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 124506595 307 EKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTTplyVLNNIDEHNKGHLQRFRSYI 386
Cdd:cd13994   90 EKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAE---VFGMPAEKESPMSAGLCGSE 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 387 PYVgktkyaPPEcwnlkkkykelgienplvylkTLKDYEYkdtlyfDVLAADIYMLGILFIWISSNRYLWGNFDMSqNSN 466
Cdd:cd13994  167 PYM------APE---------------------VFTSGSY------DGRAVDVWSCGIVLFALFTGRFPWRSAKKS-DSA 212

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 124506595 467 FKKFVNSDMNFDL--FPLTREWPEGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd13994  213 YKAYEKSGDFTNGpyEPIENLLPSECRRLIYRMLHPDPEKRITIDEALNDPW 264

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 307 EKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTTplyVLNNIDEHNKGHLQRFRSYI 386
Cdd:cd13994   90 EKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAE---VFGMPAEKESPMSAGLCGSE 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 387 PYVgktkyaPPEcwnlkkkykelgienplvylkTLKDYEYkdtlyfDVLAADIYMLGILFIWISSNRYLWGNFDMSqNSN 466
Cdd:cd13994  167 PYM------APE---------------------VFTSGSY------DGRAVDVWSCGIVLFALFTGRFPWRSAKKS-DSA 212

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 124506595 467 FKKFVNSDMNFDL--FPLTREWPEGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd13994  213 YKAYEKSGDFTNGpyEPIENLLPSECRRLIYRMLHPDPEKRITIDEALNDPW 264

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 124506595 288 YVVMiwEFF-GQNLKEFLHSEKenlVIT-KERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFG 360
Cdd:COG0515   83 YLVM--EYVeGESLADLLRRRG---PLPpAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFG 152

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 285 KKGYVVMIWEFFGQNLKEFLHSekeNLVITKERKK-ILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTT 363
Cdd:PTZ00024  91 EGDFINLVMDIMASDLKKVVDR---KIRLTESQVKcILLQILNGLNVLHKWYFMHRDLSPANIFINSKGICKIADFGLAR 167

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 124506595 364 PLYVLNNIDEHNK-GHLQRFRSYIPYVGKTKYAPPE 398
Cdd:PTZ00024 168 RYGYPPYSDTLSKdETMQRREEMTSKVVTLWYRAPE 203

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 307 EKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTTplyVLNNIDEHNKGHLQRFRSYI 386
Cdd:cd13994   90 EKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAE---VFGMPAEKESPMSAGLCGSE 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 387 PYVgktkyaPPEcwnlkkkykelgienplvylkTLKDYEYkdtlyfDVLAADIYMLGILFIWISSNRYLWGNFDMSqNSN 466
Cdd:cd13994  167 PYM------APE---------------------VFTSGSY------DGRAVDVWSCGIVLFALFTGRFPWRSAKKS-DSA 212

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 124506595 467 FKKFVNSDMNFDL--FPLTREWPEGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd13994  213 YKAYEKSGDFTNGpyEPIENLLPSECRRLIYRMLHPDPEKRITIDEALNDPW 264

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595   288 YVVMiwEFF-GQNLKEFLHSEKEnlvIT-KERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTTpl 365
Cdd:smart00220  73 YLVM--EYCeGGDLFDLLKKRGR---LSeDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLAR-- 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595   366 yvlnnidehnkgHLQRFRSYIPYVGKTKYAPPECWnLKKKYKElgienplvylktlkdyeykdtlyfdvlAADIYMLGIL 445
Cdd:smart00220 146 ------------QLDPGEKLTTFVGTPEYMAPEVL-LGKGYGK---------------------------AVDIWSLGVI 185

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 124506595   446 FIWISSNRYLWGNfDMSQNSNFKKFVNSDMNFDLFPLtrEWPEGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:smart00220 186 LYELLTGKPPFPG-DDQLLELFKKIGKPKPPFPPPEW--DISPEAKDLIRKLLVKDPEKRLTAEEALQHPF 253

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 250 YESENDYSELKGLNELmfCDIDIFKN--ELIKIRNRNKKGYVVMIWEFFGQNLKEFLhsEKENLVITKER-KKILFECLK 326
Cdd:cd05118   37 RHPKAALREIKLLKHL--NDVEGHPNivKLLDVFEHRGGNHLCLVFELMGMNLYELI--KDYPRGLPLDLiKSYLYQLLQ 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 327 LINKLHKAGLTHLDISPENILI-GENYEMRLCDFGKTTPLYVlnnidehnkghlqrfRSYIPYVGKTKYAPPECwnlkkk 405
Cdd:cd05118  113 ALDFLHSNGIIHRDLKPENILInLELGQLKLADFGLARSFTS---------------PPYTPYVATRWYRAPEV------ 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 406 ykelgienplvyLKTLKDYEYkdtlyfdvlAADIYMLGILFIWISSNRYLW-GNFDMSQNSNFKKFVNSDMNFDLfpltr 484
Cdd:cd05118  172 ------------LLGAKPYGS---------SIDIWSLGCILAELLTGRPLFpGDSEVDQLAKIVRLLGTPEALDL----- 225

                        250       260       270
                 ....*....|....*....|....*....|..
gi 124506595 485 ewpeglkyiIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd05118  226 ---------LSKMLKYDPAKRITASQALAHPY 248

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 124506595 315 KERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGkttplyvLNNIDEHNKghlqrfRSyiPYVGKTKY 394
Cdd:cd14007  100 KEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFG-------WSVHAPSNR------RK--TFCGTLDY 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 395 APPECwnlkkkykelgIENplvylktlKDYEYKdtlyfdvlaADIYMLGILFiwissnrY--LWGN--FDM-SQNSNFKK 469
Cdd:cd14007  165 LPPEM-----------VEG--------KEYDYK---------VDIWSLGVLC-------YelLVGKppFESkSHQETYKR 209

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 124506595 470 FVNSDMNFDLFpltreWPEGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd14007  210 IQNVDIKFPSS-----VSPEAKDLISKLLQKDPSKRLSLEQVLNHPW 251

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 124506595 288 YVVMiwEFF-GQNLKEFLhseKENLVITKERK-KILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFG 360
Cdd:cd14014   76 YIVM--EYVeGGSLADLL---RERGPLPPREAlRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFG 145

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 124506595 287 GYVVMiwEFFG-QNLKEFLHsEKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGKTTPL 365
Cdd:cd13979   77 GLIIM--EYCGnGTLQQLIY-EGSEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKL 153

                         90
                 ....*....|..
gi 124506595 366 YVLNNIDEHNKG 377
Cdd:cd13979  154 GEGNEVGTPRSH 165

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 271 DIFKNelikirnrnkKGYVVMIWEFF-GQNLKEFLhSEKENLViTKERKKILFECLKLINKLHKAGLTHLDISPENI-LI 348
Cdd:cd14194   75 EVYEN----------KTDVILILELVaGGELFDFL-AEKESLT-EEEATEFLKQILNGVYYLHSLQIAHFDLKPENImLL 142

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 349 GENY---EMRLCDFGkttplyVLNNIDEHNKghlqrFRSYIpyvGKTKYAPPECWNlkkkYKELGIEnplvylktlkdye 425
Cdd:cd14194  143 DRNVpkpRIKIIDFG------LAHKIDFGNE-----FKNIF---GTPEFVAPEIVN----YEPLGLE------------- 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 426 ykdtlyfdvlaADIYMLGIL-FIWISSNRYLWGNFDMSQNSNFKKfVNSDMNFDLFPLTREWPeglKYIIRKLLDYESRK 504
Cdd:cd14194  192 -----------ADMWSIGVItYILLSGASPFLGDTKQETLANVSA-VNYEFEDEYFSNTSALA---KDFIRRLLVKDPKK 256

                        250
                 ....*....|..
gi 124506595 505 SLDLNELIEHPW 516
Cdd:cd14194  257 RMTIQDSLQHPW 268

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 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 124506595 271 DIFKNelikirnrnkKGYVVMIWEFF-GQNLKEFLhSEKENLViTKERKKILFECLKLINKLHKAGLTHLDISPENILIG 349
Cdd:cd14195   75 DIFEN----------KTDVVLILELVsGGELFDFL-AEKESLT-EEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLL 142

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 350 E----NYEMRLCDFGkttplyVLNNIDEHNKghlqrFRSYIpyvGKTKYAPPECWNlkkkYKELGIEnplvylktlkdye 425
Cdd:cd14195  143 DknvpNPRIKLIDFG------IAHKIEAGNE-----FKNIF---GTPEFVAPEIVN----YEPLGLE------------- 191

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 426 ykdtlyfdvlaADIYMLGIL-FIWISSNRYLWGNFDMSQNSNFKKfVNSDMNFDLFPLTREWPeglKYIIRKLLDYESRK 504
Cdd:cd14195  192 -----------ADMWSIGVItYILLSGASPFLGETKQETLTNISA-VNYDFDEEYFSNTSELA---KDFIRRLLVKDPKK 256

                        250
                 ....*....|..
gi 124506595 505 SLDLNELIEHPW 516
Cdd:cd14195  257 RMTIAQSLEHSW 268

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 277 LIKIRN---RNKKGYVVMiwEFFGQNLKEFLHSEKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYE 353
Cdd:cd07830   60 IVKLKEvfrENDELYFVF--EYMEGNLYQLMKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEV 137

                 ....*..
gi 124506595 354 MRLCDFG 360
Cdd:cd07830  138 VKIADFG 144

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 124506595 318 KKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFG 360
Cdd:cd07847  103 KKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFG 145

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 276 ELIKIRNRNKKGYVVMiwEFFGQNLKEFLHSEKENLVItKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMR 355
Cdd:cd07829   62 KLLDVIHTENKLYLVF--EYCDQDLKKYLDKRPGPLPP-NLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLK 138

                 ....*
gi 124506595 356 LCDFG 360
Cdd:cd07829  139 LADFG 143

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 289 VVMIWEFFGQNLKEFLHSEKENLVITkERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFGkttpLYVL 368
Cdd:cd07832   75 FVLVFEYMLSSLSEVLRDEERPLTEA-QVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFG----LARL 149

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 124506595 369 NNIDEHnkghlqrfRSYIPYVGKTKYAPPECWNLKKKYKEL 409
Cdd:cd07832  150 FSEEDP--------RLYSHQVATRWYRAPELLYGSRKYDEG 182

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 289 VVMIWEFF-GQNLKEFLhSEKENLViTKERKKILFECLKLINKLHKAGLTHLDISPENILIGE----NYEMRLCDFGktt 363
Cdd:cd14105   83 VVLILELVaGGELFDFL-AEKESLS-EEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDknvpIPRIKLIDFG--- 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 364 plyVLNNIDEHNKghlqrFRSYIpyvGKTKYAPPECWNlkkkYKELGIEnplvylktlkdyeykdtlyfdvlaADIYMLG 443
Cdd:cd14105  158 ---LAHKIEDGNE-----FKNIF---GTPEFVAPEIVN----YEPLGLE------------------------ADMWSIG 198

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 124506595 444 -ILFIWISSNRYLWGNFDMSQNSNFKKfVNSDMNFDLFPLTREWPeglKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd14105  199 vITYILLSGASPFLGDTKQETLANITA-VNYDFDDEYFSNTSELA---KDFIRQLLVKDPRKRMTIQESLRHPW 268

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 244 KFYNLLYESENDY--SELKGLNELMfcdidifKNELIKIRNRNKKGY-VVMIWEFF-GQNLKEFLHSEkENLVITKERKK 319
Cdd:cd14114   33 KFIMTPHESDKETvrKEIQIMNQLH-------HPKLINLHDAFEDDNeMVLILEFLsGGELFERIAAE-HYKMSEAEVIN 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 320 ILFECLKLINKLHKAGLTHLDISPENIL--IGENYEMRLCDFGKTTplyvlnnidehnkgHLQRFRSYIPYVGKTKYAPP 397
Cdd:cd14114  105 YMRQVCEGLCHMHENNIVHLDIKPENIMctTKRSNEVKLIDFGLAT--------------HLDPKESVKVTTGTAEFAAP 170

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 398 ECWNLKkkykelgienPLVYLktlkdyeykdtlyfdvlaADIYMLGIL-FIWISSNRYLWGNFDMSQNSNFKKfvnSDMN 476
Cdd:cd14114  171 EIVERE----------PVGFY------------------TDMWAVGVLsYVLLSGLSPFAGENDDETLRNVKS---CDWN 219

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|
gi 124506595 477 FDLFPLTREWPEGlKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd14114  220 FDDSAFSGISEEA-KDFIRKLLLADPNKRMTIHQALEHPW 258

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 289 VVMIWEFFGQNLKEFLhSEKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFG----KTTP 364
Cdd:cd07872   79 LTLVFEYLDKDLKQYM-DDCGNIMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGlaraKSVP 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 365 LYVLNnidehNKGHLQRFRSYIPYVGKTKYAPP-ECWNLKKKYKELGIENPLVYLKTLKDYEYkdtLYFDVLAADIYMlg 443
Cdd:cd07872  158 TKTYS-----NEVVTLWYRPPDVLLGSSEYSTQiDMWGVGCIFFEMASGRPLFPGSTVEDELH---LIFRLLGTPTEE-- 227

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 444 ilfIW--ISSNrylwgnfDMSQNSNFKKFVNSdmnfdlfPLTREWP----EGLKyIIRKLLDYESRKSLDLNELIEHPWW 517
Cdd:cd07872  228 ---TWpgISSN-------DEFKNYNFPKYKPQ-------PLINHAPrldtEGIE-LLTKFLQYESKKRISAEEAMKHAYF 289

                 ..
gi 124506595 518 ST 519
Cdd:cd07872  290 RS 291

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 124506595 315 KERKKILFECLKLINKLHKAGLTHLDISPENILI---GENYEMRLCDFGkttplyvlNNIDEHNKGHLQRFrsyipyVGK 391
Cdd:cd05117   99 REAAKIMKQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFG--------LAKIFEEGEKLKTV------CGT 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 392 TKYAPPECwnLKKKYkelgienplvylktlkdYEYKdtlyfdvlaADIYMLG-ILFIWISSNRYLWGNfdmSQNSNFKKF 470
Cdd:cd05117  165 PYYVAPEV--LKGKG-----------------YGKK---------CDIWSLGvILYILLCGYPPFYGE---TEQELFEKI 213

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 124506595 471 VNSDMNFDlfplTREWP---EGLKYIIRKLLDYESRKSLDLNELIEHPW 516
Cdd:cd05117  214 LKGKYSFD----SPEWKnvsEEAKDLIKRLLVVDPKKRLTAAEALNHPW 258

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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 124506595 300 LKEFLHSEKENLVITKER------KKILFECLKLINKLHKAGLTHLDISPENILIGENYEMRLCDFG 360
Cdd:cd07853   82 VTELMQSDLHKIIVSPQPlssdhvKVFLYQILRGLKYLHSAGILHRDIKPGNLLVNSNCVLKICDFG 148

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 308 KENLVITKERKKILFECLKL-INKLHKAGLTHLDISPENILIGENYEMRLCDFG--KTTPLYVlnnideHNKGHLQRfrs 384
Cdd:cd14162   92 RKNGALPEPQARRWFRQLVAgVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGfaRGVMKTK------DGKPKLSE--- 162

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 385 yiPYVGKTKYAPPEcwnlkkkykelgienplvylkTLKDYEYkdtlyfDVLAADIYMLG-ILFIwissnrYLWGN--FDm 461
Cdd:cd14162  163 --TYCGSYAYASPE---------------------ILRGIPY------DPFLSDIWSMGvVLYT------MVYGRlpFD- 206

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 124506595 462 sqNSNFKKFVNSDMNFDLFPLTREWPEGLKYIIRKLLDYESRKsLDLNELIEHPW 516
Cdd:cd14162  207 --DSNLKVLLKQVQRRVVFPKNPTVSEECKDLILRMLSPVKKR-ITIEEIKRDPW 258

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 124506595 286 KGYVVMIWEFFGQNLKEFLHSEKENLVITKERKKILFECLKLINKLHKAGLTHLDISPENIL----IGENYEMRLCDFGK 361
Cdd:cd14229   73 RNHTCLVFEMLEQNLYDFLKQNKFSPLPLKVIRPILQQVATALKKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGS 152

                 ..
gi 124506595 362 TT 363
Cdd:cd14229  153 AS 154