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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284    83 GKGGFGTVngskYKimVTCDPNKKRYqaqvipvndVVKIQKPNDAlpyKQLLQRAAKEA--LKQKNHG--VKVAAVIGAG 158
Cdd:smart00220   8 GEGSFGKV----YL--ARDKKTGKLV---------AIKVIKKKKI---KKDRERILREIkiLKKLKHPniVRLYDVFEDE 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284   159 DKVITVVEDC-GISLDKLLpftpNNKYSFyyRLQVAARIASEMLL----LQQNGVVHRDLKPANIcyknLGKEQFLIIFI 233
Cdd:smart00220  70 DKLYLVMEYCeGGDLFDLL----KKRGRL--SEDEARFYLRQILSaleyLHSKGIVHRDLKPENI----LLDEDGHVKLA 139

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 966423284   234 DFGLAEDADSKNNFNSS-GTPCYMAPEVLMYDRSTYQSDMYALAAILGEIF 283
Cdd:smart00220 140 DFGLARQLDPGEKLTTFvGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELL 190

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284   83 GKGGFGTVngskYKIMVTCDPNKKRyqaqvIPVndVVKIQKPNDALPYKQLLQRAAKeALKQKNHgVKVAAVIGA---GD 159
Cdd:pfam07714   8 GEGAFGEV----YKGTLKGEGENTK-----IKV--AVKTLKEGADEEEREDFLEEAS-IMKKLDH-PNIVKLLGVctqGE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  160 KVITVVEDC-GISLDKLLPfTPNNKYSFYYRLQVAARIASEMLLLQQNGVVHRDLKPANIcyknLGKEQFLIIFIDFGLA 238
Cdd:pfam07714  75 PLYIVTEYMpGGDLLDFLR-KHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNC----LVSENLVVKISDFGLS 149

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 966423284  239 EDADSKNNFNSSGT----PCYMAPEVLMYDRSTYQSDMYALAAILGEIF 283
Cdd:pfam07714 150 RDIYDDDYYRKRGGgklpIKWMAPESLKDGKFTSKSDVWSFGVLLWEIF 198

TOMM system kinase/cyclase fusion protein; This model represents proteins of 1350 in length, in multiple species of Burkholderia, in Acidovorax avenae subsp. citrulli AAC00-1 and Delftia acidovorans SPH-1, and in multiple copies in Sorangium cellulosum, in genomic neighborhoods that include a cyclodehydratase/docking scaffold fusion protein (TIGR03882) and a member of the thiazole/oxazole modified metabolite (TOMM) precursor family TIGR03795. It has a kinase domain in the N-terminal 300 amino acids, followed by a cyclase homology domain, followed by regions without named domain definitions. It is a probable bacteriocin-like metabolite biosynthesis protein. [Cellular processes, Toxin production and resistance]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284   206 NGVVHRDLKPANICYKNLGKEQFLIIfIDFGL------AEDADSKNNFNSS---GTPCYMAPEVLMYDRSTYQSDMYALA 276
Cdd:TIGR03903   98 QGIVHRDLKPQNIMVSQTGVRPHAKV-LDFGIgtllpgVRDADVATLTRTTevlGTPTYCAPEQLRGEPVTPNSDLYAWG 176

                   ....*
gi 966423284   277 AILGE 281
Cdd:TIGR03903  177 LIFLE 181

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 966423284  83 GKGGFGTVngskYKimVTCDPNKKRYqaqvipvndVVKIQKPNDALPYKQLLQRAAkEALKQKNHG--VKVAAVIGAGDK 160
Cdd:cd00180    2 GKGSFGKV----YK--ARDKETGKKV---------AVKVIPKEKLKKLLEELLREI-EILKKLNHPniVKLYDVFETENF 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 161 VITVVEDC-GISLDKLLpftpnNKYSFYYRLQVAARIASEMLL----LQQNGVVHRDLKPANIcyknLGKEQFLIIFIDF 235
Cdd:cd00180   66 LYLVMEYCeGGSLKDLL-----KENKGPLSEEEALSILRQLLSaleyLHSNGIIHRDLKPENI----LLDSDGTVKLADF 136

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 236 GLAEDADSKNNFNS----SGTPCYMAPEVLMYDRSTYQSDMYALAAILGEIFGATHIMKY 291
Cdd:cd00180  137 GLAKDLDSDDSLLKttggTTPPYYAPPELLGGRYYGPKVDIWSLGVILYELEELKDLIRR 196

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVngskYKimVTcDPNKKRyqaqviPVndVVKIQKPNDALPYKqLLQRAAKEA--LKQKNHG--VKVAAVIGAG 158
Cdd:COG0515   16 GRGGMGVV----YL--AR-DLRLGR------PV--ALKVLRPELAADPE-ARERFRREAraLARLNHPniVRVYDVGEED 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 159 DKVITVVEDC-GISLDKLL----PFTPnnkysfyyrlQVAARIASEMLL----LQQNGVVHRDLKPANICyknLGKEQFL 229
Cdd:COG0515   80 GRPYLVMEYVeGESLADLLrrrgPLPP----------AEALRILAQLAEalaaAHAAGIVHRDIKPANIL---LTPDGRV 146

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 966423284 230 IIfIDFGLAEDADSKNNFNSS---GTPCYMAPEVLMYDRSTYQSDMYALAAIL 279
Cdd:COG0515  147 KL-IDFGIARALGGATLTQTGtvvGTPGYMAPEQARGEPVDPRSDVYSLGVTL 198

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVngskYKimVTCDPNKKRYQAQVIPVNDVVKiqkpndalpYKQLLQRAAkeALKQKNHGvKVAAVIGA---GD 159
Cdd:cd05122    9 GKGGFGVV----YK--ARHKKTGQIVAIKKINLESKEK---------KESILNEIA--ILKKCKHP-NIVKYYGSylkKD 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 160 KVITVVEDC-GISLDKLL-----PFTPNnkysfyyrlQVAArIASEMLL----LQQNGVVHRDLKPANIcyknLGKEQFL 229
Cdd:cd05122   71 ELWIVMEFCsGGSLKDLLkntnkTLTEQ---------QIAY-VCKEVLKgleyLHSHGIIHRDIKAANI----LLTSDGE 136

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 966423284 230 IIFIDFGLAED-ADSKNNFNSSGTPCYMAPEVLMYDRSTYQSDMYALAAILGE 281
Cdd:cd05122  137 VKLIDFGLSAQlSDGKTRNTFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIE 189

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 177 PFTPNNKYSF------------------YYRLQ--------VAARIASEMLL----LQQNGVVHRDLKPANIcyknLGKE 226
Cdd:cd05123   53 PFIVKLHYAFqteeklylvldyvpggelFSHLSkegrfpeeRARFYAAEIVLaleyLHSLGIIYRDLKPENI----LLDS 128

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966423284 227 QFLIIFIDFGLAEDADSKNNFNSS--GTPCYMAPEVLMYDRSTYQSDMYALAAILGE-IFGAT 286
Cdd:cd05123  129 DGHIKLTDFGLAKELSSDGDRTYTfcGTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEmLTGKP 191

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 966423284  83 GKGGFGTV-------NGSKY--KIMvtcdpNKKRYQAqvipvndvvKIQKPNDALPYKQLLQRAAKE--ALKQKNHG--V 149
Cdd:cd14008    2 GRGSFGKVklaldteTGQLYaiKIF-----NKSRLRK---------RREGKNDRGKIKNALDDVRREiaIMKKLDHPniV 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 150 KVAAVIG--AGDKVITVVEDC-GISLDKLLPFTPNNKYSFyyrlQVAARIASEMLL----LQQNGVVHRDLKPANICYKN 222
Cdd:cd14008   68 RLYEVIDdpESDKLYLVLEYCeGGPVMELDSGDRVPPLPE----ETARKYFRDLVLgleyLHENGIVHRDIKPENLLLTA 143

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 223 LGKeqfliIFI-DFGLAEDADSKNN--FNSSGTPCYMAPEVLMYDRSTY---QSDMYALAA-----ILGEI-FGATHIMK 290
Cdd:cd14008  144 DGT-----VKIsDFGVSEMFEDGNDtlQKTAGTPAFLAPELCDGDSKTYsgkAADIWALGVtlyclVFGRLpFNGDNILE 218

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 966423284 291 YKEAVNtraelayapfcfdglfTGYDVSEVDPFLLKDIKNLLFRLQSKKAGERPTINQV 349
Cdd:cd14008  219 LYEAIQ----------------NQNDEFPIPPELSPELKDLLRRMLEKDPEKRITLKEI 261

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVNGSKYKI---MVTCDP-NKKRYQaqvipvndvvKIQKPNDALPYKQLLQRAAKE-------ALKQKNHGVKV 151
Cdd:cd05577    2 GRGGFGEVCACQVKAtgkMYACKKlDKKRIK----------KKKGETMALNEKIILEKVSSPfivslayAFETKDKLCLV 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 152 AAVIGAGDKV--ITVVEDCGISLDKLLpftpnnkysFYyrlqvAARIASEMLLLQQNGVVHRDLKPANICYKNLGKeqfl 229
Cdd:cd05577   72 LTLMNGGDLKyhIYNVGTRGFSEARAI---------FY-----AAEIICGLEHLHNRFIVYRDLKPENILLDDHGH---- 133

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 966423284 230 IIFIDFGLAEDADSKNNFNSS-GTPCYMAPEVLMYDRS-TYQSDMYALAAILGE-IFGATHIMKYKEAV 295
Cdd:cd05577  134 VRISDLGLAVEFKGGKKIKGRvGTHGYMAPEVLQKEVAyDFSVDWFALGCMLYEmIAGRSPFRQRKEKV 202

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284   83 GKGGFGTVngskYKIMVTCDPNKKRyqaqvIPVndVVKIQKPNDALPYKQLLQRAAKeALKQKNHgVKVAAVIGA---GD 159
Cdd:pfam07714   8 GEGAFGEV----YKGTLKGEGENTK-----IKV--AVKTLKEGADEEEREDFLEEAS-IMKKLDH-PNIVKLLGVctqGE 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  160 KVITVVEDC-GISLDKLLPfTPNNKYSFYYRLQVAARIASEMLLLQQNGVVHRDLKPANIcyknLGKEQFLIIFIDFGLA 238
Cdd:pfam07714  75 PLYIVTEYMpGGDLLDFLR-KHKRKLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNC----LVSENLVVKISDFGLS 149

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 966423284  239 EDADSKNNFNSSGT----PCYMAPEVLMYDRSTYQSDMYALAAILGEIF 283
Cdd:pfam07714 150 RDIYDDDYYRKRGGgklpIKWMAPESLKDGKFTSKSDVWSFGVLLWEIF 198

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 203 LQQNGVVHRDLKPANIcyknlgkeqFL----IIFI-DFGLAEDADSKNNFNSS--GTPCYMAPEVLMYDRSTYQSDMYAL 275
Cdd:cd08215  119 LHSRKILHRDLKTQNI---------FLtkdgVVKLgDFGISKVLESTTDLAKTvvGTPYYLSPELCENKPYNYKSDIWAL 189

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 276 AAILGEI------FGATHImkyKEAVNTRAELAYAPfcfdgLFTGYDvsevdpfllKDIKNLLFRLQSKKAGERPTINQV 349
Cdd:cd08215  190 GCVLYELctlkhpFEANNL---PALVYKIVKGQYPP-----IPSQYS---------SELRDLVNSMLQKDPEKRPSANEI 252

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 151 VAAVIGA---GDKVITVvedcgisldklLPFTPNNKYSFYYRLQVAARIASEM--LL-----LQQNGVVHRDLKPANICY 220
Cdd:cd14019   66 VSGLITAfrnEDQVVAV-----------LPYIEHDDFRDFYRKMSLTDIRIYLrnLFkalkhVHSFGIIHRDVKPGNFLY 134

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 966423284 221 kNLGKEQFLIifIDFGLAEDADSKNNF--NSSGTPCYMAPEVLMydRSTYQS---DMYALAAIL 279
Cdd:cd14019  135 -NRETGKGVL--VDFGLAQREEDRPEQraPRAGTRGFRAPEVLF--KCPHQTtaiDIWSAGVIL 193

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVNGSKYKimvtcdpnkkryQAQVIpvndVVKIQKPNDALPYKQLLqRAAKEALKQKN-HGVKVAAVIGAGDK- 160
Cdd:cd13979   12 GSGGFGSVYKATYK------------GETVA----VKIVRRRRKNRASRQSF-WAELNAARLRHeNIVRVLAAETGTDFa 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 161 ---VITVvEDCG-ISLDKLLpFTPNNKYSFYYRLQVAARIASEMLLLQQNGVVHRDLKPANIcyknLGKEQFLIIFIDFG 236
Cdd:cd13979   75 slgLIIM-EYCGnGTLQQLI-YEGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANI----LISEQGVCKLCDFG 148

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 966423284 237 LAEDADSKNNFNSS-----GTPCYMAPEVLMYDRSTYQSDMYALA 276
Cdd:cd13979  149 CSVKLGEGNEVGTPrshigGTYTYRAPELLKGERVTPKADIYSFG 193

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVngskYKIMvtcDPNKKRYQAQVIPVNDVvkiqKPNDALPYKQ---LLQRaakeaLKQKNHGVK-VAAVIGAG 158
Cdd:cd14131   10 GKGGSSKV----YKVL---NPKKKIYALKRVDLEGA----DEQTLQSYKNeieLLKK-----LKGSDRIIQlYDYEVTDE 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 159 DKVITVVEDCG-ISLDKLLPFTPNNKYSFYYRlqvaARIASEMLL----LQQNGVVHRDLKPANicyknlgkeqFLII-- 231
Cdd:cd14131   74 DDYLYMVMECGeIDLATILKKKRPKPIDPNFI----RYYWKQMLEavhtIHEEGIVHSDLKPAN----------FLLVkg 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 232 ---FIDFGLA----EDADSKNNFNSSGTPCYMAPEVLMYDRSTYQ----------SDMYALAAILGE-IFGAT---HIM- 289
Cdd:cd14131  140 rlkLIDFGIAkaiqNDTTSIVRDSQVGTLNYMSPEAIKDTSASGEgkpkskigrpSDVWSLGCILYQmVYGKTpfqHITn 219

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 966423284 290 ---KYKEAVNTRAELAYAPFcfdglftgydvseVDPFLLKDIKNLLFRlQSKKageRPTINQV 349
Cdd:cd14131  220 piaKLQAIIDPNHEIEFPDI-------------PNPDLIDVMKRCLQR-DPKK---RPSIPEL 265

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  77 LDNSTRGKGGFGTVNGSKYKI---MVTCDP-NKKRYQaqvipvndvvKIQKPNDALPYKQLLQRAAKE-------ALKQK 145
Cdd:cd05608    4 LDFRVLGKGGFGEVSACQMRAtgkLYACKKlNKKRLK----------KRKGYEGAMVEKRILAKVHSRfivslayAFQTK 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 146 NHGVKVAAVIGAGDKVITVVedcgiSLDKLLPFTPNNKYSFYyrlqvAARIASEMLLLQQNGVVHRDLKPANICYKNLGK 225
Cdd:cd05608   74 TDLCLVMTIMNGGDLRYHIY-----NVDEENPGFQEPRACFY-----TAQIISGLEHLHQRRIIYRDLKPENVLLDDDGN 143

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 966423284 226 eqflIIFIDFGLA-EDADSKNNFNS-SGTPCYMAPEVLMYDRSTYQSDMYALAAILGEIFGA 285
Cdd:cd05608  144 ----VRISDLGLAvELKDGQTKTKGyAGTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAA 201

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 966423284 149 VKVAAVIGAGDKVITVVEDC--GISLDKLLpftpnNKYSFYYR--LQVAARIASEMLLLQQNGVVHRDLKPANICY-KNL 223
Cdd:cd14091   57 ITLRDVYDDGNSVYLVTELLrgGELLDRIL-----RQKFFSEReaSAVMKTLTKTVEYLHSQGVVHRDLKPSNILYaDES 131

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 966423284 224 GKEQFLIIfIDFGLAEDADSKNnfnssG---TPCY----MAPEVLM---YDRSTyqsDMYALAAIL 279
Cdd:cd14091  132 GDPESLRI-CDFGFAKQLRAEN-----GllmTPCYtanfVAPEVLKkqgYDAAC---DIWSLGVLL 188

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284  83 GKGGFGTVngskYKIMvtcdpnKKRYQAQVIpvndvVKIQK--PNDALPYKQLLQRAakEALKQKNHGvKVAAVIGagdk 160
Cdd:cd13978    2 GSGGFGTV----SKAR------HVSWFGMVA-----IKCLHssPNCIEERKALLKEA--EKMERARHS-YVLPLLG---- 59

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 161 VITVVEDCGI--------SLDKLLP-FTPNNKYSFyyRLQVAARIASEMLLLQ--QNGVVHRDLKPANIcyknLGKEQFL 229
Cdd:cd13978   60 VCVERRSLGLvmeymengSLKSLLErEIQDVPWSL--RFRIIHEIALGMNFLHnmDPPLLHHDLKPENI----LLDNHFH 133

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 230 IIFIDFGLA----------EDADSKNNFnssGTPCYMAPEVL--MYDRSTYQSDMYALAAILGEIFgathimkykeavnT 297
Cdd:cd13978  134 VKISDFGLSklgmksisanRRRGTENLG---GTPIYMAPEAFddFNKKPTSKSDVYSFAIVIWAVL-------------T 197

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 966423284 298 RAElayapfcfdglftgydvsevdPFLlkDIKNLLFRLQSKKAGERPTINQV 349
Cdd:cd13978  198 RKE---------------------PFE--NAINPLLIMQIVSKGDRPSLDDI 226

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 190 LQVAARIASEMLLLQQNGVVHRDLKPANiCyknLGKEQFLIIFIDFGLAEDADSKNNFNSSGTPC----YMAPEVLMYDR 265
Cdd:cd05050  133 LCIAKQVAAGMAYLSERKFVHRDLATRN-C---LVGENMVVKIADFGLSRNIYSADYYKASENDAipirWMPPESIFYNR 208

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966423284 266 STYQSDMYALAAILGEIF--------GATH--IMKYKEAVNTRAelayapfCFDGLftgydvsevdPFllkDIKNLLFRL 335
Cdd:cd05050  209 YTTESDVWAYGVVLWEIFsygmqpyyGMAHeeVIYYVRDGNVLS-------CPDNC----------PL---ELYNLMRLC 268

                        170
                 ....*....|....*...
gi 966423284 336 QSKKAGERPTINQVNKFL 353
Cdd:cd05050  269 WSKLPSDRPSFASINRIL 286