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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 266 PKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFF 345
Cdd:cd14084     1 PKELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIINKRKFTIGSRREINKPRNIETEIEILKKLSHPCIIKIEDFF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462583676 346 DAED-YYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14084    81 DAEDdYYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKY 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 266 PKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFF 345
Cdd:cd14084     1 PKELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIINKRKFTIGSRREINKPRNIETEIEILKKLSHPCIIKIEDFF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462583676 346 DAED-YYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14084    81 DAEDdYYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKY 126

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676  273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAReadpalnVETEIEILKKLNHPCIIKIKNFFDAEDY-Y 351
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKDRER-------ILREIKILKKLKHPNIVRLYDVFEDEDKlY 73

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2462583676  352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:smart00220  74 LVMEYCEGGDLFDLLKKRGRLSEDEARFYLRQILSALEY 112

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 269 LRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISkrkfaigSAREADPALNV--ETEIEILKKLNHPCIIKIKNFFD 346
Cdd:COG0515     5 LLGRYRILRLLGRGGMGVVYLARDLRLGRPVALKVLR-------PELAADPEARErfRREARALARLNHPNIVRVYDVGE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462583676 347 AED-YYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:COG0515    78 EDGrPYLVMEYVEGESLADLLRRRGPLPPAEALRILAQLAEALAA 122

FHA domain; The FHA (Forkhead-associated) domain is a phosphopeptide binding motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 166 YWFGRDKSCEYCFDEPLLkrtdkyrtySKKHFRIFRevgpKNSYIAYIEDH-SGNGTFVNTELVGKgKRRPLNNNSEIAL 244
Cdd:pfam00498   1 VTIGRSPDCDIVLDDPSV---------SRRHAEIRY----DGGGRFYLEDLgSTNGTFVNGQRLGP-EPVRLKDGDVIRL 66

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 266 PKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFF 345
Cdd:cd14084     1 PKELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIINKRKFTIGSRREINKPRNIETEIEILKKLSHPCIIKIEDFF 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2462583676 346 DAED-YYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14084    81 DAEDdYYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKY 126

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGsAREadpalNVETEIEILKKLNHPCIIKIKNFF-DAEDYY 351
Cdd:cd05117     2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIDKKKLKSE-DEE-----MLRREIEILKRLDHPNIVKLYEVFeDDKNLY 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd05117    76 LVMELCTGGELFDRIVKKGSFSEREAAKIMKQILSAVAY 114

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676  273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAReadpalnVETEIEILKKLNHPCIIKIKNFFDAEDY-Y 351
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKDRER-------ILREIKILKKLKHPNIVRLYDVFEDEDKlY 73

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 2462583676  352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:smart00220  74 LVMEYCEGGDLFDLLKKRGRLSEDEARFYLRQILSALEY 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAReadpaLNVETEIEILKKLNHPCIIKIKNFFDAEDY-Y 351
Cdd:cd14081     3 YRLGKTLGKGQTGLVKLAKHCVTGQKVAIKIVNKEKLSKESVL-----MKVEREIAIMKLIEHPNVLKLYDVYENKKYlY 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14081    78 LVLEYVSGGELFDYLVKKGRLTEKEARKFFRQIISALDY 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 279 LGSGACGEVKLAFERKTCKKVAIKIISKRK------FAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFD--AEDY 350
Cdd:cd14008     1 LGRGSFGKVKLALDTETGQLYAIKIFNKSRlrkrreGKNDRGKIKNALDDVRREIAIMKKLDHPNIVRLYEVIDdpESDK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2462583676 351 -YIVLELMEGGEL--FDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14008    81 lYLVLEYCEGGPVmeLDSGDRVPPLPEETARKYFRDLVLGLEY 123

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 277 KTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigsaREADPALNVETEIEILKKLNHPCIIKIKNFF-DAEDYYIVLE 355
Cdd:cd14007     6 KPLGKGKFGNVYLAREKKSGFIVALKVISKSQL-----QKSGLEHQLRREIEIQSHLRHPNILRLYGYFeDKKRIYLILE 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462583676 356 LMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14007    81 YAPNGELYKELKKQKRFDEKEAAKYIYQLALALDY 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 269 LRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigSAREAdpalNVETEIEILKKLNHPCIIKIKNFFD-A 347
Cdd:cd14083     1 IRDKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKAL---KGKED----SLENEIAVLRKIKHPNIVQLLDIYEsK 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 2462583676 348 EDYYIVLELMEGGELFDKVV--GNKRLKEATckLYFYQMLLAVQF 390
Cdd:cd14083    74 SHLYLVMELVTGGELFDRIVekGSYTEKDAS--HLIRQVLEAVDY 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 279 LGSGACGEVKLAFERKTCKKVAIKIISKRKfaigSAREADPALNvetEIEILKKLNHPCIIKIKNFFDAED-YYIVLELM 357
Cdd:cd00180     1 LGKGSFGKVYKARDKETGKKVAVKVIPKEK----LKKLLEELLR---EIEILKKLNHPNIVKLYDVFETENfLYLVMEYC 73

                          90       100       110
                  ....*....|....*....|....*....|....
gi 2462583676 358 EGGELFDKVVGN-KRLKEATCKLYFYQMLLAVQF 390
Cdd:cd00180    74 EGGSLKDLLKENkGPLSEEEALSILRQLLSALEY 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigsAREADpALNVETEIEILKKLNHPCIIKIKNFFDAED-YY 351
Cdd:cd14073     3 YELLETLGKGTYGKVKLAIERATGREVAIKSIKKDKI----EDEQD-MVRIRREIEIMSSLNHPHIIRIYEVFENKDkIV 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14073    78 IVMEYASGGELYDYISERRRLPEREARRIFRQIVSAVHY 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 272 EYIMSKTLGSGACGEVKLAFERKTC-----KKVAIKIISKrkfaiGSAREADPALNVETEIEILKKLNHPCIIKIKNFFD 346
Cdd:cd14076     2 PYILGRTLGEGEFGKVKLGWPLPKAnhrsgVQVAIKLIRR-----DTQQENCQTSKIMREINILKGLTHPNIVRLLDVLK 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2462583676 347 AEDYY-IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF---------SMILENMV------VCITAYGF 406
Cdd:cd14076    77 TKKYIgIVLEFVSGGELFDYILARRRLKDSVACRLFAQLISGVAYlhkkgvvhrDLKLENLLldknrnLVITDFGF 152

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 279 LGSGACGEVKLAFeRKTCKK--VAIKIISKRKFAiGSAREadpalNVETEIEILKKLNHPCIIKIKNFF-DAEDYYIVLE 355
Cdd:cd14121     3 LGSGTYATVYKAY-RKSGARevVAVKCVSKSSLN-KASTE-----NLLTEIELLKKLKHPHIVELKDFQwDEEHIYLIME 75

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462583676 356 LMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14121    76 YCSGGDLSRFIRSRRTLPESTVRRFLQQLASALQF 110

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREadpalnVETEIEILKKLNHPCIIKIKNFFDAED-YY 351
Cdd:cd14072     2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIDKTQLNPSSLQK------LFREVRIMKILNHPNIVKLFEVIETEKtLY 75

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14072    76 LVMEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQY 114

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 269 LRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigSAREAdpalNVETEIEILKKLNHPCIIKIKNFFDAE 348
Cdd:cd14167     1 IRDIYDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKAL---EGKET----SIENEIAVLHKIKHPNIVALDDIYESG 73

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2462583676 349 DY-YIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14167    74 GHlYLIMQLVSGGELFDRIVEKGFYTERDASKLIFQILDAVKY 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 272 EYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigsareadpalNVETEIEILKKL-NHPCIIKIKNFFDAEDY 350
Cdd:cd14091     1 EYEIKEEIGKGSYSVCKRCIHKATGKEYAVKIIDKSKR------------DPSEEIEILLRYgQHPNIITLRDVYDDGNS 68

                          90       100
                  ....*....|....*....|....*
gi 2462583676 351 -YIVLELMEGGELFDKVVGNKRLKE 374
Cdd:cd14091    69 vYLVTELLRGGELLDRILRQKFFSE 93

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 269 LRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKfaigSAREAdpalNVETEIEILKKLNHPCIIKIKNFFDAE 348
Cdd:cd14166     1 IRETFIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKKSP----LSRDS----SLENEIAVLKRIKHENIVTLEDIYEST 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 2462583676 349 D-YYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQFsmILENMVV 399
Cdd:cd14166    73 ThYYLVMQLVSGGELFDRILERGVYTEKDASRVINQVLSAVKY--LHENGIV 122

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRkfaiGSAREADPALnVETEIEILKKLNHPCIIKIKNFFDAED--Y 350
Cdd:cd14163     2 YQLGKTIGEGTYSKVKEAFSKKHQRKVAIKIIDKS----GGPEEFIQRF-LPRELQIVERLDHKNIIHVYEMLESADgkI 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2462583676 351 YIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF--------------SMILENMVVCITAYGFTQL 409
Cdd:cd14163    77 YLVMELAEDGDVFDCVLHGGPLPEHRAKALFRQLVEAIRYchgcgvahrdlkceNALLQGFTLKLTDFGFAKQ 149

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 272 EYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKfAIGsaREAdpalNVETEIEILKKLNHPCIIK-IKNFFDAEDY 350
Cdd:cd14095     1 KYDIGRVIGDGNFAVVKECRDKATDKEYALKIIDKAK-CKG--KEH----MIENEVAILRRVKHPNIVQlIEEYDTDTEL 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2462583676 351 YIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF---------SMILENMVVC 400
Cdd:cd14095    74 YLVMELVKGGDLFDAITSSTKFTERDASRMVTDLAQALKYlhslsivhrDIKPENLLVV 132

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREadpalnVETEIEILKKLNHPCIIKIKNFFDA-EDYY 351
Cdd:cd14075     4 YRIRGELGSGNFSQVKLGIHQLTKEKVAIKILDKTKLDQKTQRL------LSREISSMEKLHHPNIIRLYEVVETlSKLH 77

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQ 389
Cdd:cd14075    78 LVMEYASGGELYTKISTEGKLSESEAKPLFAQIVSAVK 115

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 273 YIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFaigSAREAdpalNVETEIEILKKLNHPCIIKIKNFFDAEDY-Y 351
Cdd:cd14169     5 YELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKAL---RGKEA----MVENEIAVLRRINHENIVSLEDIYESPTHlY 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 2462583676 352 IVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14169    78 LAMELVTGGELFDRIIERGSYTEKDASQLIGQVLQAVKY 116

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 279 LGSGACGEVKLAFERKTCKKVAIKIISKRKFaigsareaDPAL--NVETEIEILKKLNHPCIIKIKNFFDAEDY-YIVLE 355
Cdd:cd14009     1 IGRGSFATVWKGRHKQTGEVVAIKEISRKKL--------NKKLqeNLESEIAILKSIKHPNIVRLYDVQKTEDFiYLVLE 72

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462583676 356 LMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd14009    73 YCAGGDLSQYIRKRGRLPEAVARHFMQQLASGLKF 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462583676 277 KTLGSGACGEVKLAFERKTCKKVAIKIISKRKfaIGSAREADpalNVETEIEILKKLNHPCIIKIKNFF-DAEDYYIVLE 355
Cdd:cd05580     7 KTLGTGSFGRVRLVKHKDSGKYYALKILKKAK--IIKLKQVE---HVLNEKRILSEVRHPFIVNLLGSFqDDRNLYMVME 81

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2462583676 356 LMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQF 390
Cdd:cd05580    82 YVPGGELFSLLRRSGRFPNDVAKFYAAEVVLALEY 116