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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:cd14072   78 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKLDT 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14072  158 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLVLN 237

                        170
                 ....*....|....*.
gi 966956806 161 PIKRGTLEQIMKDRWI 176
Cdd:cd14072  238 PSKRGTLEQIMKDRWM 253

UBA domain found in MAP/microtubule affinity-regulating kinase MARK3, MARK4, and similar proteins; MARK3, also called C-TAK1, Cdc25C-associated protein kinase 1, ELKL motif kinase 2 (EMK-2), protein kinase STK10, Ser/Thr protein kinase PAR-1 (Par-1a), or serine/threonine-protein kinase p78, is a known regulator of KSR1, a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. It binds plakophilin 2 (PKP2), phosphorylates human Cdc25C on serine 216, and promotes 14-3-3 protein binding and protein localization. It also interacts with microphthalmia-associated transcription factor, Mitf which is necessary for regulating genes involved in osteoclast differentiation. Moreover, MARK3 is involved in regulating localization and activity of class IIa histone deacetylases. The lack of MARK3 leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis. MARK4, also called MAP/microtubule affinity-regulating kinase-like 1 (MARKL1), or Par-1d, is a member of the AMP-activated protein kinase (AMPK)-related family of kinases. It plays a key role in energy metabolism and may act as a novel drug target for the treatment of obesity and type 2 diabetes. MARK4 also functions as the substrate of ubiquitin specific protease-9 (USP9X) and can be regulated by unusual Lys(29)/Lys(33)-linked polyubiquitin chains. Furthermore, MARK4 may play some role in hepatocellular carcinogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 966956806 194 DISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITATYLLLGRK 236
Cdd:cd14407    1 DISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITATYLLLGRK 43

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK 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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:cd14072   78 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKLDT 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14072  158 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLVLN 237

                        170
                 ....*....|....*.
gi 966956806 161 PIKRGTLEQIMKDRWI 176
Cdd:cd14072  238 PSKRGTLEQIMKDRWM 253

C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinases 1-3; Microtubule-associated protein/microtubule affinity regulating kinases (MARKs), also called partition-defective (Par-1) kinases, are serine/threonine protein kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. They phosphorylate the tau protein and related microtubule-associated proteins (MAPs) on tubulin binding sites to induce detachment from microtubules, and are involved in the regulation of cell shape and polarity, cell cycle control, transport, and the cytoskeleton. Mammals contain four proteins, MARK1-4, encoded by distinct genes belonging to this subfamily, with additional isoforms arising from alternative splicing. MARK1/2, through their activation by death-associated protein kinase (DAPK), modulates polarized neurite outgrowth. MARK1, also called Par-1c, is also involved in axon-dendrite specification, and SNPs on the MARK1 gene is associated with autism spectrum disorders. MARK2, also called Par-1b, is implicated in many physiological processes including fertility, immune system homeostasis, learning and memory, growth, and metabolism. MARK3, also called Par-1a, is implicated in gluconeogenesis and adiposity; mice deficient with MARK3 display reduced adiposity, resistance to hepatic steatosis, and defective gluconeogensis. MARKs contain an N-terminal catalytic kinase domain, a ubiquitin-associated domain (UBA), and a C-terminal kinase associated domain (KA1). The KA1 domain binds anionic phospholipids and may be involved in membrane localization as well as in auto-inhibition of the kinase domain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806 575 KPRSLRFTWSMKTTSSMDPGDMMREIRKVLDANNCDYEQRERFLLFCVHGDGHAENLVQWEMEVCKLPRLSLNGVRFKRI 654
Cdd:cd12196    1 KPRSLRFTWSMKTTSSMDPNDMMREIRKVLDANNCDYEQRERFLLFCVHGDGRTDSLVQWEMEVCKLPRLSLNGVRFKRI 80

                         90
                 ....*....|....*...
gi 966956806 655 SGTSIAFKNIASKIANEL 672
Cdd:cd12196   81 SGTSIAFKNIASKIANEL 98

protein kinase A catalytic subunit; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEftVGSKLDT 80
Cdd:PTZ00263  97 LEFVVGGELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKK--VPDRTFT 174

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYdGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:PTZ00263 175 LCGTPEYLAPEVIQSKGH-GKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNWFDGRARDLVKGLLQTD 253

                        170
                 ....*....|....
gi 966956806 161 PIKR-GTLEQIMKD 173
Cdd:PTZ00263 254 HTKRlGTLKGGVAD 267

UBA domain found in MAP/microtubule affinity-regulating kinase MARK3, MARK4, and similar proteins; MARK3, also called C-TAK1, Cdc25C-associated protein kinase 1, ELKL motif kinase 2 (EMK-2), protein kinase STK10, Ser/Thr protein kinase PAR-1 (Par-1a), or serine/threonine-protein kinase p78, is a known regulator of KSR1, a molecular scaffold of the Raf/MEK/ERK MAP kinase cascade that regulates the intensity and duration of ERK activation. It binds plakophilin 2 (PKP2), phosphorylates human Cdc25C on serine 216, and promotes 14-3-3 protein binding and protein localization. It also interacts with microphthalmia-associated transcription factor, Mitf which is necessary for regulating genes involved in osteoclast differentiation. Moreover, MARK3 is involved in regulating localization and activity of class IIa histone deacetylases. The lack of MARK3 leads to reduced adiposity, resistance to hepatic steatosis, and defective gluconeogenesis. MARK4, also called MAP/microtubule affinity-regulating kinase-like 1 (MARKL1), or Par-1d, is a member of the AMP-activated protein kinase (AMPK)-related family of kinases. It plays a key role in energy metabolism and may act as a novel drug target for the treatment of obesity and type 2 diabetes. MARK4 also functions as the substrate of ubiquitin specific protease-9 (USP9X) and can be regulated by unusual Lys(29)/Lys(33)-linked polyubiquitin chains. Furthermore, MARK4 may play some role in hepatocellular carcinogenesis.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 966956806 194 DISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITATYLLLGRK 236
Cdd:cd14407    1 DISDQKRIDIMVGMGYSQEEIQESLSKMKYDEITATYLLLGRK 43

Kinase associated domain 1;

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|...
gi 966956806  632 VQWEMEVCKLPRLSLNGVRFKRISGTSIAFKNIASKIANELKL 674
Cdd:pfam02149   2 VKFEIEVCKLPRLSLYGVDFKRLSGDTWQYKDLASKILSELRL 44

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK 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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:cd14072   78 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPGNKLDT 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14072  158 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKKFLVLN 237

                        170
                 ....*....|....*.
gi 966956806 161 PIKRGTLEQIMKDRWI 176
Cdd:cd14072  238 PSKRGTLEQIMKDRWM 253

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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:cd14003   78 MEYASGGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGGSLLKT 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14003  158 FCGTPAYAAPEVLLGRKYDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPSHLSPDARDLIRRMLVVD 237

                        170
                 ....*....|....*
gi 966956806 161 PIKRGTLEQIMKDRW 175
Cdd:cd14003  238 PSKRITIEEILNHPW 252

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:cd14081   80 LEYVSGGELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEGSLLET 159

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14081  160 SCGSPHYACPEVIKGEKYDGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRGVFHIPHFISPDAQDLLRRMLEVN 239

                        170
                 ....*....|....*.
gi 966956806 161 PIKRGTLEQIMKDRWI 176
Cdd:cd14081  240 PEKRITIEEIKKHPWF 255

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806     1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDT 80
Cdd:smart00220  76 MEYCEGGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDPGEKLTT 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806    81 FCGSPPYAAPELFQGKKYDGPeVDVWSLGVILYTLVSGSLPFDG-QNLKELRERVLRGKYRIPFYM---STDCENLLKRF 156
Cdd:smart00220 156 FVGTPEYMAPEVLLGKGYGKA-VDIWSLGVILYELLTGKPPFPGdDQLLELFKKIGKPKPPFPPPEwdiSPEAKDLIRKL 234

                          170       180
                   ....*....|....*....|
gi 966956806   157 LVLNPIKRGTLEQIMKDRWI 176
Cdd:smart00220 235 LVKDPEKRLTAEEALQHPFF 254

Catalytic domain of Kin1, Kin2, and simlar 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 yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806   2 EYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSKLDTF 81
Cdd:cd14077   93 EYVDGGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNLYDPRRLLRTF 172

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  82 CGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLNP 161
Cdd:cd14077  173 CGSLYFAAPELLQAQPYTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPSYLSSECKSLISRMLVVDP 252

                        170
                 ....*....|....*
gi 966956806 162 IKRGTLEQIMKDRWI 176
Cdd:cd14077  253 KKRATLEQVLNHPWM 267

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLL---DADMNIKIADFGFSNEFTVGSK 77
Cdd:cd05117   78 MELCTGGELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLaskDPDSPIKIIDFGLAKIFEEGEK 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  78 LDTFCGSPPYAAPELFQGKKYdGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYM----STDCENLL 153
Cdd:cd05117  158 LKTVCGTPYYVAPEVLKGKGY-GKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFDSPEwknvSEEAKDLI 236

                        170       180
                 ....*....|....*....|..
gi 966956806 154 KRFLVLNPIKRGTLEQIMKDRW 175
Cdd:cd05117  237 KRLLVVDPKKRLTAAEALNHPW 258

Catalytic domain of testis-specific serine/threonine kinases 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. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFS-----NEFTVG 75
Cdd:cd14080   81 MEYAEHGDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLDSNNNVKLSDFGFArlcpdDDGDVL 160

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  76 SKldTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIP---FYMSTDCENL 152
Cdd:cd14080  161 SK--TFCGSAAYAAPEILQGIPYDPKKYDIWSLGVILYIMLCGSMPFDDSNIKKMLKDQQNRKVRFPssvKKLSPECKDL 238

                        170       180
                 ....*....|....*....|....
gi 966956806 153 LKRFLVLNPIKRGTLEQIMKDRWI 176
Cdd:cd14080  239 IDQLLEPDPTKRATIEEILNHPWL 262

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK 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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVG--SKL 78
Cdd:cd14078   80 LEYCPGGELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQNLKLIDFGLCAKPKGGmdHHL 159

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  79 DTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLV 158
Cdd:cd14078  160 ETCCGSPAYAAPELIQGKPYIGSEADVWSMGVLLYALLCGFLPFDDDNVMALYRKIQSGKYEEPEWLSPSSKLLLDQMLQ 239

                        170
                 ....*....|....*...
gi 966956806 159 LNPIKRGTLEQIMKDRWI 176
Cdd:cd14078  240 VDPKKRITVKELLNHPWV 257

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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTvGSKLDT 80
Cdd:cd14007   79 LEYAPNGELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSVHAP-SNRRKT 157

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  81 FCGSPPYAAPELFQGKKYDgPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVLN 160
Cdd:cd14007  158 FCGTLDYLPPEMVEGKEYD-YKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPSSVSPEAKDLISKLLQKD 236

                        170
                 ....*....|....*.
gi 966956806 161 PIKRGTLEQIMKDRWI 176
Cdd:cd14007  237 PSKRLSLEQVLNHPWI 252

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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEF-TVGSKLD 79
Cdd:cd05123   72 LDYVPGGELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELsSDGDRTY 151

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  80 TFCGSPPYAAPELFQGKKYdGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPFYMSTDCENLLKRFLVL 159
Cdd:cd05123  152 TFCGTPEYLAPEVLLGKGY-GKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPEYVSPEAKSLISGLLQK 230

                        170
                 ....*....|....*....
gi 966956806 160 NPIKR---GTLEQIMKDRW 175
Cdd:cd05123  231 DPTKRlgsGGAEEIKAHPF 249

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEF--TVGSKL 78
Cdd:cd14076   85 LEFVSGGELFDYILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRNLVITDFGFANTFdhFNGDLM 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  79 DTFCGSPPYAAPELFQGKK-YDGPEVDVWSLGVILYTLVSGSLPFD-------GQNLKELRERVLRGKYRIPFYMSTDCE 150
Cdd:cd14076  165 STSCGSPCYAAPELVVSDSmYAGRKADIWSCGVILYAMLAGYLPFDddphnpnGDNVPRLYRYICNTPLIFPEYVTPKAR 244

                        170       180
                 ....*....|....*....|....*.
gi 966956806 151 NLLKRFLVLNPIKRGTLEQIMKDRWI 176
Cdd:cd14076  245 DLLRRILVPNPRKRIRLSAIMRHAWL 270

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 966956806   1 MEYASGGEVFDYLVAHGR--MKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGS-K 77
Cdd:cd14008   85 LEYCEGGPVMELDSGDRVppLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFEDGNdT 164

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  78 LDTFCGSPPYAAPELFQG--KKYDGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIPF--YMSTDCENLL 153
Cdd:cd14008  165 LQKTAGTPAFLAPELCDGdsKTYSGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNDEFPIppELSPELKDLL 244

                        170       180
                 ....*....|....*....|...
gi 966956806 154 KRFLVLNPIKRGTLEQIMKDRWI 176
Cdd:cd14008  245 RRMLEKDPEKRITLKEIKEHPWV 267

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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTVGSK--- 77
Cdd:cd14069   79 LEYASGGELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFRYKGKerl 158

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  78 LDTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFDG--------QNLKELRERVLRGKYRIpfymSTDC 149
Cdd:cd14069  159 LNKMCGTLPYVAPELLAKKKYRAEPVDVWSCGIVLFAMLAGELPWDQpsdscqeySDWKENKKTYLTPWKKI----DTAA 234

                        170       180
                 ....*....|....*....|....*.
gi 966956806 150 ENLLKRFLVLNPIKRGTLEQIMKDRW 175
Cdd:cd14069  235 LSLLRKILTENPNKRITIEDIKKHPW 260

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to 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 966956806   1 MEYASGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADM--NIKIADFGFSNEFTVGSKL 78
Cdd:cd14662   75 MEYAAGGELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPapRLKICDFGYSKSSVLHSQP 154

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  79 DTFCGSPPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPF----DGQNLKELRERVLRGKYRIPFY--MSTDCENL 152
Cdd:cd14662  155 KSTVGTPAYIAPEVLSRKEYDGKVADVWSCGVTLYVMLVGAYPFedpdDPKNFRKTIQRIMSVQYKIPDYvrVSQDCRHL 234

                        170       180
                 ....*....|....*....|...
gi 966956806 153 LKRFLVLNPIKRGTLEQIMKDRW 175
Cdd:cd14662  235 LSRIFVANPAKRITIPEIKNHPW 257

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 966956806   5 SGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGfSNEFTVGSKLDTFCGS 84
Cdd:cd14004   92 SGMDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFG-SAAYIKSGPFDTFVGT 170

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 966956806  85 PPYAAPELFQGKKYDGPEVDVWSLGVILYTLVSGSLPFdgQNLKElrerVLRGKYRIPFYMSTDCENLLKRFLVLNPIKR 164
Cdd:cd14004  171 IDYAAPEVLRGNPYGGKEQDIWALGVLLYTLVFKENPF--YNIEE----ILEADLRIPYAVSEDLIDLISRMLNRDVGDR 244

                        170
                 ....*....|..
gi 966956806 165 GTLEQIMKDRWI 176
Cdd:cd14004  245 PTIEELLTDPWL 256