTVDPKDR 259
                          250
                   ....*....|...
gi 1844139549  953 PRFRELVSEFSRM 965
Cdd:cd05035    260 PTFTKLREVLENI 272
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
717-958 5.60e-51

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 181.67  E-value: 5.60e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  717 ETELRKgiwiPDGENVKipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ------LVTQLMPY 789
Cdd:cd14204     25 EGELQQ----PDGTNHK--VAVKTMKlDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLEVGSQripkpmVILPFMKY 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 GCLldHVRENRGRLGS-------QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETE 862
Cdd:cd14204     99 GDL--HSFLLRSRLGSgpqhvplQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVADFGLSK--KIYSGD 174
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  863 YHADG--GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMI 940
Cdd:cd14204    175 YYRQGriAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLKQPEDCLDELYDI 254
                          250
                   ....*....|....*...
gi 1844139549  941 MVKCWMIDSECRPRFREL 958
Cdd:cd14204    255 MYSCWRSDPTDRPTFTQL 272
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
736-960 7.11e-51

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 180.46  E-value: 7.11e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd05113     31 VAIKMIKEGS--MSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQrPIFIITEYMANGCLLNYLREMRKRFQTQQLLEMCKD 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSY 894
Cdd:cd05113    109 VCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYV-LDDEYTSSVGSKFPVRWSPPEVLMYSKFSSKSDVWAF 187
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  895 GVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05113    188 GVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHEKADERPTFKILLS 253
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
691-962 2.38e-50

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 179.73  E-value: 2.38e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  691 LQETELVEPLTPSGAMPNQAQMRILKETELRkgiwIPDGENVKipVAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVS 769
Cdd:cd05074      1 LKDVLIQEQQFTLGRMLGKGEFGSVREAQLK----SEDGSFQK--VAVKMLKADIFSSSDiEEFLREAACMKEFDHPNVI 74
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  770 RLLGICLTSTVQ-------LVTQLMPYG-----CLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNV 837
Cdd:cd05074     75 KLIGVSLRSRAKgrlpipmVILPFMKHGdlhtfLLMSRIGEEPFTLPLQTLVRFMIDIASGMEYLSSKNFIHRDLAARNC 154
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  838 LVKSPNHVKITDFGLARllDIDETEYHADG--GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAR 915
Cdd:cd05074    155 MLNENMTVCVADFGLSK--KIYSGDYYRQGcaSKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENS 232
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  916 EIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEF 962
Cdd:cd05074    233 EIYNYLIKGNRLKQPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQL 279
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
727-958 1.17e-49

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 177.78  E-value: 1.17e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTsPKANKEILDEAYVMAGVGSPYVSRLLGICLTS---TVQLVTQLMPYGCLLDHVRENRGRL 803
Cdd:cd05081     27 PLGDNTGALVAVKQLQHSG-PDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrrSLRLVMEYLPSGCLRDFLQRHRARL 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALESILR 882
Cdd:cd05081    106 DASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLLPLDKDYYVVrEPGQSPIFWYAPESLSD 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAK-------------PYDGIPAR-EIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 948
Cdd:cd05081    186 NIFSRQSDVWSFGVVLYELFTYCDKscspsaeflrmmgCERDVPALcRLLELLEEGQRLPAPPACPAEVHELMKLCWAPS 265
                          250
                   ....*....|
gi 1844139549  949 SECRPRFREL 958
Cdd:cd05081    266 PQDRPSFSAL 275
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
719-960 1.33e-48

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 174.56  E-value: 1.33e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC--LTSTVQLVTQLMPYGCL---- 792
Cdd:cd05043     21 RIFHGILR-DEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCieDGEKPMVLYPYMNWGNLklfl 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 --LDHVRENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH--ADG 867
Cdd:cd05043    100 qqCRLSEANNPQaLSTQQLVHMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKITDNALSR--DLFPMDYHclGDN 177
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  868 GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 947
Cdd:cd05043    178 ENRPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINCPDELFAVMACCWAL 257
                          250
                   ....*....|...
gi 1844139549  948 DSECRPRFRELVS 960
Cdd:cd05043    258 DPEERPSFQQLVQ 270
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
726-958 3.75e-48

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 173.42  E-value: 3.75e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  726 IPDGEnvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVREN----- 799
Cdd:cd05049     30 EPEQD--KMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEGdPLLMVFEYMEHGDLNKFLRSHgpdaa 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 --------RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK-- 869
Cdd:cd05049    108 flasedsaPGELTLSQLLHIAVQIASGMVYLASQHFVHRDLATRNCLVGTNLVVKIGDFGMSR--DIYSTDYYRVGGHtm 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  870 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd05049    186 LPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQGRLLQRPRTCPSEVYAVMLGCWKREP 265

                   ....*....
gi 1844139549  950 ECRPRFREL 958
Cdd:cd05049    266 QQRLNIKDI 274
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
735-955 4.61e-48

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 172.04  E-value: 4.61e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd05084     23 PVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQpIYIVMELVQGGDFLTFLRTEGPRLKVKELIRMVE 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGG--KVPIKWMALESILRRRFTHQSDV 891
Cdd:cd05084    103 NAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGMSR--EEEDGVYAATGGmkQIPVKWTAPEALNYGRYSSESDV 180
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  892 WSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05084    181 WSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPRKRPSF 244
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
734-968 1.30e-47

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 171.73  E-value: 1.30e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKANKE-ILDEAYVMAGVGSPYVSRLLGICLTSTVQ-------LVTQLMPYGCLldHVRENRGRLG- 804
Cdd:cd05075     28 LKVAVKTMKIAICTRSEMEdFLSEAVCMKEFDHPNVMRLIGVCLQNTESegypspvVILPFMKHGDL--HSFLLYSRLGd 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  805 ------SQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADG--GKVPIKWMA 876
Cdd:cd05075    106 cpvylpTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADFGLSK--KIYNGDYYRQGriSKMPVKWIA 183
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd05075    184 IESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLLNPKDRPSFE 263
                          250
                   ....*....|..
gi 1844139549  957 ELVSEFSRMARD 968
Cdd:cd05075    264 TLRCELEKILKD 275
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
736-963 2.01e-47

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 171.90  E-value: 2.01e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPY-VSRLLGICLTSTVQL--VTQLMPYGCLLDHVRENR------------ 800
Cdd:cd05054     40 VAVKMLKEGATASEHKALMTELKILIHIGHHLnVVNLLGACTKPGGPLmvIVEFCKFGNLSNYLRSKReefvpyrdkgar 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 -------------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADG 867
Cdd:cd05054    120 dveeeedddelykEPLTLEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGD 199
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  868 GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWM 946
Cdd:cd05054    200 ARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQMdEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWH 279
                          250
                   ....*....|....*..
gi 1844139549  947 IDSECRPRFRELVSEFS 963
Cdd:cd05054    280 GEPKERPTFSELVEKLG 296
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
736-959 1.56e-46

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 168.99  E-value: 1.56e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT-QLMPYGCLLDHVR-------ENRGRLGS-- 805
Cdd:cd05061     39 VAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVmELMAHGDLKSYLRslrpeaeNNPGRPPPtl 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIKWMALESILRR 883
Cdd:cd05061    119 QEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAHDFTVKIGDFGMTR--DIYETDYYRKGGKglLPVRWMAPESLKDG 196
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05061    197 VFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPTFLEIV 272
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
730-965 1.07e-45

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 165.98  E-value: 1.07e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENR------- 800
Cdd:cd05047     19 DGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHhPNIINLLGACEHrGYLYLAIEYAPHGNLLDFLRKSRvletdpa 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 --------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldiDETEYHADGGKVPI 872
Cdd:cd05047     99 faianstaSTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG---QEVYVKKTMGRLPV 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd05047    176 RWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYER 255
                          250
                   ....*....|...
gi 1844139549  953 PRFRELVSEFSRM 965
Cdd:cd05047    256 PSFAQILVSLNRM 268
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
719-970 1.27e-45

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 166.01  E-value: 1.27e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVR 797
Cdd:cd05070     24 EVWMGTW-----NGNTKVAIKTLKPGTmSPES---FLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLK 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWM 875
Cdd:cd05070     96 DGEGRaLKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARL--IEDNEYTArQGAKFPIKWT 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05070    174 APEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTF 253
                          250
                   ....*....|....*..
gi 1844139549  956 RELVS--EFSRMARDPQ 970
Cdd:cd05070    254 EYLQGflEDYFTATEPQ 270
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
736-960 1.45e-45

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 165.60  E-value: 1.45e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENRG-RLGSQDLLNWCM 813
Cdd:cd05072     34 VAVKTLKPGT--MSVQAFLEEANLMKTLQHDKLVRLYAVVTkEEPIYIITEYMAKGSLLDFLKSDEGgKVLLPKLIDFSA 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWMALESILRRRFTHQSDVW 892
Cdd:cd05072    112 QIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARV--IEDNEYTArEGAKFPIKWTAPEAINFGSFTIKSDVW 189
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05072    190 SFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKTCWKEKAEERPTFDYLQS 257
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
727-958 4.72e-45

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 164.80  E-value: 4.72e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTS---TVQLVTQLMPYGCLLDHVRENRGRL 803
Cdd:cd14205     27 PLQDNTGEVVAVKKLQHSTEEHL-RDFEREIEILKSLQHDNIVKYKGVCYSAgrrNLRLIMEYLPYGSLRDYLQKHKERI 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALESILR 882
Cdd:cd14205    106 DHIKLLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLPQDKEYYKVkEPGESPIFWYAPESLTE 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAKPYDGiPAR----------------EIPDLLEKGERLPQPPICTIDVYMIMVKCWM 946
Cdd:cd14205    186 SKFSVASDVWSFGVVLYELFTYIEKSKSP-PAEfmrmigndkqgqmivfHLIELLKNNGRLPRPDGCPDEIYMIMTECWN 264
                          250
                   ....*....|..
gi 1844139549  947 IDSECRPRFREL 958
Cdd:cd14205    265 NNVNQRPSFRDL 276
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
733-973 2.00e-44

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 163.25  E-value: 2.00e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENR---------- 800
Cdd:cd05089     29 KMNAAIKMLKEFASENDHRDFAGELEVLCKLGHhPNIINLLGACENrGYLYIAIEYAPYGNLLDFLRKSRvletdpafak 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 -----GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldiDETEYHADGGKVPIKWM 875
Cdd:cd05089    109 ehgtaSTLTSQQLLQFASDVAKGMQYLSEKQFIHRDLAARNVLVGENLVSKIADFGLSRG---EEVYVKKTMGRLPVRWM 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05089    186 AIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDDEVYELMRQCWRDRPYERPPF 265
                          250
                   ....*....|....*...
gi 1844139549  956 RELVSEFSRMARDPQRFV 973
Cdd:cd05089    266 SQISVQLSRMLEARKAYV 283
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
736-958 2.48e-44

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 162.69  E-value: 2.48e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVR----------------- 797
Cdd:cd05050     38 VAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCaVGKPMCLLFEYMAYGDLNEFLRhrspraqcslshstssa 117
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ----ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH-ADGGK-VP 871
Cdd:cd05050    118 rkcgLNPLPLSCTEQLCIAKQVAAGMAYLSERKFVHRDLATRNCLVGENMVVKIADFGLSR--NIYSADYYkASENDaIP 195
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 IKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSEC 951
Cdd:cd05050    196 IRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIYYVRDGNVLSCPDNCPLELYNLMRLCWSKLPSD 275

                   ....*..
gi 1844139549  952 RPRFREL 958
Cdd:cd05050    276 RPSFASI 282
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
733-965 2.62e-44

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 162.02  E-value: 2.62e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05064     33 ELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRgNTMMIVTEYMSNGALDSFLRKHEGQLVAGQLMGM 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFG-LARllDIDETEYHADGGKVPIKWMALESILRRRFTHQSD 890
Cdd:cd05064    113 LPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGFRrLQE--DKSEAIYTTMSGKSPVLWAAPEAIQYHHFSSASD 190
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  891 VWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd05064    191 VWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKERGERPRFSQIHSILSKM 265
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
731-960 6.76e-44

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 160.58  E-value: 6.76e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  731 NVKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRG-RLGSQDLL 809
Cdd:cd05073     33 NKHTKVAVKTMKPGS--MSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGsKQPLPKLI 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWMALESILRRRFTHQ 888
Cdd:cd05073    111 DFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARV--IEDNEYTArEGAKFPIKWTAPEAINFGSFTIK 188
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  889 SDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05073    189 SDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQS 260
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
719-958 2.01e-43

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 159.85  E-value: 2.01e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVR 797
Cdd:cd05071     24 EVWMGTW-----NGTTRVAIKTLKPGTmSPEA---FLQEAQVMKKLRHEKLVQLYAVVSEEPIYIVTEYMSKGSLLDFLK 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWM 875
Cdd:cd05071     96 GEMGKyLRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARL--IEDNEYTArQGAKFPIKWT 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05071    174 APEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLMCQCWRKEPEERPTF 253

                   ...
gi 1844139549  956 REL 958
Cdd:cd05071    254 EYL 256
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
727-965 2.85e-43

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 159.32  E-value: 2.85e-43
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT---STVQLVTQLMPYGCLLDHVRENRGRL 803
Cdd:cd05079     27 PEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEdggNGIKLIMEFLPSGSLKEYLPRNKNKI 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALESILR 882
Cdd:cd05079    107 NLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVkDDLDSPVFWYAPECLIQ 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAK-------------PYDG-IPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 948
Cdd:cd05079    187 SKFYIASDVWSFGVTLYELLTYCDSesspmtlflkmigPTHGqMTVTRLVRVLEEGKRLPRPPNCPEEVYQLMRKCWEFQ 266
                          250
                   ....*....|....*..
gi 1844139549  949 SECRPRFRELVSEFSRM 965
Cdd:cd05079    267 PSKRTTFQNLIEGFEAI 283
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
719-970 2.76e-42

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 156.39  E-value: 2.76e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVR 797
Cdd:cd05069     27 EVWMGTW-----NGTTKVAIKTLKPGTmMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMGKGSLLDFLK 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGR-LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHA-DGGKVPIKWM 875
Cdd:cd05069     99 EGDGKyLKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARL--IEDNEYTArQGAKFPIKWT 176
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05069    177 APEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHELMKLCWKKDPDERPTF 256
                          250
                   ....*....|....*..
gi 1844139549  956 RELVS--EFSRMARDPQ 970
Cdd:cd05069    257 EYIQSflEDYFTATEPQ 273
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
730-964 2.77e-42

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 156.66  E-value: 2.77e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSpKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREN--------- 799
Cdd:cd05092     32 EQDKMLVAVKALKEATE-SARQDFQREAELLTVLQHQHIVRFYGVCTEGEpLIMVFEYMRHGDLNRFLRSHgpdakildg 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 -----RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPI 872
Cdd:cd05092    111 gegqaPGQLTLGQMLQIASQIASGMVYLASLHFVHRDLATRNCLVGQGLVVKIGDFGMSR--DIYSTDYYRVGGRtmLPI 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd05092    189 RWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELERPRTCPPEVYAIMQGCWQREPQQR 268
                          250
                   ....*....|..
gi 1844139549  953 PRFRELVSEFSR 964
Cdd:cd05092    269 HSIKDIHSRLQA 280
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
731-960 3.18e-42

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 153.97  E-value: 3.18e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  731 NVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENRGRLGSQDLL 809
Cdd:cd00180     16 ETGKKVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETEnFLYLVMEYCEGGSLKDLLKENKGPLSEEEAL 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQS 889
Cdd:cd00180     96 SILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYYAPPELLGGRYYGPKV 175
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  890 DVWSYGVTVWELmtfgakpydgipaREIPDLLEkgerlpqppictidvymimvKCWMIDSECRPRFRELVS 960
Cdd:cd00180    176 DIWSLGVILYEL-------------EELKDLIR--------------------RMLQYDPKKRPSAKELLE 213
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
730-958 4.81e-42

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 156.31  E-value: 4.81e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHV--RENRGRLGS- 805
Cdd:cd05095     43 ENQPVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIRLLAVCITDDpLCMITEYMENGDLNQFLsrQQPEGQLALp 122
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 --------QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIKWM 875
Cdd:cd05095    123 snaltvsySDLRFMAAQIASGMKYLSSLNFVHRDLATRNCLVGKNYTIKIADFGMSR--NLYSGDYYRIQGRavLPIRWM 200
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMTF-GAKPYDGIPAREIPD-----LLEKGER--LPQPPICTIDVYMIMVKCWMI 947
Cdd:cd05095    201 SWESILLGKFTTASDVWAFGVTLWETLTFcREQPYSQLSDEQVIEntgefFRDQGRQtyLPQPALCPDSVYKLMLSCWRR 280
                          250
                   ....*....|.
gi 1844139549  948 DSECRPRFREL 958
Cdd:cd05095    281 DTKDRPSFQEI 291
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
727-963 6.13e-42

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 155.31  E-value: 6.13e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENRGR--- 802
Cdd:cd05046     29 IEEEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCReAEPHYMILEYTDLGDLKQFLRATKSKdek 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 -----LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHA-DGGKVPIKWMA 876
Cdd:cd05046    109 lkpppLSTKQKVALCTQIALGMDHLSNARFVHRDLAARNCLVSSQREVKVSLLSLSK--DVYNSEYYKlRNALIPLRWLA 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd05046    187 PEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGKlELPVPEGCPSRLYKLMTRCWAVNPKDRPSF 266

                   ....*...
gi 1844139549  956 RELVSEFS 963
Cdd:cd05046    267 SELVSALG 274
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
803-959 8.69e-42

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 157.09  E-value: 8.69e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGG--KVPIKWMALESI 880
Cdd:cd14207    177 LTMEDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLAR--DIYKNPDYVRKGdaRLPLKWMAPESI 254
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd14207    255 FDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIDEdFCSKLKEGIRMRAPEFATSEIYQIMLDCWQGDPNERPRFSELV 334
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
724-958 3.05e-41

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 153.63  E-value: 3.05e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  724 IWIPDGENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIclTSTVQLVTQLMPY-------------- 789
Cdd:cd05090     26 LYLPGMDHAQL-VAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGV--VTQEQPVCMLFEFmnqgdlheflimrs 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 -----GCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYH 864
Cdd:cd05090    103 phsdvGCSSDEDGTVKSSLDHGDFLHIAIQIAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISDLGLSR--EIYSSDYY 180
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  865 ADGGK--VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMV 942
Cdd:cd05090    181 RVQNKslLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRKRQLLPCSEDCPPRMYSLMT 260
                          250
                   ....*....|....*.
gi 1844139549  943 KCWMIDSECRPRFREL 958
Cdd:cd05090    261 ECWQEIPSRRPRFKDI 276
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 7.48e-41

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 147.20  E-value: 7.48e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
736-958 1.52e-40

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 152.05  E-value: 1.52e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHV--RENRGRL--------- 803
Cdd:cd05097     47 VAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGVCVSDDpLCMITEYMENGDLNQFLsqREIESTFthannipsv 126
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIKWMALESIL 881
Cdd:cd05097    127 SIANLLYMAVQIASGMKYLASLNFVHRDLATRNCLVGNHYTIKIADFGMSR--NLYSGDYYRIQGRavLPIRWMAWESIL 204
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELMTF-GAKPYDGIPAREIPD-----LLEKGER--LPQPPICTIDVYMIMVKCWMIDSECRP 953
Cdd:cd05097    205 LGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQVIEntgefFRNQGRQiyLSQTPLCPSPVFKLMMRCWSRDIKDRP 284

                   ....*
gi 1844139549  954 RFREL 958
Cdd:cd05097    285 TFNKI 289
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
803-959 2.04e-40

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 153.21  E-value: 2.04e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILR 882
Cdd:cd05103    176 LTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGDARLPLKWMAPETIFD 255
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05103    256 RVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWHGEPSQRPTFSELV 333
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
736-958 3.86e-40

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 151.24  E-value: 3.86e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCL--------LDHVRENRGRLGSQ 806
Cdd:cd05096     49 VAVKILRPDANKNARNDFLKEVKILSRLKDPNIIRLLGVCVDEDpLCMITEYMENGDLnqflsshhLDDKEENGNDAVPP 128
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 D----------LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKV-PIKWM 875
Cdd:cd05096    129 AhclpaisyssLLHVALQIASGMKYLSSLNFVHRDLATRNCLVGENLTIKIADFGMSRNLYAGDY-YRIQGRAVlPIRWM 207
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWE-LMTFGAKPYDGIPAREIPD-----LLEKGER--LPQPPICTIDVYMIMVKCWMI 947
Cdd:cd05096    208 AWECILMGKFTTASDVWAFGVTLWEiLMLCKEQPYGELTDEQVIEnagefFRDQGRQvyLFRPPPCPQGLYELMLQCWSR 287
                          250
                   ....*....|.
gi 1844139549  948 DSECRPRFREL 958
Cdd:cd05096    288 DCRERPSFSDI 298
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
736-965 4.10e-40

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 150.44  E-value: 4.10e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT---STVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWC 812
Cdd:cd05080     36 VAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqggKSLQLIMEYVPLGSLRDYLPKHS--IGLAQLLLFA 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHA-DGGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd05080    114 QQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVrEDGDSPVFWYAPECLKEYKFYYASDV 193
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  892 WSYGVTVWELMTFgAKPYDGIPAR---------------EIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd05080    194 WSFGVTLYELLTH-CDSSQSPPTKflemigiaqgqmtvvRLIELLERGERLPCPDKCPQEVYHLMKNCWETEASFRPTFE 272

                   ....*....
gi 1844139549  957 ELVSEFSRM 965
Cdd:cd05080    273 NLIPILKTV 281
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
736-960 5.94e-40

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 149.80  E-value: 5.94e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLV-TQLMPYGCLLDHVRENRGRLGS--------- 805
Cdd:cd05062     39 VAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLViMELMTRGDLKSYLRSLRPEMENnpvqappsl 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIKWMALESILRR 883
Cdd:cd05062    119 KKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTR--DIYETDYYRKGGKglLPVRWMSPESLKDG 196
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd05062    197 VFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIIS 273
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
803-959 7.47e-40

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 151.29  E-value: 7.47e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILR 882
Cdd:cd05102    169 LTMEDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIYKDPDYVRKGSARLPLKWMAPESIFD 248
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05102    249 KVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEeFCQRLKDGTRMRAPEYATPEIYRIMLSCWHGDPKERPTFSDLV 326
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
730-973 8.76e-40

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 150.15  E-value: 8.76e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVRENR------- 800
Cdd:cd05088     31 DGLRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHhPNIINLLGACeHRGYLYLAIEYAPHGNLLDFLRKSRvletdpa 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 --------GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldiDETEYHADGGKVPI 872
Cdd:cd05088    111 faianstaSTLSSQQLLHFAADVARGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSRG---QEVYVKKTMGRLPV 187
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd05088    188 RWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMRQCWREKPYER 267
                          250       260
                   ....*....|....*....|.
gi 1844139549  953 PRFRELVSEFSRMARDPQRFV 973
Cdd:cd05088    268 PSFAQILVSLNRMLEERKTYV 288
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
721-958 2.27e-39

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 147.29  E-value: 2.27e-39
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   721 RKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREn 799
Cdd:smart00220   16 YLARDKKTGK----LVAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDkLYLVMEYCEGGDLFDLLKK- 90
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   800 RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDEteyHADGGKVPIKWMALES 879
Cdd:smart00220   91 RGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGE---KLTTFVGTPEYMAPEV 167
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   880 ILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGI-PAREIPDLLEKGERLPQPPICTI--DVYMIMVKCWMIDSECRPRFR 956
Cdd:smart00220  168 LLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDdQLLELFKKIGKPKPPFPPPEWDIspEAKDLIRKLLVKDPEKRLTAE 246

                    ..
gi 1844139549   957 EL 958
Cdd:smart00220  247 EA 248
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
803-965 5.75e-38

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 147.46  E-value: 5.75e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDI-DETEYHADGGK-VPIKWMALESI 880
Cdd:cd05107    236 LSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLICEGKLVKICDFGLAR--DImRDSNYISKGSTfLPLKWMAPESI 313
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05107    314 FNNLYTTLSDVWSFGILLWEIFTLGGTPYPELPMNEqFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEKFEIRPDFSQLV 393

                   ....*.
gi 1844139549  960 SEFSRM 965
Cdd:cd05107    394 HLVGDL 399
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
733-958 2.86e-37

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 142.07  E-value: 2.86e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSpKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR-------------- 797
Cdd:cd05094     35 KMLVAVKTLKDPTL-AARKDFQREAELLTNLQHDHIVKFYGVCGDGDpLIMVFEYMKHGDLNKFLRahgpdamilvdgqp 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 -ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VPIKW 874
Cdd:cd05094    114 rQAKGELGLSQMLHIATQIASGMVYLASQHFVHRDLATRNCLVGANLLVKIGDFGMSR--DVYSTDYYRVGGHtmLPIRW 191
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd05094    192 MPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQGRVLERPRVCPKEVYDIMLGCWQREPQQRLN 271

                   ....
gi 1844139549  955 FREL 958
Cdd:cd05094    272 IKEI 275
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
803-959 9.89e-37

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 143.12  E-value: 9.89e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILR 882
Cdd:cd05104    211 LDTEDLLSFSYQVAKGMEFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIRNDSNYVVKGNARLPVKWMAPESIFE 290
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd05104    291 CVYTFESDVWSYGILLWEIFSLGSSPYPGMPVdSKFYKMIKEGYRMDSPEFAPSEMYDIMRSCWDADPLKRPTFKQIV 368
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
729-958 1.13e-36

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 140.54  E-value: 1.13e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  729 GENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIclTSTVQLVTQLMPYGCLLD-H----VRENRGRL 803
Cdd:cd05091     33 GEQTQA-VAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGV--VTKEQPMSMIFSYCSHGDlHeflvMRSPHSDV 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQD-------------LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK- 869
Cdd:cd05091    110 GSTDddktvkstlepadFLHIVTQIAAGMEYLSSHHVVHKDLATRNVLVFDKLNVKISDLGLFR--EVYAADYYKLMGNs 187
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  870 -VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 948
Cdd:cd05091    188 lLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVIEMIRNRQVLPCPDDCPAWVYTLMLECWNEF 267
                          250
                   ....*....|
gi 1844139549  949 SECRPRFREL 958
Cdd:cd05091    268 PSRRPRFKDI 277
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
803-958 1.40e-36

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 143.63  E-value: 1.40e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDI-DETEYHADGGK-VPIKWMALESI 880
Cdd:cd05105    234 LTTLDLLSFTYQVARGMEFLASKNCVHRDLAARNVLLAQGKIVKICDFGLAR--DImHDSNYVSKGSTfLPVKWMAPESI 311
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYDG-IPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd05105    312 FDNLYTTLSDVWSYGILLWEIFSLGGTPYPGmIVDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSEPEKRPSFLHL 390
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
727-967 1.77e-36

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 139.79  E-value: 1.77e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  727 PDGEnvKIPVAIKVLREnTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR-------- 797
Cdd:cd05093     31 PEQD--KILVAVKTLKD-ASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDpLIMVFEYMKHGDLNKFLRahgpdavl 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ----ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGK--VP 871
Cdd:cd05093    108 maegNRPAELTQSQMLHIAQQIAAGMVYLASQHFVHRDLATRNCLVGENLLVKIGDFGMSR--DVYSTDYYRVGGHtmLP 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 IKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSEC 951
Cdd:cd05093    186 IRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLMLGCWQREPHM 265
                          250
                   ....*....|....*.
gi 1844139549  952 RPRFRELVSEFSRMAR 967
Cdd:cd05093    266 RLNIKEIHSLLQNLAK 281
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
807-967 1.92e-36

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 142.29  E-value: 1.92e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 DLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDI-DETEYHADG-GKVPIKWMALESILRRR 884
Cdd:cd05106    213 DLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKICDFGLAR--DImNDSNYVVKGnARLPVKWMAPESIFDCV 290
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  885 FTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:cd05106    291 YTVQSDVWSYGILLWEIFSLGKSPYPGILVnSKFYKMVKRGYQMSRPDFAPPEIYSIMKMCWNLEPTERPTFSQISQLIQ 370

                   ....
gi 1844139549  964 RMAR 967
Cdd:cd05106    371 RQLG 374
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
722-965 4.78e-33

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 128.54  E-value: 4.78e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDGENVkipvAIKvlrentspKANKeILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRENR 800
Cdd:cd14060     11 RAIWVSQDKEV----AVK--------KLLK-IEKEAEILSVLSHRNIIQFYGAILEApNYGIVTEYASYGSLFDYLNSNE 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 G-RLGSQDLLNWCMQIAKGMSYLED---VRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGKVPikWMA 876
Cdd:cd14060     78 SeEMDMDQIMTWATDIAKGMHYLHMeapVKVIHRDLKSRNVVIAADGVLKICDFGASRF--HSHTTHMSLVGTFP--WMA 153
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTFGAkPYDGIPAREIPDL-LEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRF 955
Cdd:cd14060    154 PEVIQSLPVSETCDTYSYGVVLWEMLTREV-PFKGLEGLQVAWLvVEKNERPTIPSSCPRSFAELMRRCWEADVKERPSF 232
                          250
                   ....*....|
gi 1844139549  956 RELVSEFSRM 965
Cdd:cd14060    233 KQIIGILESM 242
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
52-173 2.47e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.47e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
722-965 1.33e-31

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 124.81  E-value: 1.33e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWipDGENVkipvAIKVLR---ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVtqlMPY--GCLLDH 795
Cdd:cd14061     12 RGIW--RGEEV----AVKAARqdpDEDISVTLENVRQEARLFWMLRHPNIIALRGVCLqPPNLCLV---MEYarGGALNR 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  796 VRENRgRLGSQDLLNWCMQIAKGMSYLED---VRLVHRDLAARNVLVKSP-------NHV-KITDFGLARllDIDETEYH 864
Cdd:cd14061     83 VLAGR-KIPPHVLVDWAIQIARGMNYLHNeapVPIIHRDLKSSNILILEAienedleNKTlKITDFGLAR--EWHKTTRM 159
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  865 ADGGKVpiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIP-DLLEKGERLPQPPICTIDVYMIMVK 943
Cdd:cd14061    160 SAAGTY--AWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDGLAVAyGVAVNKLTLPIPSTCPEPFAQLMKD 236
                          250       260
                   ....*....|....*....|..
gi 1844139549  944 CWMIDSECRPRFRELVSEFSRM 965
Cdd:cd14061    237 CWQPDPHDRPSFADILKQLENI 258
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
766-960 5.09e-31

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 122.60  E-value: 5.09e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  766 PYVSRLLGICLTSTVQ-LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH 844
Cdd:cd14059     41 PNIIKFKGVCTQAPCYcILMEYCPYGQLYEVLRAGR-EITPSLLVDWSKQIASGMNYLHLHKIIHRDLKSPNVLVTYNDV 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  845 VKITDFGLARLLDIDETEYHADGgkvPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIpdLLEKG 924
Cdd:cd14059    120 LKISDFGTSKELSEKSTKMSFAG---TVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAI--IWGVG 193
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1844139549  925 E---RLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd14059    194 SnslQLPVPSTCPDGFKLLMKQCWNSKPRNRPSFRQILM 232
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
722-963 2.55e-30

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 121.69  E-value: 2.55e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDgenvkiPVAIKVLRENTSPKANKEILD---EAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRE 798
Cdd:cd14145     24 RAIWIGD------EVAVKAARHDPDEDISQTIENvrqEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLS 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRgRLGSQDLLNWCMQIAKGMSYLED---VRLVHRDLAARNVLVK--------SPNHVKITDFGLARLLDiDETEYHADG 867
Cdd:cd14145     98 GK-RIPPDILVNWAVQIARGMNYLHCeaiVPVIHRDLKSSNILILekvengdlSNKILKITDFGLAREWH-RTTKMSAAG 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  868 GKVpikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWM 946
Cdd:cd14145    176 TYA---WMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAMNKlSLPIPSTCPEPFARLMEDCWN 251
                          250
                   ....*....|....*..
gi 1844139549  947 IDSECRPRFRELVSEFS 963
Cdd:cd14145    252 PDPHSRPPFTNILDQLT 268
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
735-1161 4.41e-29

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 122.81  E-value: 4.41e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPyGCLLDHVRENRGRLGSQDLLNW 811
Cdd:COG0515     34 PVALKVLRPElaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPyLVMEYVE-GESLADLLRRRGPLPPAEALRI 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE-TEYHADGGKVPikWMALESILRRRFTHQSD 890
Cdd:COG0515    113 LAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGATlTQTGTVVGTPG--YMAPEQARGEPVDPRSD 190
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  891 VWSYGVTVWELMTfGAKPYDGIPAREipdLLEKGERLPQPPICTidvymimvkcwmIDSECRPRFRELVsefSRM-ARDP 969
Cdd:COG0515    191 VYSLGVTLYELLT-GRPPFDGDSPAE---LLRAHLREPPPPPSE------------LRPDLPPALDAIV---LRAlAKDP 251
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  970 -QRFvviQN-----EDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFFCPDPAPGAGGMVHHR---HRSSSTRS 1040
Cdd:COG0515    252 eERY---QSaaelaAALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAaaaAAPAAAAA 328
                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549 1041 GGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQRYSEDPTVPLPSETDGYVAPLTCS 1120
Cdd:COG0515    329 AAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAA 408
                          410       420       430       440
                   ....*....|....*....|....*....|....*....|.
gi 1844139549 1121 PQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSP 1161
Cdd:COG0515    409 AAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAA 449
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
722-955 7.92e-28

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 113.93  E-value: 7.92e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWipDGENVkipvAIKVLRENTSPKAN---KEILDEAYVMAGVGSPYVSRLLGICLTstvqlvtqlMPYGCL-LDHVR 797
Cdd:cd14148     12 KGLW--RGEEV----AVKAARQDPDEDIAvtaENVRQEARLFWMLQHPNIIALRGVCLN---------PPHLCLvMEYAR 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 E---NRGRLGSQD----LLNWCMQIAKGMSYLED---VRLVHRDLAARNVLVKSP--NH------VKITDFGLARLLDiD 859
Cdd:cd14148     77 GgalNRALAGKKVpphvLVNWAVQIARGMNYLHNeaiVPIIHRDLKSSNILILEPieNDdlsgktLKITDFGLAREWH-K 155
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  860 ETEYHADGgkvPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPICTIDVY 938
Cdd:cd14148    156 TTKMSAAG---TYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNKlTLPIPSTCPEPFA 231
                          250
                   ....*....|....*..
gi 1844139549  939 MIMVKCWMIDSECRPRF 955
Cdd:cd14148    232 RLLEECWDPDPHGRPDF 248
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
736-957 1.47e-27

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 113.32  E-value: 1.47e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTS-PKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCL---LDHVREN-----RGRLGS 805
Cdd:cd13978     21 VAIKCLHSSPNcIEERKALLKEAEKMERARHSYVLPLLGVCVeRRSLGLVMEYMENGSLkslLEREIQDvpwslRFRIIH 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QdllnwcmqIAKGMSYLE--DVRLVHRDLAARNVLVKSPNHVKITDFGLARL----LDIDETEYHADGGKVPIkWMALES 879
Cdd:cd13978    101 E--------IALGMNFLHnmDPPLLHHDLKPENILLDNHFHVKISDFGLSKLgmksISANRRRGTENLGGTPI-YMAPEA 171
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  880 I--LRRRFTHQSDVWSYGVTVWELMTfGAKPYDGipAREIpdLLE-----KGERLPQPPICTIDVYM-------IMVKCW 945
Cdd:cd13978    172 FddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFEN--AINP--LLImqivsKGDRPSLDDIGRLKQIEnvqelisLMIRCW 246
                          250
                   ....*....|..
gi 1844139549  946 MIDSECRPRFRE 957
Cdd:cd13978    247 DGNPDARPTFLE 258
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
736-963 1.87e-27

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 113.21  E-value: 1.87e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKAN---KEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCL---------LDHVRENRgR 802
Cdd:cd14146     20 VAVKAARQDPDEDIKataESVRQEAKLFSMLRHPNIIKLEGVCLEEpNLCLVMEFARGGTLnralaaanaAPGPRRAR-R 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLED---VRLVHRDLAARNVLV-KSPNH-------VKITDFGLARllDIDETEYHADGGKVp 871
Cdd:cd14146     99 IPPHILVNWAVQIARGMLYLHEeavVPILHRDLKSSNILLlEKIEHddicnktLKITDFGLAR--EWHRTTKMSAAGTY- 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 iKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWMIDSE 950
Cdd:cd14146    176 -AWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAVNKlTLPIPSTCPEPFAKLMKECWEQDPH 253
                          250
                   ....*....|...
gi 1844139549  951 CRPRFRELVSEFS 963
Cdd:cd14146    254 IRPSFALILEQLT 266
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
736-960 6.60e-27

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 110.99  E-value: 6.60e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLrENTSPKanKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLD--HVRENRGRLGSQDLLNWC 812
Cdd:cd14058     19 VAVKII-ESESEK--KAFEVEVRQLSRVDHPNIIKLYGACSNqKPVCLVMEYAEGGSLYNvlHGKEPKPIYTAAHAMSWA 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVR---LVHRDLAARNVLVKSPNHV-KITDFGLArlLDIdetEYHADGGKVPIKWMALESILRRRFTHQ 888
Cdd:cd14058     96 LQCAKGVAYLHSMKpkaLIHRDLKPPNLLLTNGGTVlKICDFGTA--CDI---STHMTNNKGSAAWMAPEVFEGSKYSEK 170
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYDGI--PAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd14058    171 CDVFSWGIILWEVIT-RRKPFDHIggPAFRIMWAVHNGERPPLIKNCPKPIESLMTRCWSKDPEKRPSMKEIVK 243
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
735-932 8.34e-27

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 111.14  E-value: 8.34e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTS--PKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPyGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd14014     27 PVAIKVLRPELAedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPyIVMEYVE-GGSLADLLRERGPLPPREALRI 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd14014    106 LAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALG-DSGLTQTGSVLGTPAYMAPEQARGGPVDPRSDI 184
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1844139549  892 WSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGERLPQPPI 932
Cdd:cd14014    185 YSLGVVLYELLT-GRPPFDGDSPAAVLAKHLQEAPPPPSPL 224
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
722-965 1.02e-26

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 110.89  E-value: 1.02e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWipDGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRg 801
Cdd:cd14147     21 RGSW--RGELVAVKAARQDPDEDISVTA-ESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSRALAGR- 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSQDLLNWCMQIAKGMSYLED---VRLVHRDLAARNVLVKSPNH--------VKITDFGLARllDIDETEYHADGGKV 870
Cdd:cd14147     97 RVPPHVLVNWAVQIARGMHYLHCealVPVIHRDLKSNNILLLQPIEnddmehktLKITDFGLAR--EWHKTTQMSAAGTY 174
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  871 piKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd14147    175 --AWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAVNKlTLPIPSTCPEPFAQLMADCWAQDP 251
                          250
                   ....*....|....*.
gi 1844139549  950 ECRPRFRELVSEFSRM 965
Cdd:cd14147    252 HRRPDFASILQQLEAL 267
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
735-910 7.45e-24

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 102.74  E-value: 7.45e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYGCLLDHVRENRGR--LGSQDLLNW 811
Cdd:cd14066     19 VVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKlLVYEYMPNGSLEDRLHCHKGSppLPWPQRLKI 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYL---EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFTHQ 888
Cdd:cd14066     99 AKGIARGLEYLheeCPPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPSESVSKTSAVKGTIGYLAPEYIRTGRVSTK 178
                          170       180
                   ....*....|....*....|..
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14066    179 SDVYSFGVVLLELLT-GKPAVD 199
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
736-909 1.67e-22

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 98.36  E-value: 1.67e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCM 813
Cdd:cd06606     28 MAVKEVElSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTeNTLNIFLEYVPGGSLASLL-KKFGKLPEPVVRKYTR 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEyhadGGKVPIK----WMALESILRRRFTHQS 889
Cdd:cd06606    107 QILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAKRLAEIATG----EGTKSLRgtpyWMAPEVIRGEGYGRAA 182
                          170       180
                   ....*....|....*....|
gi 1844139549  890 DVWSYGVTVWELMTfGAKPY 909
Cdd:cd06606    183 DIWSLGCTVIEMAT-GKPPW 201
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
750-962 4.58e-22

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 97.19  E-value: 4.58e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  750 NKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLdHVREN-------RGRLgsqdllnwCMQIAKGMSY 821
Cdd:cd14027     35 NEALLEEGKMMNRLRHSRVVKLLGVILEEgKYSLVMEYMEKGNLM-HVLKKvsvplsvKGRI--------ILEIIEGMAY 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  822 LEDVRLVHRDLAARNVLVKSPNHVKITDFGLA--------------RLLDIDETEYHADGgkvPIKWMALESI--LRRRF 885
Cdd:cd14027    106 LHGKGVIHKDLKPENILVDNDFHIKIADLGLAsfkmwskltkeehnEQREVDGTAKKNAG---TLYYMAPEHLndVNAKP 182
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  886 THQSDVWSYGVTVWELMTfGAKPY-DGIPAREIPDLLEKGERlPQ----PPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd14027    183 TEKSDVYSFAIVLWAIFA-NKEPYeNAINEDQIIMCIKSGNR-PDvddiTEYCPREIIDLMKLCWEANPEARPTFPGIEE 260

                   ..
gi 1844139549  961 EF 962
Cdd:cd14027    261 KF 262
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
733-909 1.03e-21

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 96.12  E-value: 1.03e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd05122     25 GQIVAIKKINLESKEK-KESILNEIAILKKCKHPNIVKYYGSYLKkDELWIVMEFCSGGSLKDLLKNTNKTLTEQQIAYV 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKvpiKWMALESILRRRFTHQSDV 891
Cdd:cd05122    104 CKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRNTFVGTP---YWMAPEVIQGKPYGFKADI 180
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWElMTFGAKPY 909
Cdd:cd05122    181 WSLGITAIE-MAEGKPPY 197
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
736-959 1.14e-21

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 96.06  E-value: 1.14e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENT-SPKANKEIL-DEAYVMAGVGSPYVSRLLGICLTSTVQ--LVTQLMPYGCLLDHVRENRGRLGSQDLLNW 811
Cdd:cd14064     19 VAIKRYRANTyCSKSDVDMFcREVSILCRLNHPCVIQFVGACLDDPSQfaIVTQYVSGGSLFSLLHEQKRVIDLQSKLII 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVR--LVHRDLAARNVLVKSPNHVKITDFGLARLL-DIDETEYHADGGKvpIKWMALESILR-RRFTH 887
Cdd:cd14064     99 AVDVAKGMEYLHNLTqpIIHRDLNSHNILLYEDGHAVVADFGESRFLqSLDEDNMTKQPGN--LRWMAPEVFTQcTRYSI 176
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  888 QSDVWSYGVTVWELMTfGAKPYDGI-PAREIPDLLEKGERLPQP-----PICTidvymIMVKCWMIDSECRPRFRELV 959
Cdd:cd14064    177 KADVFSYALCLWELLT-GEIPFAHLkPAAAAADMAYHHIRPPIGysipkPISS-----LLMRGWNAEPESRPSFVEIV 248
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
740-961 1.28e-21

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 95.64  E-value: 1.28e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  740 VLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLldhvrenRGRLGSQDL-LNWCMQ--- 814
Cdd:cd14065     22 VMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKdNKLNFITEYVNGGTL-------EELLKSMDEqLPWSQRvsl 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 ---IAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGLARLLDIDETEYHADGGKVPI----KWMALESILRRR 884
Cdd:cd14065     95 akdIASGMAYLHSKNIIHRDLNSKNCLVREANrgrNAVVADFGLAREMPDEKTKKPDRKKRLTVvgspYWMAPEMLRGES 174
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  885 FTHQSDVWSYGVTVWELMT-FGAKPyDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd14065    175 YDEKVDVFSFGIVLCEIIGrVPADP-DYLPRTMDFGLDVRAFRTLYVPDCPPSFLPLAIRCCQLDPEKRPSFVELEHH 251
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
728-961 4.21e-21

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 94.47  E-value: 4.21e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQD 807
Cdd:cd05037     25 DGRVQEVEVLLKVLDSDHRDIS-ESFFETASLMSQISHKHLVKLYGVCVADENIMVQEYVRYGPLDKYLRRMGNNVPLSW 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV------KSPNHVKITDFGLAR-LLDIDETEyhadggkVPIKWMALE-- 878
Cdd:cd05037    104 KLQVAKQLASALHYLEDKKLIHGNVRGRNILLaregldGYPPFIKLSDPGVPItVLSREERV-------DRIPWIAPEcl 176
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIdvYMIMVKCWMIDSECRPRFREL 958
Cdd:cd05037    177 RNLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPDCAEL--AELIMQCWTYEPTKRPSFRAI 254

                   ...
gi 1844139549  959 VSE 961
Cdd:cd05037    255 LRD 257
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
366-482 1.15e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.15e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69
                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139549  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
736-958 1.26e-20

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 93.48  E-value: 1.26e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIClTSTVQ--LVTQLMPYGCLLDHVRENRGRLG-SQDLLN-- 810
Cdd:cd14206     27 VVVKELRVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLC-TETIPflLIMEFCQLGDLKRYLRAQRKADGmTPDLPTrd 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 ------WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALE------ 878
Cdd:cd14206    106 lrtlqrMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDYGLSHNNYKEDYYLTPDRLWIPLRWVAPElldelh 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 -SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERL----PQPPICTIDV-YMIMVKCWMIDSEcR 952
Cdd:cd14206    186 gNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQMklakPRLKLPYADYwYEIMQSCWLPPSQ-R 264

                   ....*.
gi 1844139549  953 PRFREL 958
Cdd:cd14206    265 PSVEEL 270
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
736-967 2.52e-20

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 92.41  E-value: 2.52e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTspkaNKEILDEAY---VMAGVGSPY--VSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLL 809
Cdd:cd14063     25 VAIKLLNIDY----LNEEQLEAFkeeVAAYKNTRHdnLVLFMGACMDpPHLAIVTSLCKGRTLYSLIHERKEKFDFNKTV 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSpNHVKITDFGLARLLDIDETEYHADGGKVPIKW---MALESILRRR-- 884
Cdd:cd14063    101 QIAQQICQGMGYLHAKGIIHKDLKSKNIFLEN-GRVVITDFGLFSLSGLLQPGRREDTLVIPNGWlcyLAPEIIRALSpd 179
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  885 --------FTHQSDVWSYGvTVW-ELMTfGAKPYDGIPAREIPDLLEKGERLPQPPI-CTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd14063    180 ldfeeslpFTKASDVYAFG-TVWyELLA-GRWPFKEQPAESIIWQVGCGKKQSLSQLdIGREVKDILMQCWAYDPEKRPT 257
                          250
                   ....*....|...
gi 1844139549  955 FRELVSEFSRMAR 967
Cdd:cd14063    258 FSDLLRMLERLPK 270
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
736-958 3.53e-20

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 91.97  E-value: 3.53e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRG--RLGSQDLLNWC 812
Cdd:cd05087     27 VVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTpYLLVMEFCPLGDLKGYLRSCRAaeSMAPDPLTLQR 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 M--QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALE-------SILRR 883
Cdd:cd05087    107 MacEVACGLLHLHRNNFVHSDLALRNCLLTADLTVKIGDYGLSHCKYKEDYFVTADQLWVPLRWIAPElvdevhgNLLVV 186
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIP--DLLEKGERLPQP--PICTIDV-YMIMVKCWMiDSECRPRFREL 958
Cdd:cd05087    187 DQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLtyTVREQQLKLPKPqlKLSLAERwYEVMQFCWL-QPEQRPTAEEV 265
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
736-958 8.89e-20

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 90.72  E-value: 8.89e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENR-GRLGSQD---LLN 810
Cdd:cd05042     25 VVVKELKASANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIpYLLVMEFCDLGDLKAYLRSEReHERGDSDtrtLQR 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI--LRRRF--- 885
Cdd:cd05042    105 MACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYKEDYIETDDKLWFPLRWTAPELVteFHDRLlvv 184
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  886 --THQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLL--EKGERLPQPPI---CTIDVYMIMVKCWMiDSECRPRFREL 958
Cdd:cd05042    185 dqTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQLelpYSDRWYEVLQFCWL-SPEQRPAAEDV 263
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
736-960 9.42e-20

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 90.36  E-value: 9.42e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENrGRLGsQDLLNWCM 813
Cdd:cd06627     28 VAIKQISLEKIPKSDlKSVMGEIDLLKKLNHPNIVKYIGSVKTKDsLYIILEYVENGSLASIIKKF-GKFP-ESLVAVYI 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 -QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVpiKWMALESILRRRFTHQSDVW 892
Cdd:cd06627    106 yQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDENSVVGTP--YWMAPEVIEMSGVTTASDIW 183
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  893 SYGVTVWELMTfGAKPY---DGIPA--REIPDllekgERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd06627    184 SVGCTVIELLT-GNPPYydlQPMAAlfRIVQD-----DHPPLPENISPELRDFLLQCFQKDPTLRPSAKELLK 250
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
722-968 2.70e-19

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 89.35  E-value: 2.70e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDgenvkipVAIKVLRENT-SPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENR 800
Cdd:cd14151     26 KGKWHGD-------VAVKMLNVTApTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGSSLYHHLHIIE 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI 880
Cdd:cd14151     99 TKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSGSHQFEQLSGSILWMAPEVI 178
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 L---RRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAR-EIPDLLEKGERLPQ----PPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd14151    179 RmqdKNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNRdQIIFMVGRGYLSPDlskvRSNCPKAMKRLMAECLKKKRDER 257
                          250
                   ....*....|....*.
gi 1844139549  953 PRFRELVSEFSRMARD 968
Cdd:cd14151    258 PLFPQILASIELLARS 273
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
740-968 4.25e-19

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 88.72  E-value: 4.25e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  740 VLRE--NTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA 816
Cdd:cd14154     22 VMKEliRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKdKKLNLITEYIPGGTLKDVLKDMARPLPWAQRVRFAKDIA 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  817 KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE---YHADGGKVPIK---------------WMALE 878
Cdd:cd14154    102 SGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLARLIVEERLPsgnMSPSETLRHLKspdrkkrytvvgnpyWMAPE 181
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELM-TFGAKPyDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRE 957
Cdd:cd14154    182 MLNGRSYDEKVDIFSFGIVLCEIIgRVEADP-DYLPRTKDFGLNVDSFREKFCAGCPPPFFKLAFLCCDLDPEKRPPFET 260
                          250
                   ....*....|.
gi 1844139549  958 LVSEFSRMARD 968
Cdd:cd14154    261 LEEWLEALYLH 271
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
737-958 8.79e-19

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 87.79  E-value: 8.79e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLlDHVRENRGRLGSQDLLNWCMQI 815
Cdd:cd06605     30 AVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGdISICMEYMDGGSL-DKILKEVGRIPERILGKIAVAV 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  816 AKGMSYLEDVR-LVHRDLAARNVLVKSPNHVKITDFGLA-RLLDideTEYHADGGKVPikWMALESILRRRFTHQSDVWS 893
Cdd:cd06605    109 VKGLIYLHEKHkIIHRDVKPSNILVNSRGQVKLCDFGVSgQLVD---SLAKTFVGTRS--YMAPERISGGKYTVKSDIWS 183
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  894 YGVTVWELMT--FGAKPYDGIPAREIPDLL-----EKGERLPQPPIcTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd06605    184 LGLSLVELATgrFPYPPPNAKPSMMIFELLsyivdEPPPLLPSGKF-SPDFQDFVSQCLQKDPTERPSYKEL 254
Pkinase pfam00069
Protein kinase domain;
721-960 1.83e-18

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 85.37  E-value: 1.83e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  721 RKGIWIPDGEnvkiPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRE 798
Cdd:pfam00069   16 YKAKHRDTGK----IVAIKKIKkEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDnLYLVLEYVEGGSLFDLLSE 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NrGRLGSQDLLNWCMQIAKGMSYLEDVrlvhrdlaarNVLVKSPNhvkitdfglarlldideteyhadggkvpikWMALE 878
Cdd:pfam00069   92 K-GAFSEREAKFIMKQILEGLESGSSL----------TTFVGTPW------------------------------YMAPE 130
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIP--DLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:pfam00069  131 VLGGNPYGPKVDVWSLGCILYELLT-GKPPFPGINGNEIYelIIDQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRLTAT 209

                   ....
gi 1844139549  957 ELVS 960
Cdd:pfam00069  210 QALQ 213
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
722-967 4.30e-18

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 85.84  E-value: 4.30e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDgenvkipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENR 800
Cdd:cd14150     18 RGKWHGD-------VAVKILKvTEPTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPNFAIITQWCEGSSLYRHLHVTE 90
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI 880
Cdd:cd14150     91 TRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRWSGSQQVEQPSGSILWMAPEVI 170
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRR---FTHQSDVWSYGVTVWELMTfGAKPYDGIPARE-----------IPDLLEKGERLPQPpictidVYMIMVKCWM 946
Cdd:cd14150    171 RMQDtnpYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDqiifmvgrgylSPDLSKLSSNCPKA------MKRLLIDCLK 243
                          250       260
                   ....*....|....*....|.
gi 1844139549  947 IDSECRPRFRELVSEFSRMAR 967
Cdd:cd14150    244 FKREERPLFPQILVSIELLQR 264
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
735-958 4.30e-18

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 85.52  E-value: 4.30e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd14062     17 DVAVKKLNvTDPTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQLAIVTQWCEGSSLYKHLHVLETKFEMLQLIDIAR 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESIlRRR----FTHQS 889
Cdd:cd14062     97 QTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLATVKTRWSGSQQFEQPTGSILWMAPEVI-RMQdenpYSFQS 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  890 DVWSYGVTVWELMTfGAKPYDGIPAREI-----------PDLLEKGERLPQPpictidVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd14062    176 DVYAFGIVLYELLT-GQLPYSHINNRDQilfmvgrgylrPDLSKVRSDTPKA------LRRLMEDCIKFQRDERPLFPQI 248
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
736-923 1.05e-17

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 84.11  E-value: 1.05e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVL-RENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCM 813
Cdd:cd14003     28 VAIKIIdKSKLKEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENkIYLVMEYASGGELFDYIV-NNGRLSEDEARRFFQ 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDET--------EYhadggkvpikwMALESILRRRF 885
Cdd:cd14003    107 QLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLlktfcgtpAY-----------AAPEVLLGRKY 175
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1844139549  886 -THQSDVWSYGVTVWeLMTFGAKPYDGipaREIPDLLEK 923
Cdd:cd14003    176 dGPKADVWSLGVILY-AMLTGYLPFDD---DNDSKLFRK 210
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
723-965 1.66e-17

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 83.98  E-value: 1.66e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  723 GIWIPDGENVKIPVAIKVLreNTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDhVRENRG 801
Cdd:cd13992     15 KYVKKVGVYGGRTVAIKHI--TFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPnIAVVTEYCTRGSLQD-VLLNRE 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLgsqdlLNWCMQ------IAKGMSYLEDVRL-VHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggkVPIK- 873
Cdd:cd13992     92 IK-----MDWMFKssfikdIVKGMNYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDE---DAQHk 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  874 ---WMALE----SILRRRFTHQSDVWSYGVTVWELMtFGAKPYDGIPAREIPDLLEKGERLPQPPI-------CTIDVYM 939
Cdd:cd13992    164 kllWTAPEllrgSLLEVRGTQKGDVYSFAIILYEIL-FRSDPFALEREVAIVEKVISGGNKPFRPElavlldeFPPRLVL 242
                          250       260
                   ....*....|....*....|....*.
gi 1844139549  940 IMVKCWMIDSECRPRFRELVSEFSRM 965
Cdd:cd13992    243 LVKQCWAENPEKRPSFKQIKKTLTEN 268
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
722-914 2.25e-17

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 83.47  E-value: 2.25e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDGEnvkiPVAIKVLRENTSpkaNKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVtqLMPY---GCLLDHVRE 798
Cdd:cd06612     21 KAIHKETGQ----VVAIKVVPVEED---LQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWI--VMEYcgaGSVSDIMKI 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdideTEYHADGGKV---PIkWM 875
Cdd:cd06612     92 TNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGVSGQL----TDTMAKRNTVigtPF-WM 166
                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDGIPA 914
Cdd:cd06612    167 APEVIQEIGYNNKADIWSLGITAIE-MAEGKPPYSDIHP 204
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
731-963 2.92e-17

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 83.43  E-value: 2.92e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  731 NVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLtSTVQLVTQLMPYGCL---LDHVRENRGRLGSQD 807
Cdd:cd14000     35 NVPADTMLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGI-HPLMLVLELAPLGSLdhlLQQDSRSFASLGRTL 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV-----KSPNHVKITDFGLARlldiDETEYHADGGKVPIKWMALEsILR 882
Cdd:cd14000    114 QQRIALQVADGLRYLHSAMIIYRDLKSHNVLVwtlypNSAIIIKIADYGISR----QCCRMGAKGSEGTPGFRAPE-IAR 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  883 RR--FTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEK-----GERLPQPPICTIDvymIMVKCWMIDSECRPRF 955
Cdd:cd14000    189 GNviYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHGGlrpplKQYECAPWPEVEV---LMKKCWKENPQQRPTA 265

                   ....*...
gi 1844139549  956 RELVSEFS 963
Cdd:cd14000    266 VTVVSILN 273
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
721-960 3.14e-17

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 83.02  E-value: 3.14e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  721 RKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDhVREN 799
Cdd:cd06623     18 YKVRHKPTGK----IYALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEgEISIVLEYMDGGSLAD-LLKK 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 RGRLGSQDLLNWCMQIAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPikWMALE 878
Cdd:cd06623     93 VGKIPEPVLAYIARQILKGLDYLhTKRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENTLDQCNTFVGTVT--YMSPE 170
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLE---KGERLPQPPI-CTIDVYMIMVKCWMIDSECRPR 954
Cdd:cd06623    171 RIQGESYSYAADIWSLGLTLLECAL-GKFPFLPPGQPSFFELMQaicDGPPPSLPAEeFSPEFRDFISACLQKDPKKRPS 249

                   ....*.
gi 1844139549  955 FRELVS 960
Cdd:cd06623    250 AAELLQ 255
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
736-909 3.62e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 82.64  E-value: 3.62e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENtspKANKE-ILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd06614     28 VAIKKMRLR---KQNKElIINEILIMKECKHPNIVDYYDSYLVgDELWVVMEYMDGGSLTDIITQNPVRMNESQIAYVCR 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE--------TEYhadggkvpikWMALESILRRRF 885
Cdd:cd06614    105 EVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKskrnsvvgTPY----------WMAPEVIKRKDY 174
                          170       180
                   ....*....|....*....|....
gi 1844139549  886 THQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06614    175 GPKVDIWSLGIMCIE-MAEGEPPY 197
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
736-910 6.29e-17

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 82.54  E-value: 6.29e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQL-VTQLMPYGCLLDHVREnrgRLGSQDLLNW--- 811
Cdd:cd14664     20 VAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLlVYEYMPNGSLGELLHS---RPESQPPLDWetr 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 ---CMQIAKGMSYLED---VRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE-YHADGGKvpIKWMALESILRRR 884
Cdd:cd14664     97 qriALGSARGLAYLHHdcsPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHvMSSVAGS--YGYIAPEYAYTGK 174
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14664    175 VSEKSDVYSYGVVLLELIT-GKRPFD 199
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
748-958 9.00e-17

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 81.93  E-value: 9.00e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR 826
Cdd:cd14221     32 ETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKrLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFAKDIASGMAYLHSMN 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  827 LVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEY--HADGGKVPIK-----------WMALESILRRRFTHQSDVWS 893
Cdd:cd14221    112 IIHRDLNSHNCLVRENKSVVVADFGLARLM-VDEKTQpeGLRSLKKPDRkkrytvvgnpyWMAPEMINGRSYDEKVDVFS 190
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  894 YGVTVWELMTFGAKPYDGIPaREIPDLLEKGERLPQ--PPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd14221    191 FGIVLCEIIGRVNADPDYLP-RTMDFGLNVRGFLDRycPPNCPPSFFPIAVLCCDLDPEKRPSFSKL 256
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
719-959 1.90e-16

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 81.26  E-value: 1.90e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIwipdGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR 797
Cdd:cd06642     19 EVYKGI----DNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTkLWIIMEYLGGGSALDLLK 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 EnrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMAL 877
Cdd:cd06642     95 P--GPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVG-TPF-WMAP 170
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  878 ESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGerlpQPPIC----TIDVYMIMVKCWMIDSECRP 953
Cdd:cd06642    171 EVIKQSAYDFKADIWSLGITAIELAK-GEPPNSDLHPMRVLFLIPKN----SPPTLegqhSKPFKEFVEACLNKDPRFRP 245

                   ....*.
gi 1844139549  954 RFRELV 959
Cdd:cd06642    246 TAKELL 251
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
735-932 3.46e-16

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 79.81  E-value: 3.46e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVtqLMPY---GCLLDHVRENR--GRLGSQD- 807
Cdd:cd08215     27 LYVLKEIDlSNMSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCI--VMEYadgGDLAQKIKKQKkkGQPFPEEq 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE--------TEYhadggkvpikWMALES 879
Cdd:cd08215    105 ILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGISKVLESTTdlaktvvgTPY----------YLSPEL 174
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  880 ILRRRFTHQSDVWSYGVTVWELMTFgAKPYDgipAREIPDLLEKGERLPQPPI 932
Cdd:cd08215    175 CENKPYNYKSDIWALGCVLYELCTL-KHPFE---ANNLPALVYKIVKGQYPPI 223
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
721-925 3.94e-16

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 79.83  E-value: 3.94e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  721 RKGIWIPDGEnvkiPVAIKVL-RENTSPKANKEILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPYGCLLDHVrE 798
Cdd:cd05117     17 RLAVHKKTGE----EYAVKIIdKKKLKSEDEEMLRREIEILKRLDHPNIVKLYEVfEDDKNLYLVMELCTGGELFDRI-V 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGLARLLDIDET--------EYhadg 867
Cdd:cd05117     92 KKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDpdsPIKIIDFGLAKIFEEGEKlktvcgtpYY---- 167
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  868 gkvpikwMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE 925
Cdd:cd05117    168 -------VAPEVLKGKGYGKKCDIWSLGVILYILLC-GYPPFYGETEQELFEKILKGK 217
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
722-960 4.33e-16

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 80.08  E-value: 4.33e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDgenvkipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENR 800
Cdd:cd14149     30 KGKWHGD-------VAVKILKvVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQE 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI 880
Cdd:cd14149    103 TKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSILWMAPEVI 182
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRR---FTHQSDVWSYGVTVWELMTfGAKPYDGIPARE-----------IPDLLEKGERLPQPpictidVYMIMVKCWM 946
Cdd:cd14149    183 RMQDnnpFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqiifmvgrgyaSPDLSKLYKNCPKA------MKRLVADCIK 255
                          250
                   ....*....|....
gi 1844139549  947 IDSECRPRFRELVS 960
Cdd:cd14149    256 KVKEERPLFPQILS 269
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
717-917 5.04e-16

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 79.71  E-value: 5.04e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  717 ETELRKGIWIPDGENVkipvAIKVLRENTSPKANKEILDEAYVMAGVGSP-----YVSRLLGICLtstvQLVTQLMPYGC 791
Cdd:cd06610     14 TAVVYAAYCLPKKEKV----AIKRIDLEKCQTSMDELRKEIQAMSQCNHPnvvsyYTSFVVGDEL----WLVMPLLSGGS 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRE--NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdideteyhADGGK 869
Cdd:cd06610     86 LLDIMKSsyPRGGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGVSASL--------ATGGD 157
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  870 VPIK----------WMALESILRRR-FTHQSDVWSYGVTVWELMTfGAKPYDGIPAREI 917
Cdd:cd06610    158 RTRKvrktfvgtpcWMAPEVMEQVRgYDFKADIWSFGITAIELAT-GAAPYSKYPPMKV 215
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
810-960 6.92e-16

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 79.12  E-value: 6.92e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIK----WMALESILRRRF 885
Cdd:cd06628    110 NFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLEANSLSTKNNGARPSLQgsvfWMAPEVVKQTSY 189
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  886 THQSDVWSYGVTVWELMTfGAKPY-DGIPAREIPDLLEKGERLPqPPICTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd06628    190 TRKADIWSLGCLVVEMLT-GTHPFpDCTQMQAIFKIGENASPTI-PSNISSEARDFLEKTFEIDHNKRPTADELLK 263
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
719-932 1.94e-15

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 78.19  E-value: 1.94e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIwipDGENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVR 797
Cdd:cd06641     19 EVFKGI---DNRTQKV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTkLWIIMEYLGGGSALDLLE 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 EnrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMAL 877
Cdd:cd06641     95 P--GPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRN*FVG-TPF-WMAP 170
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  878 ESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGerlpQPPI 932
Cdd:cd06641    171 EVIKQSAYDSKADIWSLGITAIELAR-GEPPHSELHPMKVLFLIPKN----NPPT 220
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
744-958 2.06e-15

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 77.45  E-value: 2.06e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  744 NTSPKANKEILDEAYVMAGVGSPYVSRLLGiCLTSTVQL--VTQLMPYGCLLDHVRENRGRLGSQDLLnW--CMQIAKGM 819
Cdd:cd08529     37 RMSRKMREEAIDEARVLSKLNSPYVIKYYD-SFVDKGKLniVMEYAENGDLHSLIKSQRGRPLPEDQI-WkfFIQTLLGL 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  820 SYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIkWMALESILRRRFTHQSDVWSYGVTVW 899
Cdd:cd08529    115 SHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILS-DTTNFAQTIVGTPY-YLSPELCEDKPYNEKSDVWALGCVLY 192
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  900 ELMTFgAKPYD----GIPAREIPdlleKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd08529    193 ELCTG-KHPFEaqnqGALILKIV----RGKYPPISASYSQDLSQLIDSCLTKDYRQRPDTTEL 250
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
733-911 2.55e-15

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 77.34  E-value: 2.55e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKA--NKEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCLLDHVR------ENRGRL 803
Cdd:cd14162     25 KCKVAIKIVSKKKAPEDylQKFLPREIEVIKGLKHPNLICFYeAIETTSRVYIIMELAENGDLLDYIRkngalpEPQARR 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 gsqdllnWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidETEYHADGGKVPIKWM------AL 877
Cdd:cd14162    105 -------WFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGFAR-----GVMKTKDGKPKLSETYcgsyayAS 172
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1844139549  878 ESILrrRFT----HQSDVWSYGVTVWElMTFGAKPYDG 911
Cdd:cd14162    173 PEIL--RGIpydpFLSDIWSMGVVLYT-MVYGRLPFDD 207
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
752-960 3.58e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270800 [Multi-domain]  Cd Length: 268  Bit Score: 77.08  E-value: 3.58e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  752 EILDEAYVMAGVGSPYVSRLLG-ICLTSTVQLVTQLMPYGCLlDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHR 830
Cdd:cd06630     49 AIREEIRMMARLNHPNIVRMLGaTQHKSHFNIFVEWMAGGSV-ASLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHR 127
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  831 DLAARNVLVKSP-NHVKITDFGLARLLDIDETEYHADGGKV--PIKWMALESILRRRFTHQSDVWSYGVTVWElMTFGAK 907
Cdd:cd06630    128 DLKGANLLVDSTgQRLRIADFGAAARLASKGTGAGEFQGQLlgTIAFMAPEVLRGEQYGRSCDVWSVGCVIIE-MATAKP 206
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  908 PYDgipAREIPD---LLEK---GERLPQPPIC-TIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd06630    207 PWN---AEKISNhlaLIFKiasATTPPPIPEHlSPGLRDVTLRCLELQPEDRPPARELLK 263
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
719-931 4.59e-15

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270972 [Multi-domain]  Cd Length: 262  Bit Score: 76.78  E-value: 4.59e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIPDGENVkipvAIKVLRENTSPK---ANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLD 794
Cdd:cd14070     17 KVREGLHAVTGEKV----AIKVIDKKKAKKdsyVTKNLRREGRIQQMIRHPNITQLLDILETeNSYYLVMELCPGGNLMH 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  795 HVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGL---ARLLDIDETEYHADGGKVp 871
Cdd:cd14070     93 RIYDKK-RLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLsncAGILGYSDPFSTQCGSPA- 170
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  872 ikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIP--AREIPDLLEKGERLPQPP 931
Cdd:cd14070    171 --YAAPELLARKKYGPKVDVWSIGVNMYAMLT-GTLPFTVEPfsLRALHQKMVDKEMNPLPT 229
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
737-929 4.60e-15

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 76.40  E-value: 4.60e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKE--ILDEAYVMAGVGSPYVsrllgICLTSTVQ------LVTQLMPYGCLLDHVREnRGRLGSQDL 808
Cdd:cd05123     22 AMKVLRKKEIIKRKEVehTLNERNILERVNHPFI-----VKLHYAFQteeklyLVLDYVPGGELFSHLSK-EGRFPEERA 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPikWMALESILRRRFTHQ 888
Cdd:cd05123     96 RFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDRTYTFCGTPE--YLAPEVLLGKGYGKA 173
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQ 929
Cdd:cd05123    174 VDWWSLGVLLYEMLT-GKPPFYAENRKEIYEKILKSPlKFPE 214
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
735-920 4.65e-15

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 76.90  E-value: 4.65e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRenRGRLGSQDLLNWCM 813
Cdd:cd06609     28 VVAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLkGSKLWIIMEYCGGGSVLDLLK--PGPLDETYIAFILR 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDVWS 893
Cdd:cd06609    106 EVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNTFVG-TPF-WMAPEVIKQSGYDEKADIWS 183
                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1844139549  894 YGVTVWELMTfGAKPYDG---------IPAREIPDL 920
Cdd:cd06609    184 LGITAIELAK-GEPPLSDlhpmrvlflIPKNNPPSL 218
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
736-923 4.78e-15

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 76.45  E-value: 4.78e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKA--NKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWC 812
Cdd:cd14080     30 VACKIIDKKKAPKDflEKFLPRELEILRKLRHPNIIQVYSIFeRGSKVFIFMEYAEHGDLLEYIQ-KRGALSESQARIWF 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidetEYHADGGKVPIK-------WMALEsILRRRF 885
Cdd:cd14080    109 RQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFAR-------LCPDDDGDVLSKtfcgsaaYAAPE-ILQGIP 180
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1844139549  886 TH--QSDVWSYGVTVWeLMTFGAKPYDGipaREIPDLLEK 923
Cdd:cd14080    181 YDpkKYDIWSLGVILY-IMLCGSMPFDD---SNIKKMLKD 216
STKc_Nek5 cd08225
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
786-959 1.01e-14

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173765 [Multi-domain]  Cd Length: 257  Bit Score: 75.76  E-value: 1.01e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY---GCLLDHVRENRGRLGSQD-LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHV-KITDFGLARLLDiDE 860
Cdd:cd08225     77 VMEYcdgGDLMKRINRQRGVLFSEDqILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLN-DS 155
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  861 TEYHADGGKVPIkWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMI 940
Cdd:cd08225    156 MELAYTCVGTPY-YLSPEICQNRPYNNKTDIWSLGCVLYELCTL-KHPFEGNNLHQLVLKICQGYFAPISPNFSRDLRSL 233
                          170
                   ....*....|....*....
gi 1844139549  941 MVKCWMIDSECRPRFRELV 959
Cdd:cd08225    234 ISQLFKVSPRDRPSITSIL 252
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
736-968 1.28e-14

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 75.71  E-value: 1.28e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDhVRENrgrlgsQDL-LNW-- 811
Cdd:cd14042     33 VAIKKVNKKRIDL-TREVLKELKHMRDLQHDNLTRFIGACVDPPnICILTEYCPKGSLQD-ILEN------EDIkLDWmf 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 ----CMQIAKGMSYLEDVRLV-HRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALEsILRR--- 883
Cdd:cd14042    105 ryslIHDIVKGMHYLHDSEIKsHGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEPPDDSHAYYAKLLWTAPE-LLRDpnp 183
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  884 --RFTHQSDVWSYGVTVWELMT----FGAKPYDGIPaREIpdLLEKGERLPQPP--------ICTIDVYMIMVKCWMIDS 949
Cdd:cd14042    184 ppPGTQKGDVYSFGIILQEIATrqgpFYEEGPDLSP-KEI--IKKKVRNGEKPPfrpsldelECPDEVLSLMQRCWAEDP 260
                          250
                   ....*....|....*....
gi 1844139549  950 ECRPRFRELVSEFSRMARD 968
Cdd:cd14042    261 EERPDFSTLRNKLKKLNKG 279
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
736-958 1.75e-14

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 75.29  E-value: 1.75e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRL--GSQDLLNWC 812
Cdd:cd05086     27 VVVKELKASANPKEQDDFLQQGEPYYILQHPNILQCVGQCVEAIpYLLVFEFCDLGDLKTYLANQQEKLrgDSQIMLLQR 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 M--QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL---DIDETEyhaDGGKVPIKWMALE-------SI 880
Cdd:cd05086    107 MacEIAAGLAHMHKHNFLHSDLALRNCYLTSDLTVKVGDYGIGFSRykeDYIETD---DKKYAPLRWTAPElvtsfqdGL 183
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPD--LLEKGERLPQPPI---CTIDVYMIMVKCWMiDSECRPRF 955
Cdd:cd05086    184 LAAEQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNhvIKERQVKLFKPHLeqpYSDRWYEVLQFCWL-SPEKRPTA 262

                   ...
gi 1844139549  956 REL 958
Cdd:cd05086    263 EEV 265
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
746-961 1.76e-14

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 75.22  E-value: 1.76e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  746 SPKANKEILDEAYVMAGVGSPYVSRLLGIClTSTVQLVTQLMPYGCLldhvrenrGRLGSQDLLNWCM------QIAKGM 819
Cdd:cd14025     35 DDSERMELLEEAKKMEMAKFRHILPVYGIC-SEPVGLVMEYMETGSL--------EKLLASEPLPWELrfriihETAVGM 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  820 SYLEDVR--LVHRDLAARNVLVKSPNHVKITDFGLARLLDI-DETEYHADGGKVPIKWMALESILR--RRFTHQSDVWSY 894
Cdd:cd14025    106 NFLHCMKppLLHLDLKPANILLDAHYHVKISDFGLAKWNGLsHSHDLSRDGLRGTIAYLPPERFKEknRCPDTKHDVYSF 185
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  895 GVTVWELMTfGAKPYDGipAREIPDLL---EKGERLPQPPICTI------DVYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd14025    186 AIVIWGILT-QKKPFAG--ENNILHIMvkvVKGHRPSLSPIPRQrpsecqQMICLMKRCWDQDPRKRPTFQDITSE 258
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
726-959 2.28e-14

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 75.17  E-value: 2.28e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  726 IPDGenvkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL--TSTVQLVTQLMPYGCLlDHVRENRGRL 803
Cdd:cd06620     27 IPTG----TIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAFLneNNNIIICMEYMDCGSL-DKILKKKGPF 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDV-RLVHRDLAARNVLVKSPNHVKITDFGLARLLdideTEYHADGGKVPIKWMALESILR 882
Cdd:cd06620    102 PEEVLGKIAVAVLEGLTYLYNVhRIIHRDIKPSNILVNSKGQIKLCDFGVSGEL----INSIADTFVGTSTYMSPERIQG 177
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTfGAKPYDGIPARE--------IPDLL-----EKGERLPQ----PPICT--IDvymimvK 943
Cdd:cd06620    178 GKYSVKSDVWSLGLSIIELAL-GEFPFAGSNDDDdgyngpmgILDLLqrivnEPPPRLPKdrifPKDLRdfVD------R 250
                          250
                   ....*....|....*.
gi 1844139549  944 CWMIDSECRPRFRELV 959
Cdd:cd06620    251 CLLKDPRERPSPQLLL 266
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
776-909 2.35e-14

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 74.57  E-value: 2.35e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  776 LTSTVQLVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKGMSYL--EDVRLVHRDLAARNVLVKSPN-HVKITDFGL 852
Cdd:cd13983     73 SKKEVIFITELMTSGTLKQYLKRF-KRLKLKVIKSWCRQILEGLNYLhtRDPPIIHRDLKCDNIFINGNTgEVKIGDLGL 151
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  853 ARLLDIDET-------EYhadggkvpikwMALEsILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd13983    152 ATLLRQSFAksvigtpEF-----------MAPE-MYEEHYDEKVDIYAFGMCLLEMAT-GEYPY 202
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
748-966 2.70e-14

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 74.60  E-value: 2.70e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVR 826
Cdd:cd14222     32 ETQKTFLTEVKVMRSLDHPNVLKFIGVLYKdKRLNLLTEFIEGGTLKDFLRAD-DPFPWQQKVSFAKGIASGMAYLHSMS 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  827 LVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGKVPIK--------------------WMALESILRRRFT 886
Cdd:cd14222    111 IIHRDLNSHNCLIKLDKTVVVADFGLSRL--IVEEKKKPPPDKPTTKkrtlrkndrkkrytvvgnpyWMAPEMLNGKSYD 188
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  887 HQSDVWSYGVTVWELM-TFGAKPydgipaREIPDLLEKGERLPQ------PPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd14222    189 EKVDIFSFGIVLCEIIgQVYADP------DCLPRTLDFGLNVRLfwekfvPKDCPPAFFPLAAICCRLEPDSRPAFSKLE 262

                   ....*..
gi 1844139549  960 SEFSRMA 966
Cdd:cd14222    263 DSFEALS 269
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
728-963 3.17e-14

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 74.17  E-value: 3.17e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLrENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVREN--RGRLGS 805
Cdd:cd14208     25 DDERCETEVLLKVM-DPTHGNCQESFLEAASIMSQISHKHLVLLHGVCVGKDSIMVQEFVCHGALDLYLKKQqqKGPVAI 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVK------SPNHVKITDFGLArlLDIDETEYHADggKVPikWMALES 879
Cdd:cd14208    104 SWKLQVVKQLAYALNYLEDKQLVHGNVSAKKVLLSregdkgSPPFIKLSDPGVS--IKVLDEELLAE--RIP--WVAPEC 177
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  880 ILR-RRFTHQSDVWSYGVTVWELMTFGAKPYDGI-PAREIpDLLEKGERLPQPPicTIDVYMIMVKCWMIDSECRPRFRE 957
Cdd:cd14208    178 LSDpQNLALEADKWGFGATLWEIFSGGHMPLSALdPSKKL-QFYNDRKQLPAPH--WIELASLIQQCMSYNPLLRPSFRA 254

                   ....*.
gi 1844139549  958 LVSEFS 963
Cdd:cd14208    255 IIRDLN 260
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
740-967 3.47e-14

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 74.05  E-value: 3.47e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  740 VLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLlDHVRENRGRLGSQDLLNWCMQIAKG 818
Cdd:cd14155     22 ALKMNTLSSNRANMLREVQLMNRLSHPNILRFMGVCVhQGQLHALTEYINGGNL-EQLLDSNEPLSWTVRVKLALDIARG 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  819 MSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLdideTEYHADGGKVPI----KWMALESILRRRFTHQSDV 891
Cdd:cd14155    101 LSYLHSKGIFHRDLTSKNCLIKRDENgytAVVGDFGLAEKI----PDYSDGKEKLAVvgspYWMAPEVLRGEPYNEKADV 176
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  892 WSYGVTVWELMTfgakpydGIPAReiPDLLEKGERL--------PQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:cd14155    177 FSYGIILCEIIA-------RIQAD--PDYLPRTEDFgldydafqHMVGDCPPDFLQLAFNCCNMDPKSRPSFHDIVKTLE 247

                   ....
gi 1844139549  964 RMAR 967
Cdd:cd14155    248 EILE 251
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
736-901 3.57e-14

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 74.32  E-value: 3.57e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnrGRLGSQDLLNWCMQ 814
Cdd:cd06640     32 VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTkLWIIMEYLGGGSALDLLRA--GPFDEFQIATMLKE 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDVWSY 894
Cdd:cd06640    110 ILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRNTFVG-TPF-WMAPEVIQQSAYDSKADIWSL 187

                   ....*..
gi 1844139549  895 GVTVWEL 901
Cdd:cd06640    188 GITAIEL 194
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
737-930 3.94e-14

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 74.38  E-value: 3.94e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL---TSTVQLVTQLMPYGCL---LDHVRENRGRLGSQDLLN 810
Cdd:cd06621     30 ALKTITTDPNPDVQKQILRELEINKSCASPYIVKYYGAFLdeqDSSIGIAMEYCEGGSLdsiYKKVKKKGGRIGEKVLGK 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL------DIDETEYhadggkvpikWMALESILRRR 884
Cdd:cd06621    110 IAESVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELvnslagTFTGTSY----------YMAPERIQGGP 179
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1844139549  885 FTHQSDVWSYGVTVWEL----MTFgakPYDGIPAREIPDLLEKGERLPQP 930
Cdd:cd06621    180 YSITSDVWSLGLTLLEVaqnrFPF---PPEGEPPLGPIELLSYIVNMPNP 226
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
814-922 4.02e-14

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 73.98  E-value: 4.02e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdidETEYHADGGKVPIKWMALESILRR--RFTHQSDV 891
Cdd:cd06632    110 QILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAKHV---EAFSFAKSFKGSPYWMAPEVIMQKnsGYGLAVDI 186
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  892 WSYGVTVWELMTfGAKP---YDGIPA----------REIPDLLE 922
Cdd:cd06632    187 WSLGCTVLEMAT-GKPPwsqYEGVAAifkignsgelPPIPDHLS 229
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
736-917 4.36e-14

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 73.79  E-value: 4.36e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRE-NTSPK-ANKEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYG---CLLDHVrenrGRLGSQDLL 809
Cdd:cd05579     21 YAIKVIKKrDMIRKnQVDSVLAERNILSQAQNPFVVKLYySFQGKKNLYLVMEYLPGGdlySLLENV----GALDEDVAR 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIK-------------WMA 876
Cdd:cd05579     97 IYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGLSKVGLVRRQIKLSIQKKSNGApekedrrivgtpdYLA 176
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1844139549  877 LESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREI 917
Cdd:cd05579    177 PEILLGQGHGKTVDWWSLGVILYEFLV-GIPPFHAETPEEI 216
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
737-932 6.90e-14

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 73.19  E-value: 6.90e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCLLdHVRENRGRLG----SQDLLN 810
Cdd:cd08530     29 ALKEVNlGSLSQKEREDSVNEIRLLASVNHPNIIRYKeAFLDGNRLCIVMEYAPFGDLS-KLISKRKKKRrlfpEDDIWR 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdideteyHADGGKVPIK---WMALESILRRRFTH 887
Cdd:cd08530    108 IFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVL-------KKNLAKTQIGtplYAAPEVWKGRPYDY 180
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1844139549  888 QSDVWSYGVTVWELMTFgAKPYDgipAREIPDLLEKGERLPQPPI 932
Cdd:cd08530    181 KSDIWSLGCLLYEMATF-RPPFE---ARTMQELRYKVCRGKFPPI 221
STKc_MEKK3_like cd06625
Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) ...
785-962 9.99e-14

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270795 [Multi-domain]  Cd Length: 260  Bit Score: 72.77  E-value: 9.99e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  785 QLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdidETEYH 864
Cdd:cd06625     82 EYMPGGSVKDEIK-AYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRL---QTICS 157
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  865 ADGGKVPIK---WMALESILRRRFTHQSDVWSYGVTVWELMTfgAKP----YDGIPA-------REIPDLlekgerlpqP 930
Cdd:cd06625    158 STGMKSVTGtpyWMSPEVINGEGYGRKADIWSVGCTVVEMLT--TKPpwaeFEPMAAifkiatqPTNPQL---------P 226
                          170       180       190
                   ....*....|....*....|....*....|..
gi 1844139549  931 PICTIDVYMIMVKCWMIDSECRPRFRELVSEF 962
Cdd:cd06625    227 PHVSEDARDFLSLIFVRNKKQRPSAEELLSHS 258
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
735-902 1.13e-13

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 73.13  E-value: 1.13e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIK-VLRENTSPKANKEILDEAYVMAGV-GSPYVSRLLGICLTST-VQLVTQLMPYGcLLDHVRENRGRLGSQDLLNW 811
Cdd:cd07832     27 TVALKkVALRKLEGGIPNQALREIKALQACqGHPYVVKLRDVFPHGTgFVLVFEYMLSS-LSEVLRDEERPLTEAQVKRY 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL--DIDETEYHadggKVPIKW-MALESIL-RRRFTH 887
Cdd:cd07832    106 MRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFseEDPRLYSH----QVATRWyRAPELLYgSRKYDE 181
                          170
                   ....*....|....*
gi 1844139549  888 QSDVWSYGVTVWELM 902
Cdd:cd07832    182 GVDLWAVGCIFAELL 196
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
736-909 2.13e-13

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 72.22  E-value: 2.13e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLG-ICLTSTVQLVTQLMPYGCLldhvrENRGRLGSQDLLNWCMQ 814
Cdd:cd06619     29 LAVKVIPLDITVELQKQIMSELEILYKCDSPYIIGFYGaFFVENRISICTEFMDGGSL-----DVYRKIPEHVLGRIAVA 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL--DIDETEYHADGgkvpikWMALESILRRRFTHQSDVW 892
Cdd:cd06619    104 VVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGVSTQLvnSIAKTYVGTNA------YMAPERISGEQYGIHSDVW 177
                          170
                   ....*....|....*..
gi 1844139549  893 SYGVTVWElMTFGAKPY 909
Cdd:cd06619    178 SLGISFME-LALGRFPY 193
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
736-936 3.06e-13

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 72.39  E-value: 3.06e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLlDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd06650     33 MARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDgEISICMEHMDGGSL-DQVLKKAGRIPEQILGKVSIA 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKvpiKWMALESILRRRFTHQSDVWS 893
Cdd:cd06650    112 VIKGLTYLrEKHKIMHRDVKPSNILVNSRGEIKLCDFGVSGQL-IDSMANSFVGTR---SYMSPERLQGTHYSVQSDIWS 187
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1844139549  894 YGVTVWElMTFGAKPydgIPAreiPDLLEkgerLPQPPICTID 936
Cdd:cd06650    188 MGLSLVE-MAVGRYP---IPP---PDAKE----LELMFGCQVE 219
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
732-932 3.60e-13

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 70.97  E-value: 3.60e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  732 VKIPVAIKVLRENTSPKANKEILDeayVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDHVRENrGRLGSQDLLN 810
Cdd:cd14098     30 IKQIVKRKVAGNDKNLQLFQREIN---ILKSLEHPGIVRLIDWYEdDQHIYLVMEYVEGGDLMDFIMAW-GAIPEQHARE 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLV--KSPNHVKITDFGLARLLDID---ETEYHADGGKVPIKWMALESILRRRF 885
Cdd:cd14098    106 LTKQILEAMAYTHSMGITHRDLKPENILItqDDPVIVKISDFGLAKVIHTGtflVTFCGTMAYLAPEILMSKEQNLQGGY 185
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  886 THQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGeRLPQPPI 932
Cdd:cd14098    186 SNLVDMWSVGCLVYVMLT-GALPFDGSSQLPVEKRIRKG-RYTQPPL 230
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
753-966 4.59e-13

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 70.63  E-value: 4.59e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  753 ILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRD 831
Cdd:cd14156     35 IVREISLLQKLSHPNIVRYLGICVKdEKLHPILEYVSGGCLEELLAREELPLSWREKVELACDISRGMVYLHSKNIYHRD 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  832 LAARNVLVKSPNHVK---ITDFGLARLLdideteyhadgGKVPIK-------------WMALESILRRRFTHQSDVWSYG 895
Cdd:cd14156    115 LNSKNCLIRVTPRGReavVTDFGLAREV-----------GEMPANdperklslvgsafWMAPEMLRGEPYDRKVDVFSFG 183
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  896 VTVWELMTfgakpydGIPAReiPDLLEKGERL--------PQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMA 966
Cdd:cd14156    184 IVLCEILA-------RIPAD--PEVLPRTGDFgldvqafkEMVPGCPEPFLDLAASCCRMDAFKRPSFAELLDELEDIA 253
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
733-910 5.17e-13

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 70.64  E-value: 5.17e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLreNTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNW 811
Cdd:cd14087     26 RQPYAIKMI--ETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKErVYMVMELATGGELFDRII-AKGSFTERDATRV 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDIDETEYHADGGKVPiKWMALESILRRRFTHQ 888
Cdd:cd14087    103 LQMVLDGVKYLHGLGITHRDLKPENLLYYHPGPdskIMITDFGLASTRKKGPNCLMKTTCGTP-EYIAPEILLRKPYTQS 181
                          170       180
                   ....*....|....*....|..
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14087    182 VDMWAVGVIAYILLS-GTMPFD 202
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
728-903 7.01e-13

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 69.96  E-value: 7.01e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIpVAIKVLR--ENTSPKANKEI--LDEAYvmAGVGSPYVSRLLGICLTSTVQ---LVTQLMPYGcLLDHVRENR 800
Cdd:cd05118     20 DKVTGEK-VAIKKIKndFRHPKAALREIklLKHLN--DVEGHPNIVKLLDVFEHRGGNhlcLVFELMGMN-LYELIKDYP 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN-HVKITDFGLARLLDIDE-TEYhadggKVPIKWMALE 878
Cdd:cd05118     96 RGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSFTSPPyTPY-----VATRWYRAPE 170
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  879 SILR-RRFTHQSDVWSYGVTVWELMT 903
Cdd:cd05118    171 VLLGaKPYGSSIDIWSLGCILAELLT 196
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
735-933 8.01e-13

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 69.94  E-value: 8.01e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIK-VLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWC 812
Cdd:cd14009     20 VVAIKeISRKKLNKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDfIYLVLEYCAGGDLSQYIRK-RGRLPEAVARHFM 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLdidETEYHAD---GGkvPIkWMALESILRRRFT 886
Cdd:cd14009     99 QQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDdpvLKIADFGFARSL---QPASMAEtlcGS--PL-YMAPEILQFQKYD 172
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  887 HQSDVWSYGVTVWElMTFGAKPYDGIPAREIPDLLEKGERLPQPPIC 933
Cdd:cd14009    173 AKADLWSVGAILFE-MLVGKPPFRGSNHVQLLRNIERSDAVIPFPIA 218
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
814-911 9.24e-13

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 70.89  E-value: 9.24e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVpiKWMALESILRRRFTHQSDVWS 893
Cdd:cd05582    105 ELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKAYSFCGTV--EYMAPEVVNRRGHTQSADWWS 182
                           90
                   ....*....|....*...
gi 1844139549  894 YGVTVWELMTfGAKPYDG 911
Cdd:cd05582    183 FGVLMFEMLT-GSLPFQG 199
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
780-960 9.44e-13

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 69.89  E-value: 9.44e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDid 859
Cdd:cd14099     76 VYILLELCSNGSLMELLK-RRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENMNVKIGDFGLAARLE-- 152
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  860 eteyHADGGKVPI----KWMALEsILRRRFTH--QSDVWSYGVTVWeLMTFGAKPYDGIPAREIPDLLEKGE-RLPQPPI 932
Cdd:cd14099    153 ----YDGERKKTLcgtpNYIAPE-VLEKKKGHsfEVDIWSLGVILY-TLLVGKPPFETSDVKETYKRIKKNEySFPSHLS 226
                          170       180
                   ....*....|....*....|....*...
gi 1844139549  933 CTIDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd14099    227 ISDEAKDLIRSMLQPDPTKRPSLDEILS 254
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
782-932 1.24e-12

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 69.50  E-value: 1.24e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDhVREN--RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiD 859
Cdd:cd14008     83 LVLEYCEGGPVME-LDSGdrVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFE-D 160
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  860 ETEYHADGGKVPIkWMALE--SILRRRF-THQSDVWSYGVTVWeLMTFGAKPYDGipaREIPDLLEKGERLPQPPI 932
Cdd:cd14008    161 GNDTLQKTAGTPA-FLAPElcDGDSKTYsGKAADIWALGVTLY-CLVFGRLPFNG---DNILELYEAIQNQNDEFP 231
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
737-862 1.31e-12

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 69.63  E-value: 1.31e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM-- 813
Cdd:cd13996     35 AIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYTAwVEEPPLYIQMELCEGGTLRDWIDRRNSSSKNDRKLALELfk 114
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV-KSPNHVKITDFGLARLLDIDETE 862
Cdd:cd13996    115 QILKGVSYIHSKGIVHRDLKPSNIFLdNDDLQVKIGDFGLATSIGNQKRE 164
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
819-928 1.62e-12

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 69.43  E-value: 1.62e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  819 MSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILR-RRFTHQSDVWSYGVT 897
Cdd:cd06917    114 LKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKRSTFVG-TPY-WMAPEVITEgKYYDTKADIWSLGIT 191
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1844139549  898 VWELMTfGAKPYDGIPAREIPDLLEKGE--RLP 928
Cdd:cd06917    192 TYEMAT-GNPPYSDVDALRAVMLIPKSKppRLE 223
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
735-903 1.68e-12

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 69.17  E-value: 1.68e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVL------RENTSPKANKEILdeayVMAGVGSPYVSRLLGicltsTVQ------LVTQLMPYGCLLDHVRENrGR 802
Cdd:cd05581     28 EYAIKVLdkrhiiKEKKVKYVTIEKE----VLSRLAHPGIVKLYY-----TFQdesklyFVLEYAPNGDLLEYIRKY-GS 97
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE------TEYHADGGKVPIK--- 873
Cdd:cd05581     98 LDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPDSspestkGDADSQIAYNQARaas 177
                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1844139549  874 ------WMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd05581    178 fvgtaeYVSPELLNEKPAGKSSDLWALGCIIYQMLT 213
STKc_SIK cd14071
Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the ...
733-911 2.43e-12

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270973 [Multi-domain]  Cd Length: 253  Bit Score: 68.57  E-value: 2.43e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVReNRGRLGSQDLLN 810
Cdd:cd14071     25 KTEVAIKIIDKSQLDEENlKKIYREVQIMKMLNHPHIIKLYQVMETkDMLYLVTEYASNGEIFDYLA-QHGRMSEKEARK 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKVPikWMALESILRRRFTH-QS 889
Cdd:cd14071    104 KFWQILSAVEYCHKRHIVHRDLKAENLLLDANMNIKIADFGFSNFFKPGEL-LKTWCGSPP--YAAPEVFEGKEYEGpQL 180
                          170       180
                   ....*....|....*....|..
gi 1844139549  890 DVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14071    181 DIWSLGVVLYVLVC-GALPFDG 201
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
736-923 2.58e-12

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 68.43  E-value: 2.58e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLrentspkaNKEILDEAYVMAGVGS----------PYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENrGRLG 804
Cdd:cd14081     29 VAIKIV--------NKEKLSKESVLMKVEReiaimkliehPNVLKLYDVYENKKyLYLVLEYVSGGELFDYLVKK-GRLT 99
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  805 SQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldideteyhadggKVPIKWM--------- 875
Cdd:cd14081    100 EKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASL-------------QPEGSLLetscgsphy 166
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESILRRRFTH--QSDVWSYGVTVWELMTfGAKPYDGipaREIPDLLEK 923
Cdd:cd14081    167 ACPEVIKGEKYDgrKADIWSCGVILYALLV-GALPFDD---DNLRQLLEK 212
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
733-903 2.61e-12

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 68.79  E-value: 2.61e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTsPKANKE---ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnrgrlgsQDL 808
Cdd:cd14026     22 RVTVAIKCLKLDS-PVGDSErncLLKEAEILHKARFSYILPILGICNEPEfLGIVTEYMTNGSLNELLHE-------KDI 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 ---LNWCM------QIAKGMSYLEDVR--LVHRDLAARNVLVKSPNHVKITDFGLA--RLLDIDETEYHA---DGGKvpI 872
Cdd:cd14026     94 ypdVAWPLrlrilyEIALGVNYLHNMSppLLHHDLKTQNILLDGEFHVKIADFGLSkwRQLSISQSRSSKsapEGGT--I 171
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1844139549  873 KWMALESI---LRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14026    172 IYMPPEEYepsQKRRASVKHDIYSYAIIMWEVLS 205
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
736-922 2.86e-12

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 68.68  E-value: 2.86e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRE---NTSPKANKEILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPYGCLLDhvrenrgRLGSQD---L 808
Cdd:cd14158     41 VAVKKLAAmvdISTEDLTKQFEQEIQVMAKCQHENLVELLGYsCDGPQLCLVYTYMPNGSLLD-------RLACLNdtpP 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQI------AKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESiLR 882
Cdd:cd14158    114 LSWHMRCkiaqgtANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARASEKFSQTIMTERIVGTTAYMAPEA-LR 192
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTfGAKPYDgiPAREIPDLLE 922
Cdd:cd14158    193 GEITPKSDIFSFGVVLLEIIT-GLPPVD--ENRDPQLLLD 229
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
811-911 3.20e-12

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 68.05  E-value: 3.20e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdidETEYHADGGKVPIKWMALESILRRRFTHQSD 890
Cdd:cd05578    105 YICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKL---TDGTLATSTSGTKPYMAPEVFMRAGYSFAVD 181
                           90       100
                   ....*....|....*....|.
gi 1844139549  891 VWSYGVTVWELMtFGAKPYDG 911
Cdd:cd05578    182 WWSLGVTAYEML-RGKRPYEI 201
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
729-963 4.12e-12

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 68.05  E-value: 4.12e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  729 GENVKIPVAIKVLrENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYGCLLDHVRENRGRLGSQD 807
Cdd:cd05078     27 GQLHETEVLLKVL-DKAHRNYSESFFEAASMMSQLSHKHLVLNYGVCVCGDENiLVQEYVKFGSLDTYLKKNKNCINILW 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV--------KSPNHVKITDFGlarlldIDETEYHADGGKVPIKWMALES 879
Cdd:cd05078    106 KLEVAKQLAWAMHFLEEKTLVHGNVCAKNILLireedrktGNPPFIKLSDPG------ISITVLPKDILLERIPWVPPEC 179
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  880 ILR-RRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPicTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd05078    180 IENpKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPK--WTELANLINNCMDYEPDHRPSFRAI 257

                   ....*
gi 1844139549  959 VSEFS 963
Cdd:cd05078    258 IRDLN 262
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
735-953 4.34e-12

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 67.79  E-value: 4.34e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPY---GCLLDHVRENRGRLGSQDLLN 810
Cdd:cd13979     28 TVAVKIVRRRRKNRASRQSFWAELNAARLRHENIVRVLAAeTGTDFASLGLIIMEYcgnGTLQQLIYEGSEPLPLAHRIL 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVkSPNHV-KITDFGLARLL-DIDETEYHADGGKVPIKWMALESILRRRFTHQ 888
Cdd:cd13979    108 ISLDIARALRFCHSHGIVHLDVKPANILI-SEQGVcKLCDFGCSVKLgEGNEVGTPRSHIGGTYTYRAPELLKGERVTPK 186
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  889 SDVWSYGVTVWElMTFGAKPYDGIPAREIPDLLEKGERLPQPPIC---TIDVY-MIMVKCWMIDSECRP 953
Cdd:cd13979    187 ADIYSFGITLWQ-MLTRELPYAGLRQHVLYAVVAKDLRPDLSGLEdseFGQRLrSLISRCWSAQPAERP 254
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
786-904 4.40e-12

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173759 [Multi-domain]  Cd Length: 255  Bit Score: 67.69  E-value: 4.40e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY---GCLLDHVRENRGRLGSQD-LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID-- 859
Cdd:cd08219     76 VMEYcdgGDLMQKIKLQRGKLFPEDtILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLTSPga 155
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  860 ------ETEYHADggkvPIKWMALEsilrrrFTHQSDVWSYGVTVWELMTF 904
Cdd:cd08219    156 yactyvGTPYYVP----PEIWENMP------YNNKSDIWSLGCILYELCTL 196
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
735-909 6.59e-12

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 67.60  E-value: 6.59e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLrentsPKA----NKE---ILDEAYVMAGVGSPYVSRLLGicltsTVQ------LVTQLMPYGCLLDHVReNRG 801
Cdd:cd05580     28 YYALKIL-----KKAkiikLKQvehVLNEKRILSEVRHPFIVNLLG-----SFQddrnlyMVMEYVPGGELFSLLR-RSG 96
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDET-------EYhadggkvpikw 874
Cdd:cd05580     97 RFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFGFAKRVK-DRTytlcgtpEY----------- 164
                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd05580    165 LAPEIILSKGHGKAVDWWALGILIYE-MLAGYPPF 198
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
782-957 7.15e-12

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 67.74  E-value: 7.15e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGsqDLLNWCMQIAKGMSYL-EDVR---------LVHRDLAARNVLVKSPNHVKITDFG 851
Cdd:cd14053     70 LITEFHERGSLCDYLKGNVISWN--ELCKIAESMARGLAYLhEDIPatngghkpsIAHRDFKSKNVLLKSDLTACIADFG 147
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  852 LARLLDIDET--EYHadgGKVPIK-WMALEsILRR--RFTHQS----DVWSYGVTVWELMTFGAKPYDGIPAREIPDLLE 922
Cdd:cd14053    148 LALKFEPGKScgDTH---GQVGTRrYMAPE-VLEGaiNFTRDAflriDMYAMGLVLWELLSRCSVHDGPVDEYQLPFEEE 223
                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1844139549  923 KGerlPQPpicTIDVymiMVKCwMIDSECRPRFRE 957
Cdd:cd14053    224 VG---QHP---TLED---MQEC-VVHKKLRPQIRD 248
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
736-959 7.82e-12

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 67.26  E-value: 7.82e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKanKE-ILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVRE---NRGRLGSQdlln 810
Cdd:cd06647     35 VAIKQMNLQQQPK--KElIINEILVMRENKNPNIVNYLDSYLVGdELWVVMEYLAGGSLTDVVTEtcmDEGQIAAV---- 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 wCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSD 890
Cdd:cd06647    109 -CRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVG-TPY-WMAPEVVTRKAYGPKVD 185
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  891 VWSYGVTVWElMTFGAKPY-DGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd06647    186 IWSLGIMAIE-MVEGEPPYlNENPLRALYLIATNGTpELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELL 255
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
736-908 8.35e-12

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 67.08  E-value: 8.35e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIK--VLRENTSPKANKE---ILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRenrgRLGSQDLL 809
Cdd:cd06631     28 IAVKqvELDTSDKEKAEKEyekLQEEVDLLKTLKHVNIVGYLGTCLEdNVVSIFMEFVPGGSIASILA----RFGALEEP 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCM---QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEY-HADGGK----VPIkWMALESIL 881
Cdd:cd06631    104 VFCRytkQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGsQSQLLKsmrgTPY-WMAPEVIN 182
                          170       180
                   ....*....|....*....|....*..
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELMTfgAKP 908
Cdd:cd06631    183 ETGHGRKSDIWSIGCTVFEMAT--GKP 207
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
736-928 8.68e-12

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270974 [Multi-domain]  Cd Length: 253  Bit Score: 66.77  E-value: 8.68e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVL-RENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCM 813
Cdd:cd14072     28 VAIKIIdKTQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEkTLYLVMEYASGGEVFDYL-VAHGRMKEKEARAKFR 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlldideTEYhADGGKVPI-----KWMALESILRRRFTH- 887
Cdd:cd14072    107 QIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFS-------NEF-TPGNKLDTfcgspPYAAPELFQGKKYDGp 178
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  888 QSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLP 928
Cdd:cd14072    179 EVDVWSLGVILYTLVS-GSLPFDGQNLKELRERVLRGKyRIP 219
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
814-903 9.72e-12

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 67.94  E-value: 9.72e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE-----TEYhadggkVPIKWM-ALESILR-RRFT 886
Cdd:cd07834    111 QILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGVDPDEdkgflTEY------VVTRWYrAPELLLSsKKYT 184
                           90
                   ....*....|....*..
gi 1844139549  887 HQSDVWSYGVTVWELMT 903
Cdd:cd07834    185 KAIDIWSVGCIFAELLT 201
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
796-903 1.08e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 66.68  E-value: 1.08e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  796 VRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSpNHVKITDFGLARLLdIDETEYHADGGKVPIkWM 875
Cdd:cd08222     96 YKKSGTTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLKN-NVIKVGDFGISRIL-MGTSDLATTFTGTPY-YM 172
                           90       100
                   ....*....|....*....|....*...
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd08222    173 SPEVLKHEGYNSKSDIWSLGCILYEMCC 200
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
736-967 1.09e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 67.06  E-value: 1.09e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQ 814
Cdd:cd06655     47 VAIKQINLQKQPK-KELIINEILVMKELKNPNIVNFLDSFLVgDELFVVMEYLAGGSLTDVVTETC--MDEAQIAAVCRE 123
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDVWSY 894
Cdd:cd06655    124 CLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRSTMVG-TPY-WMAPEVVTRKAYGPKVDIWSL 201
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  895 GVTVWElMTFGAKPY-DGIPAREIPDLLEKGERLPQPPICTIDVYM-IMVKCWMIDSECRPRFRELVSE-FSRMAR 967
Cdd:cd06655    202 GIMAIE-MVEGEPPYlNENPLRALYLIATNGTPELQNPEKLSPIFRdFLNRCLEMDVEKRGSAKELLQHpFLKLAK 276
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
806-961 1.31e-11

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270799 [Multi-domain]  Cd Length: 270  Bit Score: 66.64  E-value: 1.31e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideTEYHADGG---KVPIKWMALESI- 880
Cdd:cd06629    107 EDLVRFFTrQILDGLAYLHSKGILHRDLKADNILVDLEGICKISDFGISKKSD---DIYGNNGAtsmQGSVFWMAPEVIh 183
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  881 -LRRRFTHQSDVWSYGVTVWELMTfGAKPYDgiPAREIPDLLEKGERLPQPPICTiDVYM------IMVKCWMIDSECRP 953
Cdd:cd06629    184 sQGQGYSAKVDIWSLGCVVLEMLA-GRRPWS--DDEAIAAMFKLGNKRSAPPVPE-DVNLspealdFLNACFAIDPRDRP 259

                   ....*...
gi 1844139549  954 RFRELVSE 961
Cdd:cd06629    260 TAAELLSH 267
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
736-909 1.43e-11

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 66.12  E-value: 1.43e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLreNTSPKANKEIL---DEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPyGCLLDhVRENRGRLGSQDLLNW 811
Cdd:cd14002     29 VALKFI--PKRGKSEKELRnlrQEIEILRKLNHPNIIEMLDSFETKKeFVVVTEYAQ-GELFQ-ILEDDGTLPEEEVRSI 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDV 891
Cdd:cd14002    105 AKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARAMSCNTLVLTSIKG-TPL-YMAPELVQEQPYDHTADL 182
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd14002    183 WSLGCILYELFV-GQPPF 199
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
736-965 1.64e-11

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 66.42  E-value: 1.64e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSpKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYGCLLDhvrenrgRLGSQDL-LNW-- 811
Cdd:cd14045     33 VAIKKIAKKSF-TLSKRIRKEVKQVRELDHPNLCKFIGGCIeVPNVAIITEYCPKGSLND-------VLLNEDIpLNWgf 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 ----CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE----YHADGGKVpikWMALE--SIL 881
Cdd:cd14045    105 rfsfATDIARGMAYLHQHKIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSEnasgYQQRLMQV---YLPPEnhSNT 181
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELMTFGakpyDGIPAREIPdlLEKGERLPQPPI----------CTIDVYMIMVKCWMIDSEC 951
Cdd:cd14045    182 DTEPTQATDVYSYAIILLEIATRN----DPVPEDDYS--LDEAWCPPLPELisgktenscpCPADYVELIRRCRKNNPAQ 255
                          250
                   ....*....|....
gi 1844139549  952 RPRFRELVSEFSRM 965
Cdd:cd14045    256 RPTFEQIKKTLHKI 269
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
737-919 2.20e-11

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 65.58  E-value: 2.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEI---LDEAYVMAGVGSPYVSRLLgicltSTVQ------LVTQLMPYGCLLDHVREnRGRLGSQD 807
Cdd:cd05611     25 AIKVLKKSDMIAKNQVTnvkAERAIMMIQGESPYVAKLY-----YSFQskdylyLVMEYLNGGDCASLIKT-LGGLPEDW 98
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTH 887
Cdd:cd05611     99 AKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEKRHNKKFVG--TP-DYLAPETILGVGDDK 175
                          170       180       190
                   ....*....|....*....|....*....|..
gi 1844139549  888 QSDVWSYGVTVWELMtFGAKPYDGiparEIPD 919
Cdd:cd05611    176 MSDWWSLGCVIFEFL-FGYPPFHA----ETPD 202
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
736-953 2.29e-11

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 65.36  E-value: 2.29e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEildEAYVMAGVGSPYVSRLLGIClTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQI 815
Cdd:cd14068     20 VAVKIFNKHTSFRLLRQ---ELVVLSHLHHPSLVALLAAG-TAPRMLVMELAPKGSLDALLQQDNASLTRTLQHRIALHV 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  816 AKGMSYLEDVRLVHRDLAARNVLVKS--PNH---VKITDFGLARL---LDIDETEYHAdGGKVPikWMALESILrrrFTH 887
Cdd:cd14068     96 ADGLRYLHSAMIIYRDLKPHNVLLFTlyPNCaiiAKIADYGIAQYccrMGIKTSEGTP-GFRAP--EVARGNVI---YNQ 169
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  888 QSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQP-------PICTIDVymIMVKCWMIDSECRP 953
Cdd:cd14068    170 QADVYSFGLLLYDILTCGERIVEGLKFPNEFDELAIQGKLPDPvkeygcaPWPGVEA--LIKDCLKENPQCRP 240
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
790-907 2.35e-11

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 65.54  E-value: 2.35e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 GCLLDHVRENRGRLGSQD-LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdidetEYHADGG 868
Cdd:cd08223     85 GDLYTRLKEQKGVLLEERqVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVL-----ESSSDMA 159
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1844139549  869 KVPIK---WMALESILRRRFTHQSDVWSYGVTVWELMT----FGAK 907
Cdd:cd08223    160 TTLIGtpyYMSPELFSNKPYNHKSDVWALGCCVYEMATlkhaFNAK 205
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
736-910 2.83e-11

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 65.55  E-value: 2.83e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKV--------LRENTSPKANKEILDEAYVM--AGVGS----PYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnR 800
Cdd:cd14077     29 CAIKIiprasnagLKKEREKRLEKEISRDIRTIreAALSSllnhPHICRLRDFLRTPNhYYMLFEYVDGGQLLDYIIS-H 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKvpIKWMALESI 880
Cdd:cd14077    108 GKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLYD-PRRLLRTFCGS--LYFAAPELL 184
                          170       180       190
                   ....*....|....*....|....*....|.
gi 1844139549  881 LRRRFTH-QSDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14077    185 QAQPYTGpEVDVWSFGVVLYVLVC-GKVPFD 214
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
736-942 3.76e-11

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 64.98  E-value: 3.76e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSpKANKEILD---EAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNW 811
Cdd:cd14161     30 VAIKSIRKDRI-KDEQDLLHirrEIEIMSSLNHPHIISVYEVFENSSkIVIVMEYASRGDLYDYISE-RQRLSELEARHF 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVpikWMALESILRRRFTH-QSD 890
Cdd:cd14161    108 FRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQDKFLQTYCGSPL---YASPEIVNGRPYIGpEVD 184
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  891 VWSYGVTVWELMtFGAKPYDGIPAREIPDLLEKGE-RLPQPP--ICTIDVYMIMV 942
Cdd:cd14161    185 SWSLGVLLYILV-HGTMPFDGHDYKILVKQISSGAyREPTKPsdACGLIRWLLMV 238
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
736-967 3.80e-11

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 65.52  E-value: 3.80e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRE---NRGRLGSQdllnw 811
Cdd:cd06654     48 VAIRQMNLQQQPK-KELIINEILVMRENKNPNIVNYLDSYLVgDELWVVMEYLAGGSLTDVVTEtcmDEGQIAAV----- 121
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDV 891
Cdd:cd06654    122 CRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVG-TPY-WMAPEVVTRKAYGPKVDI 199
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  892 WSYGVTVWELMTfGAKPY-DGIPAREIPDLLEKGE-RLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS-EFSRMAR 967
Cdd:cd06654    200 WSLGIMAIEMIE-GEPPYlNENPLRALYLIATNGTpELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQhQFLKIAK 277
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
813-958 3.90e-11

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 65.14  E-value: 3.90e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPikWMALESI----LRRRFTH 887
Cdd:cd06617    110 VSIVKALEYLhSKLSVIHRDVKPSNVLINRNGQVKLCDFGISGYL-VDSVAKTIDAGCKP--YMAPERInpelNQKGYDV 186
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  888 QSDVWSYGVTVWELMTfGAKPYD--GIPAREIPDLLEK-GERLPQPPIcTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd06617    187 KSDVWSLGITMIELAT-GRFPYDswKTPFQQLKQVVEEpSPQLPAEKF-SPEFQDFVNKCLKKNYKERPNYPEL 258
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
779-903 3.98e-11

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 65.07  E-value: 3.98e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdi 858
Cdd:cd06652     80 TLSIFMEYMPGGSIKDQLK-SYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRL-- 156
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1844139549  859 dETEYHADGGKVPIK----WMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd06652    157 -QTICLSGTGMKSVTgtpyWMSPEVISGEGYGRKADIWSVGCTVVEMLT 204
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
734-903 4.87e-11

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 65.46  E-value: 4.87e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPK--ANKEIldeaYVMAGVGSPYVSRLLGICLTSTV------QLVTQLMPYGCLLDHVRENRGRLGS 805
Cdd:cd14054     19 RPVAVKVFPARHRQNfqNEKDI----YELPLMEHSNILRFIGADERPTAdgrmeyLLVLEYAPKGSLCSYLRENTLDWMS 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 qdLLNWCMQIAKGMSYL-EDVRL--------VHRDLAARNVLVKSPNHVKITDFGLA---RLLDIDETEYHADGGKVP-- 871
Cdd:cd14054     95 --SCRMALSLTRGLAYLhTDLRRgdqykpaiAHRDLNSRNVLVKADGSCVICDFGLAmvlRGSSLVRGRPGAAENASIse 172
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  872 ---IKWMALESI-----LR--RRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14054    173 vgtLRYMAPEVLegavnLRdcESALKQVDVYALGLVLWEIAM 214
STKc_MEKK3_like_u1 cd06653
Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP) ...
779-903 5.58e-11

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270819 [Multi-domain]  Cd Length: 264  Bit Score: 64.66  E-value: 5.58e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdi 858
Cdd:cd06653     80 KLSIFVEYMPGGSVKDQLKA-YGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRI-- 156
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1844139549  859 dETEYHADGGKVPIK----WMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd06653    157 -QTICMSGTGIKSVTgtpyWMSPEVISGEGYGRKADVWSVACTVVEMLT 204
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
737-911 6.13e-11

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 65.02  E-value: 6.13e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENT---SPKANKEILDEAYVMAGV-GSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNW 811
Cdd:cd05613     32 AMKVLKKATivqKAKTAEHTRTERQVLEHIrQSPFLVTLHYAFQTDTkLHLILDYINGGELFTHLSQ-RERFTENEVQIY 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE--YHADGgkvPIKWMALESILRRRFTHQS 889
Cdd:cd05613    111 IGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENEraYSFCG---TIEYMAPEIVRGGDSGHDK 187
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  890 --DVWSYGVTVWELMTfGAKPY--DG 911
Cdd:cd05613    188 avDWWSLGVLMYELLT-GASPFtvDG 212
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
737-909 6.50e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 64.25  E-value: 6.50e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGI-------------CLTSTVQlvtQLMPYGCLLDHVRENRgr 802
Cdd:cd06626     29 AMKEIRfQDNDPKTIKEIADEMKVLEGLDHPNLVRYYGVevhreevyifmeyCQEGTLE---ELLRHGRILDEAVIRV-- 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 lgsqdllnWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLA-RLLDIDETEYHADG---GKVPIkWMALE 878
Cdd:cd06626    104 --------YTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAvKLKNNTTTMAPGEVnslVGTPA-YMAPE 174
                          170       180       190
                   ....*....|....*....|....*....|....
gi 1844139549  879 SILRRRFTHQ---SDVWSYGVTVWELMTfGAKPY 909
Cdd:cd06626    175 VITGNKGEGHgraADIWSLGCVVLEMAT-GKRPW 207
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
768-972 7.30e-11

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 64.60  E-value: 7.30e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  768 VSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSpNHVK 846
Cdd:cd14152     58 VVLFMGACMHPPhLAIITSFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGYLHAKGIVHKDLKSKNVFYDN-GKVV 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  847 ITDFGLARLLDIDETEYHADGGKVPIKWMAL--ESILRRR----------FTHQSDVWSYGvTVWELMTFGAKPYDGIPA 914
Cdd:cd14152    137 ITDFGLFGISGVVQEGRRENELKLPHDWLCYlaPEIVREMtpgkdedclpFSKAADVYAFG-TIWYELQARDWPLKNQPA 215
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  915 REIPDLLEKGERLPQpPICTI----DVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRF 972
Cdd:cd14152    216 EALIWQIGSGEGMKQ-VLTTIslgkEVTEILSACWAFDLEERPSFTLLMDMLEKLPKLNRRL 276
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
814-909 7.83e-11

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 64.35  E-value: 7.83e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHV-KITDFG----LARLLDIDETeyhadgGKVPIKWMALESILR--RRFT 886
Cdd:cd06624    116 QILEGLKYLHDNKIVHRDIKGDNVLVNTYSGVvKISDFGtskrLAGINPCTET------FTGTLQYMAPEVIDKgqRGYG 189
                           90       100
                   ....*....|....*....|...
gi 1844139549  887 HQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd06624    190 PPADIWSLGCTIIEMAT-GKPPF 211
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
782-953 8.55e-11

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 64.22  E-value: 8.55e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLE-DVR-------LVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14056     70 LITEYHEHGSLYDYLQRNT--LDTEEALRLAYSAASGLAHLHtEIVgtqgkpaIAHRDLKSKNILVKRDGTCCIADLGLA 147
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  854 -----RLLDIDETEYHADGGKvpiKWMALE----SILRRRFTH--QSDVWSYGVTVWELMTFG---------AKPYDGIP 913
Cdd:cd14056    148 vrydsDTNTIDIPPNPRVGTK---RYMAPEvlddSINPKSFESfkMADIYSFGLVLWEIARRCeiggiaeeyQLPYFGMV 224
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  914 AREiPDLLE-------KGERLPQPPICTIDVYM-----IMVKCWMIDSECRP 953
Cdd:cd14056    225 PSD-PSFEEmrkvvcvEKLRPPIPNRWKSDPVLrsmvkLMQECWSENPHARL 275
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
790-959 8.80e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 63.99  E-value: 8.80e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 GCLLDHVRENRGRLGSQDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideTEYH-ADG 867
Cdd:cd08221     84 GNLHDKIAQQKNQLFPEEVVLWYLyQIVSAVSHIHKAGILHRDIKTLNIFLTKADLVKLGDFGISKVLD---SESSmAES 160
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  868 GKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGI-PAREIPDLLeKGERLPQPPICTIDVYMIMVKCWM 946
Cdd:cd08221    161 IVGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTL-KRTFDATnPLRLAVKIV-QGEYEDIDEQYSEEIIQLVHDCLH 238
                          170
                   ....*....|...
gi 1844139549  947 IDSECRPRFRELV 959
Cdd:cd08221    239 QDPEDRPTAEELL 251
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
776-931 9.20e-11

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 63.88  E-value: 9.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  776 LTSTVQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVK-------SPNH--VK 846
Cdd:cd14202     72 IANSVYLVMEYCNGGDLADYL-HTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSysggrksNPNNirIK 150
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  847 ITDFGLARLLDIDETEYHADGGKVpikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGER 926
Cdd:cd14202    151 IADFGFARYLQNNMMAATLCGSPM---YMAPEVIMSQHYDAKADLWSIGTIIYQCLT-GKAPFQASSPQDLRLFYEKNKS 226

                   ....*.
gi 1844139549  927 L-PQPP 931
Cdd:cd14202    227 LsPNIP 232
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
735-910 9.64e-11

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 63.58  E-value: 9.64e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENrGRLGSQDLLNW 811
Cdd:cd14663     27 SVAIKIIDKEQVAREGmvEQIKREIAIMKLLRHPNIVELHEVMATKTkIFFVMELVTGGELFSKIAKN-GRLKEDKARKY 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD--IDETEYHADGGkVPiKWMALESILRRRFT-HQ 888
Cdd:cd14663    106 FQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGLSALSEqfRQDGLLHTTCG-TP-NYVAPEVLARRGYDgAK 183
                          170       180
                   ....*....|....*....|..
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14663    184 ADIWSCGVILFVLLA-GYLPFD 204
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
736-967 1.00e-10

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 64.36  E-value: 1.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRE---NRGRLGSQdllnw 811
Cdd:cd06656     47 VAIKQMNLQQQPK-KELIINEILVMRENKNPNIVNYLDSYLVgDELWVVMEYLAGGSLTDVVTEtcmDEGQIAAV----- 120
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDV 891
Cdd:cd06656    121 CRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTMVG-TPY-WMAPEVVTRKAYGPKVDI 198
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  892 WSYGVTVWElMTFGAKPY-DGIPAREIPDLLEKGERLPQPPICTIDVYM-IMVKCWMIDSECRPRFRELVSE-FSRMAR 967
Cdd:cd06656    199 WSLGIMAIE-MVEGEPPYlNENPLRALYLIATNGTPELQNPERLSAVFRdFLNRCLEMDVDRRGSAKELLQHpFLKLAK 276
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
736-923 1.08e-10

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 63.46  E-value: 1.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKE-ILDEAYVMAGVGSPYVSRLLG-------ICLtstvqlvtqLMPY--GCLLDHVRENRGRLGS 805
Cdd:cd14121     24 VAVKCVSKSSLNKASTEnLLTEIELLKKLKHPHIVELKDfqwdeehIYL---------IMEYcsGGDLSRFIRSRRTLPE 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHV--KITDFGLARLLDIDETEYHADGGkvPIkWMALESILRR 883
Cdd:cd14121     95 STVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRYNPvlKLADFGFAQHLKPNDEAHSLRGS--PL-YMAPEMILKK 171
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1844139549  884 RFTHQSDVWSYGVTVWELMtFGAKPYdgiPAREIPDLLEK 923
Cdd:cd14121    172 KYDARVDLWSVGVILYECL-FGRAPF---ASRSFEELEEK 207
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
809-902 1.17e-10

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 63.74  E-value: 1.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE---------YHADGGKVPIK-WMALE 878
Cdd:cd14048    121 LNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDQGEPEqtvltpmpaYAKHTGQVGTRlYMSPE 200
                           90       100
                   ....*....|....*....|....
gi 1844139549  879 SILRRRFTHQSDVWSYGVTVWELM 902
Cdd:cd14048    201 QIHGNQYSEKVDIFALGLILFELI 224
STKc_MEKK3 cd06651
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
779-960 1.21e-10

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270817 [Multi-domain]  Cd Length: 271  Bit Score: 63.56  E-value: 1.21e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdi 858
Cdd:cd06651     85 TLTIFMEYMPGGSVKDQLKA-YGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRL-- 161
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  859 dETEYHADGGKVPIK----WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGERLPQPPICT 934
Cdd:cd06651    162 -QTICMSGTGIRSVTgtpyWMSPEVISGEGYGRKADVWSLGCTVVEMLT-EKPPWAEYEAMAAIFKIATQPTNPQLPSHI 239
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  935 IDVYMIMVKCWMIDSECRPRFRELVS 960
Cdd:cd06651    240 SEHARDFLGCIFVEARHRPSAEELLR 265
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
753-910 1.41e-10

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 63.58  E-value: 1.41e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  753 ILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRD 831
Cdd:cd14209     48 TLNEKRILQAINFPFLVKLEySFKDNSNLYMVMEYVPGGEMFSHLRR-IGRFSEPHARFYAAQIVLAFEYLHSLDLIYRD 126
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  832 LAARNVLVKSPNHVKITDFGLARLLDiDET-------EYhadggkvpikwMALESILRRRFTHQSDVWSYGVTVWElMTF 904
Cdd:cd14209    127 LKPENLLIDQQGYIKVTDFGFAKRVK-GRTwtlcgtpEY-----------LAPEIILSKGYNKAVDWWALGVLIYE-MAA 193

                   ....*.
gi 1844139549  905 GAKPYD 910
Cdd:cd14209    194 GYPPFF 199
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
737-925 1.42e-10

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 63.34  E-value: 1.42e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIK-VLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLmpygCLLDHVRE--NRGRLGSQDLLNWC 812
Cdd:cd14097     30 AIKkINREKAGSSAVKLLEREVDILKHVNHAHIIHLEEVFETPKrMYLVMEL----CEDGELKEllLRKGFFSENETRHI 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQ-IAKGMSYLEDVRLVHRDLAARNVLVKS----PN---HVKITDFGLA-RLLDIDETEYHADGGkVPIkWMALESILRR 883
Cdd:cd14097    106 IQsLASAVAYLHKNDIVHRDLKLENILVKSsiidNNdklNIKVTDFGLSvQKYGLGEDMLQETCG-TPI-YMAPEVISAH 183
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  884 RFTHQSDVWSYGVTVWeLMTFGAKPYDGIPAREIPDLLEKGE 925
Cdd:cd14097    184 GYSQQCDIWSIGVIMY-MLLCGEPPFVAKSEEKLFEEIRKGD 224
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
719-958 1.50e-10

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 63.55  E-value: 1.50e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWIPDGENVKIPVAIKVLR--ENTSPKANKEIldeaYVMAGVGSPYV-----SRLLGICLTSTVQLVTQLMPYGC 791
Cdd:cd14055     10 EVWKAKLKQNASGQYETVAVKIFPyeEYASWKNEKDI----FTDASLKHENIlqfltAEERGVGLDRQYWLITAYHENGS 85
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRgrLGSQDLLNWCMQIAKGMSYLED---------VRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID-ET 861
Cdd:cd14055     86 LQDYLTRHI--LSWEDLCKMAGSLARGLAHLHSdrtpcgrpkIPIAHRDLKSSNILVKNDGTCVLADFGLALRLDPSlSV 163
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  862 EYHADGGKV-PIKWMALEsILRRRFT-------HQSDVWSYGVTVWELM-----TFGAKPYD---GIPAREIP------D 919
Cdd:cd14055    164 DELANSGQVgTARYMAPE-ALESRVNledlesfKQIDVYSMALVLWEMAsrceaSGEVKPYElpfGSKVRERPcvesmkD 242
                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  920 LLEKGERLPQPP--------ICTIDVymIMVKCWMIDSECR-------PRFREL 958
Cdd:cd14055    243 LVLRDRGRPEIPdswlthqgMCVLCD--TITECWDHDPEARltascvaERFNEL 294
STKc_MAP4K4_6_N cd06636
N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase ...
782-917 1.52e-10

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270806 [Multi-domain]  Cd Length: 282  Bit Score: 63.49  E-value: 1.52e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQDLLNW-CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE 860
Cdd:cd06636     96 LVMEFCGAGSVTDLVKNTKGNALKEDWIAYiCREILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTV 175
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  861 TEYHADGGkVPIkWMALESIL-----RRRFTHQSDVWSYGVTVWElMTFGAKPY-DGIPAREI 917
Cdd:cd06636    176 GRRNTFIG-TPY-WMAPEVIAcdenpDATYDYRSDIWSLGITAIE-MAEGAPPLcDMHPMRAL 235
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
747-924 1.73e-10

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 63.01  E-value: 1.73e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  747 PKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR 826
Cdd:cd14110     40 PEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSGPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRR 119
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  827 LVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWeLMTFGA 906
Cdd:cd14110    120 ILHLDLRSENMIITEKNLLKIVDLGNAQPFNQGKV-LMTDKKGDYVETMAPELLEGQGAGPQTDIWAIGVTAF-IMLSAD 197
                          170
                   ....*....|....*...
gi 1844139549  907 KPYDGIPAREIPDLLEKG 924
Cdd:cd14110    198 YPVSSDLNWERDRNIRKG 215
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
766-901 2.15e-10

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 63.06  E-value: 2.15e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  766 PYVSRLLGICLTSTVQLVTQLMpygCLLDHVRENRGR---------LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARN 836
Cdd:cd07838     61 PNVVRLLDVCHGPRTDRELKLT---LVFEHVDQDLATyldkcpkpgLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQN 137
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  837 VLVKSPNHVKITDFGLARLLDIDeteyhadggkvpikwMALESI------------LRRRFTHQSDVWSYGVTVWEL 901
Cdd:cd07838    138 ILVTSDGQVKLADFGLARIYSFE---------------MALTSVvvtlwyrapevlLQSSYATPVDMWSVGCIFAEL 199
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
725-914 2.41e-10

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 62.89  E-value: 2.41e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  725 WIPDGENVKIP--VAIKVLRENTSPKANKE--ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREN 799
Cdd:cd14076     21 WPLPKANHRSGvqVAIKLIRRDTQQENCQTskIMREINILKGLTHPNIVRLLDVLKTKKyIGIVLEFVSGGELFDYILAR 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 RgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPIkWMALES 879
Cdd:cd14076    101 R-RLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFDHFNGDLMSTSCGSPC-YAAPEL 178
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1844139549  880 ILRRRFTH--QSDVWSYGVTVWElMTFGAKPYDGIPA 914
Cdd:cd14076    179 VVSDSMYAgrKADIWSCGVILYA-MLAGYLPFDDDPH 214
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
778-903 2.46e-10

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 63.47  E-value: 2.46e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMpyGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd07851     93 QDVYLVTHLM--GADLNNIVKCQ-KLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDCELKILDFGLARHTD 169
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  858 IDETEYhadggkVPIKW-MALESIL-RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07851    170 DEMTGY------VATRWyRAPEIMLnWMHYNQTVDIWSVGCIMAELLT 211
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
728-909 2.69e-10

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 62.68  E-value: 2.69e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLreNTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQ 806
Cdd:cd14113     27 DQRGTKRAVATKFV--NKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTsYILVLEMADQGRLLDYVVR-WGNLTEE 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 DLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV-KSPNH--VKITDFGLArlLDIDETEY-HADGGKVpiKWMALESILR 882
Cdd:cd14113    104 KIRFYLREILEALQYLHNCRIAHLDLKPENILVdQSLSKptIKLADFGDA--VQLNTTYYiHQLLGSP--EFAAPEIILG 179
                          170       180
                   ....*....|....*....|....*..
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14113    180 NPVSLTSDLWSIGVLTYVLLS-GVSPF 205
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
768-971 2.91e-10

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 62.33  E-value: 2.91e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  768 VSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSpNHVK 846
Cdd:cd14153     58 VVLFMGACMSPPhLAIITSLCKGRTLYSVVRDAKVVLDVNKTRQIAQEIVKGMGYLHAKGILHKDLKSKNVFYDN-GKVV 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  847 ITDFGLARLLDIDETEYHADGGKVPIKWMA--LESILRR----------RFTHQSDVWSYGvTVWELMTFGAKPYDGIPA 914
Cdd:cd14153    137 ITDFGLFTISGVLQAGRREDKLRIQSGWLChlAPEIIRQlspeteedklPFSKHSDVFAFG-TIWYELHAREWPFKTQPA 215
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  915 REIPDLLEKGERlpqPPICTI----DVYMIMVKCWMIDSECRPRFRELVSEFSRMardPQR 971
Cdd:cd14153    216 EAIIWQVGSGMK---PNLSQIgmgkEISDILLFCWAYEQEERPTFSKLMEMLEKL---PKR 270
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
787-911 3.36e-10

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 64.05  E-value: 3.36e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  787 MPY--GCLL-DHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD---IDE 860
Cdd:NF033483    86 MEYvdGRTLkDYIREH-GPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSsttMTQ 164
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  861 TE-------Y----HADGGKVpikwmalesilrrrfTHQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:NF033483   165 TNsvlgtvhYlspeQARGGTV---------------DARSDIYSLGIVLYEMLT-GRPPFDG 210
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
737-909 3.47e-10

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 62.45  E-value: 3.47e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVL--RENTSPKANKEILDEAYVMAGVGSPYVSRLLgiCLTSTVQLVTQLMPYGC---LLDHVReNRGRLGSQDLLNW 811
Cdd:cd05612     30 ALKVMaiPEVIRLKQEQHVHNEKRVLKEVSHPFIIRLF--WTEHDQRFLYMLMEYVPggeLFSYLR-NSGRFSNSTGLFY 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDET-------EYhadggkvpikwMALESILRRR 884
Cdd:cd05612    107 ASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFGFAKKL-RDRTwtlcgtpEY-----------LAPEVIQSKG 174
                          170       180
                   ....*....|....*....|....*
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd05612    175 HNKAVDWWALGILIYEMLV-GYPPF 198
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
747-922 4.08e-10

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 62.45  E-value: 4.08e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  747 PKANKEILDEAYVMAGVGSPYVSRLLG---------ICltstvqlvtqlMPY--GCLLDHVRENRGRLGSQDLLNWCMQI 815
Cdd:cd06615     40 PAIRNQIIRELKVLHECNSPYIVGFYGafysdgeisIC-----------MEHmdGGSLDQVLKKAGRIPENILGKISIAV 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  816 AKGMSYLEDVR-LVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKvpiKWMALESILRRRFTHQSDVWSY 894
Cdd:cd06615    109 LRGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGVSGQL-IDSMANSFVGTR---SYMSPERLQGTHYTVQSDIWSL 184
                          170       180
                   ....*....|....*....|....*...
gi 1844139549  895 GVTVWElMTFGAKPydgIPAreiPDLLE 922
Cdd:cd06615    185 GLSLVE-MAIGRYP---IPP---PDAKE 205
PHA03212 PHA03212
serine/threonine kinase US3; Provisional
742-903 4.17e-10

serine/threonine kinase US3; Provisional


Pssm-ID: 165478 [Multi-domain]  Cd Length: 391  Bit Score: 63.48  E-value: 4.17e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  742 RENTSPKANKE--ILDEAYVMAGVGSPYVSRLLGiclTSTVQLVTQL-MP-YGCLLDHVRENRGRLGSQDLLNWCMQIAK 817
Cdd:PHA03212   117 CEHVVIKAGQRggTATEAHILRAINHPSIIQLKG---TFTYNKFTCLiLPrYKTDLYCYLAAKRNIAICDILAIERSVLR 193
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  818 GMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL-LDIDETEYHADGGKVPIKwmALESILRRRFTHQSDVWSYGV 896
Cdd:PHA03212   194 AIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGAACFpVDINANKYYGWAGTIATN--APELLARDPYGPAVDIWSAGI 271

                   ....*..
gi 1844139549  897 TVWELMT 903
Cdd:PHA03212   272 VLFEMAT 278
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
790-967 4.46e-10

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 62.04  E-value: 4.46e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 GCLLDH-----VRENRGRLGSQDLLN-------WC------MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFG 851
Cdd:cd14043     63 GLFVDCgilaiVSEHCSRGSLEDLLRnddmkldWMfkssllLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYG 142
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  852 LARLLD----IDETEYHADggkvpIKWMALEsILR-----RRFTHQSDVWSYGVTVWELMTFGAkPYD--GIPAREIPDL 920
Cdd:cd14043    143 YNEILEaqnlPLPEPAPEE-----LLWTAPE-LLRdprleRRGTFPGDVFSFAIIMQEVIVRGA-PYCmlGLSPEEIIEK 215
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  921 LEKgerlpQPPICTIDVYM---------IMVKCWMIDSECRPRFRELVSEFSRMAR 967
Cdd:cd14043    216 VRS-----PPPLCRPSVSMdqapleciqLMKQCWSEAPERRPTFDQIFDQFKSINK 266
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
739-959 4.52e-10

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132969 [Multi-domain]  Cd Length: 286  Bit Score: 62.34  E-value: 4.52e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  739 KVLRENTSPKANKEILD-----------EAYVMAGVGS-PYVSRLLGICLTSTVQ------LVTQLMPYGCLLDHVRE-- 798
Cdd:cd06638     36 KVLNKKNGSKAAVKILDpihdideeieaEYNILKALSDhPNVVKFYGMYYKKDVKngdqlwLVLELCNGGSVTDLVKGfl 115
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIA-KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMAL 877
Cdd:cd06638    116 KRGERMEEPIIAYILHEAlMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSTRLRRNTSVG-TPF-WMAP 193
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  878 ESI-----LRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAR---EIPDllEKGERLPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd06638    194 EVIaceqqLDSTYDARCDVWSLGITAIELGDGDPPLADLHPMRalfKIPR--NPPPTLHQPELWSNEFNDFIRKCLTKDY 271
                          250
                   ....*....|
gi 1844139549  950 ECRPRFRELV 959
Cdd:cd06638    272 EKRPTVSDLL 281
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
814-928 4.58e-10

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 61.90  E-value: 4.58e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNH-----VKITDFGLARLLDIDETEYHADGGkVP--IKWMA---LESILRR 883
Cdd:cd13982    107 QIASGLAHLHSLNIVHRDLKPQNILISTPNAhgnvrAMISDFGLCKKLDVGRSSFSRRSG-VAgtSGWIApemLSGSTKR 185
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE---------IPDLLEKGERLP 928
Cdd:cd13982    186 RQTRAVDIFSLGCVFYYVLSGGSHPFGDKLEREanilkgkysLDKLLSLGEHGP 239
PKc_MKK4 cd06616
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
737-965 4.79e-10

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270790 [Multi-domain]  Cd Length: 291  Bit Score: 62.00  E-value: 4.79e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEIL-DEAYVMAGVGSPYVSRLLGICLTSTVQLV-TQLMPYGclLDH----VREN-RGRLGSQDLL 809
Cdd:cd06616     35 AVKRIRSTVDEKEQKRLLmDLDVVMRSSDCPYIVKFYGALFREGDCWIcMELMDIS--LDKfykyVYEVlDSVIPEEILG 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPikWMALESIL----RRR 884
Cdd:cd06616    113 KIAVATVKALNYLkEELKIIHRDVKPSNILLDRNGNIKLCDFGISGQL-VDSIAKTRDAGCRP--YMAPERIDpsasRDG 189
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPYDGIpaREIPDLLE---KGErlpqPPICTIDVYMI----MVK----CWMIDSECRP 953
Cdd:cd06616    190 YDVRSDVWSLGITLYEVAT-GKFPYPKW--NSVFDQLTqvvKGD----PPILSNSEEREfspsFVNfvnlCLIKDESKRP 262
                          250
                   ....*....|...
gi 1844139549  954 RFRELVS-EFSRM 965
Cdd:cd06616    263 KYKELLKhPFIKM 275
STKc_p70S6K cd05584
Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs ...
814-936 4.82e-10

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270736 [Multi-domain]  Cd Length: 323  Bit Score: 62.42  E-value: 4.82e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKvpIKWMALESILRRRFTHQSDVWS 893
Cdd:cd05584    108 EITLALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGLCKESIHDGTVTHTFCGT--IEYMAPEILTRSGHGKAVDWWS 185
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1844139549  894 YGVTVWELMTfGAKPYDGIPAREIPDLLEKGeRLPQPPICTID 936
Cdd:cd05584    186 LGALMYDMLT-GAPPFTAENRKKTIDKILKG-KLNLPPYLTNE 226
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
812-963 5.21e-10

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 62.07  E-value: 5.21e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGL-ARLLDIDE-------TEYhadggkvpikWMALESILRR 883
Cdd:cd06611    109 CRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGVsAKNKSTLQkrdtfigTPY----------WMAPEVVACE 178
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  884 RFT-----HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLeKGE--RLPQPPICTIDVYMIMVKCWMIDSECRPRFR 956
Cdd:cd06611    179 TFKdnpydYKADIWSLGITLIELAQMEPPHHELNPMRVLLKIL-KSEppTLDQPSKWSSSFNDFLKSCLVKDPDDRPTAA 257
                          170
                   ....*....|..
gi 1844139549  957 EL-----VSEFS 963
Cdd:cd06611    258 ELlkhpfVSDQS 269
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
815-965 5.78e-10

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 61.44  E-value: 5.78e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRL-VHRDLAARNVLVKSPNHVKITDFGLARLLDideteyhadggkvPIK--WMALESILRRRFTHQSDV 891
Cdd:cd14044    118 IAKGMSYLHSSKTeVHGRLKSTNCVVDSRMVVKITDFGCNSILP-------------PSKdlWTAPEHLRQAGTSQKGDV 184
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  892 WSYGVTVWELM----TF-------------------GAKPYDgipareiPDL-LEK-GERlpqppicTIDVYMIMVKCWM 946
Cdd:cd14044    185 YSYGIIAQEIIlrkeTFytaacsdrkekiyrvqnpkGMKPFR-------PDLnLESaGER-------EREVYGLVKNCWE 250
                          170
                   ....*....|....*....
gi 1844139549  947 IDSECRPRFRELVSEFSRM 965
Cdd:cd14044    251 EDPEKRPDFKKIENTLAKI 269
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
709-961 6.23e-10

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 61.52  E-value: 6.23e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  709 QAQMRILKETELRKGIWIPDGENVKIpvaIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLtSTVQLVTQLMP 788
Cdd:cd14067     16 QGQPVAVKRFHIKKCKKRTDGSADTM---LKHLRAADAMKNFSEFRQEASMLHSLQHPCIVYLIGISI-HPLCFALELAP 91
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  789 YGCLLDHVREN-RGR----LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN-----HVKITDFGLARlldi 858
Cdd:cd14067     92 LGSLNTVLEENhKGSsfmpLGHMLTFKIAYQIAAGLAYLHKKNIIFCDLKSDNILVWSLDvqehiNIKLSDYGISR---- 167
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  859 deTEYH--ADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGER--LPQP-PIC 933
Cdd:cd14067    168 --QSFHegALGVEGTPGYQAPEIRPRIVYDEKVDMFSYGMVLYELLS-GQRPSLGHHQLQIAKKLSKGIRpvLGQPeEVQ 244
                          250       260
                   ....*....|....*....|....*...
gi 1844139549  934 TIDVYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd14067    245 FFRLQALMMECWDTKPEKRPLACSVVEQ 272
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
757-963 6.49e-10

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 61.46  E-value: 6.49e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  757 AYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAAR 835
Cdd:cd05076     66 ASLMSQVSHTHLVFVHGVCVRGSENiMVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNLVHGNVCAK 145
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  836 NVLV--------KSPnHVKITDFGLArlLDIDETEYHADggkvPIKWMALESILR-RRFTHQSDVWSYGVTVWELMTFGA 906
Cdd:cd05076    146 NILLarlgleegTSP-FIKLSDPGVG--LGVLSREERVE----RIPWIAPECVPGgNSLSTAADKWGFGATLLEICFNGE 218
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  907 KPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMvkCWMIDSECRPRFRELVSEFS 963
Cdd:cd05076    219 APLQSRTPSEKERFYQRQHRLPEPSCPELATLISQ--CLTYEPTQRPSFRTILRDLT 273
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
801-903 6.62e-10

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 61.65  E-value: 6.62e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLE-DVRLVHRDLAARNVLVKSP-NHVKITDFGLARLLDiDETEYHADG-----GKVPik 873
Cdd:cd14001    105 GPFPAATILKVALSIARALEYLHnEKKILHGDIKSGNVLIKGDfESVKLCDFGVSLPLT-ENLEVDSDPkaqyvGTEP-- 181
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1844139549  874 WMALESILRRR-FTHQSDVWSYGVTVWELMT 903
Cdd:cd14001    182 WKAKEALEEGGvITDKADIFAYGLVLWEMMT 212
STKc_Nek2 cd08217
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
826-958 7.50e-10

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270857 [Multi-domain]  Cd Length: 265  Bit Score: 61.02  E-value: 7.50e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  826 RLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE--------TEYhadggkvpikWMALESILRRRFTHQSDVWSYGVT 897
Cdd:cd08217    130 KILHRDLKPANIFLDSDNNVKLGDFGLARVLSHDSsfaktyvgTPY----------YMSPELLNEQSYDEKSDIWSLGCL 199
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  898 VWELMT----FGAKPYDGIpAREIpdllEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd08217    200 IYELCAlhppFQAANQLEL-AKKI----KEGKFPRIPSRYSSELNEVIKSMLNVDPDKRPSVEEL 259
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
748-962 8.00e-10

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 61.16  E-value: 8.00e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEIldEAYVMagVGSPYVSRLLGICL------TSTVQLVTQLMPYGCLLDHV---RENRGRLGSQDLLNWCMQIAKG 818
Cdd:cd13986     43 EAMREI--ENYRL--FNHPNILRLLDSQIvkeaggKKEVYLLLPYYKRGSLQDEIerrLVKGTFFPEDRILHIFLGICRG 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  819 MSYL---EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI------------DETEYHADggkvpIKWMALE----- 878
Cdd:cd13986    119 LKAMhepELVPYAHRDIKPGNVLLSEDDEPILMDLGSMNPARIeiegrrealalqDWAAEHCT-----MPYRAPElfdvk 193
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  879 --SILRRRfthqSDVWSYGVTVWELMtFGAKPYDGIpareipdlLEKGERL-----------PQPPICTIDVYMIMVKCW 945
Cdd:cd13986    194 shCTIDEK----TDIWSLGCTLYALM-YGESPFERI--------FQKGDSLalavlsgnysfPDNSRYSEELHQLVKSML 260
                          250
                   ....*....|....*..
gi 1844139549  946 MIDSECRPRFRELVSEF 962
Cdd:cd13986    261 VVNPAERPSIDDLLSRV 277
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
786-909 8.70e-10

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 61.54  E-value: 8.70e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY---GCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETE 862
Cdd:cd06659     96 LMEYlqgGALTDIVSQTR--LNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQISKDVPK 173
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  863 YHADGGkVPIkWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06659    174 RKSLVG-TPY-WMAPEVISRCPYGTEVDIWSLGIMVIE-MVDGEPPY 217
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
777-909 1.02e-09

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 61.16  E-value: 1.02e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  777 TSTVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLA 853
Cdd:cd14166     72 TTHYYLVMQLVSGGELFDRILE-RGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLYLTPDEnskIMITDFGLS 150
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  854 RLLD--IDETEYHADGgkvpikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14166    151 KMEQngIMSTACGTPG------YVAPEVLAQKPYSKAVDCWSIGVITYILLC-GYPPF 201
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
782-909 1.06e-09

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 60.53  E-value: 1.06e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVreNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDet 861
Cdd:cd06648     81 VVMEFLEGGALTDIV--THTRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQVSKE-- 156
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  862 eyhadggkVPIK--------WMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06648    157 --------VPRRkslvgtpyWMAPEVISRLPYGTEVDIWSLGIMVIE-MVDGEPPY 203
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
784-959 1.10e-09

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 60.47  E-value: 1.10e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  784 TQLMPYGCLLDHVREN--RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDET 861
Cdd:cd13997     79 MELCENGSLQDALEELspISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLETSGD 158
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  862 EYHADGGkvpikWMALEsILRRRFTH--QSDVWSYGVTVWELMTFGAKPYDGIPAREIpdlleKGERLPQPPICTIDVYM 939
Cdd:cd13997    159 VEEGDSR-----YLAPE-LLNENYTHlpKADIFSLGVTVYEAATGEPLPRNGQQWQQL-----RQGKLPLPPGLVLSQEL 227
                          170       180
                   ....*....|....*....|..
gi 1844139549  940 IMVKCWMIDSEC--RPRFRELV 959
Cdd:cd13997    228 TRLLKVMLDPDPtrRPTADQLL 249
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
730-909 1.18e-09

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 60.46  E-value: 1.18e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVL-RENTSPKAN---KEIldeaYVMAGVGSPYVSRLLGiC--LTSTVQLVTQLMPYGCLLDHVREnRGRL 803
Cdd:cd14120     16 KKPDLPVAIKCItKKNLSKSQNllgKEI----KILKELSHENVVALLD-CqeTSSSVYLVMEYCNGGDLADYLQA-KGTL 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  804 GSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---------HVKITDFGLARLLdiDETEYHADGGKVPIkW 874
Cdd:cd14120     90 SEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFARFL--QDGMMAATLCGSPM-Y 166
                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14120    167 MAPEVIMSLQYDAKADLWSIGTIVYQCLT-GKAPF 200
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
736-958 1.20e-09

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 60.85  E-value: 1.20e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEIL-DEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPyGCLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd06618     43 MAVKQMRRSGNKEENKRILmDLDVVLKSHDCPYIVKCYGYFITdSDVFICMELMS-TCLDKLLKRIQGPIPEDILGKMTV 121
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVR-LVHRDLAARNVLVKSPNHVKITDFGLA-RLLDideTEYHADGGKVPIkWMALESILRRRFTH---Q 888
Cdd:cd06618    122 SIVKALHYLKEKHgVIHRDVKPSNILLDESGNVKLCDFGISgRLVD---SKAKTRSAGCAA-YMAPERIDPPDNPKydiR 197
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYDGIPAREipDLLEK--GERLPQPPIC---TIDVYMIMVKCWMIDSECRPRFREL 958
Cdd:cd06618    198 ADVWSLGISLVELAT-GQFPYRNCKTEF--EVLTKilNEEPPSLPPNegfSPDFCSFVDLCLTKDHRYRPKYREL 269
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
735-932 1.37e-09

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 60.43  E-value: 1.37e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLR--ENTSPKANKEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCL---LDHVRENRGRLGSQDL 808
Cdd:cd08228     29 PVALKKVQifEMMDAKARQDCVKEIDLLKQLNHPNVIKYLdSFIEDNELNIVLELADAGDLsqmIKYFKKQKRLIPERTV 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQ 888
Cdd:cd08228    109 WKYFVQLCSAVEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHSLVG-TPY-YMSPERIHENGYNFK 186
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  889 SDVWSYGVTVWELMTFGAkPYDGiPAREIPDLLEKGERLPQPPI 932
Cdd:cd08228    187 SDIWSLGCLLYEMAALQS-PFYG-DKMNLFSLCQKIEQCDYPPL 228
STKc_TNIK cd06637
Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs ...
782-917 1.63e-09

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270807 [Multi-domain]  Cd Length: 296  Bit Score: 60.50  E-value: 1.63e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQDLLNW-CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE 860
Cdd:cd06637     86 LVMEFCGAGSVTDLIKNTKGNTLKEEWIAYiCREILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLDRTV 165
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  861 TEYHADGGkVPIkWMALESIL-----RRRFTHQSDVWSYGVTVWElMTFGAKPY-DGIPAREI 917
Cdd:cd06637    166 GRRNTFIG-TPY-WMAPEVIAcdenpDATYDFKSDLWSLGITAIE-MAEGAPPLcDMHPMRAL 225
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
730-936 1.63e-09

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271067 [Multi-domain]  Cd Length: 263  Bit Score: 60.18  E-value: 1.63e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  730 ENVKIPVAIKVLRENTSPK--ANKEILDEAYVMAGVGSPYVSRLLGICLTST--VQLVTQLMPYGCLLDHVReNRGRLGS 805
Cdd:cd14165     23 ERLKCNVAIKIIDKKKAPDdfVEKFLPRELEILARLNHKSIIKTYEIFETSDgkVYIVMELGVQGDLLEFIK-LRGALPE 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeyhadgGKVpikwmalesILRRRF 885
Cdd:cd14165    102 DVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRCLRDEN------GRI---------VLSKTF 166
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  886 T------------------HQSDVWSYGVTVWeLMTFGAKPYDGIPAREIPDlLEKGERLPQPPICTID 936
Cdd:cd14165    167 CgsaayaapevlqgipydpRIYDIWSLGVILY-IMVCGSMPYDDSNVKKMLK-IQKEHRVRFPRSKNLT 233
STKc_myosinIII_N_like cd06608
N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze ...
782-901 1.66e-09

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270785 [Multi-domain]  Cd Length: 275  Bit Score: 60.39  E-value: 1.66e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRE--NRGRLGSQDLLNW-CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDi 858
Cdd:cd06608     86 LVMEYCGGGSVTDLVKGlrKKGKRLKEEWIAYiLRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQLD- 164
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1844139549  859 deTEYHADGGKV--PIkWMALESI-----LRRRFTHQSDVWSYGVTVWEL 901
Cdd:cd06608    165 --STLGRRNTFIgtPY-WMAPEVIacdqqPDASYDARCDVWSLGITAIEL 211
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
736-908 1.84e-09

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 60.43  E-value: 1.84e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANK-EILDEAYVMAGVGS---PYVSRLLGICLTSTVQLVTQLMpygCLLDHVRENRGR--------- 802
Cdd:cd07862     30 VALKRVRVQTGEEGMPlSTIREVAVLRHLETfehPNVVRLFDVCTVSRTDRETKLT---LVFEHVDQDLTTyldkvpepg 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  803 LGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIdetEYHADGGKVPIKWMALESILR 882
Cdd:cd07862    107 VPTETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKLADFGLARIYSF---QMALTSVVVTLWYRAPEVLLQ 183
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  883 RRFTHQSDVWSYGVTVWELmtFGAKP 908
Cdd:cd07862    184 SSYATPVDLWSVGCIFAEM--FRRKP 207
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
731-910 2.09e-09

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 59.87  E-value: 2.09e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  731 NVKIPVAIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQD 807
Cdd:cd14186     24 HTGLEVAIKMIDKKAMQKAGmvQRVRNEVEIHCQLKHPSILELYNYFEDSNyVYLVLEMCHNGEMSRYLKNRKKPFTEDE 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI-DETEYHADGgkVPiKWMALESILRRRFT 886
Cdd:cd14186    104 ARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLTRNMNIKIADFGLATQLKMpHEKHFTMCG--TP-NYISPEIATRSAHG 180
                          170       180
                   ....*....|....*....|....
gi 1844139549  887 HQSDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14186    181 LESDVWSLGCMFYTLLV-GRPPFD 203
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
766-908 2.33e-09

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 59.98  E-value: 2.33e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  766 PYVSRLLGICLTSTVQLVTQLMpygCLLDHVREN-RGRLGS-----------QDLLNwcmQIAKGMSYLEDVRLVHRDLA 833
Cdd:cd07863     62 PNIVRLMDVCATSRTDRETKVT---LVFEHVDQDlRTYLDKvpppglpaetiKDLMR---QFLRGLDFLHANCIVHRDLK 135
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  834 ARNVLVKSPNHVKITDFGLARlldIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELmtFGAKP 908
Cdd:cd07863    136 PENILVTSGGQVKLADFGLAR---IYSCQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEM--FRRKP 205
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
733-917 2.34e-09

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 59.49  E-value: 2.34e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVL-RENTSPK-ANKEILDEAYVMAGVGSPYVSRLLGiCLTSTVQLVTQLMPYGC--LLDHVRENrGRLGSQDL 808
Cdd:cd14164     25 CCKVAIKIVdRRRASPDfVQKFLPRELSILRRVNHPNIVQMFE-CIEVANGRLYIVMEAAAtdLLQKIQEV-HHIPKDLA 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN-HVKITDFGLARLL-DIDETEYHADGGKVpikWMALESILRRRFT 886
Cdd:cd14164    103 RDMFAQMVGAVNYLHDMNIVHRDLKCENILLSADDrKIKIADFGFARFVeDYPELSTTFCGSRA---YTPPEVILGTPYD 179
                          170       180       190
                   ....*....|....*....|....*....|..
gi 1844139549  887 HQS-DVWSYGVTVWELMTfGAKPYDGIPAREI 917
Cdd:cd14164    180 PKKyDVWSLGVVLYVMVT-GTMPFDETNVRRL 210
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
695-914 2.65e-09

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 60.66  E-value: 2.65e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  695 ELVEPLTPSgampnqaqmrilkeTELRKGIWIPDGEnvKIPVAIKVLRENTSpkankeiLDEAYVMAGVGSPYVSRLLGI 774
Cdd:PHA03209    69 TVIKTLTPG--------------SEGRVFVATKPGQ--PDPVVLKIGQKGTT-------LIEAMLLQNVNHPSVIRMKDT 125
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  775 CLTSTVQLVTqLMPYGC-LLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:PHA03209   126 LVSGAITCMV-LPHYSSdLYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAA 204
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  854 RLLDIDETEYHADGgkvPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA 914
Cdd:PHA03209   205 QFPVVAPAFLGLAG---TVETNAPEVLARDKYNSKADIWSAGIVLFEMLAYPSTIFEDPPS 262
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
736-909 2.72e-09

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271069 [Multi-domain]  Cd Length: 263  Bit Score: 59.66  E-value: 2.72e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQ 814
Cdd:cd14167     31 VAIKCIAKKALEGKETSIENEIAVLHKIKHPNIVALDDIYESgGHLYLIMQLVSGGELFDRIVE-KGFYTERDASKLIFQ 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKS---PNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSDV 891
Cdd:cd14167    110 ILDAVKYLHDMGIVHRDLKPENLLYYSldeDSKIMISDFGLSKIEGSGSVMSTACG--TP-GYVAPEVLAQKPYSKAVDC 186
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd14167    187 WSIGVIAYILLC-GYPPF 203
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
748-925 2.80e-09

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270779 [Multi-domain]  Cd Length: 285  Bit Score: 59.65  E-value: 2.80e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVReNRGRLGSQD--LLNWCMQIAKGMSYLED 824
Cdd:cd05630     42 KGEAMALNEKQILEKVNSRFVVSLAYAYETKdALCLVLTLMNGGDLKFHIY-HMGQAGFPEarAVFYAAEICCGLEDLHR 120
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  825 VRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeyhaDGGKV-PIKWMALESILRRRFTHQSDVWSYGVTVWElMT 903
Cdd:cd05630    121 ERIVYRDLKPENILLDDHGHIRISDLGLAVHVPEGQT----IKGRVgTVGYMAPEVVKNERYTFSPDWWALGCLLYE-MI 195
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  904 FGAKPYD----GIPAREIPDLLEKGE 925
Cdd:cd05630    196 AGQSPFQqrkkKIKREEVERLVKEVP 221
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
776-932 2.90e-09

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 59.64  E-value: 2.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  776 LTSTVQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---------HVK 846
Cdd:cd14201     76 MPNSVFLVMEYCNGGDLADYL-QAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASrkkssvsgiRIK 154
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  847 ITDFGLARLLDIDETEYHADGGKVpikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGER 926
Cdd:cd14201    155 IADFGFARYLQSNMMAATLCGSPM---YMAPEVIMSQHYDAKADLWSIGTVIYQCLV-GKPPFQANSPQDLRMFYEKNKN 230

                   ....*.
gi 1844139549  927 LpQPPI 932
Cdd:cd14201    231 L-QPSI 235
PKc_MEK2 cd06649
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
736-917 3.21e-09

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132980 [Multi-domain]  Cd Length: 331  Bit Score: 60.06  E-value: 3.21e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLlDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd06649     33 MARKLIHLEIKPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDgEISICMEHMDGGSL-DQVLKEAKRIPEEILGKVSIA 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKvpiKWMALESILRRRFTHQSDVWS 893
Cdd:cd06649    112 VLRGLAYLrEKHQIMHRDVKPSNILVNSRGEIKLCDFGVSGQL-IDSMANSFVGTR---SYMSPERLQGTHYSVQSDIWS 187
                          170       180
                   ....*....|....*....|....
gi 1844139549  894 YGVTVWELmTFGAKPYDGIPAREI 917
Cdd:cd06649    188 MGLSLVEL-AIGRYPIPPPDAKEL 210
STKc_DAPK cd14105
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs ...
751-911 3.29e-09

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271007 [Multi-domain]  Cd Length: 269  Bit Score: 59.42  E-value: 3.29e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  751 KEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGrLGSQDLLNWCMQIAKGMSYLEDVRLVH 829
Cdd:cd14105     53 EDIEREVSILRQVLHPNIITLHDVFENKTdVVLILELVAGGELFDFLAEKES-LSEEEATEFLKQILDGVNYLHTKNIAH 131
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  830 RDLAARNVLVKSPN----HVKITDFGLARLLDiDETEYHADGGkVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfG 905
Cdd:cd14105    132 FDLKPENIMLLDKNvpipRIKLIDFGLAHKIE-DGNEFKNIFG-TP-EFVAPEIVNYEPLGLEADMWSIGVITYILLS-G 207

                   ....*.
gi 1844139549  906 AKPYDG 911
Cdd:cd14105    208 ASPFLG 213
STKc_cPKC_beta cd05616
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs ...
737-911 3.35e-09

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270767 [Multi-domain]  Cd Length: 323  Bit Score: 60.01  E-value: 3.35e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLLGICLTSTVQL--VTQLMPYGCLLDHVREnRGRLGSQDLLNWC 812
Cdd:cd05616     29 AVKILKKDVVIQDDdvECTMVEKRVLALSGKPPFLTQLHSCFQTMDRLyfVMEYVNGGDLMYHIQQ-VGRFKEPHAVFYA 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVW 892
Cdd:cd05616    108 AEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKENIWDGVTTKTFCG-TP-DYIAPEIIAYQPYGKSVDWW 185
                          170
                   ....*....|....*....
gi 1844139549  893 SYGVTVWELMTfGAKPYDG 911
Cdd:cd05616    186 AFGVLLYEMLA-GQAPFEG 203
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
750-913 3.58e-09

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 59.67  E-value: 3.58e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  750 NKEILDEAYVMAGVGSPYVSRLLGicltSTVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLEDVRLVH 829
Cdd:cd06658     68 NEVVIMRDYHHENVVDMYNSYLVG----DELWVVMEFLEGGALTDIVTHTR--MNEEQIATVCLSVLRALSYLHNQGVIH 141
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  830 RDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06658    142 RDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKSLVG-TPY-WMAPEVISRLPYGTEVDIWSLGIMVIE-MIDGEPPY 218

                   ....
gi 1844139549  910 DGIP 913
Cdd:cd06658    219 FNEP 222
STKc_PFTAIRE2 cd07870
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer ...
736-923 3.64e-09

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270852 [Multi-domain]  Cd Length: 286  Bit Score: 59.59  E-value: 3.64e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMpYGCLLDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd07870     28 VALKVISMKTEEGVPFTAIREASLLKGLKHANIVLLHDIIHTkETLTFVFEYM-HTDLAQYMIQHPGGLHPYNVRLFMFQ 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggkVPIKWMALESIL--RRRFTHQSDVW 892
Cdd:cd07870    107 LLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARAKSIPSQTYSSE---VVTLWYRPPDVLlgATDYSSALDIW 183
                          170       180       190
                   ....*....|....*....|....*....|.
gi 1844139549  893 SYGVTVWElMTFGAKPYDGIParEIPDLLEK 923
Cdd:cd07870    184 GAGCIFIE-MLQGQPAFPGVS--DVFEQLEK 211
STKc_NIM1 cd14075
Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the ...
736-861 3.67e-09

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270977 [Multi-domain]  Cd Length: 255  Bit Score: 58.89  E-value: 3.67e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVL-RENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCM 813
Cdd:cd14075     30 VAIKILdKTKLDQKTQRLLSREISSMEKLHHPNIIRLYEVVETlSKLHLVMEYASGGELYTKI-STEGKLSESEAKPLFA 108
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDET 861
Cdd:cd14075    109 QIVSAVKHMHENNIIHRDLKAENVFYASNNCVKVGDFGFSTHAKRGET 156
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
786-903 3.77e-09

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270858 [Multi-domain]  Cd Length: 256  Bit Score: 59.05  E-value: 3.77e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY---GCLLDHVRENRGRLGSQD-LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDET 861
Cdd:cd08218     77 VMDYcdgGDLYKRINAQRGVLFPEDqILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLN-STV 155
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  862 EYHADGGKVPIkWMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd08218    156 ELARTCIGTPY-YLSPEICENKPYNNKSDIWALGCVLYEMCT 196
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
814-902 4.01e-09

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 60.14  E-value: 4.01e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggKVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07853    111 QILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESKHMTQ--EVVTQYYRAPEILmgSRHYTSAVDI 188
                           90
                   ....*....|.
gi 1844139549  892 WSYGVTVWELM 902
Cdd:cd07853    189 WSVGCIFAELL 199
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
729-961 4.13e-09

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 58.79  E-value: 4.13e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  729 GENVKIPVAIKVLrENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYGCLLDHVRENRGRLGSQD 807
Cdd:cd05077     32 SYEKEIKVILKVL-DPSHRDISLAFFETASMMRQVSHKHIVLLYGVCVRDVENiMVEEFVEFGPLDLFMHRKSDVLTTPW 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN-------HVKITDFG-----LARLLDIDEteyhadggkvpIKWM 875
Cdd:cd05077    111 KFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGidgecgpFIKLSDPGipitvLSRQECVER-----------IPWI 179
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESIL-RRRFTHQSDVWSYGVTVWELMtfgakpYDGiparEIP----DLLEK-----GERLPQPPICTiDVYMIMVKCW 945
Cdd:cd05077    180 APECVEdSKNLSIAADKWSFGTTLWEIC------YNG----EIPlkdkTLAEKerfyeGQCMLVTPSCK-ELADLMTHCM 248
                          250
                   ....*....|....*.
gi 1844139549  946 MIDSECRPRFRELVSE 961
Cdd:cd05077    249 NYDPNQRPFFRAIMRD 264
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
782-901 4.16e-09

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 59.37  E-value: 4.16e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRenRGRLGSQDLLNWCMQIAKGMSYL--EDVR-------LVHRDLAARNVLVKSPNHVKITDFGL 852
Cdd:cd13998     70 LVTAFHPNGSL*DYLS--LHTIDWVSLCRLALSVARGLAHLhsEIPGctqgkpaIAHRDLKSKNILVKNDGTCCIADFGL 147
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  853 A-RLLDIDETEYHADGGKV-PIKWMALE----SILRRRFTH--QSDVWSYGVTVWEL 901
Cdd:cd13998    148 AvRLSPSTGEEDNANNGQVgTKRYMAPEvlegAINLRDFESfkRVDIYAMGLVLWEM 204
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
737-911 4.19e-09

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270724 [Multi-domain]  Cd Length: 262  Bit Score: 58.78  E-value: 4.19e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLREN--TSPKANKEILDEAYVMAGVGSPYVsrllgICLTST------VQLVTQLMPYGCLLDHVREnRGRLGSQDL 808
Cdd:cd05572     22 ALKCVKKRhiVQTRQQEHIFSEKEILEECNSPFI-----VKLYRTfkdkkyLYMLMEYCLGGELWTILRD-RGLFDEYTA 95
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  809 LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQ 888
Cdd:cd05572     96 RFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKKLGSGRKTWTFCG--TP-EYVAPEIILNKGYDFS 172
                          170       180
                   ....*....|....*....|...
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd05572    173 VDYWSLGILLYELLT-GRPPFGG 194
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
782-931 4.24e-09

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 58.84  E-value: 4.24e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL-DIDE 860
Cdd:cd14010     71 LVVEYCTGGDLETLLRQDG-NLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREgEILK 149
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  861 TEY-----HADGGKVPIK--------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYdgiPAREIPDLLEK--GE 925
Cdd:cd14010    150 ELFgqfsdEGNVNKVSKKqakrgtpyYMAPELFQGGVHSFASDLWALGCVLYEMFT-GKPPF---VAESFTELVEKilNE 225

                   ....*.
gi 1844139549  926 RLPQPP 931
Cdd:cd14010    226 DPPPPP 231
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
780-903 4.37e-09

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 59.67  E-value: 4.37e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMpyGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID 859
Cdd:cd07877     97 VYLVTHLM--GADLNNIVKCQ-KLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSNLAVNEDCELKILDFGLARHTDDE 173
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1844139549  860 ETEYhadggkVPIKWMALESILRR--RFTHQSDVWSYGVTVWELMT 903
Cdd:cd07877    174 MTGY------VATRWYRAPEIMLNwmHYNQTVDIWSVGCIMAELLT 213
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
782-917 4.83e-09

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 58.43  E-value: 4.83e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSP--NHVKITDFGLARLLDID 859
Cdd:cd14006     66 LILELCSGGELLDRLAE-RGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADRpsPQIKIIDFGLARKLNPG 144
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  860 ETEYHADGgkVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREI 917
Cdd:cd14006    145 EELKEIFG--TP-EFVAPEIVNGEPVSLATDMWSIGVLTYVLLS-GLSPFLGEDDQET 198
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
786-903 5.25e-09

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 59.58  E-value: 5.25e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY-----GCLLDHVRENRGRLgsQDLLnwcMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE 860
Cdd:cd07880     98 VMPFmgtdlGKLMKHEKLSEDRI--QFLV---YQMLKGLKYIHAAGIIHRDLKPGNLAVNEDCELKILDFGLARQTDSEM 172
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1844139549  861 TeyhadgGKVPIKWM-ALESILR-RRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07880    173 T------GYVVTRWYrAPEVILNwMHYTQTVDIWSVGCIMAEMLT 211
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
812-901 5.28e-09

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270784 [Multi-domain]  Cd Length: 258  Bit Score: 58.62  E-value: 5.28e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE----TEYhadggkvpikWMALESIL---RRR 884
Cdd:cd06607    107 CHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLVCPANsfvgTPY----------WMAPEVILamdEGQ 176
                           90
                   ....*....|....*..
gi 1844139549  885 FTHQSDVWSYGVTVWEL 901
Cdd:cd06607    177 YDGKVDVWSLGITCIEL 193
STKc_AMPK_alpha cd14079
Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein ...
736-923 6.24e-09

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270981 [Multi-domain]  Cd Length: 256  Bit Score: 58.43  E-value: 6.24e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWC 812
Cdd:cd14079     30 VAVKILNRQkiKSLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTdIFMVMEYVSGGELFDYIVQ-KGRLSEDEARRFF 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdideteyhADGG--KVPI---KWMALESILRRRFT- 886
Cdd:cd14079    109 QQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGLSNIM--------RDGEflKTSCgspNYAAPEVISGKLYAg 180
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1844139549  887 HQSDVWSYGVTVWELMTfGAKPYDGipaREIPDLLEK 923
Cdd:cd14079    181 PEVDVWSCGVILYALLC-GSLPFDD---EHIPNLFKK 213
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
814-910 6.87e-09

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 58.11  E-value: 6.87e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADG--GKVPikWMALESILRRRFTHQ-SD 890
Cdd:cd14069    108 QLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFRYKGKERLLNKmcGTLP--YVAPELLAKKKYRAEpVD 185
                           90       100
                   ....*....|....*....|
gi 1844139549  891 VWSYGVTVWELMTfGAKPYD 910
Cdd:cd14069    186 VWSCGIVLFAMLA-GELPWD 204
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
792-908 6.97e-09

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 58.31  E-value: 6.97e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRGRLGSQDLL-NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDE----TEYhad 866
Cdd:cd07830     84 LYQLMKDRKGKPFSESVIrSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAR--EIRSrppyTDY--- 158
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  867 ggkVPIKWM-ALESILRRRF-THQSDVWSYGVTVWELMTFgaKP 908
Cdd:cd07830    159 ---VSTRWYrAPEILLRSTSySSPVDIWALGCIMAELYTL--RP 197
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
736-911 6.98e-09

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 58.39  E-value: 6.98e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTsPKANKEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd14190     32 LAAKVINKQN-SKDKEMVLLEIQVMNQLNHRNLIQLYeAIETPNEIVLFMEYVEGGELFERIVDEDYHLTEVDAMVFVRQ 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVL-VKSPNH-VKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSDVW 892
Cdd:cd14190    111 ICEGIQFMHQMRVLHLDLKPENILcVNRTGHqVKIIDFGLARRYNPREKLKVNFG--TP-EFLSPEVVNYDQVSFPTDMW 187
                          170
                   ....*....|....*....
gi 1844139549  893 SYGVTVWELMTfGAKPYDG 911
Cdd:cd14190    188 SMGVITYMLLS-GLSPFLG 205
Furin-like pfam00757
Furin-like cysteine rich region;
502-603 6.99e-09

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 55.91  E-value: 6.99e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  502 DECVGEGLACHQLCARGHCWGPGptQC-VNCSQflrgqECVEECRvlqglpreyvNARHClpCHPECQpqnGSvtCFGPE 580
Cdd:pfam00757    6 DVCPGTMEKCHSCCNNGYCWGPG--HCqKVCPE-----QCKKRCT----------KPGEC--CHEQCL---GG--CTGPN 61
                           90       100
                   ....*....|....*....|...
gi 1844139549  581 ADQCVACAHYKDPPFCVARCPSG 603
Cdd:pfam00757   62 DSDCLACRHFNDEGTCVDQCPPG 84
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
719-901 8.24e-09

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 58.61  E-value: 8.24e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipDGENVkipvAIKVL--RENTSPKANKEI-----LDEAYVMAGVGSPYVSRLLGICLtstvQLVTQLMPYGC 791
Cdd:cd14142     20 EVWRGQW--QGESV----AVKIFssRDEKSWFRETEIyntvlLRHENILGFIASDMTSRNSCTQL----WLITHYHENGS 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVreNRGRLGSQDLLNWCMQIAKGMSYLE--------DVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD-----I 858
Cdd:cd14142     90 LYDYL--QRTTLDHQEMLRLALSAASGLVHLHteifgtqgKPAIAHRDLKSKNILVKSNGQCCIADLGLAVTHSqetnqL 167
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1844139549  859 DETEYHADGGKvpiKWMAL----ESILRRRFT--HQSDVWSYGVTVWEL 901
Cdd:cd14142    168 DVGNNPRVGTK---RYMAPevldETINTDCFEsyKRVDIYAFGLVLWEV 213
STKc_SLK cd06643
Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer ...
812-901 8.40e-09

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270811 [Multi-domain]  Cd Length: 283  Bit Score: 58.11  E-value: 8.40e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGKVPIKWMALESIL-----RRRFT 886
Cdd:cd06643    109 CKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGVSA--KNTRTLQRRDSFIGTPYWMAPEVVMcetskDRPYD 186
                           90
                   ....*....|....*
gi 1844139549  887 HQSDVWSYGVTVWEL 901
Cdd:cd06643    187 YKADVWSLGVTLIEM 201
STKc_CDK12 cd07864
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs ...
814-903 9.06e-09

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270847 [Multi-domain]  Cd Length: 302  Bit Score: 58.28  E-value: 9.06e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggKVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07864    124 QLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLARLYNSEESRPYTN--KVITLWYRPPELLlgEERYGPAIDV 201
                           90
                   ....*....|..
gi 1844139549  892 WSYGVTVWELMT 903
Cdd:cd07864    202 WSCGCILGELFT 213
STKc_p38beta cd07878
Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase ...
778-902 9.64e-09

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143383 [Multi-domain]  Cd Length: 343  Bit Score: 58.52  E-value: 9.64e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMpyGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd07878     93 NEVYLVTNLM--GADLNNIVKCQ-KLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNVAVNEDCELRILDFGLARQAD 169
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  858 IDETEYhadggkVPIKWM-ALESILRRRFTHQS-DVWSYGVTVWELM 902
Cdd:cd07878    170 DEMTGY------VATRWYrAPEIMLNWMHYNQTvDIWSVGCIMAELL 210
STKc_obscurin_rpt1 cd14107
Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
741-903 1.11e-08

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271009 [Multi-domain]  Cd Length: 257  Bit Score: 57.59  E-value: 1.11e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  741 LRENTSPKANKEildeAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGM 819
Cdd:cd14107     37 LRSSTRARAFQE----RDILARLSHRRLTCLLDQFETrKTLILILELCSSEELLDRLFL-KGVVTEAEVKLYIQQVLEGI 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  820 SYLEDVRLVHRDLAARNVLVKSPNH--VKITDFGLARLLDIDETEYHADGGKvpiKWMALESILRRRFTHQSDVWSYGVT 897
Cdd:cd14107    112 GYLHGMNILHLDIKPDNILMVSPTRedIKICDFGFAQEITPSEHQFSKYGSP---EFVAPEIVHQEPVSAATDIWALGVI 188

                   ....*.
gi 1844139549  898 VWELMT 903
Cdd:cd14107    189 AYLSLT 194
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
776-911 1.15e-08

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 58.17  E-value: 1.15e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  776 LTSTVQLVTQL---MPY---GCLLDHVR------ENRGRLgsqdllnWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN 843
Cdd:cd05592     61 LFCTFQTESHLffvMEYlngGDLMFHIQqsgrfdEDRARF-------YGAEIICGLQFLHSRGIIYRDLKLDNVLLDREG 133
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  844 HVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDG 911
Cdd:cd05592    134 HIKIADFGMCKENIYGENKASTFCG-TP-DYIAPEILKGQKYNQSVDWWSFGVLLYE-MLIGQSPFHG 198
STKc_DAPK1 cd14194
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs ...
738-916 1.15e-08

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271096 [Multi-domain]  Cd Length: 269  Bit Score: 57.72  E-value: 1.15e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  738 IKVLRENTSPK--ANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGrLGSQDLLNWCMQ 814
Cdd:cd14194     38 IKKRRTKSSRRgvSREDIEREVSILKEIQHPNVITLHEVYENKTdVILILELVAGGELFDFLAEKES-LTEEEATEFLKQ 116
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPN----HVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSD 890
Cdd:cd14194    117 ILNGVYYLHSLQIAHFDLKPENIMLLDRNvpkpRIKIIDFGLAHKIDFGNEFKNIFG--TP-EFVAPEIVNYEPLGLEAD 193
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  891 VWSYGVTVWELMTfGAKPYDGIPARE 916
Cdd:cd14194    194 MWSIGVITYILLS-GASPFLGDTKQE 218
STKc_STK10 cd06644
Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase ...
737-901 1.21e-08

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132975 [Multi-domain]  Cd Length: 292  Bit Score: 57.73  E-value: 1.21e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLrENTSPKANKEILDEAYVMAGVGSPYVSRLLG-ICLTSTVQLVTQLMPYGCLLDHVRE-NRGrLGSQDLLNWCMQ 814
Cdd:cd06644     41 AAKVI-ETKSEEELEDYMVEIEILATCNHPYIVKLLGaFYWDGKLWIMIEFCPGGAVDAIMLElDRG-LTEPQIQVICRQ 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGL-ARLLdidETEYHADGGKVPIKWMALESILRRR-----FTHQ 888
Cdd:cd06644    119 MLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGVsAKNV---KTLQRRDSFIGTPYWMAPEVVMCETmkdtpYDYK 195
                          170
                   ....*....|...
gi 1844139549  889 SDVWSYGVTVWEL 901
Cdd:cd06644    196 ADIWSLGITLIEM 208
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
811-917 1.39e-08

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 58.01  E-value: 1.39e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSD 890
Cdd:cd05619    111 YAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTSTFCG-TP-DYIAPEILLGQKYNTSVD 188
                           90       100
                   ....*....|....*....|....*..
gi 1844139549  891 VWSYGVTVWElMTFGAKPYDGIPAREI 917
Cdd:cd05619    189 WWSFGVLLYE-MLIGQSPFHGQDEEEL 214
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
782-961 1.48e-08

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 57.05  E-value: 1.48e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQD-LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV-KSPNHVKITDFGLARLLDID 859
Cdd:cd08220     76 IVMEYAPGGTLFEYIQQRKGSLLSEEeILHFFVQILLALHHVHSKQILHRDLKTQNILLnKKRTVVKIGDFGISKILSSK 155
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  860 ETEYHADGgkVPIkWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDgipAREIPDLLEK---GERLPQPPICTID 936
Cdd:cd08220    156 SKAYTVVG--TPC-YISPELCEGKPYNQKSDIWALGCVLYELASL-KRAFE---AANLPALVLKimrGTFAPISDRYSEE 228
                          170       180
                   ....*....|....*....|....*
gi 1844139549  937 VYMIMVKCWMIDSECRPRFRELVSE 961
Cdd:cd08220    229 LRHLILSMLHLDPNKRPTLSEIMAQ 253
STKc_CaMKK2 cd14199
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; ...
798-909 1.48e-08

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271101 [Multi-domain]  Cd Length: 286  Bit Score: 57.67  E-value: 1.48e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGRLGSQDLLnwcmqiaKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMAL 877
Cdd:cd14199    125 EDQARFYFQDLI-------KGIEYLHYQKIIHRDVKPSNLLVGEDGHIKIADFGVSNEFEGSDALLTNTVG-TP-AFMAP 195
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1844139549  878 ESI--LRRRFTHQS-DVWSYGVTVWeLMTFGAKPY 909
Cdd:cd14199    196 ETLseTRKIFSGKAlDVWAMGVTLY-CFVFGQCPF 229
STKc_p38delta cd07879
Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase ...
786-931 1.51e-08

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143384 [Multi-domain]  Cd Length: 342  Bit Score: 57.99  E-value: 1.51e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPYgcLLDHVRENRGRLGSQDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYh 864
Cdd:cd07879     98 VMPY--MQTDLQKIMGHPLSEDKVQYLVyQMLCGLKYIHSAGIIHRDLKPGNLAVNEDCELKILDFGLARHADAEMTGY- 174
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  865 adggkVPIKWM-ALESILR-RRFTHQSDVWSYGVTVWELMT----FGAKPY----------DGIPAREIPDLLEKGE--- 925
Cdd:cd07879    175 -----VVTRWYrAPEVILNwMHYNQTVDIWSVGCIMAEMLTgktlFKGKDYldqltqilkvTGVPGPEFVQKLEDKAaks 249

                   ....*....
gi 1844139549  926 ---RLPQPP 931
Cdd:cd07879    250 yikSLPKYP 258
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
812-901 1.52e-08

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 57.32  E-value: 1.52e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD---------IDeTEYhadggkvpikWMALESILR 882
Cdd:cd06613    103 CRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGVSAQLTatiakrksfIG-TPY----------WMAPEVAAV 171
                           90       100
                   ....*....|....*....|..
gi 1844139549  883 RR---FTHQSDVWSYGVTVWEL 901
Cdd:cd06613    172 ERkggYDGKCDIWALGITAIEL 193
STKc_SBK1 cd13987
Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the ...
735-903 1.54e-08

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270889 [Multi-domain]  Cd Length: 259  Bit Score: 56.95  E-value: 1.54e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKAN--KEIldeAYVMAGVGSPYVSRLLGICLTSTVQLV--TQLMPYGCLLDHVRENRGrLGsQDLLN 810
Cdd:cd13987     20 KMALKFVPKPSTKLKDflREY---NISLELSVHPHIIKTYDVAFETEDYYVfaQEYAPYGDLFSIIPPQVG-LP-EERVK 94
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPN--HVKITDFGLARlldideteyhADGGKVPIKW-----MA---LES 879
Cdd:cd13987     95 RCAaQLASALDFMHSKNLVHRDIKPENVLLFDKDcrRVKLCDFGLTR----------RVGSTVKRVSgtipyTApevCEA 164
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  880 ILRRRFT--HQSDVWSYGVTVWELMT 903
Cdd:cd13987    165 KKNEGFVvdPSIDVWAFGVLLFCCLT 190
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
748-909 1.69e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270729 [Multi-domain]  Cd Length: 278  Bit Score: 57.15  E-value: 1.69e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVrENRGRLGSQ--DLLNWCMQIAKGMSYLED 824
Cdd:cd05577     35 KGETMALNEKIILEKVSSPFIVSLAYAFETKDkLCLVLTLMNGGDLKYHI-YNVGTRGFSeaRAIFYAAEIICGLEHLHN 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  825 VRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDE-TEYHADGGKVpiKWMALESILRRR-FTHQSDVWSYGVTVWELM 902
Cdd:cd05577    114 RFIVYRDLKPENILLDDHGHVRISDLGLA--VEFKGgKKIKGRVGTH--GYMAPEVLQKEVaYDFSVDWFALGCMLYEMI 189

                   ....*..
gi 1844139549  903 TfGAKPY 909
Cdd:cd05577    190 A-GRSPF 195
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
793-909 1.73e-08

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 57.33  E-value: 1.73e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVR--LVHRDLAARNVLVKSPNH---VKITDFGLARLldIDETEYHADG 867
Cdd:cd13990     92 LDFYLKQHKSIPEREARSIIMQVVSALKYLNEIKppIIHYDLKPGNILLHSGNVsgeIKITDFGLSKI--MDDESYNSDG 169
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  868 gkvpikwMALESI-----------------LRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd13990    170 -------MELTSQgagtywylppecfvvgkTPPKISSKVDVWSVGVIFYQ-MLYGRKPF 220
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
765-903 1.77e-08

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 56.93  E-value: 1.77e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  765 SPYVSRLLGICLTSTVQLvTQLMPY---GCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKS 841
Cdd:cd13994     56 HPNIVKVLDLCQDLHGKW-CLVMEYcpgGDLFTLIEK-ADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDE 133
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  842 PNHVKITDFGLA--RLLDIDETEYHADG--GKVPikWMALESILRRRFTHQS-DVWSYGVTVWELMT 903
Cdd:cd13994    134 DGVLKLTDFGTAevFGMPAEKESPMSAGlcGSEP--YMAPEVFTSGSYDGRAvDVWSCGIVLFALFT 198
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
736-909 1.99e-08

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 57.20  E-value: 1.99e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEI----LDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPYGclLDHV-RENRGRLGSQDLL 809
Cdd:cd07841     28 VAIKKIKLGERKEAKDGInftaLREIKLLQELKHPNIIGLLDVfGHKSNINLVFEFMETD--LEKViKDKSIVLTPADIK 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldideteYHADGGkvpikwmalesilrRRFTHQS 889
Cdd:cd07841    106 SYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLAR--------SFGSPN--------------RKMTHQV 163
                          170       180
                   ....*....|....*....|....
gi 1844139549  890 dvwsygVTVW----ELMtFGAKPY 909
Cdd:cd07841    164 ------VTRWyrapELL-FGARHY 180
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
737-909 2.05e-08

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270753 [Multi-domain]  Cd Length: 339  Bit Score: 57.72  E-value: 2.05e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENT--SPKANKEILDEAYVM-AGVGSPYVSRL-LGICLTSTVQLVTQLMPYGCLLDHVRENRGRLGSQDLLnWC 812
Cdd:cd05602     36 AVKVLQKKAilKKKEEKHIMSERNVLlKNVKHPFLVGLhFSFQTTDKLYFVLDYINGGELFYHLQRERCFLEPRARF-YA 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlLDIDETEYHADGGKVPiKWMALESILRRRFTHQSDVW 892
Cdd:cd05602    115 AEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLTDFGLCK-ENIEPNGTTSTFCGTP-EYLAPEVLHKQPYDRTVDWW 192
                          170
                   ....*....|....*..
gi 1844139549  893 SYGVTVWElMTFGAKPY 909
Cdd:cd05602    193 CLGAVLYE-MLYGLPPF 208
STKc_cPKC cd05587
Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; ...
814-917 2.08e-08

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270739 [Multi-domain]  Cd Length: 320  Bit Score: 57.40  E-value: 2.08e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldideteYHADGGKV-------PiKWMALESILRRRFT 886
Cdd:cd05587    105 EIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCK--------EGIFGGKTtrtfcgtP-DYIAPEIIAYQPYG 175
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1844139549  887 HQSDVWSYGVTVWElMTFGAKPYDGIPAREI 917
Cdd:cd05587    176 KSVDWWAYGVLLYE-MLAGQPPFDGEDEDEL 205
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
735-900 2.40e-08

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 57.53  E-value: 2.40e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLldhvrENRGRLGSQDLLNWCM 813
Cdd:PLN00034   101 LYALKVIYGNHEDTVRRQICREIEILRDVNHPNVVKCHDMFdHNGEIQVLLEFMDGGSL-----EGTHIADEQFLADVAR 175
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdiDETEYHADGGKVPIKWMALESILR-----RRFTHQ 888
Cdd:PLN00034   176 QILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVSRIL--AQTMDPCNSSVGTIAYMSPERINTdlnhgAYDGYA 253
                          170
                   ....*....|..
gi 1844139549  889 SDVWSYGVTVWE 900
Cdd:PLN00034   254 GDIWSLGVSILE 265
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
746-911 2.41e-08

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 56.55  E-value: 2.41e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  746 SPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLED 824
Cdd:cd14191     39 SAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKAnIVMVLEMVSGGELFERIIDEDFELTERECIKYMRQISEGVEYIHK 118
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  825 VRLVHRDLAARNVLV--KSPNHVKITDFGLARLLDideteyhaDGGKVPI-----KWMALESILRRRFTHQSDVWSYGVT 897
Cdd:cd14191    119 QGIVHLDLKPENIMCvnKTGTKIKLIDFGLARRLE--------NAGSLKVlfgtpEFVAPEVINYEPIGYATDMWSIGVI 190
                          170
                   ....*....|....
gi 1844139549  898 VWELMTfGAKPYDG 911
Cdd:cd14191    191 CYILVS-GLSPFMG 203
STKc_SGK3 cd05604
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
737-909 2.55e-08

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270755 [Multi-domain]  Cd Length: 326  Bit Score: 57.28  E-value: 2.55e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENT--SPKANKEILDEAYVM-AGVGSPYVSRL-LGICLTSTVQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWC 812
Cdd:cd05604     25 AVKVLQKKVilNRKEQKHIMAERNVLlKNVKHPFLVGLhYSFQTTDKLYFVLDFVNGGELFFHLQRER-SFPEPRARFYA 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL-LDIDETEYHADGgkVPiKWMALESILRRRFTHQSDV 891
Cdd:cd05604    104 AEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGLCKEgISNSDTTTTFCG--TP-EYLAPEVIRKQPYDNTVDW 180
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWElMTFGAKPY 909
Cdd:cd05604    181 WCLGSVLYE-MLYGLPPF 197
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
735-899 2.57e-08

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 56.65  E-value: 2.57e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVL-RENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGCLLDHV-RENRGRLGSQDLLNWC 812
Cdd:cd14082     30 DVAIKVIdKLRFPTKQESQLRNEVAILQQLSHPGVVNLECMFETPERVFVVMEKLHGDMLEMIlSSEKGRLPERITKFLV 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGLARLldIDETEYHADGGKVPiKWMALESILRRRFTHQS 889
Cdd:cd14082    110 TQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARI--IGEKSFRRSVVGTP-AYLAPEVLRNKGYNRSL 186
                          170
                   ....*....|
gi 1844139549  890 DVWSYGVTVW 899
Cdd:cd14082    187 DMWSVGVIIY 196
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
814-908 2.57e-08

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 57.38  E-value: 2.57e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE---TEYhadggkVPIKWM-ALESILR-RRFTHQ 888
Cdd:cd07858    116 QLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDFGLARTTSEKGdfmTEY------VVTRWYrAPELLLNcSEYTTA 189
                           90       100
                   ....*....|....*....|
gi 1844139549  889 SDVWSYGVTVWELMtfGAKP 908
Cdd:cd07858    190 IDVWSVGCIFAELL--GRKP 207
STKc_MAPK15-like cd07852
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and ...
814-908 2.65e-08

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270841 [Multi-domain]  Cd Length: 337  Bit Score: 57.18  E-value: 2.65e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE--------TEYhadggkVPIKWMALESIL--RR 883
Cdd:cd07852    115 QLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLSQLEeddenpvlTDY------VATRWYRAPEILlgST 188
                           90       100
                   ....*....|....*....|....*
gi 1844139549  884 RFTHQSDVWSYGVTVWELmtFGAKP 908
Cdd:cd07852    189 RYTKGVDMWSVGCILGEM--LLGKP 211
STKc_cPKC_alpha cd05615
Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs ...
737-911 2.65e-08

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270766 [Multi-domain]  Cd Length: 341  Bit Score: 57.31  E-value: 2.65e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLLGICLtSTVQLVTQLMPY---GCLLDHVREnRGRLGSQDLLNW 811
Cdd:cd05615     39 AIKILKKDVVIQDDdvECTMVEKRVLALQDKPPFLTQLHSCF-QTVDRLYFVMEYvngGDLMYHIQQ-VGKFKEPQAVFY 116
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDV 891
Cdd:cd05615    117 AAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKEHMVEGVTTRTFCG-TP-DYIAPEIIAYQPYGRSVDW 194
                          170       180
                   ....*....|....*....|
gi 1844139549  892 WSYGVTVWELMTfGAKPYDG 911
Cdd:cd05615    195 WAYGVLLYEMLA-GQPPFDG 213
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
813-910 2.72e-08

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 56.56  E-value: 2.72e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLA----RLLDIDETEYHADGGKVPIK-----WMALESILR 882
Cdd:cd14011    121 LQISEALSFLhNDVKLVHGNICPESVVINSNGEWKLAGFDFCisseQATDQFPYFREYDPNLPPLAqpnlnYLAPEYILS 200
                           90       100
                   ....*....|....*....|....*...
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMTFGAKPYD 910
Cdd:cd14011    201 KTCDPASDMFSLGVLIYAIYNKGKPLFD 228
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
748-909 2.72e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173720 [Multi-domain]  Cd Length: 285  Bit Score: 56.92  E-value: 2.72e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVReNRGRLG--SQDLLNWCMQIAKGMSYLED 824
Cdd:cd05631     42 KGEAMALNEKRILEKVNSRFVVSLAYAYETKdALCLVLTIMNGGDLKFHIY-NMGNPGfdEQRAIFYAAELCCGLEDLQR 120
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  825 VRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDETEyhADGGKV-PIKWMALESILRRRFTHQSDVWSYGVTVWElMT 903
Cdd:cd05631    121 ERIVYRDLKPENILLDDRGHIRISDLGLA--VQIPEGE--TVRGRVgTVGYMAPEVINNEKYTFSPDWWGLGCLIYE-MI 195

                   ....*.
gi 1844139549  904 FGAKPY 909
Cdd:cd05631    196 QGQSPF 201
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
734-909 2.74e-08

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 56.65  E-value: 2.74e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENTSPKANKEIL-DEAYVMAGVGSPYVSRLLG-----ICLTSTVQLVTQLMPYGCLLDHVRENRgRLGSQD 807
Cdd:cd14031     36 VEVAWCELQDRKLTKAEQQRFkEEAEMLKGLQHPNIVRFYDswesvLKGKKCIVLVTELMTSGTLKTYLKRFK-VMKPKV 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVR--LVHRDLAARNVLVKSPN-HVKITDFGLARLLdidETEYHADGGKVPiKWMALEsILRRR 884
Cdd:cd14031    115 LRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITGPTgSVKIGDLGLATLM---RTSFAKSVIGTP-EFMAPE-MYEEH 189
                          170       180
                   ....*....|....*....|....*
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14031    190 YDESVDVYAFGMCMLEMAT-SEYPY 213
STKc_DRAK1 cd14197
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
752-911 2.81e-08

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271099 [Multi-domain]  Cd Length: 271  Bit Score: 56.48  E-value: 2.81e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  752 EILDEAYVMA-GVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDH-VRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLV 828
Cdd:cd14197     54 EIIHEIAVLElAQANPWVINLHEVYETASeMILVLEYAAGGEIFNQcVADREEAFKEKDVKRLMKQILEGVSFLHNNNVV 133
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  829 HRDLAARNVLV--KSP-NHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfG 905
Cdd:cd14197    134 HLDLKPQNILLtsESPlGDIKIVDFGLSRILKNSEELREIMG--TP-EYVAPEILSYEPISTATDMWSIGVLAYVMLT-G 209

                   ....*.
gi 1844139549  906 AKPYDG 911
Cdd:cd14197    210 ISPFLG 215
STKc_Twitchin_like cd14114
The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs ...
782-911 2.86e-08

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271016 [Multi-domain]  Cd Length: 259  Bit Score: 56.44  E-value: 2.86e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVL--VKSPNHVKITDFGLARLLDID 859
Cdd:cd14114     76 LILEFLSGGELFERIAAEHYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMctTKRSNEVKLIDFGLATHLDPK 155
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  860 ETEYHADGGKvpiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14114    156 ESVKVTTGTA---EFAAPEIVEREPVGFYTDMWAVGVLSYVLLS-GLSPFAG 203
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
733-910 3.37e-08

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 56.12  E-value: 3.37e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKE--ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVrENRGRLGSQDLL 809
Cdd:cd14116     30 KFILALKVLFKAQLEKAGVEhqLRREVEIQSHLRHPNILRLYGYFHDATrVYLILEYAPLGTVYREL-QKLSKFDEQRTA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlldideteYHADGGKVP-----IKWMALESILRRR 884
Cdd:cd14116    109 TYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWS---------VHAPSSRRTtlcgtLDYLPPEMIEGRM 179
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14116    180 HDEKVDLWSLGVLCYEFLV-GKPPFE 204
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
793-916 3.39e-08

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 56.09  E-value: 3.39e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPi 872
Cdd:cd14189     88 LAHIWKARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEPPEQRKKTICG-TP- 165
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPARE 916
Cdd:cd14189    166 NYLAPEVLLRQGHGPESDVWSLGCVMYTLLC-GNPPFETLDLKE 208
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
814-909 3.45e-08

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 56.25  E-value: 3.45e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdIDETEYHADGGKVPIKWMALESILRRRFTHQS--DV 891
Cdd:cd05583    107 EIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEF-LPGENDRAYSFCGTIEYMAPEVVRGGSDGHDKavDW 185
                           90
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd05583    186 WSLGVLTYELLT-GASPF 202
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
736-929 3.47e-08

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 56.75  E-value: 3.47e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVL--RENTSPKANKEILDEAYVMAGVGSPY-VSRLLGICLTSTVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWC 812
Cdd:PTZ00263    46 YAIKCLkkREILKMKQVQHVAQEKSILMELSHPFiVNMMCSFQDENRVYFLLEFVVGGELFTHLRK-AGRFPNDVAKFYH 124
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGgkVPiKWMALESILRRRFTHQSDVW 892
Cdd:PTZ00263   125 AELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAK--KVPDRTFTLCG--TP-EYLAPEVIQSKGHGKAVDWW 199
                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1844139549  893 SYGVTVWElMTFGAKP-YDGIPAREIPDLLEKGERLPQ 929
Cdd:PTZ00263   200 TMGVLLYE-FIAGYPPfFDDTPFRIYEKILAGRLKFPN 236
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
814-909 3.57e-08

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 56.85  E-value: 3.57e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--LLDIDETEYHADGgkvPIKWMALEsILRRRFTHQS-- 889
Cdd:cd05614    113 EIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKefLTEEKERTYSFCG---TIEYMAPE-IIRGKSGHGKav 188
                           90       100
                   ....*....|....*....|
gi 1844139549  890 DVWSYGVTVWELMTfGAKPY 909
Cdd:cd05614    189 DWWSLGILMFELLT-GASPF 207
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
736-911 3.63e-08

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 55.86  E-value: 3.63e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWC 812
Cdd:cd14073     29 VAIKSIKKDkiEDEQDMVRIRREIEIMSSLNHPHIIRIYEVFENkDKIVIVMEYASGGELYDYISE-RRRLPEREARRIF 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkvPIkwMALESILRRRFTH--QSD 890
Cdd:cd14073    108 RQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKDKLLQTFCGS--PL--YASPEIVNGTPYQgpEVD 183
                          170       180
                   ....*....|....*....|.
gi 1844139549  891 VWSYGVTVWELMtFGAKPYDG 911
Cdd:cd14073    184 CWSLGVLLYTLV-YGTMPFDG 203
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
814-908 3.77e-08

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 56.64  E-value: 3.77e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE-------TEYhadggkVPIKWM-ALESILR-RR 884
Cdd:cd07857    113 QILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPgenagfmTEY------VATRWYrAPEIMLSfQS 186
                           90       100
                   ....*....|....*....|....
gi 1844139549  885 FTHQSDVWSYGVTVWELMtfGAKP 908
Cdd:cd07857    187 YTKAIDVWSVGCILAELL--GRKP 208
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
814-910 3.88e-08

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 56.34  E-value: 3.88e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIdeteyhadggkvPIkwmalesilrRRFTHQSdvws 893
Cdd:cd07829    106 QLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFGI------------PL----------RTYTHEV---- 159
                           90       100
                   ....*....|....*....|.
gi 1844139549  894 ygVTVW----ELMtFGAKPYD 910
Cdd:cd07829    160 --VTLWyrapEIL-LGSKHYS 177
STKc_PKC cd05570
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer ...
815-911 3.94e-08

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270722 [Multi-domain]  Cd Length: 318  Bit Score: 56.45  E-value: 3.94e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--LLDIDET-------EYhadggkvpikwMALESILRRRF 885
Cdd:cd05570    105 ICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGMCKegIWGGNTTstfcgtpDY-----------IAPEILREQDY 173
                           90       100
                   ....*....|....*....|....*.
gi 1844139549  886 THQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd05570    174 GFSVDWWALGVLLYEMLA-GQSPFEG 198
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
814-909 4.24e-08

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 56.54  E-value: 4.24e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE------TEYhadggkVPIKWM-ALESILR-RRF 885
Cdd:cd07849    114 QILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLARIADPEHdhtgflTEY------VATRWYrAPEIMLNsKGY 187
                           90       100
                   ....*....|....*....|....*...
gi 1844139549  886 THQSDVWSYGVTVWELMT----FGAKPY 909
Cdd:cd07849    188 TKAIDIWSVGCILAEMLSnrplFPGKDY 215
STKc_DRAK cd14106
Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
751-911 4.34e-08

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271008 [Multi-domain]  Cd Length: 268  Bit Score: 55.82  E-value: 4.34e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  751 KEILDEAYV-MAGVGSPYVSRLLGICLTST-VQLVTQLMPyGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLV 828
Cdd:cd14106     52 NEILHEIAVlELCKDCPRVVNLHEVYETRSeLILILELAA-GGELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIV 130
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  829 HRDLAARNVLVKSP---NHVKITDFGLARLLDIDETEYHADGgkvPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfG 905
Cdd:cd14106    131 HLDLKPQNILLTSEfplGDIKLCDFGISRVIGEGEEIREILG---TPDYVAPEILSYEPISLATDMWSIGVLTYVLLT-G 206

                   ....*.
gi 1844139549  906 AKPYDG 911
Cdd:cd14106    207 HSPFGG 212
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
719-965 4.44e-08

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 55.57  E-value: 4.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  719 ELRKGIWipDGENVkipvAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHV 796
Cdd:cd14057     10 ELWKGRW--QGNDI----VAKILKvRDVTTRISRDFNEEYPRLRIFSHPNVLPVLGACNSPpNLVVISQYMPYGSLYNVL 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  797 RENRGRLGSQ-DLLNWCMQIAKGMSYLEDVRlvhrDLAARNVLvkSPNHVKITDFGLARLLDIDETEYHADGGKV--PiK 873
Cdd:cd14057     84 HEGTGVVVDQsQAVKFALDIARGMAFLHTLE----PLIPRHHL--NSKHVMIDEDMTARINMADVKFSFQEPGKMynP-A 156
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  874 WMALESILRR---RFTHQSDVWSYGVTVWELMTFGAkPYDGIPAREIP-DLLEKGERLPQPPICTIDVYMIMVKCWMIDS 949
Cdd:cd14057    157 WMAPEALQKKpedINRRSADMWSFAILLWELVTREV-PFADLSNMEIGmKIALEGLRVTIPPGISPHMCKLMKICMNEDP 235
                          250
                   ....*....|....*.
gi 1844139549  950 ECRPRFRELVSEFSRM 965
Cdd:cd14057    236 GKRPKFDMIVPILEKM 251
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
813-953 5.35e-08

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 55.57  E-value: 5.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIA----KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldideTEYHADGGKV--PIKwMALEsILRRRFT 886
Cdd:cd13975    105 LQIAldvvEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLGFCK------PEAMMSGSIVgtPIH-MAPE-LFSGKYD 176
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  887 HQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLL----EKGERLPQPPICTIDVYMIMVKCWMIDSECRP 953
Cdd:cd13975    177 NSVDVYAFGILFWYLCAGHVKLPEAFEQCASKDHLwnnvRKGVRPERLPVFDEECWNLMEACWSGDPSQRP 247
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
765-911 5.63e-08

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 56.11  E-value: 5.63e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  765 SPYVSRLlgICLTSTVQLVTQLMPY---GCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKS 841
Cdd:cd05620     55 NPFLTHL--YCTFQTKEHLFFVMEFlngGDLMFHIQD-KGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDR 131
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  842 PNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDG 911
Cdd:cd05620    132 DGHIKIADFGMCKENVFGDNRASTFCG-TP-DYIAPEILQGLKYTFSVDWWSFGVLLYE-MLIGQSPFHG 198
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
713-911 5.69e-08

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 55.34  E-value: 5.69e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  713 RILKETELRKgiwIPDGE-NVKipVAIKVLREntspkankeildeayvmagVGSPYVSRLLGICLTSTVQLVTQLMPY-- 789
Cdd:cd14119     24 KILKKRKLRR---IPNGEaNVK--REIQILRR-------------------LNHRNVIKLVDVLYNEEKQKLYMVMEYcv 79
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  790 GCL---LDHVRENRGRLG-SQDLLNwcmQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI--DETEY 863
Cdd:cd14119     80 GGLqemLDSAPDKRLPIWqAHGYFV---QLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAEALDLfaEDDTC 156
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  864 HADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWeLMTFGAKPYDG 911
Cdd:cd14119    157 TTSQGSPAFQPPEIANGQDSFSGFKVDIWSAGVTLY-NMTTGKYPFEG 203
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
732-909 5.71e-08

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 55.44  E-value: 5.71e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  732 VKIpvaIKVLRENTSPKANKEILD----EAYVMAGV-GSPYVSRLLGICLTST-VQLVTQLMPYGCLLDH------VREN 799
Cdd:cd14093     33 VKI---IDITGEKSSENEAEELREatrrEIEILRQVsGHPNIIELHDVFESPTfIFLVFELCRKGELFDYltevvtLSEK 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  800 RGRLGSQDLLnwcmqiaKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALEs 879
Cdd:cd14093    110 KTRRIMRQLF-------EAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEGEKLRELCG--TP-GYLAPE- 178
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1844139549  880 ILRRR-------FTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14093    179 VLKCSmydnapgYGKEVDMWACGVIMYTLLA-GCPPF 214
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
756-902 5.79e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 55.66  E-value: 5.79e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  756 EAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDH---VRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRD 831
Cdd:cd05608     51 EKRILAKVHSRFIVSLAYAFQTKTdLCLVMTIMNGGDLRYHiynVDEENPGFQEPRACFYTAQIISGLEHLHQRRIIYRD 130
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  832 LAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVWSYGVTVWELM 902
Cdd:cd05608    131 LKPENVLLDDDGNVRISDLGLAVELKDGQTKTKGYAG-TP-GFMAPELLLGEEYDYSVDYFTLGVTLYEMI 199
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
748-911 5.97e-08

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270780 [Multi-domain]  Cd Length: 313  Bit Score: 56.13  E-value: 5.97e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVReNRGRLGSQD--LLNWCMQIAKGMSYLED 824
Cdd:cd05632     44 KGESMALNEKQILEKVNSQFVVNLAYAYETKdALCLVLTIMNGGDLKFHIY-NMGNPGFEEerALFYAAEILCGLEDLHR 122
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  825 VRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDETEyhADGGKV-PIKWMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd05632    123 ENTVYRDLKPENILLDDYGHIRISDLGLA--VKIPEGE--SIRGRVgTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIE 198

                   ....*...
gi 1844139549  904 fGAKPYDG 911
Cdd:cd05632    199 -GQSPFRG 205
STKc_Sty1_Hog1 cd07856
Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases ...
780-902 6.74e-08

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270843 [Multi-domain]  Cd Length: 328  Bit Score: 56.04  E-value: 6.74e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMpyGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID 859
Cdd:cd07856     85 IYFVTELL--GTDLHRLLTSR-PLEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIQDPQ 161
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1844139549  860 ETEYhadggkVPIKWMALESILR--RRFTHQSDVWSYGVTVWELM 902
Cdd:cd07856    162 MTGY------VSTRYYRAPEIMLtwQKYDVEVDIWSAGCIFAEML 200
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
814-857 7.13e-08

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 55.65  E-value: 7.13e-08
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLD 857
Cdd:cd07840    112 QLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYT 155
FU smart00261
Furin-like repeats;
557-603 7.37e-08

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 49.82  E-value: 7.37e-08
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1844139549   557 ARHCLPCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSG 603
Cdd:smart00261    1 DGECKPCHPECA------TCTGPGPDDCTSCKHgfFLDGGKCVSECPPG 43
STKc_CaMKIV cd14085
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
735-909 7.49e-08

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270987 [Multi-domain]  Cd Length: 294  Bit Score: 55.60  E-value: 7.49e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKAnkeILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCM 813
Cdd:cd14085     30 PYAVKKLKKTVDKKI---VRTEIGVLLRLSHPNIIKLKEIFETPTeISLVLELVTGGELFDRIVE-KGYYSERDAADAVK 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSD 890
Cdd:cd14085    106 QILEAVAYLHENGIVHRDLKPENLLYATPAPdapLKIADFGLSKIVDQQVTMKTVCG--TP-GYCAPEILRGCAYGPEVD 182
                          170
                   ....*....|....*....
gi 1844139549  891 VWSYGVTVWELMTfGAKPY 909
Cdd:cd14085    183 MWSVGVITYILLC-GFEPF 200
STKc_DAPK2 cd14196
Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs ...
737-911 8.10e-08

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271098 [Multi-domain]  Cd Length: 269  Bit Score: 54.96  E-value: 8.10e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANK-----EILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGrLGSQDLLN 810
Cdd:cd14196     34 AAKFIKKRQSRASRRgvsreEIEREVSILRQVLHPNIITLHDVYENRTdVVLILELVSGGELFDFLAQKES-LSEEEATS 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN----HVKITDFGLARLLDiDETEYHADGGkVPiKWMALESILRRRFT 886
Cdd:cd14196    113 FIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNipipHIKLIDFGLAHEIE-DGVEFKNIFG-TP-EFVAPEIVNYEPLG 189
                          170       180
                   ....*....|....*....|....*
gi 1844139549  887 HQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14196    190 LEADMWSIGVITYILLS-GASPFLG 213
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
798-909 8.98e-08

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 55.15  E-value: 8.98e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARN-VLVKSPNHV--KITDFGLARLLDIDETEYHADGgkvPIKW 874
Cdd:cd13989     94 ENCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENiVLQQGGGRViyKLIDLGYAKELDQGSLCTSFVG---TLQY 170
                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1844139549  875 MALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd13989    171 LAPELFESKKYTCTVDYWSFGTLAFECIT-GYRPF 204
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
814-982 9.17e-08

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 56.18  E-value: 9.17e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL------LDIDE----TEYhadggkvpikWMALESILRR 883
Cdd:PTZ00267   177 QIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFSKQysdsvsLDVASsfcgTPY----------YLAPELWERK 246
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDLLEKGERLPQPpiCTIDVYM--IMVKCWMIDSECRPRFRELV-S 960
Cdd:PTZ00267   247 RYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFP--CPVSSGMkaLLDPLLSKNPALRPTTQQLLhT 323
                          170       180
                   ....*....|....*....|..
gi 1844139549  961 EFSRMARDPQRFVVIQNEDLGP 982
Cdd:PTZ00267   324 EFLKYVANLFQDIVRHSETISP 345
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
817-901 9.50e-08

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 55.43  E-value: 9.50e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  817 KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE----TEYhadggkvpikWMALESIL---RRRFTHQS 889
Cdd:cd06633    132 QGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPANsfvgTPY----------WMAPEVILamdEGQYDGKV 201
                           90
                   ....*....|..
gi 1844139549  890 DVWSYGVTVWEL 901
Cdd:cd06633    202 DIWSLGITCIEL 213
STKc_CDK2_3 cd07860
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; ...
810-903 1.05e-07

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270844 [Multi-domain]  Cd Length: 284  Bit Score: 54.82  E-value: 1.05e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggKVPIKWMALESILRRRF-THQ 888
Cdd:cd07860    104 SYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFGVPVRTYTHE--VVTLWYRAPEILLGCKYySTA 181
                           90
                   ....*....|....*
gi 1844139549  889 SDVWSYGVTVWELMT 903
Cdd:cd07860    182 VDIWSLGCIFAEMVT 196
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
735-923 1.09e-07

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 55.14  E-value: 1.09e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLR------ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRenrgRLG--S 805
Cdd:cd14096     29 PVAIKVVRkadlssDNLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESdEYYYIVLELADGGEIFHQIV----RLTyfS 104
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVL-------------VKSPN--------------------HVKITDFG 851
Cdd:cd14096    105 EDLSRHVItQVASAVKYLHEIGVVHRDIKPENLLfepipfipsivklRKADDdetkvdegefipgvggggigIVKLADFG 184
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  852 LARLLDIDETeyhadggKVP---IKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKP-YDgipaREIPDLLEK 923
Cdd:cd14096    185 LSKQVWDSNT-------KTPcgtVGYTAPEVVKDERYSKKVDMWALGCVLYTLLC-GFPPfYD----ESIETLTEK 248
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
737-853 1.10e-07

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 54.68  E-value: 1.10e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGiCLTSTVQLVTQlMPY--GCLLDHVRENrGRLGSQDLLnWCM- 813
Cdd:cd14046     35 AIKKIKLRSESKNNSRILREVMLLSRLNHQHVVRYYQ-AWIERANLYIQ-MEYceKSTLRDLIDS-GLFQDTDRL-WRLf 110
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1844139549  814 -QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14046    111 rQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLA 151
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
796-903 1.29e-07

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143341 [Multi-domain]  Cd Length: 284  Bit Score: 54.79  E-value: 1.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  796 VRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggkVPIKWM 875
Cdd:cd07836     90 THGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFGIPVNTFSNE---VVTLWY 166
                           90       100       110
                   ....*....|....*....|....*....|
gi 1844139549  876 ALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07836    167 RAPDVLlgSRTYSTSIDIWSVGCIMAEMIT 196
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
815-961 1.34e-07

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 54.67  E-value: 1.34e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESIL--RRRFTHQS-DV 891
Cdd:cd14118    124 IVLGIEYLHYQKIIHRDIKPSNLLLGDDGHVKIADFGVSNEFEGDDALLSSTAG-TP-AFMAPEALSesRKKFSGKAlDI 201
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  892 WSYGVTVWELMtFGAKPYDgipAREIPDLLEKGE----RLPQPPICTIDVYMIMVKcwMIDSEcrPRFRELVSE 961
Cdd:cd14118    202 WAMGVTLYCFV-FGRCPFE---DDHILGLHEKIKtdpvVFPDDPVVSEQLKDLILR--MLDKN--PSERITLPE 267
STKc_PhKG2 cd14181
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs ...
732-909 1.42e-07

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271083 [Multi-domain]  Cd Length: 279  Bit Score: 54.59  E-value: 1.42e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  732 VKIpvaIKVLRENTSPKANKEI----LDEAYVMAGV-GSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGS 805
Cdd:cd14181     40 VKI---IEVTAERLSPEQLEEVrsstLKEIHILRQVsGHPSIITLIDSYESSTfIFLVFDLMRRGELFDYLTE-KVTLSE 115
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALEsILRRRF 885
Cdd:cd14181    116 KETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEPGEKLRELCG--TP-GYLAPE-ILKCSM 191
                          170       180       190
                   ....*....|....*....|....*....|.
gi 1844139549  886 --TH-----QSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14181    192 deTHpgygkEVDLWACGVILFTLLA-GSPPF 221
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
718-965 1.57e-07

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 54.65  E-value: 1.57e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  718 TELRKGIWIPDGenvkIPVAIKVLR--ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCL-- 792
Cdd:cd08229     38 SEVYRATCLLDG----VPVALKKVQifDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNeLNIVLELADAGDLsr 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 -LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVP 871
Cdd:cd08229    114 mIKHFKKQKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHSLVG-TP 192
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 IkWMALESILRRRFTHQSDVWSYGVTVWELMTFGAkPYDGiPAREIPDLLEKGERLPQPPI----CTIDVYMIMVKCWMI 947
Cdd:cd08229    193 Y-YMSPERIHENGYNFKSDIWSLGCLLYEMAALQS-PFYG-DKMNLYSLCKKIEQCDYPPLpsdhYSEELRQLVNMCINP 269
                          250
                   ....*....|....*...
gi 1844139549  948 DSECRPRFRELVSEFSRM 965
Cdd:cd08229    270 DPEKRPDITYVYDVAKRM 287
STKc_CaMKK1 cd14200
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; ...
815-909 1.64e-07

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271102 [Multi-domain]  Cd Length: 284  Bit Score: 54.18  E-value: 1.64e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESIL--RRRFTHQS-DV 891
Cdd:cd14200    133 IVLGIEYLHYQKIVHRDIKPSNLLLGDDGHVKIADFGVSNQFEGNDALLSSTAG-TP-AFMAPETLSdsGQSFSGKAlDV 210
                           90
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWeLMTFGAKPY 909
Cdd:cd14200    211 WAMGVTLY-CFVYGKCPF 227
STKc_NIK cd13991
Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs ...
754-893 1.69e-07

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270893 [Multi-domain]  Cd Length: 268  Bit Score: 54.05  E-value: 1.69e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  754 LDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDL 832
Cdd:cd13991     46 AEELMACAGLTSPRVVPLYGAVREGpWVNIFMDLKEGGSLGQLIKE-QGCLPEDRALHYLGQALEGLEYLHSRKILHGDV 124
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  833 AARNVLVKSP-NHVKITDFGLARLLDIDETEYHADGGKVPI---KWMALESILRRRFTHQSDVWS 893
Cdd:cd13991    125 KADNVLLSSDgSDAFLCDFGHAECLDPDGLGKSLFTGDYIPgteTHMAPEVVLGKPCDAKVDVWS 189
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
815-909 1.85e-07

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 54.08  E-value: 1.85e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideteyhADGGKVPI---KWMALESIL------RRR 884
Cdd:cd06622    111 VVKGLKFLkEEHNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLV-------ASLAKTNIgcqSYMAPERIKsggpnqNPT 183
                           90       100
                   ....*....|....*....|....*
gi 1844139549  885 FTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06622    184 YTVQSDVWSLGLSILE-MALGRYPY 207
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
780-913 1.86e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 54.64  E-value: 1.86e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVRENR---GRLGSQDLLNwcmqIAKGMSYLEDVRLVHRDLAARNVLV----KSPNHVKITDFGL 852
Cdd:cd14176     88 VYVVTELMKGGELLDKILRQKffsEREASAVLFT----ITKTVEYLHAQGVVHRDLKPSNILYvdesGNPESIRICDFGF 163
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  853 ARLLdideteyHADGGKV-----PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIP 913
Cdd:cd14176    164 AKQL-------RAENGLLmtpcyTANFVAPEVLERQGYDAACDIWSLGVLLYTMLT-GYTPFANGP 221
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
817-901 1.87e-07

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270805 [Multi-domain]  Cd Length: 317  Bit Score: 54.29  E-value: 1.87e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  817 KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideteyHADGGKVPIKWMALESIL---RRRFTHQSDVWS 893
Cdd:cd06635    136 QGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIAS------PANSFVGTPYWMAPEVILamdEGQYDGKVDVWS 209

                   ....*...
gi 1844139549  894 YGVTVWEL 901
Cdd:cd06635    210 LGITCIEL 217
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
748-909 1.88e-07

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270756 [Multi-domain]  Cd Length: 285  Bit Score: 54.28  E-value: 1.88e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLL-------GICLtstvqlVTQLMPYGCLLDHVReNRGRLG--SQDLLNWCMQIAKG 818
Cdd:cd05605     42 KGEAMALNEKQILEKVNSRFVVSLAyayetkdALCL------VLTIMNGGDLKFHIY-NMGNPGfeEERAVFYAAEITCG 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  819 MSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDETEyhADGGKV-PIKWMALESILRRRFTHQSDVWSYGVT 897
Cdd:cd05605    115 LEHLHSERIVYRDLKPENILLDDHGHVRISDLGLA--VEIPEGE--TIRGRVgTVGYMAPEVVKNERYTFSPDWWGLGCL 190
                          170
                   ....*....|..
gi 1844139549  898 VWElMTFGAKPY 909
Cdd:cd05605    191 IYE-MIEGQAPF 201
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
736-896 2.04e-07

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 53.94  E-value: 2.04e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSP-----KANK--EILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYGCLLDHVRENRgRLGSQD 807
Cdd:cd14084     34 VAIKIINKRKFTigsrrEINKprNIETEIEILKKLSHPCIIKIEDFFDAeDDYYIVLELMEGGELFDRVVSNK-RLKEAI 112
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDID---ET----------EYHADGGKVP 871
Cdd:cd14084    113 CKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEeclIKITDFGLSKILGETslmKTlcgtptylapEVLRSFGTEG 192
                          170       180
                   ....*....|....*....|....*
gi 1844139549  872 ikwmalesilrrrFTHQSDVWSYGV 896
Cdd:cd14084    193 -------------YTRAVDCWSLGV 204
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
736-911 2.05e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 53.76  E-value: 2.05e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENtSPKANKEILDEAYVMAGVGSPYVSRLLGiCLTSTVQLVTqLMPY---GCLLDHVRENRGRLGSQDLLNWC 812
Cdd:cd14193     32 LAAKIIKAR-SQKEKEEVKNEIEVMNQLNHANLIQLYD-AFESRNDIVL-VMEYvdgGELFDRIIDENYNLTELDTILFI 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLV--KSPNHVKITDFGLARLLDIDEtEYHADGGkVPiKWMALESILRRRFTHQSD 890
Cdd:cd14193    109 KQICEGIQYMHQMYILHLDLKPENILCvsREANQVKIIDFGLARRYKPRE-KLRVNFG-TP-EFLAPEVVNYEFVSFPTD 185
                          170       180
                   ....*....|....*....|.
gi 1844139549  891 VWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14193    186 MWSLGVIAYMLLS-GLSPFLG 205
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
782-909 2.08e-07

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 54.42  E-value: 2.08e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCL---LDHvRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH----VKITDFGLAR 854
Cdd:cd13988     70 LVMELCPCGSLytvLEE-PSNAYGLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRVIGEDgqsvYKLTDFGAAR 148
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  855 LLDIDET--------EY-HADggkvpikwMALESILR----RRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd13988    149 ELEDDEQfvslygteEYlHPD--------MYERAVLRkdhqKKYGATVDLWSIGVTFYHAAT-GSLPF 207
STKc_PFTAIRE1 cd07869
Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer ...
736-923 2.10e-07

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143374 [Multi-domain]  Cd Length: 303  Bit Score: 54.31  E-value: 2.10e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMpYGCLLDHVRENRGRLGSQDLLNWCMQ 814
Cdd:cd07869     33 VALKVIRLQEEEGTPFTAIREASLLKGLKHANIVLLHDIIHTkETLTLVFEYV-HTDLCQYMDKHPGGLHPENVKLFLFQ 111
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDEteyHADGGKVPIKWMALESIL--RRRFTHQSDVW 892
Cdd:cd07869    112 LLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARAKSVPS---HTYSNEVVTLWYRPPDVLlgSTEYSTCLDMW 188
                          170       180       190
                   ....*....|....*....|....*....|.
gi 1844139549  893 SYGVTVWELMTfGAKPYDGIpaREIPDLLEK 923
Cdd:cd07869    189 GVGCIFVEMIQ-GVAAFPGM--KDIQDQLER 216
STKc_RSK1_C cd14175
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called ...
780-923 2.11e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271077 [Multi-domain]  Cd Length: 291  Bit Score: 54.26  E-value: 2.11e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVRENR---GRLGSQDLLNWCmqiaKGMSYLEDVRLVHRDLAARNVLV----KSPNHVKITDFGL 852
Cdd:cd14175     70 VYLVTELMRGGELLDKILRQKffsEREASSVLHTIC----KTVEYLHSQGVVHRDLKPSNILYvdesGNPESLRICDFGF 145
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  853 ARLLdideteyHADGGKV-----PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEK 923
Cdd:cd14175    146 AKQL-------RAENGLLmtpcyTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLA-GYTPFANGPSDTPEEILTR 213
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
755-903 2.34e-07

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 53.54  E-value: 2.34e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  755 DEAYVMAGVGSPYVSRLLGICLTST-----VQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVR--L 827
Cdd:cd14032     49 EEAEMLKGLQHPNIVRFYDFWESCAkgkrcIVLVTELMTSGTLKTYLKRFK-VMKPKVLRSWCRQILKGLLFLHTRTppI 127
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  828 VHRDLAARNVLVKSPN-HVKITDFGLARLldiDETEYHADGGKVPiKWMALEsILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14032    128 IHRDLKCDNIFITGPTgSVKIGDLGLATL---KRASFAKSVIGTP-EFMAPE-MYEEHYDESVDVYAFGMCMLEMAT 199
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
788-904 2.39e-07

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 53.66  E-value: 2.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  788 PYGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYL-EDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHAD 866
Cdd:cd08528     95 PLGEHFSSLKEKNEHFTEDRIWNIFVQMVLALRYLhKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQKGPESSKMTSV 174
                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1844139549  867 GGKvpIKWMALESILRRRFTHQSDVWSYGVTVWELMTF 904
Cdd:cd08528    175 VGT--ILYSCPEIVQNEPYGEKADIWALGCILYQMCTL 210
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
750-913 2.95e-07

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 53.49  E-value: 2.95e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  750 NKEILDEAYVMAGVGSPYVSRLLGicltSTVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLEDVRLVH 829
Cdd:cd06657     66 NEVVIMRDYQHENVVEMYNSYLVG----DELWVVMEFLEGGALTDIVTHTR--MNEEQIAAVCLAVLKALSVLHAQGVIH 139
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  830 RDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIkWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd06657    140 RDIKSDSILLTHDGRVKLSDFGFCAQVS-KEVPRRKSLVGTPY-WMAPELISRLPYGPEVDIWSLGIMVIE-MVDGEPPY 216

                   ....
gi 1844139549  910 DGIP 913
Cdd:cd06657    217 FNEP 220
STKc_CDK8_like cd07842
Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs ...
814-903 3.27e-07

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270834 [Multi-domain]  Cd Length: 316  Bit Score: 53.83  E-value: 3.27e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNH----VKITDFGLARLLDID-ETEYHADGGKVPIKWMALESIL-RRRFTH 887
Cdd:cd07842    116 QILNGIHYLHSNWVLHRDLKPANILVMGEGPergvVKIGDLGLARLFNAPlKPLADLDPVVVTIWYRAPELLLgARHYTK 195
                           90
                   ....*....|....*.
gi 1844139549  888 QSDVWSYGVTVWELMT 903
Cdd:cd07842    196 AIDIWAIGCIFAELLT 211
STKc_RSK4_C cd14177
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called ...
780-913 3.37e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271079 [Multi-domain]  Cd Length: 295  Bit Score: 53.48  E-value: 3.37e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV----KSPNHVKITDFGLARL 855
Cdd:cd14177     73 VYLVTELMKGGELLDRILRQK-FFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYmddsANADSIRICDFGFAKQ 151
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  856 LdideteyHADGGKV-----PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIP 913
Cdd:cd14177    152 L-------RGENGLLltpcyTANFVAPEVLMRQGYDAACDIWSLGVLLYTMLA-GYTPFANGP 206
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
641-684 3.42e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. ErbB2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer.


Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.42e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
736-910 3.53e-07

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 53.07  E-value: 3.53e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLR--ENTSPKANKEILDEAyvmaGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWC 812
Cdd:cd14665     28 VAVKYIErgEKIDENVQREIINHR----SLRHPNIVRFKEVILTPThLAIVMEYAAGGELFERIC-NAGRFSEDEARFFF 102
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVK-SPN-HVKITDFGLARLLDIDETEYHADGGKVpikWMALESILRRRFTHQ-S 889
Cdd:cd14665    103 QQLISGVSYCHSMQICHRDLKLENTLLDgSPApRLKICDFGYSKSSVLHSQPKSTVGTPA---YIAPEVLLKKEYDGKiA 179
                          170       180
                   ....*....|....*....|.
gi 1844139549  890 DVWSYGVTVWeLMTFGAKPYD 910
Cdd:cd14665    180 DVWSCGVTLY-VMLVGAYPFE 199
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
736-903 3.81e-07

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 53.09  E-value: 3.81e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEI-LDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGcLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd07833     29 VAIKKFKESEDDEDVKKTaLREVKVLRQLRHENIVNLKEAFRRKgRLYLVFEYVERT-LLELLEASPGGLPPDAVRSYIW 107
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL----DIDETEYhadggkVPIKWM-ALESILR-RRFTH 887
Cdd:cd07833    108 QLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALtarpASPLTDY------VATRWYrAPELLVGdTNYGK 181
                          170
                   ....*....|....*.
gi 1844139549  888 QSDVWSYGVTVWELMT 903
Cdd:cd07833    182 PVDVWAIGCIMAELLD 197
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
734-911 3.82e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271094 [Multi-domain]  Cd Length: 261  Bit Score: 53.04  E-value: 3.82e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLRENtSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWC 812
Cdd:cd14192     30 LTLAAKIIKVK-GAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTnLTLIMEYVDGGELFDRITDESYQLTELDAILFT 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLV--KSPNHVKITDFGLARLLDIDEtEYHADGGkVPiKWMALESILRRRFTHQSD 890
Cdd:cd14192    109 RQICEGVHYLHQHYILHLDLKPENILCvnSTGNQIKIIDFGLARRYKPRE-KLKVNFG-TP-EFLAPEVVNYDFVSFPTD 185
                          170       180
                   ....*....|....*....|.
gi 1844139549  891 VWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14192    186 MWSVGVITYMLLS-GLSPFLG 205
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
736-909 4.00e-07

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 53.04  E-value: 4.00e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYV--SRLL--GICLTSTVQLVTQLMPY---GCLLDHVR--ENRGRLGSQ 806
Cdd:cd14038     22 VAIKQCRQELSPKNRERWCLEIQIMKRLNHPNVvaARDVpeGLQKLAPNDLPLLAMEYcqgGDLRKYLNqfENCCGLREG 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 DLLNWCMQIAKGMSYLEDVRLVHRDLAARN-VLVKSPNHV--KITDFGLARLLDIDE--TEYHADggkvpIKWMALESIL 881
Cdd:cd14038    102 AILTLLSDISSALRYLHENRIIHRDLKPENiVLQQGEQRLihKIIDLGYAKELDQGSlcTSFVGT-----LQYLAPELLE 176
                          170       180
                   ....*....|....*....|....*...
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14038    177 QQKYTVTVDYWSFGTLAFECIT-GFRPF 203
PKc_Mps1 cd14131
Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle ...
737-958 4.01e-07

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271033 [Multi-domain]  Cd Length: 271  Bit Score: 52.99  E-value: 4.01e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLR-ENTSPKANKEILDE-AYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG-CLLDHVRENRgrLGSQDLLNWCM 813
Cdd:cd14131     29 ALKRVDlEGADEQTLQSYKNEiELLKKLKGSDRIIQLYDYEVTDEDDYLYMVMECGeIDLATILKKK--RPKPIDPNFIR 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMsyLEDV------RLVHRDLAARN-VLVKspNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESILRRRFT 886
Cdd:cd14131    107 YYWKQM--LEAVhtiheeGIVHSDLKPANfLLVK--GRLKLIDFGIAKAIQNDTTSIVRDSQVGTLNYMSPEAIKDTSAS 182
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  887 HQ----------SDVWSYGVTVWElMTFGAKPYDgiparEIPDLLEKGERLPQ-------PPICTIDVYMIMVKCWMIDS 949
Cdd:cd14131    183 GEgkpkskigrpSDVWSLGCILYQ-MVYGKTPFQ-----HITNPIAKLQAIIDpnheiefPDIPNPDLIDVMKRCLQRDP 256

                   ....*....
gi 1844139549  950 ECRPRFREL 958
Cdd:cd14131    257 KKRPSIPEL 265
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
782-901 4.14e-07

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 53.21  E-value: 4.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVreNRGRLGSQDLLNWCMQIAKGMSYL--EDV------RLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14143     70 LVSDYHEHGSLFDYL--NRYTVTVEGMIKLALSIASGLAHLhmEIVgtqgkpAIAHRDLKSKNILVKKNGTCCIADLGLA 147
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  854 RLLD-----IDETEYHADGGKvpiKWMALE----SILRRRFT--HQSDVWSYGVTVWEL 901
Cdd:cd14143    148 VRHDsatdtIDIAPNHRVGTK---RYMAPEvlddTINMKHFEsfKRADIYALGLVFWEI 203
STKc_PLK1 cd14187
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the ...
814-961 4.35e-07

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271089 [Multi-domain]  Cd Length: 265  Bit Score: 53.01  E-value: 4.35e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVWS 893
Cdd:cd14187    115 QIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKVEYDGERKKTLCG-TP-NYIAPEVLSKKGHSFEVDIWS 192
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  894 YGVTVWELMTfGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMvKCWMIDSECRPRFRELVSE 961
Cdd:cd14187    193 IGCIMYTLLV-GKPPFETSCLKETYLRIKKNEYSIPKHINPVAASLIQ-KMLQTDPTARPTINELLND 258
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
782-909 4.38e-07

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 52.70  E-value: 4.38e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCL---LDHVRENRGRLgsqdLLNWCMQIAKGMSYLEDVR--LVHRDLAARNVLVKSPN-HVKITDFGLARL 855
Cdd:cd14033     81 LVTELMTSGTLktyLKRFREMKLKL----LQRWSRQILKGLHFLHSRCppILHRDLKCDNIFITGPTgSVKIGDLGLATL 156
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  856 ldideteYHADGGKVPI---KWMALEsILRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd14033    157 -------KRASFAKSVIgtpEFMAPE-MYEEKYDEAVDVYAFGMCILE-MATSEYPY 204
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
817-901 4.44e-07

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 53.10  E-value: 4.44e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  817 KGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL----DIDETEYhadggkvpikWMALESIL---RRRFTHQS 889
Cdd:cd06634    126 QGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMapanSFVGTPY----------WMAPEVILamdEGQYDGKV 195
                           90
                   ....*....|..
gi 1844139549  890 DVWSYGVTVWEL 901
Cdd:cd06634    196 DVWSLGITCIEL 207
STKc_CaMKI_beta cd14169
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
736-909 4.86e-07

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271071 [Multi-domain]  Cd Length: 277  Bit Score: 52.97  E-value: 4.86e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQ 814
Cdd:cd14169     31 VALKCIPKKALRGKEAMVENEIAVLRRINHENIVSLEDIYESPThLYLAMELVTGGELFDRIIE-RGSYTEKDASQLIGQ 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSP---NHVKITDFGLARlldIDETEYHADGGKVPiKWMALESILRRRFTHQSDV 891
Cdd:cd14169    110 VLQAVKYLHQLGIVHRDLKPENLLYATPfedSKIMISDFGLSK---IEAQGMLSTACGTP-GYVAPELLEQKPYGKAVDV 185
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd14169    186 WAIGVISYILLC-GYPPF 202
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
814-896 5.21e-07

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 52.23  E-value: 5.21e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSP--NHVKITDFGLARLLDIDEteyhadggKVPIKW-----MALESILRRRFT 886
Cdd:cd14103     99 QICEGVQYMHKQGILHLDLKPENILCVSRtgNQIKIIDFGLARKYDPDK--------KLKVLFgtpefVAPEVVNYEPIS 170
                           90
                   ....*....|
gi 1844139549  887 HQSDVWSYGV 896
Cdd:cd14103    171 YATDMWSVGV 180
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
736-896 5.28e-07

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 52.37  E-value: 5.28e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQ 814
Cdd:cd14083     31 VAIKCIDKKALKGKEDSLENEIAVLRKIKHPNIVQLLDIYeSKSHLYLVMELVTGGELFDRIVE-KGSYTEKDASHLIRQ 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVKSP---NHVKITDFGLARlldIDETEYHADGGKVPiKWMALESILRRRFTHQSDV 891
Cdd:cd14083    110 VLEAVDYLHSLGIVHRDLKPENLLYYSPdedSKIMISDFGLSK---MEDSGVMSTACGTP-GYVAPEVLAQKPYGKAVDC 185

                   ....*
gi 1844139549  892 WSYGV 896
Cdd:cd14083    186 WSIGV 190
STKc_PCTAIRE1 cd07873
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer ...
814-903 5.54e-07

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270854 [Multi-domain]  Cd Length: 297  Bit Score: 52.70  E-value: 5.54e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYhadGGKVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07873    108 QLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSIPTKTY---SNEVVTLWYRPPDILlgSTDYSTQIDM 184
                           90
                   ....*....|..
gi 1844139549  892 WSYGVTVWELMT 903
Cdd:cd07873    185 WGVGCIFYEMST 196
STKc_RSK3_C cd14178
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called ...
780-913 5.80e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271080 [Multi-domain]  Cd Length: 293  Bit Score: 52.71  E-value: 5.80e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVRENR---GRLGSQDLlnwCMqIAKGMSYLEDVRLVHRDLAARNVLVK----SPNHVKITDFGL 852
Cdd:cd14178     72 VYLVMELMRGGELLDRILRQKcfsEREASAVL---CT-ITKTVEYLHSQGVVHRDLKPSNILYMdesgNPESIRICDFGF 147
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  853 ARLLdideteyHADGGKV-----PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIP 913
Cdd:cd14178    148 AKQL-------RAENGLLmtpcyTANFVAPEVLKRQGYDAACDIWSLGILLYTMLA-GFTPFANGP 205
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
778-929 6.13e-07

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270769 [Multi-domain]  Cd Length: 364  Bit Score: 53.11  E-value: 6.13e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--L 855
Cdd:cd05618     94 SRLFFVIEYVNGGDLMFHMQRQR-KLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGMCKegL 172
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  856 LDIDETEYHADggkVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPD----------LLEKGE 925
Cdd:cd05618    173 RPGDTTSTFCG---TP-NYIAPEILRGEDYGFSVDWWALGVLMFEMMA-GRSPFDIVGSSDNPDqntedylfqvILEKQI 247

                   ....
gi 1844139549  926 RLPQ 929
Cdd:cd05618    248 RIPR 251
STKc_DRAK2 cd14198
The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related ...
777-916 6.23e-07

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271100 [Multi-domain]  Cd Length: 270  Bit Score: 52.23  E-value: 6.23e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  777 TSTVQLVTQLMPYGCLLDH-VRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGL 852
Cdd:cd14198     80 TSEIILILEYAAGGEIFNLcVPDLAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYplgDIKIVDFGM 159
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  853 ARLLDiDETEYHADGGKVpiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPARE 916
Cdd:cd14198    160 SRKIG-HACELREIMGTP--EYLAPEILNYDPITTATDMWNIGVIAYMLLT-HESPFVGEDNQE 219
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
787-908 6.52e-07

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 52.70  E-value: 6.52e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  787 MPYgclLDH----VREN-RGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDET 861
Cdd:cd07866     94 TPY---MDHdlsgLLENpSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPYDGPPP 170
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  862 EYHADGGK--------VPIKWM-ALESIL-RRRFTHQSDVWSYGVTVWELmtFGAKP 908
Cdd:cd07866    171 NPKGGGGGgtrkytnlVVTRWYrPPELLLgERRYTTAVDIWGIGCVFAEM--FTRRP 225
STKc_MSK1_C cd14179
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
782-925 6.63e-07

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271081 [Multi-domain]  Cd Length: 310  Bit Score: 52.73  E-value: 6.63e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRenRGRLGSQDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGLARLLD 857
Cdd:cd14179     79 LVMELLKGGELLERIK--KKQHFSETEASHIMrKLVSAVSHMHDVGVVHRDLKPENLLFTDESdnsEIKIIDFGFARLKP 156
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  858 IDETEYhadggKVP---IKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDG-------IPAREIPDLLEKGE 925
Cdd:cd14179    157 PDNQPL-----KTPcftLHYAAPELLNYNGYDESCDLWSLGVILYTMLS-GQVPFQChdksltcTSAEEIMKKIKQGD 228
STKc_PCTAIRE3 cd07871
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer ...
793-903 7.49e-07

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270853 [Multi-domain]  Cd Length: 288  Bit Score: 52.32  E-value: 7.49e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 LDHVRENRGRLGSQDLLNWCM-QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYhadGGKVP 871
Cdd:cd07871     89 LKQYLDNCGNLMSMHNVKIFMfQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARAKSVPTKTY---SNEVV 165
                           90       100       110
                   ....*....|....*....|....*....|....
gi 1844139549  872 IKWMALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07871    166 TLWYRPPDVLlgSTEYSTPIDMWGVGCILYEMAT 199
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
818-911 7.65e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 52.41  E-value: 7.65e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  818 GMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL----LDIDETEYHAD------GGK----VPiKWMALESILRR 883
Cdd:cd05609    112 ALEYLHSYGIVHRDLKPDNLLITSMGHIKLTDFGLSKIglmsLTTNLYEGHIEkdtrefLDKqvcgTP-EYIAPEVILRQ 190
                           90       100
                   ....*....|....*....|....*...
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd05609    191 GYGKPVDWWAMGIILYEFLV-GCVPFFG 217
STKc_GRK7 cd05607
Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; ...
751-909 7.95e-07

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270758 [Multi-domain]  Cd Length: 286  Bit Score: 52.21  E-value: 7.95e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  751 KEILDEayvmagVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVReNRGRLGSQ--DLLNWCMQIAKGMSYLEDVRL 827
Cdd:cd05607     53 KEILEK------VNSPFIVSLAYAFETKThLCLVMSLMNGGDLKYHIY-NVGERGIEmeRVIFYSAQITCGILHLHSLKI 125
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  828 VHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKvpiKWMALESILRRRFTHQSDVWSYGVTVWElMTFGAK 907
Cdd:cd05607    126 VYRDMKPENVLLDDNGNCRLSDLGLAVEVKEGKPITQRAGTN---GYMAPEILKEESYSYPVDWFAMGCSIYE-MVAGRT 201

                   ..
gi 1844139549  908 PY 909
Cdd:cd05607    202 PF 203
STKc_MOK cd07831
Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs ...
776-904 8.15e-07

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270825 [Multi-domain]  Cd Length: 282  Bit Score: 52.27  E-value: 8.15e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  776 LTSTVQLVTQLMPyGCLLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSpNHVKITDFGLARL 855
Cdd:cd07831     71 KTGRLALVFELMD-MNLYELIKGRKRPLPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKD-DILKLADFGSCRG 148
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  856 LDIDE--TEYhadggkVPIKWM-ALESILRR-RFTHQSDVWSYGVTVWELMTF 904
Cdd:cd07831    149 IYSKPpyTEY------ISTRWYrAPECLLTDgYYGPKMDIWAVGCVFFEILSL 195
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
766-910 1.01e-06

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 51.69  E-value: 1.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  766 PYVSRLLGICLTST-VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVK-SPN 843
Cdd:cd14662     56 PNIIRFKEVVLTPThLAIVMEYAAGGELFERIC-NAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDgSPA 134
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  844 -HVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQ-SDVWSYGVTVWeLMTFGAKPYD 910
Cdd:cd14662    135 pRLKICDFGYSKSSVLHSQPKSTVG--TP-AYIAPEVLSRKEYDGKvADVWSCGVTLY-VMLVGAYPFE 199
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
779-962 1.02e-06

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 51.59  E-value: 1.02e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVrenrGRLGSQDLLN---WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGL 852
Cdd:cd14012     78 KVYLLTEYAPGGSLSELL----DSVGSVPLDTarrWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAGtgiVKLTDYSL 153
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  853 ARLLDIDETEYHADGGKvPIKWMALESIL-RRRFTHQSDVWSYGVTVWELMtFGAKP---YDG-IPAREIPDLLEkgerl 927
Cdd:cd14012    154 GKTLLDMCSRGSLDEFK-QTYWLPPELAQgSKSPTRKTDVWDLGLLFLQML-FGLDVlekYTSpNPVLVSLDLSA----- 226
                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1844139549  928 pqppictiDVYMIMVKCWMIDSECRPR-FRELVSEF 962
Cdd:cd14012    227 --------SLQDFLSKCLSLDPKKRPTaLELLPHEF 254
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
734-902 1.04e-06

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 52.34  E-value: 1.04e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  734 IPVAIKVLrenTSPKANKEILDEAY----VMAGVGSPYVSRLLGICLTST-------VQLVTQLMPYG-CLLDHVRENRG 801
Cdd:cd07876     47 INVAVKKL---SRPFQNQTHAKRAYrelvLLKCVNHKNIISLLNVFTPQKsleefqdVYLVMELMDANlCQVIHMELDHE 123
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSqdLLnwcMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldIDETEYHADGGKVPIKWMALESIL 881
Cdd:cd07876    124 RMSY--LL---YQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLAR---TACTNFMMTPYVVTRYYRAPEVIL 195
                          170       180
                   ....*....|....*....|.
gi 1844139549  882 RRRFTHQSDVWSYGVTVWELM 902
Cdd:cd07876    196 GMGYKENVDIWSVGCIMGELV 216
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
737-909 1.11e-06

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173686 [Multi-domain]  Cd Length: 323  Bit Score: 51.93  E-value: 1.11e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSpKANKEI---LDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVreNRGRLGSQDLLN-W 811
Cdd:cd05595     24 AMKILRKEVI-IAKDEVahtVTESRVLQNTRHPFLTALKYAFQTHDrLCFVMEYANGGELFFHL--SRERVFTEDRARfY 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDV 891
Cdd:cd05595    101 GAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGATMKTFCG-TP-EYLAPEVLEDNDYGRAVDW 178
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd05595    179 WGLGVVMYEMMC-GRLPF 195
PTZ00024 PTZ00024
cyclin-dependent protein kinase; Provisional
736-903 1.15e-06

cyclin-dependent protein kinase; Provisional


Pssm-ID: 240233 [Multi-domain]  Cd Length: 335  Bit Score: 52.07  E-value: 1.15e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKE-------------ILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLMPYGclLDHVRENRG 801
Cdd:PTZ00024    37 VAIKKVKIIEISNDVTKdrqlvgmcgihftTLRELKIMNEIKHENIMGLVDVyVEGDFINLVMDIMASD--LKKVVDRKI 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR-------LLDIDETEYHAD----GGKV 870
Cdd:PTZ00024   115 RLTESQVKCILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLARrygyppySDTLSKDETMQRreemTSKV 194
                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1844139549  871 PIKWMALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:PTZ00024   195 VTLWYRAPELLmgAEKYHFAVDMWSVGCIFAELLT 229
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
799-903 1.17e-06

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 52.09  E-value: 1.17e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHV-KITDFGLARLLDIDETE--YHADGgkVPIKWM 875
Cdd:cd07854    107 EQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFINTEDLVlKIGDFGLARIVDPHYSHkgYLSEG--LVTKWY 184
                           90       100       110
                   ....*....|....*....|....*....|
gi 1844139549  876 ALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07854    185 RSPRLLlsPNNYTKAIDMWAAGCIFAEMLT 214
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
814-917 1.18e-06

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 51.32  E-value: 1.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldideteyHADGGKV-----PIKWMALESILRRRFTHQ 888
Cdd:cd14007    108 QLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSV---------HAPSNRRktfcgTLDYLPPEMVEGKEYDYK 178
                           90       100
                   ....*....|....*....|....*....
gi 1844139549  889 SDVWSYGVTVWELMTfGAKPYDGIPAREI 917
Cdd:cd14007    179 VDIWSLGVLCYELLV-GKPPFESKSHQET 206
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
818-959 1.41e-06

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270808 [Multi-domain]  Cd Length: 291  Bit Score: 51.53  E-value: 1.41e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  818 GMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRR-----FTHQSDVW 892
Cdd:cd06639    140 GLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSARLRRNTSVG-TPF-WMAPEVIACEQqydysYDARCDVW 217
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  893 SYGVTVWELMTFGAKPYDGIPAREipdlLEKGERLPQPPICTIDVYM-----IMVKCWMIDSECRPRFRELV 959
Cdd:cd06639    218 SLGITAIELADGDPPLFDMHPVKA----LFKIPRNPPPTLLNPEKWCrgfshFISQCLIKDFEKRPSVTHLL 285
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
792-960 1.59e-06

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 50.77  E-value: 1.59e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKvp 871
Cdd:cd14050     87 LQQYCEET-HSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFGLVVELDKEDIHDAQEGDP-- 163
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  872 iKWMALEsILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGiparEIPDLLEKGErLPQPPICTIDVYMIMVKCWMIDS-- 949
Cdd:cd14050    164 -RYMAPE-LLQGSFTKAADIFSLGITILELACNLELPSGG----DGWHQLRQGY-LPEEFTAGLSPELRSIIKLMMDPdp 236
                          170
                   ....*....|.
gi 1844139549  950 ECRPRFRELVS 960
Cdd:cd14050    237 ERRPTAEDLLA 247
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
722-904 1.66e-06

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 51.12  E-value: 1.66e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  722 KGIWIPDGENVkipvAIKVLR--ENTSPKANKEILDEAYVMAGVGSPYVSRllgiCLTSTV-----QLVTQLMPYGCL-- 792
Cdd:cd08224     18 RARCLLDGRLV----ALKKVQifEMMDAKARQDCLKEIDLLQQLNHPNIIK----YLASFIennelNIVLELADAGDLsr 89
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 -LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVP 871
Cdd:cd08224     90 lIKHFKKQKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTAAHSLVG-TP 168
                          170       180       190
                   ....*....|....*....|....*....|...
gi 1844139549  872 IkWMALESILRRRFTHQSDVWSYGVTVWELMTF 904
Cdd:cd08224    169 Y-YMSPERIREQGYDFKSDIWSLGCLLYEMAAL 200
STKc_SRPK cd14136
Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze ...
814-903 1.74e-06

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271038 [Multi-domain]  Cd Length: 320  Bit Score: 51.42  E-value: 1.74e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDV-RLVHRDLAARNVLVKSPN-HVKITDFGLA------RLLDIDETEYHAdggkvpikwmaLESILRRRF 885
Cdd:cd14136    127 QVLQGLDYLHTKcGIIHTDIKPENVLLCISKiEVKIADLGNAcwtdkhFTEDIQTRQYRS-----------PEVILGAGY 195
                           90
                   ....*....|....*...
gi 1844139549  886 THQSDVWSYGVTVWELMT 903
Cdd:cd14136    196 GTPADIWSTACMAFELAT 213
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
737-909 1.78e-06

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270745 [Multi-domain]  Cd Length: 348  Bit Score: 51.62  E-value: 1.78e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANK--EILDEAYVMAGVGSPYVSRL-LGICLTSTVQLVTQLMPYGCLLDHVreNRGRLGSQDLLN-WC 812
Cdd:cd05593     44 AMKILKKEVIIAKDEvaHTLTESRVLKNTRHPFLTSLkYSFQTKDRLCFVMEYVNGGELFFHL--SRERVFSEDRTRfYG 121
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTHQSDVW 892
Cdd:cd05593    122 AEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKEGITDAATMKTFCG-TP-EYLAPEVLEDNDYGRAVDWW 199
                          170
                   ....*....|....*..
gi 1844139549  893 SYGVTVWELMTfGAKPY 909
Cdd:cd05593    200 GLGVVMYEMMC-GRLPF 215
STKc_ROCK_NDR_like cd05573
Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear ...
828-909 1.85e-06

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270725 [Multi-domain]  Cd Length: 350  Bit Score: 51.52  E-value: 1.85e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  828 VHRDLAARNVLVKSPNHVKITDFGLA-RLLDIDETEYHADGGKVPIK--------------------------WMALESI 880
Cdd:cd05573    123 IHRDIKPDNILLDADGHIKLADFGLCtKMNKSGDRESYLNDSVNTLFqdnvlarrrphkqrrvraysavgtpdYIAPEVL 202
                           90       100
                   ....*....|....*....|....*....
gi 1844139549  881 LRRRFTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd05573    203 RGTGYGPECDWWSLGVILYE-MLYGFPPF 230
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
812-903 2.02e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 51.21  E-value: 2.02e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLdidETEYHADGGKVPIKWM-ALESIL-RRRFTHQS 889
Cdd:cd07845    114 MLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTY---GLPAKPMTPKVVTLWYrAPELLLgCTTYTTAI 190
                           90
                   ....*....|....
gi 1844139549  890 DVWSYGVTVWELMT 903
Cdd:cd07845    191 DMWAVGCILAELLA 204
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
782-909 2.10e-06

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271070 [Multi-domain]  Cd Length: 301  Bit Score: 51.20  E-value: 2.10e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDI 858
Cdd:cd14168     85 LVMQLVSGGELFDRIVE-KGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLYFSQDEeskIMISDFGLSKMEGK 163
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  859 DETEYHADGGKvpiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14168    164 GDVMSTACGTP---GYVAPEVLAQKPYSKAVDCWSIGVIAYILLC-GYPPF 210
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
235-280 2.24e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 45.59  E-value: 2.24e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  235 CCHEQCAaGCTGPKHSDCLACLHFN--HSGICELHCPALVTYNTDTFE 280
Cdd:cd00064      1 PCHPSCA-TCTGPGPDQCTSCRHGFylDGGTCVSECPEGTYADTEGGV 47
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
782-901 2.32e-06

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 50.94  E-value: 2.32e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLED--------VRLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14144     70 LITDYHENGSLYDFLRGNT--LDTQSMLKLAYSAACGLAHLHTeifgtqgkPAIAHRDIKSKNILVKKNGTCCIADLGLA 147
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  854 rlldideTEYHADGGKVPI---------KWMALE----SILRRRFT--HQSDVWSYGVTVWEL 901
Cdd:cd14144    148 -------VKFISETNEVDLppntrvgtkRYMAPEvldeSLNRNHFDayKMADMYSFGLVLWEI 203
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
793-916 2.34e-06

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 50.40  E-value: 2.34e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 LDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPi 872
Cdd:cd14188     88 MAHILKARKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRTICG-TP- 165
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  873 KWMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDGIPARE 916
Cdd:cd14188    166 NYLSPEVLNKQGHGCESDIWALGCVMYT-MLLGRPPFETTNLKE 208
STKc_SGK2 cd05603
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; ...
737-909 2.87e-06

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270754 [Multi-domain]  Cd Length: 321  Bit Score: 50.74  E-value: 2.87e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENT--SPKANKEILDEAYVM-AGVGSPYVSRLLGICLTS-TVQLVTQLMPYGCLLDHV------RENRGRLgsq 806
Cdd:cd05603     24 AVKVLQKKTilKKKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSeKLYFVLDYVNGGELFFHLqrercfLEPRARF--- 100
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  807 dllnWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL-LDIDETEYHADGgkVPiKWMALESILRRRF 885
Cdd:cd05603    101 ----YAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGLCKEgMEPEETTSTFCG--TP-EYLAPEVLRKEPY 173
                          170       180
                   ....*....|....*....|....
gi 1844139549  886 THQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd05603    174 DRTVDWWCLGAVLYE-MLYGLPPF 196
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
813-931 3.25e-06

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 51.41  E-value: 3.25e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldideteYHA----DGGK----VPIkWMALESILRRR 884
Cdd:PTZ00283   150 IQVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSKM-------YAAtvsdDVGRtfcgTPY-YVAPEIWRRKP 221
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  885 FTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDLLEKGERLPQPP 931
Cdd:PTZ00283   222 YSKKADMFSLGVLLYELLTL-KRPFDGENMEEVMHKTLAGRYDPLPP 267
PTZ00426 PTZ00426
cAMP-dependent protein kinase catalytic subunit; Provisional
735-909 3.67e-06

cAMP-dependent protein kinase catalytic subunit; Provisional


Pssm-ID: 173616 [Multi-domain]  Cd Length: 340  Bit Score: 50.75  E-value: 3.67e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  735 PVAIKVLRENTSPKANK--EILDEAYVMAGVGSPYVSRLLG-ICLTSTVQLVTQLMPYGCLLDHVRENRgRLGSQDLLNW 811
Cdd:PTZ00426    58 PVAIKRFEKSKIIKQKQvdHVFSERKILNYINHPFCVNLYGsFKDESYLYLVLEFVIGGEFFTFLRRNK-RFPNDVGCFY 136
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGKvpiKWMALESILRRRFTHQSDV 891
Cdd:PTZ00426   137 AAQIVLIFEYLQSLNIVYRDLKPENLLLDKDGFIKMTDFGFAKV--VDTRTYTLCGTP---EYIAPEILLNVGHGKAADW 211
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:PTZ00426   212 WTLGIFIYEILV-GCPPF 228
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
799-917 3.77e-06

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 49.82  E-value: 3.77e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARllDIDETEYHADGGKV-PIKWMAL 877
Cdd:cd14111     92 DRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQ--SFNPLSLRQLGRRTgTLEYMAP 169
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1844139549  878 ESILRRRFTHQSDVWSYGVTVWeLMTFGAKPYDGIPAREI 917
Cdd:cd14111    170 EMVKGEPVGPPADIWSIGVLTY-IMLSGRSPFEDQDPQET 208
STKc_SGK cd05575
Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; ...
814-912 4.06e-06

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270727 [Multi-domain]  Cd Length: 323  Bit Score: 50.39  E-value: 4.06e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlLDIDETEYHADGGKVPiKWMALESILRRRFTHQSDVWS 893
Cdd:cd05575    104 EIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGLCK-EGIEPSDTTSTFCGTP-EYLAPEVLRKQPYDRTVDWWC 181
                           90       100
                   ....*....|....*....|....*...
gi 1844139549  894 YGVTVWElMTFGAKP---------YDGI 912
Cdd:cd05575    182 LGAVLYE-MLYGLPPfysrdtaemYDNI 208
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
773-952 4.17e-06

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 50.03  E-value: 4.17e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  773 GICLTSTVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYL-EDV----------RLVHRDLAARNVLVKS 841
Cdd:cd14140     61 GSNLEMELWLITAFHDKGSLTDYLKGNI--VSWNELCHIAETMARGLSYLhEDVprckgeghkpAIAHRDFKSKNVLLKN 138
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  842 PNHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI-----LRRRFTHQSDVWSYGVTVWELMTfGAKPYDG----- 911
Cdd:cd14140    139 DLTAVLADFGLAVRFEPGKPPGDTHGQVGTRRYMAPEVLegainFQRDSFLRIDMYAMGLVLWELVS-RCKAADGpvdey 217
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  912 -IPARE-------IPDLLE-----------KGERLPQPPICTIDVymIMVKCWMIDSECR 952
Cdd:cd14140    218 mLPFEEeigqhpsLEDLQEvvvhkkmrpvfKDHWLKHPGLAQLCV--TIEECWDHDAEAR 275
STKc_RSK_C cd14091
C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs ...
779-909 4.20e-06

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270993 [Multi-domain]  Cd Length: 291  Bit Score: 49.94  E-value: 4.20e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  779 TVQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLV----KSPNHVKITDFGLAR 854
Cdd:cd14091     68 SVYLVTELLRGGELLDRIL-RQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYadesGDPESLRICDFGFAK 146
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  855 LLdideteyHADGGKV--PI---KWMALEsILRRRFTHQS-DVWSYGVTVWeLMTFGAKPY 909
Cdd:cd14091    147 QL-------RAENGLLmtPCytaNFVAPE-VLKKQGYDAAcDIWSLGVLLY-TMLAGYTPF 198
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
813-961 4.25e-06

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 50.06  E-value: 4.25e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVR--LVHRDLAARNVLV---KSPNHVKITDFGLARLLDiDETEYHADGGKVPIK------WMALESIL 881
Cdd:cd14041    118 MQIVNALKYLNEIKppIIHYDLKPGNILLvngTACGEIKITDFGLSKIMD-DDSYNSVDGMELTSQgagtywYLPPECFV 196
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 ----RRRFTHQSDVWSYGVTVWELMtFGAKPYDGIPAREipDLLEKGE-------RLPQPPICTIDVYMIMVKCWMIDSE 950
Cdd:cd14041    197 vgkePPKISNKVDVWSVGVIFYQCL-YGRKPFGHNQSQQ--DILQENTilkatevQFPPKPVVTPEAKAFIRRCLAYRKE 273
                          170
                   ....*....|.
gi 1844139549  951 CRPRFRELVSE 961
Cdd:cd14041    274 DRIDVQQLACD 284
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
814-903 4.58e-06

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 49.81  E-value: 4.58e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHV-KITDFGLARLLDIDETE--------YHAdggkvPikwmalESILR-R 883
Cdd:cd14137    114 QLFRGLAYLHSLGICHRDIKPQNLLVDPETGVlKLCDFGSAKRLVPGEPNvsyicsryYRA-----P------ELIFGaT 182
                           90       100
                   ....*....|....*....|
gi 1844139549  884 RFTHQSDVWSYGVTVWELMT 903
Cdd:cd14137    183 DYTTAIDIWSAGCVLAELLL 202
PLN00009 PLN00009
cyclin-dependent kinase A; Provisional
814-903 4.62e-06

cyclin-dependent kinase A; Provisional


Pssm-ID: 177649 [Multi-domain]  Cd Length: 294  Bit Score: 49.82  E-value: 4.62e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV-KSPNHVKITDFGLARLLDIDETEYHADggkVPIKWMALESIL--RRRFTHQSD 890
Cdd:PLN00009   110 QILRGIAYCHSHRVLHRDLKPQNLLIdRRTNALKLADFGLARAFGIPVRTFTHE---VVTLWYRAPEILlgSRHYSTPVD 186
                           90
                   ....*....|...
gi 1844139549  891 VWSYGVTVWELMT 903
Cdd:PLN00009   187 IWSVGCIFAEMVN 199
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
782-856 4.92e-06

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 49.99  E-value: 4.92e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN---HVKITDFGLARLL 856
Cdd:cd14092     76 LVMELLRGGELLERIRKKK-RFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDddaEIKIVDFGFARLK 152
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
562-607 4.97e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 44.82  E-value: 4.97e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  562 PCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSGVKPD 607
Cdd:cd00064      1 PCHPSCA------TCTGPGPDQCTSCRHgfYLDGGTCVSECPEGTYAD 42
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
814-915 5.03e-06

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 49.85  E-value: 5.03e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLArlLDIDETEYHAdGGKVPI-KWMALESILRRRFTHQS 889
Cdd:cd14094    117 QILEALRYCHDNNIIHRDVKPHCVLLASKENsapVKLGGFGVA--IQLGESGLVA-GGRVGTpHFMAPEVVKREPYGKPV 193
                           90       100
                   ....*....|....*....|....*.
gi 1844139549  890 DVWSYGVTVWELMTfGAKPYDGIPAR 915
Cdd:cd14094    194 DVWGCGVILFILLS-GCLPFYGTKER 218
STKc_PCTAIRE2 cd07872
Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer ...
814-901 5.05e-06

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143377 [Multi-domain]  Cd Length: 309  Bit Score: 49.99  E-value: 5.05e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYhadGGKVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07872    112 QILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARAKSVPTKTY---SNEVVTLWYRPPDVLlgSSEYSTQIDM 188
                           90
                   ....*....|
gi 1844139549  892 WSYGVTVWEL 901
Cdd:cd07872    189 WGVGCIFFEM 198
STKc_CaMKII cd14086
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
812-902 5.17e-06

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270988 [Multi-domain]  Cd Length: 292  Bit Score: 49.73  E-value: 5.17e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CM-QIAKGMSYLEDVRLVHRDLAARNVLV--KSPNH-VKITDFGLARLLDIDETEYHADGGkVPiKWMALESILRRRFTH 887
Cdd:cd14086    105 CIqQILESVNHCHQNGIVHRDLKPENLLLasKSKGAaVKLADFGLAIEVQGDQQAWFGFAG-TP-GYLSPEVLRKDPYGK 182
                           90
                   ....*....|....*
gi 1844139549  888 QSDVWSYGVTVWELM 902
Cdd:cd14086    183 PVDIWACGVILYILL 197
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
814-895 6.07e-06

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 49.67  E-value: 6.07e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDE-------TEYhadggkVPIKWM-ALESILR-RR 884
Cdd:cd07855    117 QLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMARGLCTSPeehkyfmTEY------VATRWYrAPELMLSlPE 190
                           90
                   ....*....|.
gi 1844139549  885 FTHQSDVWSYG 895
Cdd:cd07855    191 YTQAIDMWSVG 201
pknD PRK13184
serine/threonine-protein kinase PknD;
736-976 6.41e-06

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 50.54  E-value: 6.41e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTS--PKANKEILDEAYVMAGVGSPYVSRLLGICltSTVQLVTQLMPY------GCLLDHVRENRGRlgSQD 807
Cdd:PRK13184    30 VALKKIREDLSenPLLKKRFLREAKIAADLIHPGIVPVYSIC--SDGDPVYYTMPYiegytlKSLLKSVWQKESL--SKE 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  808 L---------LNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--------LLDID----ETEYH-- 864
Cdd:PRK13184   106 LaektsvgafLSIFHKICATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIfkkleeedLLDIDvderNICYSsm 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  865 ADGGKV--PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDllekGERLPQPpictidvymimv 942
Cdd:PRK13184   186 TIPGKIvgTPDYMAPERLLGVPASESTDIYALGVILYQMLTL-SFPYRRKKGRKISY----RDVILSP------------ 248
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1844139549  943 kcwmidSECRPrFRELVSEFSR-----MARDP-QRFVVIQ 976
Cdd:PRK13184   249 ------IEVAP-YREIPPFLSQiamkaLAVDPaERYSSVQ 281
STKc_MSK2_C cd14180
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
782-911 6.44e-06

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271082 [Multi-domain]  Cd Length: 309  Bit Score: 49.48  E-value: 6.44e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDI 858
Cdd:cd14180     78 LVMELLRGGELLDRIKKKA-RFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADESDgavLKVIDFGFARLRPQ 156
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139549  859 DETEYHADGgkVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14180    157 GSRPLQTPC--FTLQYAAPELFSNQGYDESCDLWSLGVILYTMLS-GQVPFQS 206
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
731-953 6.48e-06

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 49.25  E-value: 6.48e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  731 NVKIPVAIKVLRENTSPKaNKEILDEAYVMAGV-GSPYVSRLLG--ICLTSTVQLVTQLMPY-GCLLDHVRENR--GRLG 804
Cdd:cd13985     23 NTGRRYALKRMYFNDEEQ-LRVAIKEIEIMKRLcGHPNIVQYYDsaILSSEGRKEVLLLMEYcPGSLVDILEKSppSPLS 101
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  805 SQDLLNWCMQIAKGMSYL--EDVRLVHRDLAARNVLVKSPNHVKITDFGLA-RLLDIDETEYHADGGKVPIKWM------ 875
Cdd:cd13985    102 EEEVLRIFYQICQAVGHLhsQSPPIIHRDIKIENILFSNTGRFKLCDFGSAtTEHYPLERAEEVNIIEEEIQKNttpmyr 181
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  876 ALESI---LRRRFTHQSDVWSYGVTVWELMTFgAKPYDgipAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 952
Cdd:cd13985    182 APEMIdlySKKPIGEKADIWALGCLLYKLCFF-KLPFD---ESSKLAIVAGKYSIPEQPRYSPELHDLIRHMLTPDPAER 257

                   .
gi 1844139549  953 P 953
Cdd:cd13985    258 P 258
STKc_Sid2p_like cd05600
Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the ...
736-854 7.10e-06

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270751 [Multi-domain]  Cd Length: 386  Bit Score: 50.03  E-value: 7.10e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYG---CLLDHV---RENRGRLgsq 806
Cdd:cd05600     39 CALKIMKKKVLFKLNevNHVLTERDILTTTNSPWLVKLLyAFQDPENVYLAMEYVPGGdfrTLLNNSgilSEEHARF--- 115
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  807 dllnWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR 854
Cdd:cd05600    116 ----YIAEMFAAISSLHQLGYIHRDLKPENFLIDSSGHIKLTDFGLAS 159
STKc_Sck1_like cd05586
Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine ...
778-909 7.58e-06

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270738 [Multi-domain]  Cd Length: 330  Bit Score: 49.49  E-value: 7.58e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGL--ARL 855
Cdd:cd05586     69 TDLYLVTDYMSGGELFWHLQKE-GRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLskADL 147
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1844139549  856 LDIDETEYHADggkvPIKWMALESILRRR-FTHQSDVWSYGVTVWElMTFGAKPY 909
Cdd:cd05586    148 TDNKTTNTFCG----TTEYLAPEVLLDEKgYTKMVDFWSLGVLVFE-MCCGWSPF 197
STKc_CaMK_like cd14088
Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to ...
748-909 8.39e-06

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270990 [Multi-domain]  Cd Length: 265  Bit Score: 48.87  E-value: 8.39e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  748 KANKEILDEAYVMAGVGSPYVSRLLGICLTST-----VQLVTQLMPYGCLLDhvrenRGRLGSQDLLNWCMQIAKGMSYL 822
Cdd:cd14088     41 KVRKAAKNEINILKMVKHPNILQLVDVFETRKeyfifLELATGREVFDWILD-----QGYYSERDTSNVIRQVLEAVAYL 115
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  823 EDVRLVHRDLAARNVLVKS---PNHVKITDFGLARLldidETEYHADGGKVPiKWMALESILRRRFTHQSDVWSYGVTVW 899
Cdd:cd14088    116 HSLKIVHRNLKLENLVYYNrlkNSKIVISDFHLAKL----ENGLIKEPCGTP-EYLAPEVVGRQRYGRPVDCWAIGVIMY 190
                          170
                   ....*....|
gi 1844139549  900 ELMTfGAKPY 909
Cdd:cd14088    191 ILLS-GNPPF 199
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
813-961 8.84e-06

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 49.28  E-value: 8.84e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVR--LVHRDLAARNVLV---KSPNHVKITDFGLARLLDIDetEYHADG------GKVPIKWMALESIL 881
Cdd:cd14040    118 MQIVNALRYLNEIKppIIHYDLKPGNILLvdgTACGEIKITDFGLSKIMDDD--SYGVDGmdltsqGAGTYWYLPPECFV 195
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 ----RRRFTHQSDVWSYGVTVWELMtFGAKPYDGIPAREipDLLEKGE-------RLPQPPICTIDVYMIMVKCWMIDSE 950
Cdd:cd14040    196 vgkePPKISNKVDVWSVGVIFFQCL-YGRKPFGHNQSQQ--DILQENTilkatevQFPVKPVVSNEAKAFIRRCLAYRKE 272
                          170
                   ....*....|.
gi 1844139549  951 CRPRFRELVSE 961
Cdd:cd14040    273 DRFDVHQLASD 283
STKc_EIF2AK2_PKR cd14047
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
814-902 9.45e-06

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270949 [Multi-domain]  Cd Length: 267  Bit Score: 48.64  E-value: 9.45e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL--DIDETEyhadgGKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd14047    125 QITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGLVTSLknDGKRTK-----SKGTLSYMSPEQISSQDYGKEVDI 199
                           90
                   ....*....|.
gi 1844139549  892 WSYGVTVWELM 902
Cdd:cd14047    200 YALGLILFELL 210
STKc_SNRK cd14074
Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the ...
736-854 9.48e-06

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270976 [Multi-domain]  Cd Length: 258  Bit Score: 48.56  E-value: 9.48e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTSPKANKE-ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCM 813
Cdd:cd14074     31 VAVKVIDKTKLDDVSKAhLFQEVRCMKLVQHPNVVRLYEVIDTQTkLYLILELGDGGDMYDYIMKHENGLNEDLARKYFR 110
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV-KSPNHVKITDFGLAR 854
Cdd:cd14074    111 QIVSAISYCHKLHVVHRDLKPENVVFfEKQGLVKLTDFGFSN 152
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
755-903 9.50e-06

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 48.89  E-value: 9.50e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  755 DEAYVMAGVGSPYVSRLLGiCLTSTVQ------LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVR-- 826
Cdd:cd14030     73 EEAGMLKGLQHPNIVRFYD-SWESTVKgkkcivLVTELMTSGTLKTYLKRFK-VMKIKVLRSWCRQILKGLQFLHTRTpp 150
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  827 LVHRDLAARNVLVKSPN-HVKITDFGLARLldiDETEYHADGGKVPiKWMALEsILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14030    151 IIHRDLKCDNIFITGPTgSVKIGDLGLATL---KRASFAKSVIGTP-EFMAPE-MYEEKYDESVDVYAFGMCMLEMAT 223
STKc_CDK1_euk cd07861
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher ...
814-903 9.70e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270845 [Multi-domain]  Cd Length: 285  Bit Score: 48.96  E-value: 9.70e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggKVPIKWMALESIL-RRRFTHQSDVW 892
Cdd:cd07861    109 QILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFGIPVRVYTHE--VVTLWYRAPEVLLgSPRYSTPVDIW 186
                           90
                   ....*....|.
gi 1844139549  893 SYGVTVWELMT 903
Cdd:cd07861    187 SIGTIFAEMAT 197
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
813-903 9.94e-06

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 48.83  E-value: 9.94e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEY-HadggKVPIKWMALESIL--RRRFTHQS 889
Cdd:cd07835    106 YQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFGVPVRTYtH----EVVTLWYRAPEILlgSKHYSTPV 181
                           90
                   ....*....|....
gi 1844139549  890 DVWSYGVTVWELMT 903
Cdd:cd07835    182 DIWSVGCIFAEMVT 195
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
778-929 1.16e-05

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270768 [Multi-domain]  Cd Length: 357  Bit Score: 49.25  E-value: 1.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  778 STVQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--L 855
Cdd:cd05617     89 SRLFLVIEYVNGGDLMFHMQRQR-KLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKegL 167
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  856 LDIDETEYHADggkVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIParEIPDL----------LEKGE 925
Cdd:cd05617    168 GPGDTTSTFCG---TP-NYIAPEILRGEEYGFSVDWWALGVLMFEMMA-GRSPFDIIT--DNPDMntedylfqviLEKPI 240

                   ....
gi 1844139549  926 RLPQ 929
Cdd:cd05617    241 RIPR 244
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
814-903 1.18e-05

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 48.76  E-value: 1.18e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidetEYhadggKVPIKWM----------ALESIL-R 882
Cdd:cd07843    114 QLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAR-------EY-----GSPLKPYtqlvvtlwyrAPELLLgA 181
                           90       100
                   ....*....|....*....|.
gi 1844139549  883 RRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07843    182 KEYSTAIDMWSVGCIFAELLT 202
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
787-901 1.21e-05

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 48.45  E-value: 1.21e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  787 MPYGCLLDHVRenrgrlgsqdllNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL----DIDETE 862
Cdd:cd07848     93 MPNGVPPEKVR------------SYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLsegsNANYTE 160
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1844139549  863 YhadggkVPIKWM-ALESILRRRFTHQSDVWSYGVTVWEL 901
Cdd:cd07848    161 Y------VATRWYrSPELLLGAPYGKAVDMWSVGCILGEL 194
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
814-905 1.28e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 48.89  E-value: 1.28e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideTEYHADGGKVPIKWMALESILRRRFTHQSDVWS 893
Cdd:cd07875    134 QMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAG---TSFMMTPYVVTRYYRAPEVILGMGYKENVDIWS 210
                           90
                   ....*....|..
gi 1844139549  894 YGVTVWELMTFG 905
Cdd:cd07875    211 VGCIMGEMIKGG 222
STKc_DCKL1 cd14183
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called ...
737-911 1.30e-05

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271085 [Multi-domain]  Cd Length: 268  Bit Score: 48.45  E-value: 1.30e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVrENRGRLGSQDLLNWCMQI 815
Cdd:cd14183     35 ALKIINKSKCRGKEHMIQNEVSILRRVKHPNIVLLIEEMDMPTeLYLVMELVKGGDLFDAI-TSTNKYTERDASGMLYNL 113
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  816 AKGMSYLEDVRLVHRDLAARNVLV----KSPNHVKITDFGLARLldIDETEYHADGGKVpikWMALESILRRRFTHQSDV 891
Cdd:cd14183    114 ASAIKYLHSLNIVHRDIKPENLLVyehqDGSKSLKLGDFGLATV--VDGPLYTVCGTPT---YVAPEIIAETGYGLKVDI 188
                          170       180
                   ....*....|....*....|
gi 1844139549  892 WSYGVTVWELMTfGAKPYDG 911
Cdd:cd14183    189 WAAGVITYILLC-GFPPFRG 207
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
814-902 1.35e-05

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 48.27  E-value: 1.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPN-HVKITDFGLA--RLLDIDETEYHADGGKVPIK--------WMALESILR 882
Cdd:cd14049    128 QLLEGVTYIHSMGIVHRDLKPRNIFLHGSDiHVRIGDFGLAcpDILQDGNDSTTMSRLNGLTHtsgvgtclYAAPEQLEG 207
                           90       100
                   ....*....|....*....|
gi 1844139549  883 RRFTHQSDVWSYGVTVWELM 902
Cdd:cd14049    208 SHYDFKSDMYSIGVILLELF 227
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
812-931 1.40e-05

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 48.10  E-value: 1.40e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESILRRR---FTHQ 888
Cdd:cd06646    112 CRETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIAKRKSFIG-TPY-WMAPEVAAVEKnggYNQL 189
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1844139549  889 SDVWSYGVTVWELMTFGAKPYDGIPAREIpDLLEKGERlpQPP 931
Cdd:cd06646    190 CDIWAVGITAIELAELQPPMFDLHPMRAL-FLMSKSNF--QPP 229
STKc_Mnk cd14090
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase ...
782-911 1.78e-05

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270992 [Multi-domain]  Cd Length: 289  Bit Score: 48.18  E-value: 1.78e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVrENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARllDI 858
Cdd:cd14090     77 LVFEKMRGGPLLSHI-EKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESMDKvspVKICDFDLGS--GI 153
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139549  859 DETEYHADGGKVP--------IKWMALESIlrRRFTHQS-------DVWSYGVTVWeLMTFGAKPYDG 911
Cdd:cd14090    154 KLSSTSMTPVTTPelltpvgsAEYMAPEVV--DAFVGEAlsydkrcDLWSLGVILY-IMLCGYPPFYG 218
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
194-270 1.86e-05

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 45.44  E-value: 1.86e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  194 PCSPMCKGSRCWGESSEDCQS----LTRTVCAGGCARCKGP-----LPTDC--CHEQCA-----AGCTGPKHSDCLACLH 257
Cdd:pfam14843    1 VCDPLCSSEGCWGPGPDQCLScrnfSRGGTCVESCNILQGEpreyvVNSTCvpCHPECLpqngtATCSGPGADNCTKCAH 80
                           90
                   ....*....|...
gi 1844139549  258 FNHSGICELHCPA 270
Cdd:pfam14843   81 FRDGPHCVSSCPS 93
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
814-902 1.91e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 48.55  E-value: 1.91e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDideTEYHADGGKVPIKWMALESILRRRFTHQSDVWS 893
Cdd:cd07874    127 QMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAG---TSFMMTPYVVTRYYRAPEVILGMGYKENVDIWS 203

                   ....*....
gi 1844139549  894 YGVTVWELM 902
Cdd:cd07874    204 VGCIMGEMV 212
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
814-909 2.05e-05

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 47.70  E-value: 2.05e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVkITDFGLArlLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWS 893
Cdd:cd13995    104 HVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAV-LVDFGLS--VQMTEDVYVPKDLRGTEIYMSPEVILCRGHNTKADIYS 180
                           90
                   ....*....|....*.
gi 1844139549  894 YGVTVWELMTfGAKPY 909
Cdd:cd13995    181 LGATIIHMQT-GSPPW 195
STKc_aPKC cd05588
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the ...
782-929 2.07e-05

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270740 [Multi-domain]  Cd Length: 328  Bit Score: 48.19  E-value: 2.07e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--LLDID 859
Cdd:cd05588     73 FVIEFVNGGDLMFHMQRQR-RLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGHIKLTDYGMCKegLRPGD 151
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  860 ETEYHADggkVPiKWMALEsILR-RRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPD----------LLEKGERLP 928
Cdd:cd05588    152 TTSTFCG---TP-NYIAPE-ILRgEDYGFSVDWWALGVLMFEMLA-GRSPFDIVGSSDNPDqntedylfqvILEKPIRIP 225

                   .
gi 1844139549  929 Q 929
Cdd:cd05588    226 R 226
STKc_DCKL2 cd14184
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called ...
737-909 2.47e-05

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271086 [Multi-domain]  Cd Length: 259  Bit Score: 47.33  E-value: 2.47e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQI 815
Cdd:cd14184     30 ALKIIDKAKCCGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAeLYLVMELVKGGDLFDAITSST-KYTERDASAMVYNL 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  816 AKGMSYLEDVRLVHRDLAARNVLV-KSPN---HVKITDFGLARLldIDETEYHADGGKVpikWMALESILRRRFTHQSDV 891
Cdd:cd14184    109 ASALKYLHGLCIVHRDIKPENLLVcEYPDgtkSLKLGDFGLATV--VEGPLYTVCGTPT---YVAPEIIAETGYGLKVDI 183
                          170
                   ....*....|....*...
gi 1844139549  892 WSYGVTVWELMTfGAKPY 909
Cdd:cd14184    184 WAAGVITYILLC-GFPPF 200
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
814-908 2.74e-05

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 47.85  E-value: 2.74e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR--LLDIDETEYHADggKVPIKWM---ALESILRRRFTHQ 888
Cdd:cd07859    111 QLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARvaFNDTPTAIFWTD--YVATRWYrapELCGSFFSKYTPA 188
                           90       100
                   ....*....|....*....|
gi 1844139549  889 SDVWSYGVTVWELMTfgAKP 908
Cdd:cd07859    189 IDIWSIGCIFAEVLT--GKP 206
FU smart00261
Furin-like repeats;
509-544 2.82e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 42.50  E-value: 2.82e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139549   509 LACHQLCArgHCWGPGPTQCVNCSQ--FLRGQECVEEC 544
Cdd:smart00261    5 KPCHPECA--TCTGPGPDDCTSCKHgfFLDGGKCVSEC 40
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
801-917 3.01e-05

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 47.35  E-value: 3.01e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  801 GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGkVPIkWMALESI 880
Cdd:cd06645    103 GPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKSFIG-TPY-WMAPEVA 180
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1844139549  881 LRRR---FTHQSDVWSYGVTVWELMTFGAKPYDGIPAREI 917
Cdd:cd06645    181 AVERkggYNQLCDIWAVGITAIELAELQPPMFDLHPMRAL 220
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
510-544 3.18e-05

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 42.51  E-value: 3.18e-05
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1844139549  510 ACHQLCArgHCWGPGPTQCVNCSQF--LRGQECVEEC 544
Cdd:cd00064      1 PCHPSCA--TCTGPGPDQCTSCRHGfyLDGGTCVSEC 35
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
792-916 3.61e-05

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271011 [Multi-domain]  Cd Length: 255  Bit Score: 46.74  E-value: 3.61e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVkSPNHVKITDFGLARLLdIDETEYHADGGkVP 871
Cdd:cd14109     85 VRDNLLPGKDYYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILL-QDDKLKLADFGQSRRL-LRGKLTTLIYG-SP 161
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1844139549  872 iKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPARE 916
Cdd:cd14109    162 -EFVSPEIVNSYPVTLATDMWSVGVLTYVLLG-GISPFLGDNDRE 204
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
782-909 3.64e-05

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 46.96  E-value: 3.64e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQDLL-NWCMQIAKGMSYLEDVRLVHRDLAARNVLVK-SPNHVKITDFGLArlldID 859
Cdd:cd13993     82 IVLEYCPNGDLFEAITENRIYVGKTELIkNVFLQLIDAVKHCHSLGIYHRDIKPENILLSqDEGTVKLCDFGLA----TT 157
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  860 EtEYHADGGKVPIKWMALESI-----LRRRF-THQSDVWSYGVTVWELmTFGAKPY 909
Cdd:cd13993    158 E-KISMDFGVGSEFYMAPECFdevgrSLKGYpCAAGDIWSLGIILLNL-TFGRNPW 211
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
750-853 3.67e-05

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 46.93  E-value: 3.67e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  750 NKE--ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVR 826
Cdd:cd14095     40 GKEhmIENEVAILRRVKHPNIVQLIEEYDTDTeLYLVMELVKGGDLFDAITSST-KFTERDASRMVTDLAQALKYLHSLS 118
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1844139549  827 LVHRDLAARNVLV-KSPNH---VKITDFGLA 853
Cdd:cd14095    119 IVHRDIKPENLLVvEHEDGsksLKLADFGLA 149
STKc_YPK1_like cd05585
Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the ...
754-909 5.27e-05

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270737 [Multi-domain]  Cd Length: 313  Bit Score: 46.80  E-value: 5.27e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  754 LDEAYVMAGVGSPYVSRL-LGICLTSTVQLVTQLMPYGCLLDHVR------ENRGRLGSQDLLnwCmqiakGMSYLEDVR 826
Cdd:cd05585     42 LAERTVLAQVDCPFIVPLkFSFQSPEKLYLVLAFINGGELFHHLQregrfdLSRARFYTAELL--C-----ALECLHKFN 114
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  827 LVHRDLAARNVLVKSPNHVKITDFGLARlLDIDETEYHADGGKVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGA 906
Cdd:cd05585    115 VIYRDLKPENILLDYTGHIALCDFGLCK-LNMKDDDKTNTFCGTP-EYLAPELLLGHGYTKAVDWWTLGVLLYEMLT-GL 191

                   ...
gi 1844139549  907 KPY 909
Cdd:cd05585    192 PPF 194
STKc_MELK cd14078
Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; ...
736-910 5.96e-05

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270980 [Multi-domain]  Cd Length: 257  Bit Score: 46.22  E-value: 5.96e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENTS----PKANKEIldEAyvMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREnRGRLGSQDLLN 810
Cdd:cd14078     31 VAIKIMDKKALgddlPRVKTEI--EA--LKNLSHQHICRLYHVIETDNkIFMVLEYCPGGELFDYIVA-KDRLSEDEARV 105
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDiDETEYHADGGKVPIKWMALESILRRRFT-HQS 889
Cdd:cd14078    106 FFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAKPK-GGMDHHLETCCGSPAYAAPELIQGKPYIgSEA 184
                          170       180
                   ....*....|....*....|.
gi 1844139549  890 DVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14078    185 DVWSMGVLLYALLC-GFLPFD 204
STKc_PRP4 cd14135
Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze ...
813-903 6.11e-05

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271037 [Multi-domain]  Cd Length: 318  Bit Score: 46.45  E-value: 6.11e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  813 MQIAKGMSYLEDVRLVHRDLAARNVLV-KSPNHVKITDFGLArlLDIDE---TEYhadggKVPIKWMALESILRRRFTHQ 888
Cdd:cd14135    112 QQLFLALKHLKKCNILHADIKPDNILVnEKKNTLKLCDFGSA--SDIGEneiTPY-----LVSRFYRAPEIILGLPYDYP 184
                           90
                   ....*....|....*
gi 1844139549  889 SDVWSYGVTVWELMT 903
Cdd:cd14135    185 IDMWSVGCTLYELYT 199
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
792-903 6.29e-05

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 46.26  E-value: 6.29e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDI---DETEYhadgg 868
Cdd:cd07846     86 VLDDLEKYPNGLDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAApgeVYTDY----- 160
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1844139549  869 kVPIKWMALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07846    161 -VATRWYRAPELLvgDTKYGKAVDVWAVGCLVTEMLT 196
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
814-902 6.72e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 46.64  E-value: 6.72e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDID--ETEYhadggKVPIKWMALESILRRRFTHQSDV 891
Cdd:cd07850    110 QMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSfmMTPY-----VVTRYYRAPEVILGMGYKENVDI 184
                           90
                   ....*....|.
gi 1844139549  892 WSYGVTVWELM 902
Cdd:cd07850    185 WSVGCIMGEMI 195
FU smart00261
Furin-like repeats;
235-270 7.17e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 41.34  E-value: 7.17e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139549   235 CCHEQCAaGCTGPKHSDCLACLHFNH--SGICELHCPA 270
Cdd:smart00261    6 PCHPECA-TCTGPGPDDCTSCKHGFFldGGKCVSECPP 42
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
780-928 7.39e-05

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 45.75  E-value: 7.39e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNhVKITDFGLARLLDID 859
Cdd:cd14163     76 IYLVMELAEDGDVFDCVL-HGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFT-LKLTDFGFAKQLPKG 153
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  860 ETEYHAD--GGKVPIKWMALESILRRrfTHQSDVWSYGVTVWeLMTFGAKPYDGIparEIPDLL---EKGERLP 928
Cdd:cd14163    154 GRELSQTfcGSTAYAAPEVLQGVPHD--SRKGDIWSMGVVLY-VMLCAQLPFDDT---DIPKMLcqqQKGVSLP 221
STKc_IKK_alpha cd14039
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
798-909 7.87e-05

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270941 [Multi-domain]  Cd Length: 289  Bit Score: 46.06  E-value: 7.87e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  798 ENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN----HvKITDFGLARLLDIDETEYHADGgkvPIK 873
Cdd:cd14039     91 ENCCGLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEINgkivH-KIIDLGYAKDLDQGSLCTSFVG---TLQ 166
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1844139549  874 WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14039    167 YLAPELFENKSYTVTVDYWSFGTMVFECIA-GFRPF 201
STKc_NDR_like cd05599
Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs ...
828-909 8.77e-05

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270750 [Multi-domain]  Cd Length: 324  Bit Score: 46.07  E-value: 8.77e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  828 VHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSDVWSYGVTVWElMTFGAK 907
Cdd:cd05599    123 IHRDIKPDNLLLDARGHIKLSDFGLCTGLKKSHLAYSTVG--TP-DYIAPEVFLQKGYGKECDWWSLGVIMYE-MLIGYP 198

                   ..
gi 1844139549  908 PY 909
Cdd:cd05599    199 PF 200
STKc_PCTAIRE_like cd07844
Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
814-903 9.17e-05

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270835 [Multi-domain]  Cd Length: 286  Bit Score: 45.83  E-value: 9.17e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggkVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07844    106 QLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLARAKSVPSKTYSNE---VVTLWYRPPDVLlgSTEYSTSLDM 182
                           90
                   ....*....|..
gi 1844139549  892 WSYGVTVWELMT 903
Cdd:cd07844    183 WGVGCIFYEMAT 194
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
773-901 9.83e-05

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 45.80  E-value: 9.83e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  773 GICLTSTVQLVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYL-EDV---------RLVHRDLAARNVLVKSP 842
Cdd:cd14141     61 GTNLDVDLWLITAFHEKGSLTDYLKANV--VSWNELCHIAQTMARGLAYLhEDIpglkdghkpAIAHRDIKSKNVLLKNN 138
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  843 NHVKITDFGLARLLDIDETEYHADGGKVPIKWMALESI-----LRRRFTHQSDVWSYGVTVWEL 901
Cdd:cd14141    139 LTACIADFGLALKFEAGKSAGDTHGQVGTRRYMAPEVLegainFQRDAFLRIDMYAMGLVLWEL 202
STKc_PKN cd05589
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer ...
736-919 1.18e-04

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270741 [Multi-domain]  Cd Length: 326  Bit Score: 45.75  E-value: 1.18e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLR--------ENTSPKANKEILDeayVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVREN-----RG 801
Cdd:cd05589     27 FAIKALKkgdiiardEVESLMCEKRIFE---TVNSARHPFLVNLFACFQTPEhVCFVMEYAAGGDLMMHIHEDvfsepRA 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  802 RLGSQdllnwCMQIakGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidETEYHAD------GgkVPiKWM 875
Cdd:cd05589    104 VFYAA-----CVVL--GLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCK-----EGMGFGDrtstfcG--TP-EFL 168
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  876 ALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDGIPAREIPD 919
Cdd:cd05589    169 APEVLTDTSYTRAVDWWGLGVLIYE-MLVGESPFPGDDEEEVFD 211
STKc_PhKG1 cd14182
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs ...
782-909 1.41e-04

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271084 [Multi-domain]  Cd Length: 276  Bit Score: 45.29  E-value: 1.41e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDET 861
Cdd:cd14182     87 LVFDLMKKGELFDYLTE-KVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMNIKLTDFGFS--CQLDPG 163
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  862 EYHADGGKVPiKWMALESIL------RRRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd14182    164 EKLREVCGTP-GYLAPEIIEcsmddnHPGYGKEVDMWSTGVIMYTLLA-GSPPF 215
STKc_SPEG_rpt1 cd14108
Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle ...
814-911 1.50e-04

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271010 [Multi-domain]  Cd Length: 255  Bit Score: 44.89  E-value: 1.50e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV--KSPNHVKITDFGLARLLDIDETEYHADGgkVPiKWMALESILRRRFTHQSDV 891
Cdd:cd14108    105 QLLEGIEYLHQNDVLHLDLKPENLLMadQKTDQVRICDFGNAQELTPNEPQYCKYG--TP-EFVAPEIVNQSPVSKVTDI 181
                           90       100
                   ....*....|....*....|
gi 1844139549  892 WSYGVTVWELMTfGAKPYDG 911
Cdd:cd14108    182 WPVGVIAYLCLT-GISPFVG 200
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
723-910 1.54e-04

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 44.96  E-value: 1.54e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  723 GIWIPDGenvkIPVAIK-VLRENTS-----PKANKEILdEAYVMAGVGSPY--VSRLLGICL--TSTVQLVTQLMPYGCL 792
Cdd:cd14100     19 GIRVADG----APVAIKhVEKDRVSewgelPNGTRVPM-EIVLLKKVGSGFrgVIRLLDWFErpDSFVLVLERPEPVQDL 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  793 LDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVK-SPNHVKITDFGLARLL-DIDETEYhaDGGKV 870
Cdd:cd14100     94 FDFITE-RGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDlNTGELKLIDFGSGALLkDTVYTDF--DGTRV 170
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  871 --PIKWMALEsilrRRFTHQSDVWSYGVTVWElMTFGAKPYD 910
Cdd:cd14100    171 ysPPEWIRFH----RYHGRSAAVWSLGILLYD-MVCGDIPFE 207
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
728-851 1.56e-04

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 42.81  E-value: 1.56e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  728 DGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVS--RLLGICLTSTVQ-LVTQLMPYGCLLDHVREnrGRLG 804
Cdd:cd13968     13 EGECTTIGVAVKIGDDVNNEEG-EDLESEMDILRRLKGLELNipKVLVTEDVDGPNiLLMELVKGGTLIAYTQE--EELD 89
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  805 SQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFG 851
Cdd:cd13968     90 EKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
STKc_PKB cd05571
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer ...
814-902 1.57e-04

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.


Pssm-ID: 270723 [Multi-domain]  Cd Length: 322  Bit Score: 45.42  E-value: 1.57e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARlldidetEYHADGGKV------PiKWMALESILRRRFTH 887
Cdd:cd05571    103 EIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGLCK-------EEISYGATTktfcgtP-EYLAPEVLEDNDYGR 174
                           90
                   ....*....|....*
gi 1844139549  888 QSDVWSYGVTVWELM 902
Cdd:cd05571    175 AVDWWGLGVVMYEMM 189
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
814-923 1.62e-04

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 44.68  E-value: 1.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLldIDETEYHADGGKvpIKWMALESILRRRFTHQS-DVW 892
Cdd:cd14004    117 QVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAAY--IKSGPFDTFVGT--IDYAAPEVLRGNPYGGKEqDIW 192
                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1844139549  893 SYGVTVWELMtFGAKPYDGI-----PAREIPDLLEK 923
Cdd:cd14004    193 ALGVLLYTLV-FKENPFYNIeeileADLRIPYAVSE 227
STKc_MAPKAPK5 cd14171
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
737-918 1.94e-04

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271073 [Multi-domain]  Cd Length: 289  Bit Score: 44.76  E-value: 1.94e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLREntSPKANKEILdeAYVMAGvGSPYVSRLLGICLTSTVQ-----------LVTQLMPYGCLLDHVRENRGrLGS 805
Cdd:cd14171     35 ALKILLD--RPKARTEVR--LHMMCS-GHPNIVQIYDVYANSVQFpgessprarllIVMELMEGGELFDRISQHRH-FTE 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  806 QDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDIDE-----TEYHadggkvpIKWMAL 877
Cdd:cd14171    109 KQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLKDNSEdapIKLCDFGFAKVDQGDLmtpqfTPYY-------VAPQVL 181
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139549  878 ESILRRR--------------FTHQSDVWSYGVTVWeLMTFGAKP-YDGIPAREIP 918
Cdd:cd14171    182 EAQRRHRkersgiptsptpytYDKSCDMWSLGVIIY-IMLCGYPPfYSEHPSRTIT 236
STKc_MASTL cd05610
Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like ...
737-855 1.96e-04

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270761 [Multi-domain]  Cd Length: 349  Bit Score: 45.26  E-value: 1.96e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTSPKAN--KEILDEAYVMAGVGSPYVSRLL-GICLTSTVQLVTQLMPYGCL--LDHVRenrGRLGSQDLLNW 811
Cdd:cd05610     33 AVKVVKKADMINKNmvHQVQAERDALALSKSPFIVHLYySLQSANNVYLVMEYLIGGDVksLLHIY---GYFDEEMAVKY 109
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1844139549  812 CMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARL 855
Cdd:cd05610    110 ISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKV 153
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
782-911 2.03e-04

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 44.63  E-value: 2.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDI 858
Cdd:cd14173     77 LVFEKMRGGSILSHIHRRR-HFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILCEHPNQvspVKICDFDLGSGIKL 155
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  859 deteyhaDGGKVPI------------KWMALE---------SILRRRfthqSDVWSYGVTVWeLMTFGAKPYDG 911
Cdd:cd14173    156 -------NSDCSPIstpelltpcgsaEYMAPEvveafneeaSIYDKR----CDLWSLGVILY-IMLSGYPPFVG 217
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
799-902 2.11e-04

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270746 [Multi-domain]  Cd Length: 356  Bit Score: 45.02  E-value: 2.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  799 NRGRLGSQDLLN-WCMQIAKGMSYLEDVR-LVHRDLAARNVLVKSPNHVKITDFGLARlldidetEYHADGGKVPI---- 872
Cdd:cd05594    117 SRERVFSEDRARfYGAEIVSALDYLHSEKnVVYRDLKLENLMLDKDGHIKITDFGLCK-------EGIKDGATMKTfcgt 189
                           90       100       110
                   ....*....|....*....|....*....|.
gi 1844139549  873 -KWMALESILRRRFTHQSDVWSYGVTVWELM 902
Cdd:cd05594    190 pEYLAPEVLEDNDYGRAVDWWGLGVVMYEMM 220
STKc_DCKL3 cd14185
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called ...
737-931 2.32e-04

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271087 [Multi-domain]  Cd Length: 258  Bit Score: 44.55  E-value: 2.32e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLrENTSPKANKEILD-EAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQ 814
Cdd:cd14185     29 AMKII-DKSKLKGKEDMIEsEILIIKSLSHPNIVKLFEVYETEKeIYLILEYVRGGDLFDAIIESV-KFTEHDAALMIID 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  815 IAKGMSYLEDVRLVHRDLAARNVLVK----SPNHVKITDFGLARlldideteyHADGgkvPI-------KWMALESILRR 883
Cdd:cd14185    107 LCEALVYIHSKHIVHRDLKPENLLVQhnpdKSTTLKLADFGLAK---------YVTG---PIftvcgtpTYVAPEILSEK 174
                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  884 RFTHQSDVWSYGVTVWELMTfGAKPYDGiPAR---EIPDLLEKGERLPQPP 931
Cdd:cd14185    175 GYGLEVDMWAAGVILYILLC-GFPPFRS-PERdqeELFQIIQLGHYEFLPP 223
STKc_CDKL1_4 cd07847
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; ...
792-903 2.52e-04

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270837 [Multi-domain]  Cd Length: 286  Bit Score: 44.28  E-value: 2.52e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLL---DIDETEYhadgg 868
Cdd:cd07847     86 VLNELEKNPRGVPEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILtgpGDDYTDY----- 160
                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1844139549  869 kVPIKWMALESIL--RRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd07847    161 -VATRWYRAPELLvgDTQYGPPVDVWAIGCVFAELLT 196
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
737-953 2.53e-04

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 44.33  E-value: 2.53e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  737 AIKVLRENTS-PKANKEILDEAYVMAGV---GSPYVSRLLGIC-LTSTVQLVTQLMPYGCLlDHVRENRGRLGSQDLLN- 810
Cdd:cd14052     30 AVKKLKPNYAgAKDRLRRLEEVSILRELtldGHDNIVQLIDSWeYHGHLYIQTELCENGSL-DVFLSELGLLGRLDEFRv 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  811 WCM--QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETeYHADGGKVpikWMALESILRRRFTHQ 888
Cdd:cd14052    109 WKIlvELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVWPLIRG-IEREGDRE---YIAPEILSEHMYDKP 184
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  889 SDVWSYGVTVWELMTFGAKPYDGIP-----------AREIPDLLEKGERLPQPPICTIDVYMI--------MVKcWMI-- 947
Cdd:cd14052    185 ADIFSLGLILLEAAANVVLPDNGDAwqklrsgdlsdAPRLSSTDLHSASSPSSNPPPDPPNMPilsgsldrVVR-WMLsp 263

                   ....*.
gi 1844139549  948 DSECRP 953
Cdd:cd14052    264 EPDRRP 269
PKc_CLK cd14134
Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity ...
782-903 2.58e-04

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271036 [Multi-domain]  Cd Length: 332  Bit Score: 44.86  E-value: 2.58e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLmpYG-CLLDHVRENR-GRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVL------VKSPN---------- 843
Cdd:cd14134     91 IVFEL--LGpSLYDFLKKNNyGPFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILlvdsdyVKVYNpkkkrqirvp 168
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  844 ---HVKITDFGLArlldIDETEYHADggkvpI----KWMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14134    169 kstDIKLIDFGSA----TFDDEYHSS-----IvstrHYRAPEVILGLGWSYPCDVWSIGCILVELYT 226
STKc_CDK5 cd07839
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs ...
814-923 3.29e-04

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143344 [Multi-domain]  Cd Length: 284  Bit Score: 43.96  E-value: 3.29e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADggkVPIKWMALESIL--RRRFTHQSDV 891
Cdd:cd07839    107 QLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAFGIPVRCYSAE---VVTLWYRPPDVLfgAKLYSTSIDM 183
                           90       100       110
                   ....*....|....*....|....*....|..
gi 1844139549  892 WSYGVTVWElMTFGAKPYdgIPAREIPDLLEK 923
Cdd:cd07839    184 WSAGCIFAE-LANAGRPL--FPGNDVDDQLKR 212
PKc_DYRK_like cd14133
Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like ...
814-903 4.44e-04

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271035 [Multi-domain]  Cd Length: 262  Bit Score: 43.41  E-value: 4.44e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPN--HVKITDFGLARLLDIDETEYhadggkvpIK---WMALESILRRRFTHQ 888
Cdd:cd14133    110 QILEALVFLHSLGLIHCDLKPENILLASYSrcQIKIIDFGSSCFLTQRLYSY--------IQsryYRAPEVILGLPYDEK 181
                           90
                   ....*....|....*
gi 1844139549  889 SDVWSYGVTVWELMT 903
Cdd:cd14133    182 IDMWSLGCILAELYT 196
STKc_Mnk1 cd14174
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
782-911 5.12e-04

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271076 [Multi-domain]  Cd Length: 289  Bit Score: 43.48  E-value: 5.12e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVrENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH---VKITDFGLARLLDI 858
Cdd:cd14174     77 LVFEKLRGGSILAHI-QKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILCESPDKvspVKICDFDLGSGVKL 155
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139549  859 DET-------EYHADGGKVpiKWMALESIlrRRFTHQS-------DVWSYGVTVWeLMTFGAKPYDG 911
Cdd:cd14174    156 NSActpittpELTTPCGSA--EYMAPEVV--EVFTDEAtfydkrcDLWSLGVILY-IMLSGYPPFVG 217
STKc_HIPK3 cd14229
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; ...
814-912 5.90e-04

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271131 [Multi-domain]  Cd Length: 330  Bit Score: 43.48  E-value: 5.90e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVL----VKSPNHVKITDFGLARLLD--IDETEYHADGGKVPikwmalESILRRRFTH 887
Cdd:cd14229    110 QVATALKKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGSASHVSktVCSTYLQSRYYRAP------EIILGLPFCE 183
                           90       100       110
                   ....*....|....*....|....*....|
gi 1844139549  888 QSDVWSYGVTVWEL-----MTFGAKPYDGI 912
Cdd:cd14229    184 AIDMWSLGCVIAELflgwpLYPGALEYDQI 213
STKc_GRK2 cd14223
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs ...
780-909 7.11e-04

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271125 [Multi-domain]  Cd Length: 321  Bit Score: 43.11  E-value: 7.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  780 VQLVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlLDID 859
Cdd:cd14223     78 LSFILDLMNGGDLHYHLSQH-GVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLA--CDFS 154
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  860 ETEYHADGGKVpiKWMALEsILRRRFTHQS--DVWSYGVTVWELMTfGAKPY 909
Cdd:cd14223    155 KKKPHASVGTH--GYMAPE-VLQKGVAYDSsaDWFSLGCMLFKLLR-GHSPF 202
STKc_CDC2L6 cd07867
Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the ...
814-903 8.42e-04

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270850 [Multi-domain]  Cd Length: 318  Bit Score: 43.13  E-value: 8.42e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV--KSPN--HVKITDFGLARLLDiDETEYHADGGKVPIK-WMALESIL--RRRFT 886
Cdd:cd07867    117 QILDGIHYLHANWVLHRDLKPANILVmgEGPErgRVKIADMGFARLFN-SPLKPLADLDPVVVTfWYRAPELLlgARHYT 195
                           90
                   ....*....|....*..
gi 1844139549  887 HQSDVWSYGVTVWELMT 903
Cdd:cd07867    196 KAIDIWAIGCIFAELLT 212
STKc_CDK8 cd07868
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs ...
814-903 8.95e-04

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270851 [Multi-domain]  Cd Length: 333  Bit Score: 43.12  E-value: 8.95e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLV--KSPN--HVKITDFGLARLLDiDETEYHADGGKVPIK-WMALESIL--RRRFT 886
Cdd:cd07868    132 QILDGIHYLHANWVLHRDLKPANILVmgEGPErgRVKIADMGFARLFN-SPLKPLADLDPVVVTfWYRAPELLlgARHYT 210
                           90
                   ....*....|....*..
gi 1844139549  887 HQSDVWSYGVTVWELMT 903
Cdd:cd07868    211 KAIDIWAIGCIFAELLT 227
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
782-925 1.02e-03

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 42.51  E-value: 1.02e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRenrgRLGSQDLLNWCMQI------AKGMSYLEDVR--LVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14159     69 LIYVYLPNGSLEDRLH----CQVSCPCLSWSQRLhvllgtARAIQYLHSDSpsLIHGDVKSSNILLDAALNPKLGDFGLA 144
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  854 RLldideTEYHADGGKV-----------PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY--DG-IPAREIPD 919
Cdd:cd14159    145 RF-----SRRPKQPGMSstlartqtvrgTLAYLPEEYVKTGTLSVEIDVYSFGVVLLELLT-GRRAMevDScSPTKYLKD 218

                   ....*.
gi 1844139549  920 LLEKGE 925
Cdd:cd14159    219 LVKEEE 224
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
736-854 1.22e-03

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 42.24  E-value: 1.22e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENtspkANKEILD-EAYVMAGV-GSPYVSRLLGICLTSTVQ-LVTQLmpYGCLLDHVREN--RGRLGSQDLLN 810
Cdd:cd14017     28 VAMKVESKS----QPKQVLKmEVAVLKKLqGKPHFCRLIGCGRTERYNyIVMTL--LGPNLAELRRSqpRGKFSVSTTLR 101
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139549  811 WCMQIAKGMSYLEDVRLVHRDLAARNVL--VKSPNH--VKITDFGLAR 854
Cdd:cd14017    102 LGIQILKAIEDIHEVGFLHRDVKPSNFAigRGPSDErtVYILDFGLAR 149
STKc_PIM3 cd14102
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
792-910 1.26e-03

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271004 [Multi-domain]  Cd Length: 253  Bit Score: 42.25  E-value: 1.26e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN-HVKITDFGLARLL-DIDETEYhaDGGK 869
Cdd:cd14102     92 LFDFITE-KGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLVDLRTgELKLIDFGSGALLkDTVYTDF--DGTR 168
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1844139549  870 V--PIKWMALEsilrRRFTHQSDVWSYGVTVWElMTFGAKPYD 910
Cdd:cd14102    169 VysPPEWIRYH----RYHGRSATVWSLGVLLYD-MVCGDIPFE 206
PHA02988 PHA02988
hypothetical protein; Provisional
829-963 1.29e-03

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 42.42  E-value: 1.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  829 HRDLAARNVLVKSPNHVKITDFGLARLLDIDETEyhadggkvPIKWMALES--ILRRRF---THQSDVWSYGVTVWELMT 903
Cdd:PHA02988   146 YKNLTSVSFLVTENYKLKIICHGLEKILSSPPFK--------NVNFMVYFSykMLNDIFseyTIKDDIYSLGVVLWEIFT 217
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  904 fGAKPYDGIPAREIPDLL-EKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 963
Cdd:PHA02988   218 -GKIPFENLTTKEIYDLIiNKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEILYNLS 277
pk1 PHA03390
serine/threonine-protein kinase 1; Provisional
786-932 1.36e-03

serine/threonine-protein kinase 1; Provisional


Pssm-ID: 223069 [Multi-domain]  Cd Length: 267  Bit Score: 42.15  E-value: 1.36e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  786 LMPY---GCLLDHVReNRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVL-VKSPNHVKITDFGLARlldIDET 861
Cdd:PHA03390    87 IMDYikdGDLFDLLK-KEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLyDRAKDRIYLCDYGLCK---IIGT 162
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139549  862 EYHADGGKVpikWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREI-PDLLEKGERLPQPPI 932
Cdd:PHA03390   163 PSCYDGTLD---YFSPEKIKGHNYDVSFDWWAVGVLTYELLT-GKHPFKEDEDEELdLESLLKRQQKKLPFI 230
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
786-853 1.39e-03

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 42.27  E-value: 1.39e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139549  786 LMPY---GCLLDHVREN-RGRLGSQDLLNWCMQIAKGMSYLE--DVRLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14037     84 LMEYckgGGVIDLMNQRlQTGLTESEILKIFCDVCEAVAAMHylKPPLIHRDLKVENVLISDSGNYKLCDFGSA 157
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
782-901 1.39e-03

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 42.34  E-value: 1.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAKGMSYLE--------DVRLVHRDLAARNVLVKSPNHVKITDFGLA 853
Cdd:cd14220     70 LITDYHENGSLYDFLKCTT--LDTRALLKLAYSAACGLCHLHteiygtqgKPAIAHRDLKSKNILIKKNGTCCIADLGLA 147
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  854 RLLDIDETEYhadggKVPI-------KWMAL----ESILRRRFTH--QSDVWSYGVTVWEL 901
Cdd:cd14220    148 VKFNSDTNEV-----DVPLntrvgtkRYMAPevldESLNKNHFQAyiMADIYSFGLIIWEM 203
STKc_CRIK cd05601
Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze ...
828-911 1.52e-03

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270752 [Multi-domain]  Cd Length: 328  Bit Score: 42.30  E-value: 1.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  828 VHRDLAARNVLVKSPNHVKITDFGLARLLDIDET----------EYHAdggkvPIKWMALESILRRRFTHQSDVWSYGVT 897
Cdd:cd05601    124 VHRDIKPENILIDRTGHIKLADFGSAAKLSSDKTvtskmpvgtpDYIA-----PEVLTSMNGGSKGTYGVECDWWSLGIV 198
                           90
                   ....*....|....
gi 1844139549  898 VWElMTFGAKPYDG 911
Cdd:cd05601    199 AYE-MLYGKTPFTE 211
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
814-854 1.63e-03

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 41.97  E-value: 1.63e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|.
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLAR 854
Cdd:cd07865    127 MLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLAR 167
STKc_nPKC_eta cd05590
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the ...
766-922 1.66e-03

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270742 [Multi-domain]  Cd Length: 323  Bit Score: 42.20  E-value: 1.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  766 PYVSRLLgICLTSTVQL--VTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPN 843
Cdd:cd05590     56 PFLTQLY-CCFQTPDRLffVMEFVNGGDLMFHIQKSR-RFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEG 133
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139549  844 HVKITDFGLARlLDIDETEYHADGGKVPiKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDgipAREIPDLLE 922
Cdd:cd05590    134 HCKLADFGMCK-EGIFNGKTTSTFCGTP-DYIAPEILQEMLYGPSVDWWAMGVLLYEMLC-GHAPFE---AENEDDLFE 206
CooF_like cd10563
CooF, iron-sulfur subunit of carbon monoxide dehydrogenase; This family includes CooF, the ...
544-643 1.88e-03

CooF, iron-sulfur subunit of carbon monoxide dehydrogenase; This family includes CooF, the iron-sulfur subunit of carbon monoxide dehydrogenase (CODH), found in anaerobic bacteria and archaea. Carbon monoxide dehydrogenase is a key enzyme for carbon monoxide (CO) metabolism, where CooF is the proposed mediator of electron transfer between CODH and the CO-induced hydrogenase, catalyzing the reaction that uses CO as a single carbon and energy source, and producing only H2 and CO2. The ion-sulfur subunit contains four Fe4/S4 and/or Fe3/S4 clusters which transfer the electrons in the protein complex during reaction.


Pssm-ID: 319885 [Multi-domain]  Cd Length: 140  Bit Score: 39.93  E-value: 1.88e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  544 CRVLQGLPREY-VNARHCLpcHPEC-----------QPQNGSVTCfgpEADQCVACAhykdppFCVARCPSGV-KPDLSY 610
Cdd:cd10563     43 IRVEESGGRSFpLQCRHCD--EPPCvkacmsgamhkDPETGIVIH---DEEKCVGCW------MCVMVCPYGAiRPDKER 111
                           90       100       110
                   ....*....|....*....|....*....|...
gi 1844139549  611 MPIWKfpdeegaCQPCPINCTHSCVdlddKGCP 643
Cdd:cd10563    112 KVALK-------CDLCPDRETPACV----EACP 133
STKc_Titin cd14104
Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the ...
792-911 1.94e-03

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271006 [Multi-domain]  Cd Length: 277  Bit Score: 41.77  E-value: 1.94e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  792 LLDHVRENRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVL--VKSPNHVKITDFGLARLLdideteyhADGGK 869
Cdd:cd14104     83 IFERITTARFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIycTRRGSYIKIIEFGQSRQL--------KPGDK 154
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139549  870 VPIKWMALESILRRRFTHQS-----DVWSYGVTVWELMTfGAKPYDG 911
Cdd:cd14104    155 FRLQYTSAEFYAPEVHQHESvstatDMWSLGCLVYVLLS-GINPFEA 200
STKc_DMPK_like cd05597
Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; ...
822-909 3.45e-03

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270748 [Multi-domain]  Cd Length: 331  Bit Score: 41.18  E-value: 3.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  822 LEDVRLVHRDLAARNVLVKSPNHVKITDFGLARLLDIDETEYHADGGKVPiKWMALEsILRR------RFTHQSDVWSYG 895
Cdd:cd05597    118 IHQLGYVHRDIKPDNVLLDRNGHIRLADFGSCLKLREDGTVQSSVAVGTP-DYISPE-ILQAmedgkgRYGPECDWWSLG 195
                           90
                   ....*....|....
gi 1844139549  896 VTVWElMTFGAKPY 909
Cdd:cd05597    196 VCMYE-MLYGETPF 208
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
755-909 3.74e-03

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 41.14  E-value: 3.74e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  755 DEAYVMAGVGSPYVSRLLgiCL---TSTVQLVTQLMPYGCLLD-----HVRENRGRLgsqdllnWCMQIAKGMSYLEDVR 826
Cdd:cd05621    101 EERDIMAFANSPWVVQLF--CAfqdDKYLYMVMEYMPGGDLVNlmsnyDVPEKWAKF-------YTAEVVLALDAIHSMG 171
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  827 LVHRDLAARNVLVKSPNHVKITDFGLArlLDIDETEY-HADGGKVPIKWMALEsILRRR-----FTHQSDVWSYGVTVWE 900
Cdd:cd05621    172 LIHRDVKPDNMLLDKYGHLKLADFGTC--MKMDETGMvHCDTAVGTPDYISPE-VLKSQggdgyYGRECDWWSVGVFLFE 248

                   ....*....
gi 1844139549  901 lMTFGAKPY 909
Cdd:cd05621    249 -MLVGDTPF 256
STKc_PIM2 cd14101
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
736-959 3.95e-03

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271003 [Multi-domain]  Cd Length: 257  Bit Score: 40.60  E-value: 3.95e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  736 VAIKVLRENT----SPKAN-----KEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGC--LLDHVREnRGRLG 804
Cdd:cd14101     28 VAIKQISRNRvqqwSKLPGvnpvpNEVALLQSVGGGPGHRGVIRLLDWFEIPEGFLLVLERPQHCqdLFDYITE-RGALD 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  805 SQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKS-PNHVKITDFGLARLLDiDETEYHADGGKV--PIKWmalesIL 881
Cdd:cd14101    107 ESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILVDLrTGDIKLIDFGSGATLK-DSMYTDFDGTRVysPPEW-----IL 180
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  882 RRRFtHQ--SDVWSYGVTVWElMTFGakpydGIPAREIPDLLEKGERLPQPpiCTIDVYMIMVKCWMIDSECRPRFRELV 959
Cdd:cd14101    181 YHQY-HAlpATVWSLGILLYD-MVCG-----DIPFERDTDILKAKPSFNKR--VSNDCRSLIRSCLAYNPSDRPSLEQIL 251
STKc_Bub1_BubR1 cd13981
Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 ...
782-905 4.29e-03

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270883 [Multi-domain]  Cd Length: 298  Bit Score: 40.80  E-value: 4.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGRLGSQD----LLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVK---------------SP 842
Cdd:cd13981     78 LVMDYSSQGTLLDVVNKMKNKTGGGMdeplAMFFTIELLKVVEALHEVGIIHGDIKPDNFLLRleicadwpgegengwLS 157
                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  843 NHVKITDFGLArlldIDETEYH------ADGGkvPIKWMALESILRRRFTHQSDVwsYGV-TVWELMTFG 905
Cdd:cd13981    158 KGLKLIDFGRS----IDMSLFPknqsfkADWH--TDSFDCIEMREGRPWTYQIDY--FGIaATIHVMLFG 219
STKc_Aurora-B_like cd14117
Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs ...
733-910 4.71e-03

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271019 [Multi-domain]  Cd Length: 270  Bit Score: 40.23  E-value: 4.71e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  733 KIPVAIKVLRENTSPKANKE--ILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCLLDHVRENrGRLGSQDLL 809
Cdd:cd14117     31 KFIVALKVLFKSQIEKEGVEhqLRREIEIQSHLRHPNILRLYNYFHDRKrIYLILEYAPRGELYKELQKH-GRFDEQRTA 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  810 NWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlldideteYHADGGKV-----PIKWMALESILRRR 884
Cdd:cd14117    110 TFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWS---------VHAPSLRRrtmcgTLDYLPPEMIEGRT 180
                          170       180
                   ....*....|....*....|....*.
gi 1844139549  885 FTHQSDVWSYGVTVWELMTfGAKPYD 910
Cdd:cd14117    181 HDEKVDLWCIGVLCYELLV-GMPPFE 205
STKc_GRK3 cd05633
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs ...
782-909 4.79e-03

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270781 [Multi-domain]  Cd Length: 346  Bit Score: 40.82  E-value: 4.79e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNHVKITDFGLArlLDIDET 861
Cdd:cd05633     85 FILDLMNGGDLHYHLSQH-GVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLA--CDFSKK 161
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1844139549  862 EYHADGGKVpiKWMALESILR-RRFTHQSDVWSYGVTVWELMTfGAKPY 909
Cdd:cd05633    162 KPHASVGTH--GYMAPEVLQKgTAYDSSADWFSLGCMLFKLLR-GHSPF 207
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
782-903 5.07e-03

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 40.25  E-value: 5.07e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  782 LVTQLMPYGCLLDHVRENRGR--LGSQDLLNWCMQIAKGMSYLEDVR---LVHRDLAARNVLVKSPNHVKITDFGLAR-- 854
Cdd:cd14160     69 LVYPYMQNGTLFDRLQCHGVTkpLSWHERINILIGIAKAIHYLHNSQpctVICGNISSANILLDDQMQPKLTDFALAHfr 148
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139549  855 --LLDIDETEYHADGGKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMT 903
Cdd:cd14160    149 phLEDQSCTINMTTALHKHLWYMPEEYIRQGKLSVKTDVYSFGIVIMEVLT 199
STKc_PIM cd14005
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
788-903 5.98e-03

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270907 [Multi-domain]  Cd Length: 255  Bit Score: 39.91  E-value: 5.98e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  788 PYGC--LLDHVREnRGRLGSQDLLNWCMQIAKGMSYLEDVRLVHRDLAARNVLVKSPNH-VKITDFGLARLL-DIDETEY 863
Cdd:cd14005     88 PEPCqdLFDFITE-RGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLINLRTGeVKLIDFGCGALLkDSVYTDF 166
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1844139549  864 haDGGKVpikWMALESILRRRFtH--QSDVWSYGVTVWELMT 903
Cdd:cd14005    167 --DGTRV---YSPPEWIRHGRY-HgrPATVWSLGILLYDMLC 202
STKc_HIPK1 cd14228
Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; ...
814-912 8.06e-03

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271130 [Multi-domain]  Cd Length: 355  Bit Score: 40.07  E-value: 8.06e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549  814 QIAKGMSYLEDVRLVHRDLAARNVL----VKSPNHVKITDFGLARLLD--IDETEYHADGGKVPikwmalESILRRRFTH 887
Cdd:cd14228    125 QVATALMKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGSASHVSkaVCSTYLQSRYYRAP------EIILGLPFCE 198
                           90       100       110
                   ....*....|....*....|....*....|
gi 1844139549  888 QSDVWSYGVTVWEL-----MTFGAKPYDGI 912
Cdd:cd14228    199 AIDMWSLGCVIAELflgwpLYPGASEYDQI 228
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
236-271 8.41e-03

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 37.74  E-value: 8.41e-03
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1844139549  236 CHEQCA-AGCTGPKHSDCLACLHFNHSGICELHCPAL 271
Cdd:pfam14843    2 CDPLCSsEGCWGPGPDQCLSCRNFSRGGTCVESCNIL 38
KIND smart00750
kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to ...
812-922 9.83e-03

kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features


Pssm-ID: 214801  Cd Length: 176  Bit Score: 38.54  E-value: 9.83e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139549   812 CMQIAKGMSYLedvrlvHRDLAARNVLVKSPNHVKItdFGLARLLDiDETeyhadgGKVPIKWMALESILRRRFTHQSDV 891
Cdd:smart00750   23 CLQCLGALREL------HRQAKSGNILLTWDGLLKL--DGSVAFKT-PEQ------SRPDPYFMAPEVIQGQSYTEKADI 87
                            90       100       110
                    ....*....|....*....|....*....|.
gi 1844139549   892 WSYGVTVWELMTFGAKPYDgipAREIPDLLE 922
Cdd:smart00750   88 YSLGITLYEALDYELPYNE---ERELSAILE 115
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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