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 1620184288 412 LVLTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKStpmytTSLRHLDDSldlcifESCVPC- 490
Cdd:cd13994    93 DSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTA-----EVFGMPAEK------ESPMSAg 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 491 -VGKEAYMPPEcmaLYKEYRkmkvsspfdyansvrdrrerrkwyFDVLTAEKYMLGIFFIWIWNEGHLWDCSDPSrDEIF 569
Cdd:cd13994   162 lCGSEPYMAPE---VFTSGS------------------------YDGRAVDVWSCGIVLFALFTGRFPWRSAKKS-DSAY 213

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1620184288 570 NEIneCEMDIDKCELTE----DWPEELKVMIKRLLNFESRKELNLKDIFDDPW 618
Cdd:cd13994   214 KAY--EKSGDFTNGPYEpienLLPSECRRLIYRMLHPDPEKRITIDEALNDPW 264

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMYTTSLRHLDDSLDLCIFescvpcvgkeaYMPPECM 502
Cdd:pfam07714 118 LESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKRGGGKLPIK-----------WMAPESL 176

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 1620184288 412 LVLTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKStpmytTSLRHLDDSldlcifESCVPC- 490
Cdd:cd13994    93 DSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTA-----EVFGMPAEK------ESPMSAg 161

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 491 -VGKEAYMPPEcmaLYKEYRkmkvsspfdyansvrdrrerrkwyFDVLTAEKYMLGIFFIWIWNEGHLWDCSDPSrDEIF 569
Cdd:cd13994   162 lCGSEPYMAPE---VFTSGS------------------------YDGRAVDVWSCGIVLFALFTGRFPWRSAKKS-DSAY 213

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1620184288 570 NEIneCEMDIDKCELTE----DWPEELKVMIKRLLNFESRKELNLKDIFDDPW 618
Cdd:cd13994   214 KAY--EKSGDFTNGPYEpienLLPSECRRLIYRMLHPDPEKRITIDEALNDPW 264

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKStpmyttslRHLDDSLDLcifesCVPCVGKEAYMPPECMA-LYKEYRKM 511
Cdd:cd14008   124 LHENGIVHRDIKPENLLLTADGTVKISDFGVS--------EMFEDGNDT-----LQKTAGTPAFLAPELCDgDSKTYSGK 190

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 512 KVsspfdyansvrdrrerrkwyfDVltaekYMLGI-FFIWIWneGHL-WDCSDPSrdEIFNEINECEMDIDkceLTEDWP 589
Cdd:cd14008   191 AA---------------------DI-----WALGVtLYCLVF--GRLpFNGDNIL--ELYEAIQNQNDEFP---IPPELS 237

                         170       180
                  ....*....|....*....|....*....
gi 1620184288 590 EELKVMIKRLLNFESRKELNLKDIFDDPW 618
Cdd:cd14008   238 PELKDLLRRMLEKDPEKRITLKEIKEHPW 266

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 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTpmyttslrHLDDS--LDLCifescvpcvGKEAYMPPEcMALYKEYrk 510
Cdd:cd14007   116 LHSKNIIHRDIKPENILLGSNGELKLADFGWSV--------HAPSNrrKTFC---------GTLDYLPPE-MVEGKEY-- 175

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 511 mkvsspfDYANSVrdrrerrkWYFDVLTAEKYMlgiffiwiwneGHL-WDcsDPSRDEIFNEINECEMDIDkceltEDWP 589
Cdd:cd14007   176 -------DYKVDI--------WSLGVLCYELLV-----------GKPpFE--SKSHQETYKRIQNVDIKFP-----SSVS 222

                         170       180
                  ....*....|....*....|....*....
gi 1620184288 590 EELKVMIKRLLNFESRKELNLKDIFDDPW 618
Cdd:cd14007   223 PEAKDLISKLLQKDPSKRLSLEQVLNHPW 251

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 1620184288 378 EGNIIIISELFGQ-DLFNYIDKRRDdndmddddddlvLTVEEKKNI---LYKALNlYtrLHEAGLTHLDLSAENVLIDDN 453
Cdd:cd14003    71 ENKIYLVMEYASGgELFDYIVNNGR------------LSEDEARRFfqqLISAVD-Y--CHSNGIVHRDLKLENILLDKN 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 454 NEVRLCDLGKSTPMYTTSLRHlddsldlcifESCvpcvGKEAYMPPEcMALYKEYRKMKVsspfdyansvrdrrerrkwy 533
Cdd:cd14003   136 GNLKIIDFGLSNEFRGGSLLK----------TFC----GTPAYAAPE-VLLGRKYDGPKA-------------------- 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 534 fDVLTaekymLGI--FFIWIwneGHL-WDcsDPSRDEIFNEINECEMDIdkceltEDW-PEELKVMIKRLLNFESRKELN 609
Cdd:cd14003   181 -DVWS-----LGVilYAMLT---GYLpFD--DDNDSKLFRKILKGKYPI------PSHlSPDARDLIRRMLVVDPSKRIT 243

                  ....*....
gi 1620184288 610 LKDIFDDPW 618
Cdd:cd14003   244 IEEILNHPW 252

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They 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. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK 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 1620184288 430 YTR--------LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKStpmyttslRHLDDSldlCIFESCVPCVGKEAYMPPEC 501
Cdd:cd06606   104 YTRqilegleyLHSNGIVHRDIKGANILVDSDGVVKLADFGCA--------KRLAEI---ATGEGTKSLRGTPYWMAPEV 172

                  .
gi 1620184288 502 M 502
Cdd:cd06606   173 I 173

Uncharacterized conserved protein YegI with protein kinase and helix-hairpin-helix DNA-binding domains [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 423 LYKALNLYT---RLHEAGLTHLDLSAENVLIDDNNEVRLCDLgkstpmyttslrhldDSL---DLCIFESCVpcVGKEAY 496
Cdd:COG4248   124 LRTARNLAAavaALHAAGYVHGDVNPSNILVSDTALVTLIDT---------------DSFqvrDPGKVYRCV--VGTPEF 186

                  ....
gi 1620184288 497 MPPE 500
Cdd:COG4248   187 TPPE 190

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 1620184288 423 LYKALNLYTRLHEAGLTHLDLSAENVLI-DDNNEVRLCDLGKSTpmyttslrHLDDS-LDLCIFESCVPcVGKEAYMPPE 500
Cdd:cd13991   104 LGQALEGLEYLHSRKILHGDVKADNVLLsSDGSDAFLCDFGHAE--------CLDPDgLGKSLFTGDYI-PGTETHMAPE 174

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. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. 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 CDKL 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1620184288 414 LTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMYTTSLRHLDD 477
Cdd:cd07833    97 LPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFARALTARPASPLTD 160

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 1620184288 422 ILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMYTTSLRHldDSldlcifescvpCVGKEAYMPPEC 501
Cdd:cd06608   118 ILRETLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGVSAQLDSTLGRR--NT-----------FIGTPYWMAPEV 184

                  ..
gi 1620184288 502 MA 503
Cdd:cd06608   185 IA 186

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 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 1620184288 412 LVLTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGkstpmYTTSLRHLDDSLDLCifescvpcv 491
Cdd:cd14181   111 VTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFG-----FSCHLEPGEKLRELC--------- 176

                          90
                  ....*....|.
gi 1620184288 492 GKEAYMPPECM 502
Cdd:cd14181   177 GTPGYLAPEIL 187

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin 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 1620184288 422 ILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMYTTSLRHLDDsldlcifescvpcVGKEAYMPPEC 501
Cdd:cd06639   133 ILYGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGVSAQLTSARLRRNTS-------------VGTPFWMAPEV 199

                          90       100
                  ....*....|....*....|...
gi 1620184288 502 MALYKEYrkmkvsspfDYANSVR 524
Cdd:cd06639   200 IACEQQY---------DYSYDAR 213

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 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPM-YTTSLRHLDDSldlcifescvpcVGKEAYMPPECMAlYKEYRKM 511
Cdd:cd14069   116 LHSCGITHRDIKPENLLLDENDNLKISDFGLATVFrYKGKERLLNKM------------CGTLPYVAPELLA-KKKYRAE 182

                  ..
gi 1620184288 512 KV 513
Cdd:cd14069   183 PV 184

Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Vps15 is a large protein consisting of an N-terminal kinase domain, a C-terminal WD-repeat containing domain, and an intermediate bridge domain that contain HEAT repeats. The kinase domain is necessary for the signaling functions of Vps15. Human Vps15 was previously called p150. It associates and regulates Vps34, also called Class III phosphoinositide 3-kinase (PI3K), which catalyzes the phosphorylation of D-myo-phosphatidylinositol (PtdIns). Vps34 is the only PI3K present in yeast. It plays an important role in the regulation of protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. The Vps15 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 PI3K.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1620184288 414 LTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMY 468
Cdd:cd13980    94 LNLIEKKWIAFQLLHALNQCHKRGVCHGDIKTENVLVTSWNWVYLTDFASFKPTY 148

Catalytic kinase domain, second 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
                  ....*....|....*....|....*....|....*....|....*....|
gi 1620184288 418 EKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPM 467
Cdd:cd14110   100 EVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPF 149

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 1620184288 433 LHEAGLTHLDLSAENVLID-DNNEVRLCDLGKSTPMYTTSlrhlDDSLDLCifescvpcvGKEAYMPPEcMALYKEY--R 509
Cdd:cd14164   116 LHDMNIVHRDLKCENILLSaDDRKIKIADFGFARFVEDYP----ELSTTFC---------GSRAYTPPE-VILGTPYdpK 181

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1620184288 510 KMKVSS-------------PFDYANSVRDRRERR 530
Cdd:cd14164   182 KYDVWSlgvvlyvmvtgtmPFDETNVRRLRLQQR 215

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 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 1620184288 423 LYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCDLG 462
Cdd:cd07856   114 LYQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFG 153

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK 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 1620184288 381 IIIISELFGQDLFNYIDKRRddndmddddddlVLTVEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCD 460
Cdd:cd07834    79 VYIVTELMETDLHKVIKSPQ------------PLTDDHIQYFLYQILRGLKYLHSAGVIHRDLKPSNILVNSNCDLKICD 146

                  ..
gi 1620184288 461 LG 462
Cdd:cd07834   147 FG 148

3-deoxy-D-manno-octulosonic-acid kinase; Reviewed

                          10        20        30
                  ....*....|....*....|....*....|..
gi 1620184288 432 RLHEAGLTHLDLSAENVLIDDNNEVRLCDLGK 463
Cdd:PRK01723  157 RFHDAGVYHADLNAHNILLDPDGKFWLIDFDR 188

C-terminal catalytic domain of the atypical protein serine kinase, RIO2 kinase; RIO2 is present in archaea and eukaryotes. It contains an N-terminal winged helix (wHTH) domain and a C-terminal RIO kinase catalytic domain. The wHTH domain is primarily seen in DNA-binding proteins, although some wHTH domains may be involved in RNA recognition. RIO2 is essential for survival and is necessary for rRNA cleavage during 40S ribosomal subunit maturation. RIO kinases are atypical protein serine kinases containing a kinase catalytic signature, but otherwise show very little sequence similarity to typical PKs. Serine kinases catalyze the transfer of the gamma-phosphoryl group from ATP to serine residues in protein substrates. The RIO catalytic domain is truncated compared to the catalytic domains of typical PKs, with deletions of the loops responsible for substrate binding. The RIO2 kinase catalytic domain family is part of a larger superfamily, that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 1620184288 416 VEEKKNILYKALNLYTRLHEAGLTHLDLSAENVLIDDNNEVRLCD 460
Cdd:cd05144   109 LEDPEEVLDEILELIVKLAKHGLIHGDFSEFNILVDEDEKITVID 153

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 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
                  ....*....|....*....|....*....|....*....|
gi 1620184288 433 LHEAGLTHLDLSAENVLIDDNN--EVRLCDLGKSTPMYTT 470
Cdd:cd13987   107 MHSKNLVHRDIKPENVLLFDKDcrRVKLCDFGLTRRVGST 146

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK 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 1620184288 413 VLTVEEKKNILYKALNLYTRLHEAGLT---HLDLSAENVLIDDNNEVRLCDLGkstpmyttslrhlddsLDLCIFESCVP 489
Cdd:cd14066    89 PLPWPQRLKIAKGIARGLEYLHEECPPpiiHGDIKSSNILLDEDFEPKLTDFG----------------LARLIPPSESV 152

                          90
                  ....*....|....*.
gi 1620184288 490 CV-----GKEAYMPPE 500
Cdd:cd14066   153 SKtsavkGTIGYLAPE 168

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 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 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLGKSTPMYTTSLRHLDDSLDLCIFESCVPCVGKEAYMPPE 500
Cdd:cd14027   106 LHGKGVIHKDLKPENILVDNDFHIKIADLGLASFKMWSKLTKEEHNEQREVDGTAKKNAGTLYYMAPE 173

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

                          10        20        30
                  ....*....|....*....|....*....|
gi 1620184288 433 LHEAGLTHLDLSAENVLIDDNNEVRLCDLG 462
Cdd:cd05577   111 LHNRFIVYRDLKPENILLDDHGHVRISDLG 140

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1620184288 380 NIIIISELF--------------GQDLFNYIDKRRddndmddddddlVLTVEEKKNILYKALNLYTRLHEAGLTHLDLSA 445
Cdd:cd14073    62 HIIRIYEVFenkdkivivmeyasGGELYDYISERR------------RLPEREARRIFRQIVSAVHYCHKNGVVHRDLKL 129

                          90
                  ....*....|....*....
gi 1620184288 446 ENVLIDDNNEVRLCDLGKS 464
Cdd:cd14073   130 ENILLDQNGNAKIADFGLS 148