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 1907194849   1 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14196   140 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 219

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907194849  81 LANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14196   220 LANITAVSYDFDEEFFSHTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 269

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 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 1907194849   1 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14196   140 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 219

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907194849  81 LANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14196   220 LANITAVSYDFDEEFFSHTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 269

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849   5 KNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANI 84
Cdd:pfam00069  93 GAFSEREAKFIMKQILEGLESGSSLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELI 172

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907194849  85 TAVSYDFDEEFFSQTSElAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:pfam00069 173 IDQPYAFPELPSNLSEE-AKDLLKKLLKKDPSKRLTATQALQHPWF 217

protein kinase A catalytic subunit; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849   1 MLLDKNipiPHIKLIDFGLAHEIEDgvEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:PTZ00263  149 LLLDNK---GHVKVTDFGFAKKVPD--RTFTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRI 223

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907194849  81 LANITAVSYDFDEEFFSQtselAKDFIRKLLVKETRKRL-----TIQEALRHPW 129
Cdd:PTZ00263  224 YEKILAGRLKFPNWFDGR----ARDLVKGLLQTDHTKRLgtlkgGVADVKNHPY 273

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 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 1907194849   1 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14196   140 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 219

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907194849  81 LANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14196   220 LANITAVSYDFDEEFFSHTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 269

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 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 1907194849   1 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14194   140 MLLDRNVPKPRIKIIDFGLAHKIDFGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 219

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907194849  81 LANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14194   220 LANVSAVNYEFEDEYFSNTSALAKDFIRRLLVKDPKKRMTIQDSLQHPWI 269

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like 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 1907194849   2 LLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETL 81
Cdd:cd14006   120 ILLADRPSPQIKIIDFGLARKLNPGEELKEIFGTPEFVAPEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETL 199

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907194849  82 ANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPW 129
Cdd:cd14006   200 ANISACRVDFSEEYFSSVSQEAKDFIRKLLVKEPRKRPTAQEALQHPW 247

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK 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 1907194849   1 MLLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14106   139 ILLTSEFPLGDIKLCDFGISRVIGEGEEIREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQET 218

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1907194849  81 LANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14106   219 FLNISQCNLDFPEELFKDVSPLAIDFIKRLLVKDPEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 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 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14191   141 IKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDF 220

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14191   221 DDEAFDEISDDAKDFISNLLKKDMKARLTCTQCLQHPWL 259

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 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 1907194849  11 HIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYD 90
Cdd:cd14109   136 KLKLADFGQSRRLLRGKLTTLIYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWS 215

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907194849  91 FDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14109   216 FDSSPLGNISDDARDFIKKLLVYIPESRLTVDEALNHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 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 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14193   143 VKIIDFGLARRYKPREKLRVNFGTPEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDF 222

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14193   223 EDEEFADISEEAKDFISKLLIKEKSWRMSASEALKHPWL 261

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 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 1907194849  11 HIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYD 90
Cdd:cd14192   142 QIKIIDFGLARRYKPREKLKVNFGTPEFLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKWD 221

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907194849  91 FDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14192   222 FDAEAFENLSEEAKDFISRLLVKEKSCRMSATQCLKHEWL 261

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 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 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14190   143 VKIIDFGLARRYNPREKLKVNFGTPEFLSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNWYF 222

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14190   223 DEETFEHVSDEAKDFVSNLIIKERSARMSATQCLKHPWL 261

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14104   138 IKIIEFGQSRQLKPGDKFRLQYTSAEFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAF 217

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITSKGEarapeqwKAQPAQLKTKRLREY 157
Cdd:cd14104   218 DDEAFKNISIEALDFVDRLLVKERKSRMTAQEALNHPWLKQGME-------TVSSKDIKTTRHRRY 276

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 1907194849   2 LLDKNipiPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEP-LGLEADMWSIGVITYILLSGASPFLGDTKQET 80
Cdd:cd14003   131 LLDKN---GNLKIIDFGLSNEFRGGSLLKTFCGTPAYAAPEVLLGRKyDGPKADVWSLGVILYAMLTGYLPFDDDNDSKL 207

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907194849  81 LANITAVSYdfdeEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPW 129
Cdd:cd14003   208 FRKILKGKY----PIPSHLSPDARDLIRRMLVVDPSKRITIEEILNHPW 252

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; 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. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGD-TKQETLANITAVSYD 90
Cdd:cd14085   140 LKIADFGLSKIVDQQVTMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDErGDQYMFKRILNCDYD 219

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1907194849  91 FDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWITSKGEARA 138
Cdd:cd14085   220 FVSPWWDDVSLNAKDLVKKLIVLDPKKRLTTQQALQHPWVTGKAANFA 267

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAhEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14169   143 IMISDFGLS-KIEAQGMLSTACGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEF 221

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWIT 131
Cdd:cd14169   222 DSPYWDDISESAKDFIRHLLERDPEKRFTCEQALQHPWIS 261

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849   5 KNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANI 84
Cdd:pfam00069  93 GAFSEREAKFIMKQILEGLESGSSLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELI 172

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1907194849  85 TAVSYDFDEEFFSQTSElAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:pfam00069 173 IDQPYAFPELPSNLSEE-AKDLLKKLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL 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 1907194849  11 HIKLIDFGLAHEIEDGVefKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLG-DTKQETLAN-ITAVS 88
Cdd:cd14095   140 SLKLADFGLATEVKEPL--FTVCGTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSpDRDQEELFDlILAGE 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1907194849  89 YDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPW 129
Cdd:cd14095   218 FEFLSPYWDNISDSAKDLISRMLVVDPEKRYSAGQVLDHPW 258

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14167   143 IMISDFGLSKIEGSGSVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEF 222

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14167   223 DSPYWDDISDSAKDFIQHLMEKDPEKRFTCEQALQHPWI 261

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 1907194849   1 MLLDKNipiPHIKLIDFGL--------------AHEIEDGVEFKN--IFGTPEFVAPEIVNYEPLGLEADMWSIGVITYI 64
Cdd:cd05579   124 ILIDAN---GHLKLTDFGLskvglvrrqiklsiQKKSNGAPEKEDrrIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYE 200

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  65 LLSGASPFLGDTKQETLANITAVSYDFDEEFfsQTSELAKDFIRKLLVKETRKRL---TIQEALRHPWIT 131
Cdd:cd05579   201 FLVGIPPFHAETPEEIFQNILNGKIEWPEDP--EVSDEAKDLISKLLTPDPEKRLgakGIEEIKNHPFFK 268

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  11 HIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYD 90
Cdd:cd14108   137 QVRICDFGNAQELTPNEPQYCKYGTPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNVA 216

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  91 FDEEFFSQTSELAKDFIRKLLVKEtRKRLTIQEALRHPW 129
Cdd:cd14108   217 FEESMFKDLCREAKGFIIKVLVSD-RLRPDAEETLEHPW 254

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 1907194849   1 MLLDKNIpipHIKLIDFGLA--------HEIEDGVEFKNIF----------GTPEFVAPEIVNYEPLGLEADMWSIGVIT 62
Cdd:cd05581   132 ILLDEDM---HIKITDFGTAkvlgpdssPESTKGDADSQIAynqaraasfvGTAEYVSPELLNEKPAGKSSDLWALGCII 208

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907194849  63 YILLSGASPFLGDTKQETLANITAVSYDFDEEFFsqtsELAKDFIRKLLVKETRKRLTIQEA------LRHPW 129
Cdd:cd05581   209 YQMLTGKPPFRGSNEYLTFQKIVKLEYEFPENFP----PDAKDLIQKLLVLDPSKRLGVNENggydelKAHPF 277

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849   2 LLDKNIPIPHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNY---EPLGLEADMWSIGVITYILLSGASPFLGDTKQ 78
Cdd:cd14084   143 LLSSQEEECLIKITDFGLSKILGETSLMKTLCGTPTYLAPEVLRSfgtEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQ 222

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1907194849  79 ETLAN-ITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14084   223 MSLKEqILSGKYTFIPKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14107   139 IKICDFGFAQEITPSEHQFSKYGSPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSW 218

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPW 129
Cdd:cd14107   219 DTPEITHLSEDAKDFIKRVLQPDPEKRPSASECLSHEW 256

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 1907194849   1 MLLDKNipiPHIKLIDFGLAHEIEDG-VEFKNIFGTPEFVAPEI--VNYEPL-GLEADMWSIGVITYILLSGASPFLGDT 76
Cdd:cd14008   139 LLLTAD---GTVKISDFGVSEMFEDGnDTLQKTAGTPAFLAPELcdGDSKTYsGKAADIWALGVTLYCLVFGRLPFNGDN 215

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1907194849  77 KQETLANITAVSYDFDeeFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14008   216 ILELYEAIQNQNDEFP--IPPELSPELKDLLRRMLEKDPEKRITLKEIKEHPWV 267

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 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 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. 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 PhKG1 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 1907194849   1 MLLDKNIpipHIKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIV------NYEPLGLEADMWSIGVITYILLSGASPFLG 74
Cdd:cd14182   141 ILLDDDM---NIKLTDFGFSCQLDPGEKLREVCGTPGYLAPEIIecsmddNHPGYGKEVDMWSTGVIMYTLLAGSPPFWH 217

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1907194849  75 DTKQETLANITAVSYDFDEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPW 129
Cdd:cd14182   218 RKQMLMLRMIMSGNYQFGSPEWDDRSDTVKDLISRFLVVQPQKRYTAEEALAHPF 272

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907194849  12 IKLIDFGLAHEIEDGVEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDF 91
Cdd:cd14168   150 IMISDFGLSKMEGKGDVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEF 229

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1907194849  92 DEEFFSQTSELAKDFIRKLLVKETRKRLTIQEALRHPWI 130
Cdd:cd14168   230 DSPYWDDISDSAKDFIRNLMEKDPNKRYTCEQALRHPWI 268