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 1720400333 582 SKISIT-SLDAMDIscdysgsypMAVSPTEKGRHYTShQTPNQV-----KLG----TSYRTPKSVRRGAAPVDDGRILGT 651
Cdd:cd05610   151 SKVTLNrELNMMDI---------LTTPSMAKPKNDYS-RTPGQVlslisSLGfntpTPYRTPKSVRRGAARVEGERILGT 220

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 652 PDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKLSDNAQSAMDMLLTIDDS 731
Cdd:cd05610   221 PDYLAPELLLGKPHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIPWPEGEEELSVNAQNAIEILLTMDPT 300

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1720400333 732 KRAGMRELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFEARNNAQ 780
Cdd:cd05610   301 KRAGLKELKQHPLFHGVDWENLQNQTMPFIPQPDDETDTSYFEARNNAQ 349

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 582 SKISIT-SLDAMDIscdysgsypMAVSPTEKGRHYTShQTPNQV-----KLG----TSYRTPKSVRRGAAPVDDGRILGT 651
Cdd:cd05610   151 SKVTLNrELNMMDI---------LTTPSMAKPKNDYS-RTPGQVlslisSLGfntpTPYRTPKSVRRGAARVEGERILGT 220

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 652 PDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKLSDNAQSAMDMLLTIDDS 731
Cdd:cd05610   221 PDYLAPELLLGKPHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIPWPEGEEELSVNAQNAIEILLTMDPT 300

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1720400333 732 KRAGMRELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFEARNNAQ 780
Cdd:cd05610   301 KRAGLKELKQHPLFHGVDWENLQNQTMPFIPQPDDETDTSYFEARNNAQ 349

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333   32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVtLNRDINM 111
Cdd:smart00220  75 VMEYCEGGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQ-LDPGEKL 153

                   ....*..
gi 1720400333  112 MDILTTP 118
Cdd:smart00220 154 TTFVGTP 160

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKlsdNAQSAMDMLLTID 729
Cdd:PTZ00263  177 GTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNWFDG---RARDLVKGLLQTD 253

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720400333 730 DSKR-----AGMRELKQHPLFSEVDWENL--QHQTMPFVPQPDDETDTSYFEA-----RNNAQHLT 783
Cdd:PTZ00263  254 HTKRlgtlkGGVADVKNHPYFHGANWDKLyaRYYPAPIPVRVKSPGDTSNFEKypdspVDRLPPLT 319

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720400333  32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVT 104
Cdd:COG0515    85 VMEYVEGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARAL 157

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720400333  32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVTLNR 107
Cdd:PTZ00263   96 LLEFVVGGELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKKVPDR 171

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 1720400333  32 IMEYLIGGDVKSLLHIYGY-FDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVTLNRD 108
Cdd:pfam07714  79 VTEYMPGGDLLDFLRKHKRkLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDD 156

BREX system serine/threonine kinase PglW; Members of this family are PglW, a predicted serine/threonine kinase of the Pgl (phage growth limitation) system (now called BREX type 2) and the BREX type 3 system.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|..
gi 1720400333   66 ALDYLHRHGIIHRDLKPDNMLISNEG----HIKLTDFGLSKV 103
Cdd:NF033442   619 AVVHLEGQGVWHRDIKPDNIGIRPRPsrtlHLVLFDFSLAGA 660

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 582 SKISIT-SLDAMDIscdysgsypMAVSPTEKGRHYTShQTPNQV-----KLG----TSYRTPKSVRRGAAPVDDGRILGT 651
Cdd:cd05610   151 SKVTLNrELNMMDI---------LTTPSMAKPKNDYS-RTPGQVlslisSLGfntpTPYRTPKSVRRGAARVEGERILGT 220

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 652 PDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKLSDNAQSAMDMLLTIDDS 731
Cdd:cd05610   221 PDYLAPELLLGKPHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIPWPEGEEELSVNAQNAIEILLTMDPT 300

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1720400333 732 KRAGMRELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFEARNNAQ 780
Cdd:cd05610   301 KRAGLKELKQHPLFHGVDWENLQNQTMPFIPQPDDETDTSYFEARNNAQ 349

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 634 KSVRRGAAPVDDGRILGTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEk 713
Cdd:cd05579   154 QKKSNGAPEKEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWPEDPE- 232

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1720400333 714 LSDNAQSAMDMLLTIDDSKRAGMR---ELKQHPLFSEVDW 750
Cdd:cd05579   233 VSDEAKDLISKLLTPDPEKRLGAKgieEIKNHPFFKGIDW 272

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent 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 cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-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 1720400333 648 ILGTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAMDMLLT 727
Cdd:cd05580   158 LCGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFP---SFFDPDAKDLIKRLLV 234

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1720400333 728 IDDSKR-----AGMRELKQHPLFSEVDWENLQHQTM--PFVPQPDDETDTSYFEA 775
Cdd:cd05580   235 VDLTKRlgnlkNGVEDIKNHPWFAGIDWDALLQRKIpaPYVPKVRGPGDTSNFDK 289

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC 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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAMDMLLTID 729
Cdd:cd05570   158 GTPDYIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPFEGDDEDELFEAILNDEVLYP---RWLSREAVSILKGLLTKD 234

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1720400333 730 DSKRAGMR-----ELKQHPLFSEVDWENLQHQTM--PFVPQPDDETDTSYFEAR 776
Cdd:cd05570   235 PARRLGCGpkgeaDIKAHPFFRNIDWDKLEKKEVepPFKPKVKSPRDTSNFDPE 288

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 645 DGRILGTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKLSDNAQSAMDM 724
Cdd:cd05609   172 DKQVCGTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDEIEWPEGDDALPDDAQDLITR 251

                          90       100
                  ....*....|....*....|....*....
gi 1720400333 725 LLTIDDSKR---AGMRELKQHPLFSEVDW 750
Cdd:cd05609   252 LLQQNPLERlgtGGAEEVKQHPFFQDLDW 280

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEgEEKLSDNAQSAMDMLLTID 729
Cdd:cd05574   194 GTEEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGSNRDETFSNILKKELTFPE-SPPVSSEAKDLIRKLLVKD 272

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1720400333 730 DSKRAGMR----ELKQHPLFSEVDWENLQHQTMPFVPQPDD 766
Cdd:cd05574   273 PSKRLGSKrgasEIKRHPFFRGVNWALIRNMTPPIIPRPDD 313

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK 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 1720400333 650 GTPDYLAPELLL------GTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIL--KRDIPWPEgEEKLSDNAQSA 721
Cdd:cd05601   165 GTPDYIAPEVLTsmnggsKGTYGVECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMnfKKFLKFPE-DPKVSESAVDL 243

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720400333 722 MDMLLTiDDSKRAGMRELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFE-------ARNNAQHLTISGFS 788
Cdd:cd05601   244 IKGLLT-DAKERLGYEGLCCHPFFSGIDWNNLRQTVPPFVPTLTSDDDTSNFDefepkktRPSYENFNKSKGFS 316

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGeekLSDNAQSAMDMLLTID 729
Cdd:cd05123   155 GTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPEY---VSPEAKSLISGLLQKD 231

                          90
                  ....*....|....*....
gi 1720400333 730 DSKRAG---MRELKQHPLF 745
Cdd:cd05123   232 PTKRLGsggAEEIKAHPFF 250

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333   32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKVtLNRDINM 111
Cdd:smart00220  75 VMEYCEGGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQ-LDPGEKL 153

                   ....*..
gi 1720400333  112 MDILTTP 118
Cdd:smart00220 154 TTFVGTP 160

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720400333  32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSK 102
Cdd:cd05573    79 VMEYMPGGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCT 149

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKlsdNAQSAMDMLLTID 729
Cdd:PTZ00263  177 GTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNWFDG---RARDLVKGLLQTD 253

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720400333 730 DSKR-----AGMRELKQHPLFSEVDWENL--QHQTMPFVPQPDDETDTSYFEA-----RNNAQHLT 783
Cdd:PTZ00263  254 HTKRlgtlkGGVADVKNHPYFHGANWDKLyaRYYPAPIPVRVKSPGDTSNFEKypdspVDRLPPLT 319

Catalytic domain of Yeast Protein Kinase 1-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 fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPEGEEKlsdNAQSAMDMLLTID 729
Cdd:cd05585   156 GTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPDGFDR---DAKDLLIGLLNRD 232

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720400333 730 DSKR---AGMRELKQHPLFSEVDWENLQHQTM--PFVPQPDDETDTSYFE 774
Cdd:cd05585   233 PTKRlgyNGAQEIKNHPFFDQIDWKRLLMKKIqpPFKPAVENAIDTSNFD 282

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS 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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIlkrdIPWPE-----GEEKLSDNAqSAMDM 724
Cdd:cd05598   167 GTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKV----INWRTtlkipHEANLSPEA-KDLIL 241

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1720400333 725 LLTIDDSKRAGM---RELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFE 774
Cdd:cd05598   242 RLCCDAEDRLGRngaDEIKAHPFFAGIDWEKLRKQKAPYIPTIRHPTDTSNFD 294

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-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 1720400333 644 DDGRI-----LGTPDYLAPELLL----GTAH-GPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNIL--KRDIPWPEGE 711
Cdd:cd05597   154 EDGTVqssvaVGTPDYISPEILQamedGKGRyGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMnhKEHFSFPDDE 233

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720400333 712 EKLSDNAQSAMDMLLTIDDSK--RAGMRELKQHPLFSEVDWENLQHQTMPFVPQPDDETDTSYFE 774
Cdd:cd05597   234 DDVSEEAKDLIRRLICSRERRlgQNGIDDFKKHPFFEGIDWDNIRDSTPPYIPEVTSPTDTSNFD 298

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720400333  32 IMEYLIGGDVKSLLH-IYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSK 102
Cdd:cd00180    69 VMEYCEGGSLKDLLKeNKGPLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAK 140

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta 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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAMDMLLTID 729
Cdd:cd05595   157 GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHERLFELILMEEIRFP---RTLSPEAKSLLAGLLKKD 233

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720400333 730 DSKRAG-----MRELKQHPLFSEVDWENLQHQTM--PFVPQPDDETDTSYFEARNNAQHLTIS 785
Cdd:cd05595   234 PKQRLGggpsdAKEVMEHRFFLSINWQDVVQKKLlpPFKPQVTSEVDTRYFDDEFTAQSITIT 296

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720400333  32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLS 101
Cdd:cd14007    78 ILEYAPNGELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWS 147

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS 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 1720400333  32 IMEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGL 100
Cdd:cd05598    79 VMDYIPGGDLMSLLIKKGIFEEDLARFYIAELVCAIESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGL 147

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN 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 1720400333 650 GTPDYLAPELLLGTAHGPAVDWWALGVCLFEFLTGIPPFNDETPQQVFQNILKRDIPWPegeEKLSDNAQSAMDMLLTID 729
Cdd:cd05589   163 GTPEFLAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYP---RFLSTEAISIMRRLLRKN 239

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1720400333 730 DSKRAGMRE-----LKQHPLFSEVDWENLQHQTM--PFVPQPDDETDTSYFE 774
Cdd:cd05589   240 PERRLGASErdaedVKKQPFFRNIDWEALLARKIkpPFVPTIKSPEDVSNFD 291

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 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 1720400333  27 HDPGSI---MEYLIGGDVKSLLHIYGYFDEEMAIKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGLSKV 103
Cdd:cd05581    71 QDESKLyfvLEYAPNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKV 150

                  ....*..
gi 1720400333 104 TLNRDIN 110
Cdd:cd05581   151 LGPDSSP 157