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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923  1501 CSGLEHLKPYHVTHCDLRLENLLLVHyqpggtaqgfgpaeptptssyPTRLIVSNFSQAKQkshLVDPEILRDQ--SR-- 1576
Cdd:smart00220  107 LSALEYLHSKGIVHRDLKPENILLDE---------------------DGHVKLADFGLARQ---LDPGEKLTTFvgTPey 162

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923  1577 LAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFDENPELKE--REYTRADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:smart00220  163 MAPEVLLGKGYgKAVDIWSLGVILYELLTGKPPFPGDDQLLElfKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKR 242

                           170
                    ....*....|.
gi 2462545923  1654 IlisDAKGILQ 1664
Cdd:smart00220  243 L---TAEEALQ 250

NIMA-related protein kinase; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1548 PTRLI-VSNFSQAKQKSHLVDPEILRD----QSRLAPEIITATQY-KKCDEFQTGILIYEMLHLPNPF---DENPELKER 1618
Cdd:PTZ00267   204 PTGIIkLGDFGFSKQYSDSVSLDVASSfcgtPYYLAPELWERKRYsKKADMWSLGVILYELLTLHRPFkgpSQREIMQQV 283

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 2462545923 1619 EYTRADlpriPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:PTZ00267   284 LYGKYD----PFPCPVSSGMKALLDPLLSKNPALR 314

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923  1501 CSGLEHLKPYHVTHCDLRLENLLLVHyqpggtaqgfgpaeptptssyPTRLIVSNFSQAKQkshLVDPEILRDQ--SR-- 1576
Cdd:smart00220  107 LSALEYLHSKGIVHRDLKPENILLDE---------------------DGHVKLADFGLARQ---LDPGEKLTTFvgTPey 162

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923  1577 LAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFDENPELKE--REYTRADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:smart00220  163 MAPEVLLGKGYgKAVDIWSLGVILYELLTGKPPFPGDDQLLElfKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKDPEKR 242

                           170
                    ....*....|.
gi 2462545923  1654 IlisDAKGILQ 1664
Cdd:smart00220  243 L---TAEEALQ 250

Protein kinase domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1577 LAPEIITATQY-KKCDEFQTGILIYEML--HLPNPFDENPELKEREYtRADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:pfam00069  127 MAPEVLGGNPYgPKVDVWSLGCILYELLtgKPPFPGINGNEIYELII-DQPYAFPELPSNLSEEAKDLLKKLLKKDPSKR 205

                   ....*..
gi 2462545923 1654 ILISDAK 1660
Cdd:pfam00069  206 LTATQAL 212

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 2462545923 1502 SGLEHLKPYHVTHCDLRLENLLLVhyqpggtaqgfgpaeptpTSSYPTRLIVSNFSQAKqksHLvDPEILRDQ---SRL- 1577
Cdd:cd14009    103 SGLKFLRSKNIIHRDLKPQNLLLS------------------TSGDDPVLKIADFGFAR---SL-QPASMAETlcgSPLy 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1578 -APEIITATQY-KKCDEFQTGILIYEMLHLPNPF--DENPELkEREYTRADLP-RIPFRSPYSRGLQQLASCLLNPNPSE 1652
Cdd:cd14009    161 mAPEILQFQKYdAKADLWSVGAILFEMLVGKPPFrgSNHVQL-LRNIERSDAViPFPIAAQLSPDCKDLLRRLLRRDPAE 239

                   ..
gi 2462545923 1653 RI 1654
Cdd:cd14009    240 RI 241

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        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1476 RDSLAQHGKspdLYERQVCLLLLQLCSGLEHLkpyH---VTHCDLRLENLLLvhyqpggTAQGfgpaeptptssyptRLI 1552
Cdd:cd14014     88 ADLLRERGP---LPPREALRILAQIADALAAA---HragIVHRDIKPANILL-------TEDG--------------RVK 140

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1553 VSNFSQAKQKShlvDPEILRDQSRL------APEIITATQY-KKCDEFQTGILIYEML--HLPNPFDENPELKEREYTRA 1623
Cdd:cd14014    141 LTDFGIARALG---DSGLTQTGSVLgtpaymAPEQARGGPVdPRSDIYSLGVVLYELLtgRPPFDGDSPAAVLAKHLQEA 217

                          170       180       190
                   ....*....|....*....|....*....|
gi 2462545923 1624 DLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:cd14014    218 PPPPSPLNPDVPPALDAIILRALAKDPEER 247

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1477 DSLAQHGKSPDLYERQVCLLLLQLCSGLEHLKPYHVTHCDLRLENLLLvhyQPGGTAQ--GFGPAEPTPTSsyptrlivs 1554
Cdd:cd13997     89 DALEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFI---SNKGTCKigDFGLATRLETS--------- 156

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1555 nfsqakqkshlvdPEILRDQSR-LAPEIITATQY--KKCDEFQTGILIYEM---LHLPNPFDENPELKEreytrADLPRI 1628
Cdd:cd13997    157 -------------GDVEEGDSRyLAPELLNENYThlPKADIFSLGVTVYEAatgEPLPRNGQQWQQLRQ-----GKLPLP 218

                          170       180
                   ....*....|....*....|....*...
gi 2462545923 1629 PfRSPYSRGLQQLASCLLNPNPSERILI 1656
Cdd:cd13997    219 P-GLVLSQELTRLLKVMLDPDPTRRPTA 245

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1501 CSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTAqgfgpaeptptssyptrLIVSNFSQAKqksHLVDP--EILRDQSRLA 1578
Cdd:cd14185    108 CEALVYIHSKHIVHRDLKPENLLVQHNPDKSTT-----------------LKLADFGLAK---YVTGPifTVCGTPTYVA 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1579 PEIITATQYK-KCDEFQTGILIYEMLHLPNPFDENPELKEREYTRADLPRIPFRSPY----SRGLQQLASCLLNPNPSER 1653
Cdd:cd14185    168 PEILSEKGYGlEVDMWAAGVILYILLCGFPPFRSPERDQEELFQIIQLGHYEFLPPYwdniSEAAKDLISRLLVVDPEKR 247

                          170
                   ....*....|.
gi 2462545923 1654 IlisDAKGILQ 1664
Cdd:cd14185    248 Y---TAKQVLQ 255

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 2462545923 1503 GLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaeptpTSSYPTRLIvsNFSQAKQKSHLVDpeilRDQ-----SRL 1577
Cdd:cd05122    110 GLEYLHSHGIIHRDIKAANILL-------------------TSDGEVKLI--DFGLSAQLSDGKT----RNTfvgtpYWM 164

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2462545923 1578 APEIITATQY-KKCDEFQTGILIYEMLHLPNPFDENPELKEREYT-RADLPRIPFRSPYSRGLQQLASCLLNPNPSER 1653
Cdd:cd05122    165 APEVIQGKPYgFKADIWSLGITAIEMAEGKPPYSELPPMKALFLIaTNGPPGLRNPKKWSKEFKDFLKKCLQKDPEKR 242

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1501 CSGLEHLKPYHVTHCDLRLENLLLvhyqpggTAQG------FGpaeptptssyptrliVSNFSQAKQKshlvdpeiLRDQ 1574
Cdd:cd14003    109 ISAVDYCHSNGIVHRDLKLENILL-------DKNGnlkiidFG---------------LSNEFRGGSL--------LKTF 158

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1575 ----SRLAPEIITATQY--KKCDEFQTGILIYEML--HLpnPFDeNPELKEREY--TRADLPRIPFRSPysrGLQQLASC 1644
Cdd:cd14003    159 cgtpAYAAPEVLLGRKYdgPKADVWSLGVILYAMLtgYL--PFD-DDNDSKLFRkiLKGKYPIPSHLSP---DARDLIRR 232

                          170
                   ....*....|....*.
gi 2462545923 1645 LLNPNPSERILISDAK 1660
Cdd:cd14003    233 MLVVDPSKRITIEEIL 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 2462545923 1501 CSGLEHLKPYHVTHCDLRLENLLLvhyqpggTAQG------FGpaeptptssyptrliVSNFSQAKQKSHLV---Dpeil 1571
Cdd:cd14007    110 ALALDYLHSKNIIHRDIKPENILL-------GSNGelkladFG---------------WSVHAPSNRRKTFCgtlD---- 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1572 rdqsRLAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFdENPELKEReYTRADLPRIPFRSPYSRGLQQLASCLLNPNP 1650
Cdd:cd14007    164 ----YLPPEMVEGKEYdYKVDIWSLGVLCYELLVGKPPF-ESKSHQET-YKRIQNVDIKFPSSVSPEAKDLISKLLQKDP 237

                          170
                   ....*....|
gi 2462545923 1651 SERILISDAK 1660
Cdd:cd14007    238 SKRLSLEQVL 247

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 2462545923 1502 SGLEHLKPYHVTHCDLRLENLLLVhyqpggtaqgfgpaepTPTSSypTRLIVSNFSQAKQKSHLVDPEILRDQSRLAPEI 1581
Cdd:cd14166    111 SAVKYLHENGIVHRDLKPENLLYL----------------TPDEN--SKIMITDFGLSKMEQNGIMSTACGTPGYVAPEV 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1582 ITATQYKKC-DEFQTGILIYEMLHLPNPFDENPE------LKEREYTradlpripFRSPY----SRGLQQLASCLLNPNP 1650
Cdd:cd14166    173 LAQKPYSKAvDCWSIGVITYILLCGYPPFYEETEsrlfekIKEGYYE--------FESPFwddiSESAKDFIRHLLEKNP 244

                   ...
gi 2462545923 1651 SER 1653
Cdd:cd14166    245 SKR 247

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1578 APEIITATQY-KKCDEFQTGILIYEMLHLPNPFDE--NPELKEReYTRADLPRIPFRspYSRGLQQLASCLLNPNPSERI 1654
Cdd:cd08217    178 SPELLNEQSYdEKSDIWSLGCLIYELCALHPPFQAanQLELAKK-IKEGKFPRIPSR--YSSELNEVIKSMLNVDPDKRP 254

                   ....
gi 2462545923 1655 LISD 1658
Cdd:cd08217    255 SVEE 258

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1490 ERQVCLLLLQLCSGLEHLKPYHVTHCDLRLENLLLVHyqpggtaqgfgpaeptpTSSYPTRLIVSNFSQAKQ----KSHL 1565
Cdd:cd14175     94 EREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVD-----------------ESGNPESLRICDFGFAKQlraeNGLL 156

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1566 VDPeiLRDQSRLAPEIITATQYKK-CDEFQTGILIYEMLHLPNPFDENPE-LKEREYTRADLPRIPFR----SPYSRGLQ 1639
Cdd:cd14175    157 MTP--CYTANFVAPEVLKRQGYDEgCDIWSLGILLYTMLAGYTPFANGPSdTPEEILTRIGSGKFTLSggnwNTVSDAAK 234

                          170       180
                   ....*....|....*....|....*
gi 2462545923 1640 QLASCLLNPNPSERIlisDAKGILQ 1664
Cdd:cd14175    235 DLVSKMLHVDPHQRL---TAKQVLQ 256

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1502 SGLEHLKPyHVTHCDLRLENLLLvhyqpggTAQG------FGPAeptptssypTRLIVSnfSQAKQKSHLVDPEILRD-- 1573
Cdd:cd14037    122 AAMHYLKP-PLIHRDLKVENVLI-------SDSGnyklcdFGSA---------TTKILP--PQTKQGVTYVEEDIKKYtt 182

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1574 -QSRlAPEIITATQYK----KCDEFQTGILIYEMLHLPNPFDENPEL--KEREYTradlprIPFRSPYSRGLQQLASCLL 1646
Cdd:cd14037    183 lQYR-APEMIDLYRGKpiteKSDIWALGCLLYKLCFYTTPFEESGQLaiLNGNFT------FPDNSRYSKRLHKLIRYML 255

                   ....*..
gi 2462545923 1647 NPNPSER 1653
Cdd:cd14037    256 EEDPEKR 262

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1503 GLEHLKPYHVTHCDLRLENLLlvHYQPGGTAqgfgpaeptptssyptRLIVSNF---SQAKQKSHLVDPEILRDQSRLAP 1579
Cdd:cd14087    109 GVKYLHGLGITHRDLKPENLL--YYHPGPDS----------------KIMITDFglaSTRKKGPNCLMKTTCGTPEYIAP 170

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1580 EIITATQY-KKCDEFQTGILIYEMLHLPNPFDEnpELKEREYTRADLPRIPFRSPYSRGLQQLAS----CLLNPNPSERI 1654
Cdd:cd14087    171 EILLRKPYtQSVDMWAVGVIAYILLSGTMPFDD--DNRTRLYRQILRAKYSYSGEPWPSVSNLAKdfidRLLTVNPGERL 248

                   ....*
gi 2462545923 1655 LISDA 1659
Cdd:cd14087    249 SATQA 253

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaeptptsSYPTRLIVSNFSQAKQKSHlVDPEILRDQSR----- 1576
Cdd:cd14069    111 AGLKYLHSCGITHRDIKPENLLL---------------------DENDNLKISDFGLATVFRY-KGKERLLNKMCgtlpy 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1577 LAPEIITATQYK--KCDEFQTGILIYEMLHLPNPFDEnPELKEREYTRADLPRIPFRSPYSRgLQQLASCLLN----PNP 1650
Cdd:cd14069    169 VAPELLAKKKYRaePVDVWSCGIVLFAMLAGELPWDQ-PSDSCQEYSDWKENKKTYLTPWKK-IDTAALSLLRkiltENP 246

                          170
                   ....*....|
gi 2462545923 1651 SERILISDAK 1660
Cdd:cd14069    247 NKRITIEDIK 256

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 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 2462545923 1490 ERQVCLLLLQLCSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTAQ--GFGPAEPTPT-SSYPTRLIVSNFsqakqkshlv 1566
Cdd:cd14170    100 EREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAILKltDFGFAKETTShNSLTTPCYTPYY---------- 169

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1567 dpeilrdqsrLAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFDEN------PELKER-EYTRADLPRiPFRSPYSRGL 1638
Cdd:cd14170    170 ----------VAPEVLGPEKYdKSCDMWSLGVIMYILLCGYPPFYSNhglaisPGMKTRiRMGQYEFPN-PEWSEVSEEV 238

                          170       180
                   ....*....|....*....|
gi 2462545923 1639 QQLASCLLNPNPSERILISD 1658
Cdd:cd14170    239 KMLIRNLLKTEPTQRMTITE 258

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1502 SGLEHLKPYHVTHCDLRLENLLLvhyqpggtaqgfgpaeptptSSYPTRLIVSNFSQAKQKShlvDPEILR-----DQSR 1576
Cdd:cd14164    111 GAVNYLHDMNIVHRDLKCENILL--------------------SADDRKIKIADFGFARFVE---DYPELSttfcgSRAY 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1577 LAPEIITATQY--KKCDEFQTGILIYEMLHLPNPFDEnpelkereyTRADLPRIPFRS-PYSRGLQQLASC------LLN 1647
Cdd:cd14164    168 TPPEVILGTPYdpKKYDVWSLGVVLYVMVTGTMPFDE---------TNVRRLRLQQRGvLYPSGVALEEPCralirtLLQ 238

                   ....*.
gi 2462545923 1648 PNPSER 1653
Cdd:cd14164    239 FNPSTR 244

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated 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 MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1490 ERQVCLLLLQLCSGLEHLKPYHVTHCDLRLENLLLVHYQPGGTAQ--GFGPA-EPTPTSSYPTRLIVSNFsqakqkshlv 1566
Cdd:cd14089     99 EREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGPNAILKltDFGFAkETTTKKSLQTPCYTPYY---------- 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2462545923 1567 dpeilrdqsrLAPEIITATQY-KKCDEFQTGILIYEMLHLPNPFDEN------PELKER----EYTRADlpriPFRSPYS 1635
Cdd:cd14089    169 ----------VAPEVLGPEKYdKSCDMWSLGVIMYILLCGYPPFYSNhglaisPGMKKRirngQYEFPN----PEWSNVS 234

                          170       180
                   ....*....|....*....|...
gi 2462545923 1636 RGLQQLASCLLNPNPSERILISD 1658
Cdd:cd14089    235 EEAKDLIRGLLKTDPSERLTIEE 257