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Conserved domains on  [gi|1958777789|ref|XP_038966422|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [Rattus norvegicus]

Protein Classification

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta( domain architecture ID 10490333)

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 679-1046 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 808.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  679 THHMKVLMKQGEALSKLKALNDFVKASSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 758
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  759 KMKPLWIMYSSEKAGGaGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 838
Cdd:cd05174     80 KMKPLWIMYSSEEAGA-GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  839 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 918
Cdd:cd05174    159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  919 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 998
Cdd:cd05174    239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1958777789  999 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 6.46e-90

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


:

Pssm-ID: 176075  Cd Length: 173  Bit Score: 284.97  E-value: 6.46e-90
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  314 VSLWSLEQPFCIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELMNPAGTVRGNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1958777789  469 AALVIYLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-687 5.51e-82

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


:

Pssm-ID: 214537  Cd Length: 184  Bit Score: 264.12  E-value: 5.51e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   584 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSV 663
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1958777789   664 ALRFGLIMEAYCRGSTHHMKVLMK 687
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.81e-35

PI3-kinase family, p85-binding domain;


:

Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.17  E-value: 1.81e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958777789   34 FPVSRNANLSTIKQVLWHRAQYEPFFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 3.91e-30

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


:

Pssm-ID: 395642  Cd Length: 106  Bit Score: 115.08  E-value: 3.91e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  182 LLHVSNRPLLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVErpEEYALQVNGRHEYLYGSYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVT--DDYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1958777789  262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 679-1046 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 808.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  679 THHMKVLMKQGEALSKLKALNDFVKASSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 758
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  759 KMKPLWIMYSSEKAGGaGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 838
Cdd:cd05174     80 KMKPLWIMYSSEEAGA-GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  839 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 918
Cdd:cd05174    159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  919 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 998
Cdd:cd05174    239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1958777789  999 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 6.46e-90

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 284.97  E-value: 6.46e-90
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  314 VSLWSLEQPFCIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELMNPAGTVRGNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1958777789  469 AALVIYLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-687 5.51e-82

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 264.12  E-value: 5.51e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   584 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSV 663
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1958777789   664 ALRFGLIMEAYCRGSTHHMKVLMK 687
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 780-997 2.71e-80

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 261.46  E-value: 2.71e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   780 IIFKNGDDLRQDMLTLQMIQLMDFLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 844
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   845 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 911
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   912 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 991
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1958777789   992 ELSCSK 997
Cdd:smart00146  235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 777-994 3.55e-76

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.32  E-value: 3.55e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  777 SVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAA 853
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  854 FN-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 908
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  909 GQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAA 988
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*.
gi 1958777789  989 GLPELS 994
Cdd:pfam00454  235 GLPDWS 240
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-678 7.95e-75

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 243.76  E-value: 7.95e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSALE 584
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ---MYQLLKRWPKLKPEQALE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  585 LLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVA 664
Cdd:cd00872     77 LLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVS 156

                          170
                   ....*....|....
gi 1958777789  665 LRFGLIMEAYCRGS 678
Cdd:cd00872    157 QRFGLLLEAYLRGC 170
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 499-687 2.53e-60

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 204.10  E-value: 2.53e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  499 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELP 578
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAE---ALSLLLKWAPID 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  579 VLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEM 658
Cdd:pfam00613   77 PVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEI 156

                          170       180
                   ....*....|....*....|....*....
gi 1958777789  659 HVPSVALRFGLIMEAYCRGSTHHMKVLMK 687
Cdd:pfam00613  157 HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
780-1019 9.62e-36

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 148.01  E-value: 9.62e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  780 IIFKNGDDLRQDMLTLQMIQLMDFLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANI------QLNKS-NM 848
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkRKNISiDQ 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  849 AATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-R 906
Cdd:COG5032   1879 EKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  907 ESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFRGYCERAYTILRRHGLLFLHLFALMR 986
Cdd:COG5032   1959 SSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFRELCETAFRALRKNADSLMNVLELFV 2032

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1958777789  987 AAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 1019
Cdd:COG5032   2033 RDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.81e-35

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.17  E-value: 1.81e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958777789   34 FPVSRNANLSTIKQVLWHRAQYEPFFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 4.60e-31

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 117.45  E-value: 4.60e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   312 SSVSLWSLEQPFCIELIEGRKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 1958777789   391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 3.91e-30

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 115.08  E-value: 3.91e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  182 LLHVSNRPLLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVErpEEYALQVNGRHEYLYGSYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVT--DDYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1958777789  262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 1.54e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 94.36  E-value: 1.54e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISICDLPRMARLCFALYAVvekakkarstkKKSKKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1958777789  418 IAWANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 9.38e-21

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 87.15  E-value: 9.38e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958777789    31 YLNFPVSRNANLSTIKQVLWHRAQYEPFFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 187-281 4.34e-14

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 69.28  E-value: 4.34e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   187 NRPLLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVERPEEYALQVNGRHEYLYGSYPLCHFQYICSCL 266
Cdd:smart00144   15 ANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYIRNCL 93

                            90
                    ....*....|....*
gi 1958777789   267 HSGLTPHLTMVHSSS 281
Cdd:smart00144   94 KNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 679-1046 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 808.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  679 THHMKVLMKQGEALSKLKALNDFVKASSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 758
Cdd:cd05174      1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  759 KMKPLWIMYSSEKAGGaGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 838
Cdd:cd05174     80 KMKPLWIMYSSEEAGA-GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  839 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 918
Cdd:cd05174    159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  919 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 998
Cdd:cd05174    239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1958777789  999 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 1046
Cdd:cd05174    319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 682-1044 0e+00

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 649.31  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  682 MKVLMKQGEALSKLKALNDFVKasSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDSKMK 761
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILK--EKKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELI-IEKCKVMDSKKR 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  762 PLWIMYSSE--KAGGAGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 839
Cdd:cd05165     78 PLWLVFENAdpLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIA 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  840 NIQLNKSNMAaTAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 918
Cdd:cd05165    158 NIQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  919 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSK 997
Cdd:cd05165    237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1958777789  998 DIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd05165    317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 682-1045 0e+00

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 624.29  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  682 MKVLMKQGEALSKLKALNDFVKASSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMK 761
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSEL-NVEKCKYMDSKMK 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  762 PLWIMYSSeKAGGAGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 841
Cdd:cd05173     80 PLWIVYNN-KLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  842 QLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLG 921
Cdd:cd05173    159 QLNSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILG 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  922 NFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQY 1001
Cdd:cd05173    239 NFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQY 318

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 1958777789 1002 LKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 1045
Cdd:cd05173    319 LKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 682-1028 2.00e-148

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 445.48  E-value: 2.00e-148
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  682 MKVLMKQGEALSKLKALNDFVK-ASSQKttkpqtkemmhmcmRQETYMEALSHLQS------PLDPSTlleEVCS--VEQ 752
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIKeEPSEE--------------RKEVLEKLLQKLELpkkftlPLDPRM---EVKGliVEK 63

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  753 CTFMDSKMKPLWIMYSSEKAGGaGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVV 832
Cdd:cd00891     64 CKVMDSKKLPLWLVFKNADPGG-DPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVV 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  833 LHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 911
Cdd:cd00891    143 PNSETTAAIQ--KKYGGFGAAFKDTPISNWLKKHNPTEEeYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHL 220

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  912 FHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 991
Cdd:cd00891    221 FHIDFGHFLGNFKKKFGIKRERAPFVFTPEMAYVM-GGE--DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIP 297

                          330       340       350
                   ....*....|....*....|....*....|....*..
gi 1958777789  992 ELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALR 1028
Cdd:cd00891    298 ELQSIEDIEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 685-1042 1.58e-116

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 362.76  E-value: 1.58e-116
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  685 LMKQGEALSKLKALNDFVKASSQKttkpqtkemmhmcMRQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTF 755
Cdd:cd05166      4 FLKQHVLVQALTSIAEKVKSAKDS-------------ARENALRRELEQLASfllensfrlPLDPALEVTGV-DVRSCSY 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  756 MDSKMKPLWIMYSSEKAGgAGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHS 835
Cdd:cd05166     70 FNSNALPLKLVFRNADPR-AEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEA 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  836 DTIANIQlnkSNMAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHI 914
Cdd:cd05166    149 ETLREIQ---TEHGLTGSFKDRPLADWLQKHNPSElEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHI 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  915 DFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELS 994
Cdd:cd05166    226 DFGKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT 304

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1958777789  995 cSKDIQYLKDSLALGKTEEEALKHFRVKFNEALReSWKTKVNWLAHNV 1042
Cdd:cd05166    305 -QDDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 681-1044 4.06e-107

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 338.57  E-value: 4.06e-107
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  681 HMKVLMKQGEALSKLKALNDFVKASSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKM 760
Cdd:cd05175      4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNL-RLEECRIMSSAK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  761 KPLWIMYSSEKAGGA---GSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDT 837
Cdd:cd05175     83 RPLWLNWENPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHT 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  838 IANIQLnKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 917
Cdd:cd05175    163 IMQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFG 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  918 HFLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSC 995
Cdd:cd05175    242 HFLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQS 321

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1958777789  996 SKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd05175    322 FDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 732-1042 1.15e-104

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 332.21  E-value: 1.15e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  732 SHLQSPLDPStLLEEVCSVEQCTFMDSKMKPLWIMYS--SEKAGGAGSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEG 809
Cdd:cd00894     53 ESFRVPYDPG-LRAGALVIEKCKVMASKKKPLWLEFKcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETES 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  810 LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCV 888
Cdd:cd00894    132 LDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCV 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  889 ATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAY 968
Cdd:cd00894    210 ATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAY 289

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958777789  969 TILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 1042
Cdd:cd00894    290 LALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 314-481 6.46e-90

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 284.97  E-value: 6.46e-90
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  314 VSLWSLEQPFCIELIEGRKVNADER-MKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARLCF 392
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERtMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  393 ALYAVVEKAKKARSTK----KKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELMNPAGTVRGNPNTESA 468
Cdd:cd08693     81 AIYEVSKKAKGKRSRKnqtkKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESA 160

                          170
                   ....*....|...
gi 1958777789  469 AALVIYLPEVAPH 481
Cdd:cd08693    161 TALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 723-1044 3.67e-84

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 276.47  E-value: 3.67e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  723 RQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTFMDSKMKPLWI-MYSSEKAGGagSVGIIFKNGDDLRQDM 792
Cdd:cd05176     29 RQVALQDGMERVQSffqknkcrlPLSPSLVAKEL-NIKACSFFSSNAVPLKVaLVNADPLGE--EINVMFKVGEDLRQDM 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  793 LTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNksnMAATAAFNKDALLNWLKSKNPGEA- 871
Cdd:cd05176    106 LALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVE---YGVTGSFKDKPLAEWLRKYNPSEEe 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  872 LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKT 951
Cdd:cd05176    183 YEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEK 262

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  952 NNSeKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESW 1031
Cdd:cd05176    263 PTI-RFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEATIFF-TRLIESSLGSV 340

                          330
                   ....*....|...
gi 1958777789 1032 KTKVNWLAHNVSK 1044
Cdd:cd05176    341 ATKFNFFIHNLAQ 353
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 504-687 5.51e-82

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 264.12  E-value: 5.51e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSAL 583
Cdd:smart00145    4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQ---ALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   584 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSV 663
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1958777789   664 ALRFGLIMEAYCRGSTHHMKVLMK 687
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 780-997 2.71e-80

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 261.46  E-value: 2.71e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   780 IIFKNGDDLRQDMLTLQMIQLMDFLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 844
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   845 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 911
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   912 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 991
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1958777789   992 ELSCSK 997
Cdd:smart00146  235 DWRSGK 240
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 683-1027 7.23e-79

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 261.70  E-value: 7.23e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  683 KVLMKQGEALSKLKALNDFVKASSQKTTKpQTKEMMHMCMRQETYMEALSH-LQSPLDPSTLLEEVCSvEQCTFMDSKMK 761
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVKNEKGSRDK-KIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIP-EKSTVFKSALM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  762 PLWIMYSSEKAGgagSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 841
Cdd:cd00896     80 PLKLTFKTLDGG---EYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  842 qLNKSNmaataafnkdALLNWLKSKNPGEA-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 916
Cdd:cd00896    157 -LKKYG----------SILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  917 GHFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPE 992
Cdd:cd00896    226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPD 293

                          330       340       350
                   ....*....|....*....|....*....|....*..
gi 1958777789  993 LSCSKD--IQYLKDSLALGKTEEEALKHFRVKFNEAL 1027
Cdd:cd00896    294 IALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 710-1044 2.60e-77

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 257.90  E-value: 2.60e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  710 TKPQTKEMMHMCMRQ-ETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMKPLWIMYSSEKAGGaGSVGIIFKNGDDL 788
Cdd:cd05177     25 SDTRRKEVLKREASRlEDFFQDVVSCCLPLNPALRVKGI-DADACSYFTSNAAPLKISFINANPLA-KNISIIFKTGDDL 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  789 RQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlNKSNMAATaaFNKDALLNWLKSKNP 868
Cdd:cd05177    103 RQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIH-RESGLIGP--LKENTIEKWFHMHNK 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  869 GEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQ 947
Cdd:cd05177    180 LKEdYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRAPFIFTSEMEYFIT 259

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  948 QGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEAL 1027
Cdd:cd05177    260 EGG-KKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKESL 338

                          330
                   ....*....|....*..
gi 1958777789 1028 rESWKTKVNWLAHNVSK 1044
Cdd:cd05177    339 -ECFPVKLNNLIHTLAQ 354
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 777-994 3.55e-76

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.32  E-value: 3.55e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  777 SVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAA 853
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  854 FN-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 908
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  909 GQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAA 988
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*.
gi 1958777789  989 GLPELS 994
Cdd:pfam00454  235 GLPDWS 240
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 505-678 7.95e-75

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 243.76  E-value: 7.95e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELPVLSALE 584
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQ---MYQLLKRWPKLKPEQALE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  585 LLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVA 664
Cdd:cd00872     77 LLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVS 156

                          170
                   ....*....|....
gi 1958777789  665 LRFGLIMEAYCRGS 678
Cdd:cd00872    157 QRFGLLLEAYLRGC 170
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 737-1044 3.76e-74

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 249.15  E-value: 3.76e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  737 PLDPSTLLEEVcSVEQCTFMDSKMKPLWIMYSSEKAGGAgSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTP 816
Cdd:cd00895     53 PLSPSLLVKGI-VPRDCSYFNSNAVPLKLSFQNVDPLGE-NIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVI 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  817 YGCLPTGDRTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGI 895
Cdd:cd00895    131 FRCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTEdEYEKAVENFIYSCAGCCVATYVLGI 207

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  896 GDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHG 975
Cdd:cd00895    208 CDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHT 286

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958777789  976 LLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 1044
Cdd:cd00895    287 HLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 499-687 2.53e-60

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 204.10  E-value: 2.53e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  499 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQlsqMLYLLCSWPELP 578
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAE---ALSLLLKWAPID 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  579 VLSALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEM 658
Cdd:pfam00613   77 PVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEI 156

                          170       180
                   ....*....|....*....|....*....
gi 1958777789  659 HVPSVALRFGLIMEAYCRGSTHHMKVLMK 687
Cdd:pfam00613  157 HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 506-659 7.63e-51

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


Pssm-ID: 238440  Cd Length: 152  Bit Score: 175.87  E-value: 7.63e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  506 EEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVaqlSQMLYLLCSWPELPVLSALEL 585
Cdd:cd00864      2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNV-PKALPKLLKSVNWNDDEEV---SELYQLLKWWAPLSPEDALEL 77

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958777789  586 LDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 659
Cdd:cd00864     78 LSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 781-1034 2.99e-49

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 177.02  E-value: 2.99e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  781 IFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSdtianiqlnKS--NMAATAAFNkda 858
Cdd:cd05167     53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNS---------KSrdQIGRETDNG--- 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  859 LLNWLKSK--NPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFL------GNFKTkfgi 929
Cdd:cd05167    121 LYEYFLSKygDEStPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIfeispgGNLGF---- 195

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  930 nrERVPFILTYDFVHVIqqGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPelsC--SKDIQYLKDSLA 1007
Cdd:cd05167    196 --ESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CfrGQTIKNLRERFA 268

                          250       260
                   ....*....|....*....|....*..
gi 1958777789 1008 LGKTEEEALKHFRVKFNEALrESWKTK 1034
Cdd:cd05167    269 LEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 778-1034 2.81e-47

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 170.90  E-value: 2.81e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  778 VGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAniQLNKSNMAATAAFNkd 857
Cdd:cd00893     28 VSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSID--SLKKKLDSFNKFVS-- 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  858 aLLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERVPFI 937
Cdd:cd00893    104 -LSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPFK 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  938 LTYDFVHVIqqgKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALK 1017
Cdd:cd00893    181 LSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEV 257

                          250
                   ....*....|....*..
gi 1958777789 1018 HFRVKFNEALReSWKTK 1034
Cdd:cd00893    258 YVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 778-1034 1.61e-44

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 163.04  E-value: 1.61e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  778 VGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTGLIEVVlhSDTIANIQLNKSNMAATaafnkd 857
Cdd:cd05168     31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI--PDTVSIDSLKKRFPNFT------ 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  858 ALLNWLKSK---NPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERV 934
Cdd:cd05168    103 SLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  935 PFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG-LPELSCSKD--IQYLKDSLALGKT 1011
Cdd:cd05168    181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                          250       260
                   ....*....|....*....|...
gi 1958777789 1012 EEEALKHFRVKFNEALReSWKTK 1034
Cdd:cd05168    258 EEECAQFVDSLIDKSLN-NWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 750-985 1.05e-42

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 155.18  E-value: 1.05e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  750 VEQCTFMDSKMKPLWImysseKAGGAGSV--GIIFKNGDDLRQDMLTLQMIQLMDFLWKQEGLDLRMTPYGCLPTGDRTG 827
Cdd:cd00142      5 VGILKVIHSKQRPKKI-----TLIGADGKtySFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  828 LIEVVLHSDTIANiqlnksnmaataafnkdaLLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIR 906
Cdd:cd00142     80 LIEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIE 141

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958777789  907 ESGQLFHIDFGHFLGNFKTKFGInrERVPFILTYDFVHVIQQGKTNNsekfeRFRGYCERAYTILRRHGLLFLHLFALM 985
Cdd:cd00142    142 PSGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 314-483 3.18e-40

C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes of PI3Ks. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains members with the first C2 repeat, C2A, and a type-I topology, as well as some with a single C2 repeat.


Pssm-ID: 176026  Cd Length: 156  Bit Score: 145.58  E-value: 3.18e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  314 VSLWSLEQPFCIEL--IEGRKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARLC 391
Cdd:cd08380      1 KSLWDINFNLRIKIhgITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  392 FALYAVvekakkarsTKKKSKKaDCPIAWANLMLFDYKDQLKTGERCLYMWPSVPDekgelMNPAGTVRGNPNTESAAAL 471
Cdd:cd08380     81 LSIYAV---------SEPGSKK-EVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKT-----DPRIACTPCNNSNENSTRL 145

                          170
                   ....*....|..
gi 1958777789  472 VIYLPEVaPHPV 483
Cdd:cd08380    146 LIELPEF-SKPV 156
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
780-1019 9.62e-36

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 148.01  E-value: 9.62e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  780 IIFKNGDDLRQDMLTLQMIQLMDFLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANI------QLNKS-NM 848
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkRKNISiDQ 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  849 AATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-R 906
Cdd:COG5032   1879 EKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  907 ESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERFRGYCERAYTILRRHGLLFLHLFALMR 986
Cdd:COG5032   1959 SSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSFRELCETAFRALRKNADSLMNVLELFV 2032

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1958777789  987 AAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 1019
Cdd:COG5032   2033 RDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.81e-35

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 129.17  E-value: 1.81e-35
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1958777789   34 FPVSRNANLSTIKQVLWHRAQYEPFFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGD 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 315-467 6.35e-34

C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, alpha isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176043  Cd Length: 158  Bit Score: 127.98  E-value: 6.35e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  315 SLWSLEQPFCIELIEGRKVNADERMKLVVQAGLFHGNEMLCKTVSSSEVNvCSEPVWKQRLEFDISICDLPRMARLCFAL 394
Cdd:cd08398      2 SLWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLSI 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958777789  395 YAVvekakkarSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMWPsVPDEKGELMNPAGTVRGNPNTES 467
Cdd:cd08398     81 CSV--------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDT 144
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 312-407 4.60e-31

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 117.45  E-value: 4.60e-31
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   312 SSVSLWSLEQPFCIELIEGRKVNADERM-KLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARL 390
Cdd:smart00142    4 ESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARL 83

                            90
                    ....*....|....*..
gi 1958777789   391 CFALYAVVEKAKKARST 407
Cdd:smart00142   84 CITIYAVKNPSKGSEFG 100
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 182-281 3.91e-30

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 115.08  E-value: 3.91e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  182 LLHVSNRPLLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPLVErpEEYALQVNGRHEYLYGSYPLCHFQY 261
Cdd:pfam00794    9 LPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVT--DDYVLKVCGRDEYLLGDHPLGQFEY 86

                           90       100
                   ....*....|....*....|
gi 1958777789  262 ICSCLHSGLTPHLTMVHSSS 281
Cdd:pfam00794   87 IRNCLKSGREPHLTLVEQSS 106
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 504-659 2.13e-27

Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III phosphorylate phosphoinositol (PtdIns) only. The prototypical PI3K class III, yeast Vps34, is involved in trafficking proteins from Golgi to the vacuole.


Pssm-ID: 238442  Cd Length: 166  Bit Score: 109.34  E-value: 2.13e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  504 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNkheDVAQLSQMLYLLCSWPELPVLSAL 583
Cdd:cd00870      7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNN-KKALTKFLKSVNWS---DEQEVKQALELMPKWAKIDIEDAL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  584 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESY-------LDCELTKFLLGRALANRKIGHFLFWHLRS 656
Cdd:cd00870     83 ELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKV 162


                   ...
gi 1958777789  657 EMH 659
Cdd:cd00870    163 ELE 165
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 505-659 7.42e-26

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 105.23  E-value: 7.42e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  505 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLL-LVTKWnkheDVAQLSQMLYLLCSWPELPVLSAL 583
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNE-PNALPLVLaSAPSW----DWANLMDVYQLLHQWAPLRPLIAL 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1958777789  584 ELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 659
Cdd:cd00869     76 ELLLPKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALD 151
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 756-975 4.04e-23

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 98.88  E-value: 4.04e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  756 MDSKMKP--LWIMYSSEKaggagSVGIIFKNGDDLRQDMLTLQMIQLMDFLWKQEG----LDLRMTPYGCLPTGDRTGLI 829
Cdd:cd05164     11 LASLQKPkkITILGSDGK-----EYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLI 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  830 EVVLHSDTIANIqlnksnmaataaFNKDAllnWLKSKNPGEALDrAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RES 908
Cdd:cd05164     86 EWVDNTTTLKPV------------LKKWF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKT 149

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958777789  909 GQLFHIDFGHFLGNFKTkFGINrERVPFILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRRHG 975
Cdd:cd05164    150 GEVVHIDFGMIFNKGKT-LPVP-EIVPFRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHK 209
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 339-448 1.54e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 94.36  E-value: 1.54e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  339 MKLVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISICDLPRMARLCFALYAVvekakkarstkKKSKKADCP 417
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVP 71

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1958777789  418 IAWANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:pfam00792   72 IGWVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 9.38e-21

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 87.15  E-value: 9.38e-21
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1958777789    31 YLNFPVSRNANLSTIKQVLWHRAQYEPFFHMLSDPEAYVFTCVNQTAEQQELEDEQRRLCDIQPFLPVLRLVAREGDR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 756-975 5.47e-20

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 91.39  E-value: 5.47e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  756 MDSKMKP--LWIMyssekaggaGSVGIIF----KNGDDLRQDMLTLQMIQLMDFLWKQE----GLDLRMTPYGCLPTGDR 825
Cdd:cd05169     11 ITSKQRPrkLTIV---------GSDGKEYkfllKGHEDLRLDERVMQLFGLVNTLLKNDsetsRRNLSIQRYSVIPLSPN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  826 TGLIEVVLHSDTIA----------NIQLN--KSNMAATA-------------AFN-----------KDALlnWLKSKNPG 869
Cdd:cd05169     82 SGLIGWVPGCDTLHslirdyrekrKIPLNieHRLMLQMApdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSE 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  870 EALDRAIeEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFG-------HflgnfKTKFginRERVPFILTYD 941
Cdd:cd05169    160 AWLERRT-NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRM 230

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1958777789  942 FVHVIQQGKTNNSekferFRGYCERAYTILRRHG 975
Cdd:cd05169    231 LVNAMEVSGVEGT-----FRSTCEDVMRVLRENK 259
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 781-947 3.24e-19

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 88.02  E-value: 3.24e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  781 IFKNGDDLRQDMLTLQMIQLMDFLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIqlnksnmaataaFNK 856
Cdd:cd05172     33 LVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI------------LEN 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  857 DALLNWLK--SKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrER 933
Cdd:cd05172    101 DLLRRALLslASSP-EAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQFLPIP-EL 178

                          170
                   ....*....|....
gi 1958777789  934 VPFILTYDFVHVIQ 947
Cdd:cd05172    179 VPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 776-974 1.43e-18

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 87.21  E-value: 1.43e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  776 GSVGI----IFKNGDDLRQDMLTLQMIQLMDFLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSN 847
Cdd:cd05171     24 GSDGKkykqLVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASS 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  848 ---------------------MAATAAFNKDALLN-----------------WLKSKNPGEALDRaIEEFTLSCAGYCVA 889
Cdd:cd05171    104 ksgaharyrpkdwtastcrkkMREKAKASAEERLKvfdeicknfkpvfrhffLEKFPDPSDWFER-RLAYTRSVATSSIV 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  890 TYVLGIGDRHSDNIMI-RESGQLFHIDFG-HFlgnfktKFGIN---RERVPFILTYDFVHVIQQGKTNNSekferFRGYC 964
Cdd:cd05171    183 GYILGLGDRHLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDGMGITGVEGV-----FRRCC 251

                          250
                   ....*....|
gi 1958777789  965 ERAYTILRRH 974
Cdd:cd05171    252 EETLRVLREN 261
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 345-479 6.19e-18

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 82.41  E-value: 6.19e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  345 AGLFHGNEMLCKTVSSSEVNVCSE----PVWKQRLEFDISICDLPRMARLCFALYAVVEKAKKARSTKKKSKKadcPIAW 420
Cdd:cd04012     35 CSLYHGGRLLCSPVTTKPVKITKSffprVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGSNKQRMGPE---ELGW 111

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  421 ANLMLFDYKDQLKTGERCLYMWPSVPDekgelmNPAG-TVRGNPNTESAAALVIYLPEVA 479
Cdd:cd04012    112 VSLPLFDFRGVLRQGSLLLGLWPPSKD------NPLGpAPPPLFEQPDRVILQIDFPSSA 165
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 313-483 1.15e-16

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 78.80  E-value: 1.15e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  313 SVSLWSLEQPFCIEL----IEGRKVNADerMKLVVQAGLFHGNEMLCKTVSSSEvNVCSEPVWKQRLEFDISICDLPRMA 388
Cdd:cd08399      2 TVSLWDCDRKFRVKIlgidIPVLPRNTD--LTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGA 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  389 RLCFALYAV----VEKAKKARSTKKKSKKADCPIAWANLMLFDYKDQLKTGERCLYMW--PSVPDEKGELMNPAGTVRGN 462
Cdd:cd08399     79 LLNLQIYCGkapaLSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTSATN 158

                          170       180
                   ....*....|....*....|.
gi 1958777789  463 PNTESAAALVIYLPEVApHPV 483
Cdd:cd08399    159 PDKENSMSISILLDNYC-HPV 178
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 756-974 1.69e-15

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 77.16  E-value: 1.69e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  756 MDSKMKPlwimyssEKAGGAGSVG----IIFKNGDDLRQDMLTLQMIQLMDFLWKQ----EGLDLRMTPYGCLPTGDRTG 827
Cdd:cd00892     11 MPSLQKP-------KKITLVGSDGkkypFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  828 LIEVVLHSDTIANIqLNKsnmaataaFNKDALLNWLKSK--NPGEALdRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI 905
Cdd:cd00892     84 IIEWVPNTVTLRSI-LST--------LYPPVLHEWFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILF 153

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958777789  906 -RESGQLFHIDFGHFLGNFKTkFGInRERVPFILTYDFVHVIqqGKTnnseKFE-RFRGYCERAYTILRRH 974
Cdd:cd00892    154 dSTTGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAM--GVT----GVEgTFRRTCEVTLRVLREN 216
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 187-281 4.34e-14

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 69.28  E-value: 4.34e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789   187 NRPLLVNVKFEGSEESFTFQVSTKDMPLALMACALRKKATVFRQPlVERPEEYALQVNGRHEYLYGSYPLCHFQYICSCL 266
Cdd:smart00144   15 ANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQV-DPTSEDYILKVCGRDEYLLGDHPLGSFEYIRNCL 93

                            90
                    ....*....|....*
gi 1958777789   267 HSGLTPHLTMVHSSS 281
Cdd:smart00144   94 KNGTEPHLVLMTLSA 108
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 862-982 1.35e-08

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 57.65  E-value: 1.35e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  862 WLKSKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfktkfginR--E 932
Cdd:cd05170    178 WCSSPSS-AEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpE 246

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1958777789  933 RVPFILTYDFVHVIqqGKTNnsekFE-RFRGYCERAYTILRRHGLLFLHLF 982
Cdd:cd05170    247 KVPFRLTQNIEHAL--GPTG----VEgTFRLSCEQVLKILRKGRETLLTLL 291
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 541-658 1.44e-07

Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 52.36  E-value: 1.44e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  541 HFPEALArlLLVTKWNKHEDVAQLSQMLYllcsWPELPVLSALELLDFSFP-DCYVGSFAIKSLRKLTDDELFQYLLQLV 619
Cdd:cd00871     38 KIPEALP--FLVTGKSVDENSPDLKYLLY----WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIV 111

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1958777789  620 QVLKYESylDCELTKFLLGRALANRKIGHFLFWHLRSEM 658
Cdd:cd00871    112 QALRYDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNC 148
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 341-448 2.17e-07

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176042  Cd Length: 159  Bit Score: 51.48  E-value: 2.17e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  341 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISICDLPRMARLCFALYAVVEKAKKarstkkkskkadCPIAW 420
Cdd:cd08397     32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKA------------VPFGG 99

                           90       100
                   ....*....|....*....|....*...
gi 1958777789  421 ANLMLFDYKDQLKTGERCLYMWPSVPDE 448
Cdd:cd08397    100 TTLSLFNKDGTLRRGRQKLRVWPDVEAD 127
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 777-917 6.84e-07

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: 49.75  E-value: 6.84e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958777789  777 SVGIIFKNGDDlRQDMLTLQMIQLMDFLWKQEGLDLrmTPYGCLPTGDRTG----LIEVVlhsdtianiqlnksnmaata 852
Cdd:cd13968     18 TIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELV-------------------- 74

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958777789  853 afnKDALLNWLKSKnpGEALDRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 917
Cdd:cd13968     75 ---KGGTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 878-939 6.02e-04

Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs to the the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. It contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain and has a large molecular weight. Unlike most PIKK proteins, however, it contains an inactive PI3K-like pseudokinase domain, which lacks the conserved residues necessary for ATP binding and catalytic activity. TRRAP also contains many motifs that may be critical for protein-protein interactions. TRRAP is a common component of many histone acetyltransferase (HAT) complexes, and is responsible for the recruitment of these complexes to chromatin during transcription, replication, and DNA repair. TRRAP also exists in non-HAT complexes such as the p400 and MRN complexes, which are implicated in ATP-dependent remodeling and DNA repair, respectively. The TRRAP pseudokinase domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270707  Cd Length: 252  Bit Score: 42.89  E-value: 6.02e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958777789  878 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHFLGNFKTKFGINRERVPFILT 939
Cdd:cd05163    140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPSINSQGPLLDNNEPVPFRLT 201
 
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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