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 2187430147  11 ERESVHFLVSEFVscrPGEassmTLQDALDRPTELlmKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrTADPr 90
Cdd:cd14014    70 EDDGRPYIVMEYV---EGG----SLADLLRERGPL--PPREALRILAQIADALAAAHRAGIVHRDIKPANILL--TEDG- 137

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2187430147  91 akaRAKLIDLGNACWESRPACFDVDSSRSS--HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:cd14014   138 ---RVKLTDFGIARALGDSGLTQTGSVLGTpaYMAPEQARGGPVDPRSDIYSLG 188

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 2187430147  11 ERESVHFLVSEFVscrPGEassmTLQDALDRPTELlmKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrTADPr 90
Cdd:cd14014    70 EDDGRPYIVMEYV---EGG----SLADLLRERGPL--PPREALRILAQIADALAAAHRAGIVHRDIKPANILL--TEDG- 137

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2187430147  91 akaRAKLIDLGNACWESRPACFDVDSSRSS--HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:cd14014   138 ---RVKLTDFGIARALGDSGLTQTGSVLGTpaYMAPEQARGGPVDPRSDIYSLG 188

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2187430147   47 MKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVYRtadpraKARAKLIDLGNACwesrpaCFDVDSSRSS------ 120
Cdd:smart00220  94 LSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDE------DGHVKLADFGLAR------QLDPGEKLTTfvgtpe 161

                           90       100
                   ....*....|....*....|..
gi 2187430147  121 HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:smart00220 162 YMAPEVLLGKGYGKAVDIWSLG 183

serine/threonine-protein kinase 1; Provisional

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2187430147  54 NVLHEVATGVHYLHAQHILHNDIKTDNVLvYRtadpRAKARAKLIDLGNACWESRPACFD 113
Cdd:PHA03390  113 KIIRQLVEALNDLHKHNIIHNDIKLENVL-YD----RAKDRIYLCDYGLCKIIGTPSCYD 167

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 2187430147  11 ERESVHFLVSEFVscrPGEassmTLQDALDRPTELlmKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrTADPr 90
Cdd:cd14014    70 EDDGRPYIVMEYV---EGG----SLADLLRERGPL--PPREALRILAQIADALAAAHRAGIVHRDIKPANILL--TEDG- 137

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2187430147  91 akaRAKLIDLGNACWESRPACFDVDSSRSS--HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:cd14014   138 ---RVKLTDFGIARALGDSGLTQTGSVLGTpaYMAPEQARGGPVDPRSDIYSLG 188

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2187430147  11 ERESVHFLVSEFVscrPGEassmTLQDALDRPTELLMKdyEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrtadpR 90
Cdd:COG0515    77 EEDGRPYLVMEYV---EGE----SLADLLRRRGPLPPA--EALRILAQLAEALAAAHAAGIVHRDIKPANILL------T 141

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2187430147  91 AKARAKLIDLGNACWESRPACFDVDSSRSS--HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:COG0515   142 PDGRVKLIDFGIARALGGATLTQTGTVVGTpgYMAPEQARGEPVDPRSDVYSLG 195

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 2187430147  55 VLHEVATGVHYLHAQHILHNDIKTDNVLVYRtadpraKARAKLIDLGnacwesrpACFDVDSSRSSH--------IAPEV 126
Cdd:cd05122   103 VCKEVLKGLEYLHSHGIIHRDIKAANILLTS------DGEVKLIDFG--------LSAQLSDGKTRNtfvgtpywMAPEV 168

                          90
                  ....*....|....*.
gi 2187430147 127 AVGGPVSSYSDIYSFG 142
Cdd:cd05122   169 IQGKPYGFKADIWSLG 184

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK 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 2187430147  27 PGEASSMTLQDALDRPTELLMKDYEYInvLHEVATGVHYLHAQHILHNDIKTDNVLVyrtadpRAKARAKLIDLGNAC-W 105
Cdd:cd14004    88 EKHGSGMDLFDFIERKPNMDEKEAKYI--FRQVADAVKHLHDQGIVHRDIKDENVIL------DGNGTIKLIDFGSAAyI 159

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2187430147 106 ESRPacFDVDSSRSSHIAPEVAVGGP-VSSYSDIYSFGYL 144
Cdd:cd14004   160 KSGP--FDTFVGTIDYAAPEVLRGNPyGGKEQDIWALGVL 197

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 2187430147  34 TLQDALDRPTELLMKdYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVYRTADPrakaraKLIDLGNACWESRPACFD 113
Cdd:cd13979    88 TLQQLIYEGSEPLPL-AHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVC------KLCDFGCSVKLGEGNEVG 160

                          90       100       110
                  ....*....|....*....|....*....|...
gi 2187430147 114 VDSSRS----SHIAPEVAVGGPVSSYSDIYSFG 142
Cdd:cd13979   161 TPRSHIggtyTYRAPELLKGERVTPKADIYSFG 193

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK 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 2187430147  46 LMKDYEY----INVLHEVAT----GVHYLHAQ-HILHNDIKTDNVLVYRTadpraKARAKLIDLGNACWesrpacfdVDS 116
Cdd:cd14136   107 LIKRYNYrgipLPLVKKIARqvlqGLDYLHTKcGIIHTDIKPENVLLCIS-----KIEVKIADLGNACW--------TDK 173

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2187430147 117 SRSSHI------APEVAVGGPVSSYSDIYSFGYLA 145
Cdd:cd14136   174 HFTEDIqtrqyrSPEVILGAGYGTPADIWSTACMA 208

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK 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 2187430147  56 LHEVATGVHYLHAQHILHNDIKTDNVLVyrTADPRakaRAKLIDLG------NACWESRPACFDVDSSRSSHIAPEVAVG 129
Cdd:cd13991   104 LGQALEGLEYLHSRKILHGDVKADNVLL--SSDGS---DAFLCDFGhaecldPDGLGKSLFTGDYIPGTETHMAPEVVLG 178

                          90
                  ....*....|.
gi 2187430147 130 GPVSSYSDIYS 140
Cdd:cd13991   179 KPCDAKVDVWS 189

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 2187430147  47 MKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrtaDPRAKARAKLIDLGNACWESRPACFDVDSSRSSHIAPEV 126
Cdd:cd14114    97 MSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMC----TTKRSNEVKLIDFGLATHLDPKESVKVTTGTAEFAAPEI 172

                          90
                  ....*....|....*....
gi 2187430147 127 AVGGPVSSYSDIYSFGYLA 145
Cdd:cd14114   173 VEREPVGFYTDMWAVGVLS 191

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 2187430147  12 RESVHF-LVSEFVScrpgeassMTLQDAL-DRPTEL---LMKDYeyinvLHEVATGVHYLHAQHILHNDIKTDNVLV-YR 85
Cdd:cd05118    71 RGGNHLcLVFELMG--------MNLYELIkDYPRGLpldLIKSY-----LYQLLQALDFLHSNGIIHRDLKPENILInLE 137

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2187430147  86 TADPrakaraKLIDLGNACWESRPACFDVDSSRsSHIAPEVAVGGPVSSYS-DIYSFG 142
Cdd:cd05118   138 LGQL------KLADFGLARSFTSPPYTPYVATR-WYRAPEVLLGAKPYGSSiDIWSLG 188

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin 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 2187430147  31 SSMTLQDALDRP---TELLMKDYeyinvLHEVATGVHYLHAQHILHNDIKTDNVLVYRTadprAKARAKLIDLGnacwes 107
Cdd:cd14107    81 SSEELLDRLFLKgvvTEAEVKLY-----IQQVLEGIGYLHGMNILHLDIKPDNILMVSP----TREDIKICDFG------ 145

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2187430147 108 rpACFDVDSSRSSH--------IAPEVAVGGPVSSYSDIYSFGYLA 145
Cdd:cd14107   146 --FAQEITPSEHQFskygspefVAPEIVHQEPVSAATDIWALGVIA 189

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 2187430147  54 NVLHEVATGVHYLHAQHILHNDIKTDNVLVYrtaDPRAKARAKLIDLGNACWESR-PACFDVDSSRS-SHIAPEVAVGGP 131
Cdd:cd14087   101 RVLQMVLDGVKYLHGLGITHRDLKPENLLYY---HPGPDSKIMITDFGLASTRKKgPNCLMKTTCGTpEYIAPEILLRKP 177

                          90
                  ....*....|....
gi 2187430147 132 VSSYSDIYSFGYLA 145
Cdd:cd14087   178 YTQSVDMWAVGVIA 191

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 2187430147  55 VLHEVATGVHYLHAQHILHNDIKTDNVLVyrtADP-RAKARAKLIDLGNACWESRPACFDVDSSRsSHIAPEVAVGGPVS 133
Cdd:cd14229   107 ILQQVATALKKLKSLGLIHADLKPENIML---VDPvRQPYRVKVIDFGSASHVSKTVCSTYLQSR-YYRAPEIILGLPFC 182

                  ....*....
gi 2187430147 134 SYSDIYSFG 142
Cdd:cd14229   183 EAIDMWSLG 191

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG 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 2187430147  35 LQDALDRPTELlmkDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrtADPRAKaRAKLIDLGNAcWESRPA---- 110
Cdd:cd14108    85 LERITKRPTVC---ESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLM---ADQKTD-QVRICDFGNA-QELTPNepqy 156

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 2187430147 111 CfdvDSSRSSHIAPEVAVGGPVSSYSDIYSFGYLA 145
Cdd:cd14108   157 C---KYGTPEFVAPEIVNQSPVSKVTDIWPVGVIA 188

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-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 2187430147  18 LVSEFvsCRPGEASSMtLQDALDRPTELLMKDYEYInvLHEVATGVHYLHAQHILHNDIKTDNVLVYRtadpraKARAKL 97
Cdd:cd06608    86 LVMEY--CGGGSVTDL-VKGLRKKGKRLKEEWIAYI--LRETLRGLAYLHENKVIHRDIKGQNILLTE------EAEVKL 154

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2187430147  98 IDLGnacwesrpACFDVDSS---RSSHI------APEV--AVGGPVSSY---SDIYSFG 142
Cdd:cd06608   155 VDFG--------VSAQLDSTlgrRNTFIgtpywmAPEViaCDQQPDASYdarCDVWSLG 205

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha 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 2187430147  35 LQDALDRPTELL-MKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrtADPRAKARAKLIDLGNACwesrpacfD 113
Cdd:cd14039    83 LRKLLNKPENCCgLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVL---QEINGKIVHKIIDLGYAK--------D 151

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2187430147 114 VDSSR--------SSHIAPEVAVGGPVSSYSDIYSFGYLA 145
Cdd:cd14039   152 LDQGSlctsfvgtLQYLAPELFENKSYTVTVDYWSFGTMV 191

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG 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 2187430147  62 GVHYLHAQHILHNDIKTDNVLVYRTadprakARAKLIDLGNAcWESRPACFDVDSSRS---SHIAPEVAVGGPVSSYSDI 138
Cdd:cd14111   111 GLEYLHGRRVLHLDIKPDNIMVTNL------NAIKIVDFGSA-QSFNPLSLRQLGRRTgtlEYMAPEMVKGEPVGPPADI 183

                  ....*.
gi 2187430147 139 YSFGYL 144
Cdd:cd14111   184 WSIGVL 189

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 2187430147   5 VFGVSSERESvHFLVSEFVScrpgEASSMTLQDALDRPTELLMKdyeyINVLHEVATGVHYLH--AQHILHNDIKTDNVL 82
Cdd:cd13978    57 LLGVCVERRS-LGLVMEYME----NGSLKSLLEREIQDVPWSLR----FRIIHEIALGMNFLHnmDPPLLHHDLKPENIL 127

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2187430147  83 VyrtadpRAKARAKLIDLGNACW------ESRPACFDVDSSRSSHIAPEV--AVGGPVSSYSDIYSFGYL 144
Cdd:cd13978   128 L------DNHFHVKISDFGLSKLgmksisANRRRGTENLGGTPIYMAPEAfdDFNKKPTSKSDVYSFAIV 191

Catalytic domain of Cyclin-Dependent protein Kinase 8-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 CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. 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 CDK8-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
                  ....*....|....*....|....*....|....*....|....*....|
gi 2187430147  54 NVLHEVATGVHYLHAQHILHNDIKTDNVLVyrTADPRAKARAKLIDLGNA 103
Cdd:cd07842   112 SLLWQILNGIHYLHSNWVLHRDLKPANILV--MGEGPERGVVKIGDLGLA 159

Catalytic domain of Fungal Pat1-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 Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-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 2187430147  54 NVLHEVATGVHYLHAQHILHNDIKTDNVLVYRTADprakaRAKLIDLGNACWESRPACFDVDSSRssHIAPEV--AVGGP 131
Cdd:cd13993   111 NVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDEG-----TVKLCDFGLATTEKISMDFGVGSEF--YMAPECfdEVGRS 183

                          90
                  ....*....|....*
gi 2187430147 132 VSSYS----DIYSFG 142
Cdd:cd13993   184 LKGYPcaagDIWSLG 198

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. 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 2187430147  34 TLQDALDRPTELLMKDYEYINVLHEVATGVHYLHAQHILHNDIKTDNVLVyrtadPRAKARAKLIDLGNAcwesrpacfD 113
Cdd:cd08220    85 TLFEYIQQRKGSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILL-----NKKRTVVKIGDFGIS---------K 150

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 2187430147 114 VDSSRSS---------HIAPEVAVGGPVSSYSDIYSFG 142
Cdd:cd08220   151 ILSSKSKaytvvgtpcYISPELCEGKPYNQKSDIWALG 188

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 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 2187430147  58 EVATGVHYLHAQHILHNDIKTDNVLVYrTADPRAKARAKLIDLGNACWESRpacFDVDSSRSS--HIAPEVAVGGPV-SS 134
Cdd:cd14068    94 HVADGLRYLHSAMIIYRDLKPHNVLLF-TLYPNCAIIAKIADYGIAQYCCR---MGIKTSEGTpgFRAPEVARGNVIyNQ 169

                          90
                  ....*....|
gi 2187430147 135 YSDIYSFGYL 144
Cdd:cd14068   170 QADVYSFGLL 179

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf 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 2187430147  53 INVLHEVATGVHYLHAQHILHNDIKTDNVLVYRtadpraKARAKLIDLGNACWESRPACFDVDSSRSSHI---APEV--- 126
Cdd:cd14062    92 IDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHE------DLTVKIGDFGLATVKTRWSGSQQFEQPTGSIlwmAPEVirm 165

                          90
                  ....*....|....*.
gi 2187430147 127 AVGGPVSSYSDIYSFG 142
Cdd:cd14062   166 QDENPYSFQSDVYAFG 181

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin 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 2187430147  51 EYINVLHEVATGVHYLHAQHILHNDIKTDNVlVYRTadpRAKARAKLIDLGNACWESRPACFDVDSSRSSHIAPEVAVGG 130
Cdd:cd14104    98 EIVSYVRQVCEALEFLHSKNIGHFDIRPENI-IYCT---RRGSYIKIIEFGQSRQLKPGDKFRLQYTSAEFYAPEVHQHE 173