Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLgsrpqqtldALLPPDT 137
Cdd:COG0515   184 PVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRAL---------AKDPEER 254

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQIILEQSGNSRSP 217
Cdd:COG0515   255 YQSAAELAAALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAAAAAA 334

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201 218 REEGLGVVASRAELRASPARTQSLKSGVLPQVPAETPARKRGPKPPRSPGHDPEHVEVRRQSSDPLFQLPPPGRGERPPG 297
Cdd:COG0515   335 ALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAAAAAAAA 414

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1907113201 298 ATGQPPSAPSGVKTQVRAMAPSLTSQAEAQAANQALIRSDPARGGGPRAVGARRVPSRLPREAPEPRP 365
Cdd:COG0515   415 AAAAALAAAAAAAAAAAAAAAAAAAAAARLLAAAAAAAAAAAAAPLLAALLAAAALAAAAAAAALALA 482

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201   55 SCLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEElqdlgsdysalilqnlgsrpqqtldallP 134
Cdd:smart00220 169 LGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPP----------------------------E 220

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1907113201  135 PDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:smart00220 221 WDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMeelqdlgsdysalilqnlgsrpqqtldalLPPDTP 138
Cdd:pfam00069 137 YGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPE-----------------------------LPSNLS 187

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907113201 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:pfam00069 188 EEAKDLLKKLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  55 SCLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLdALLP 134
Cdd:cd07834   179 SSKKYTKAIDIWSVGCIFAELLTRKPLFPGRDYIDQLNLIVEVLGTPSEEDLKFISSEKARNYLKSLPKKPKKPL-SEVF 257

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907113201 135 PDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQ 205
Cdd:cd07834   258 PGASPEAIDLLEKMLVFNPKKRITADEALAHPYLAQLHDPEDEPVAKPPFDFPFFDDEELTIEELKELIYE 328

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 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 1907113201  56 CLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPqqtLDALLPP 135
Cdd:cd14137   181 ATDYTTAIDIWSAGCVLAELLLGQPLFPGESSVDQLVEIIKVLGTPTREQIKAMNPNYTEFKFPQIKPHP---WEKVFPK 257

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907113201 136 DTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd14137   258 RTPPDAIDLLSKILVYNPSKRLTALEALAHPF 289

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK 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 1907113201  55 SCLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLp 134
Cdd:cd07858   182 NCSEYTTAIDVWSVGCIFAELLGRKPLFPGKDYVHQLKLITELLGSPSEEDLGFIRNEKARRYIRSLPYTPRQSFARLF- 260

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907113201 135 PDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVhEGDQLSAPEYRKRLYQIILE 209
Cdd:cd07858   261 PHANPLAIDLLEKMLVFDPSKRITVEEALAHPYLASLHDPSDEPVCQTPFSFDF-EEDALTEEDIKELIYNEMLA 334

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 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 1907113201  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDT 137
Cdd:cd07857   186 SYTKAIDVWSVGCILAELLGRKPVFKGKDYVDQLNQILQVLGTPDEETLSRIGSPKAQNYIRSLPNIPKKPFESIF-PNA 264

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1907113201 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDRE 177
Cdd:cd07857   265 NPLALDLLEKLLAFDPTKRISVEEALEHPYLAIWHDPDDE 304

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 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 1907113201  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLPPD 136
Cdd:cd07851   191 MHYNQTVDIWSVGCIMAELLTGKTLFPGSDHIDQLKRIMNLVGTPDEELLKKISSESARNYIQSLPQMPKKDFKEVFSGA 270

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201 137 TpPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARE------SDVRLPVHE 190
Cdd:cd07851   271 N-PLAIDLLEKMLVLDPDKRITAAEALAHPYLAEYHDPEDEPVAPpydqsfESRDLTVDE 329

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-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 1907113201  56 CLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLgsDYSALILQNLGSRPQQTLDALLPP 135
Cdd:cd07829   173 SKHYSTAVDIWSVGCIFAELITGKPLFPGDSEIDQLFKIFQILGTPTEESWPGV--TKLPDYKPTFPKWPKNDLEKVLPR 250

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907113201 136 DTpPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07829   251 LD-PEGIDLLSKMLQYNPAKRISAKEALKHPY 281

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta 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 1907113201  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPD 136
Cdd:cd07879   190 MHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTGVPGPEFVQKLEDKAAKSYIKSLPKYPRKDFSTLF-PK 268

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907113201 137 TPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREwaRESDVRLPVHEGDQLSAPEYRKRLYQIIL 208
Cdd:cd07879   269 ASPQAVDLLEKMLELDVDKRLTATEALEHPYFDSFRDADEE--TEQQPYDDSLENEKLSVDEWKKHIYKEVK 338

Catalytic domain of Cyclin-Dependent protein Kinase 9-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 CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-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 1907113201  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLP---SMEELQDLGSDYSALILQNLGSRPQQTLDALLP 134
Cdd:cd07840   182 RYGPEVDMWSVGCILAELFTGKPIFQGKTELEQLEKIFELCGSPteeNWPGVSDLPWFENLKPKKPYKRRLREVFKNVID 261

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907113201 135 PDtppeALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07840   262 PS----ALDLLDKLLTLDPKKRISADQALQHEY 290

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha 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 1907113201  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTL-DALLPP 135
Cdd:cd07877   193 MHYNQTVDIWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGTPGAELLKKISSESARNYIQSLTQMPKMNFaNVFIGA 272

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201 136 DtpPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREwaRESDVRLPVHEGDQLSAPEYRKRLYQ 205
Cdd:cd07877   273 N--PLAVDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDE--PVADPYDQSFESRDLLIDEWKSLTYD 338

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 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 1907113201  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSmEELQDLGSDYSALILQNLGSRPQQTLDALLPPDT 137
Cdd:cd07843   183 EYSTAIDMWSVGCIFAELLTKKPLFPGKSEIDQLNKIFKLLGTPT-EKIWPGFSELPGAKKKTFTKYPYNQLRKKFPALS 261

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907113201 138 PPEA-LDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07843   262 LSDNgFDLLNRLLTYDPAKRISAEDALKHPY 292

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-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 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDlgsdySALILQNLGSR-PQQT---LDALLP 134
Cdd:cd07830   176 YSSPVDIWALGCIMAELYTLRPLFPGSSEIDQLYKICSVLGTPTKQDWPE-----GYKLASKLGFRfPQFAptsLHQLIP 250

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1907113201 135 PdTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07830   251 N-ASPEAIDLIKDMLRWDPKKRPTASQALQHPY 282

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 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 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGS--DYSAlilqnLGSRPQQTLDALLPPD 136
Cdd:cd07841   180 YGVGVDMWSVGCIFAELLLRVPFLPGDSDIDQLGKIFEALGTPTEENWPGVTSlpDYVE-----FKPFPPTPLKQIFPAA 254

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1907113201 137 tPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07841   255 -SDDALDLLQRLLTLNPNKRITARQALEHPY 284

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK 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 1907113201  54 PSCL----RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLgsDYSALILQNLGSRPQQTL 129
Cdd:cd07831   167 PECLltdgYYGPKMDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKF--RKSRHMNYNFPSKKGTGL 244

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1907113201 130 DALLPpDTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07831   245 RKLLP-NASAEGLDLLKKLLAYDPDERITAKQALRHPY 281

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 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 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSmeELQDLGSDYSALILQNLGSRPQQTLDALLpPDTP 138
Cdd:cd07836   178 YSTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMGTPT--ESTWPGISQLPEYKPTFPRYPPQDLQQLF-PHAD 254

                          90       100
                  ....*....|....*....|....*....
gi 1907113201 139 PEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07836   255 PLGIDLLHRLLQLNPELRISAHDALQHPW 283

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLG-------SDYSALILQNLGSRPQ--- 126
Cdd:cd14210   190 LPYDTAIDMWSLGCILAELYTGYPLFPGENEEEQLACIMEVLGVPPKSLIDKASrrkkffdSNGKPRPTTNSKGKKRrpg 269

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1907113201 127 -QTLDALLPPDtPPEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:cd14210   270 sKSLAQVLKCD-DPSFLDFLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB 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 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSdysaliLQNLGSRPQ---QTLDALLpP 135
Cdd:cd07837   188 YSTPVDMWSVGCIFAEMSRKQPLFPGDSELQQLLHIFRLLGTPNEEVWPGVSK------LRDWHEYPQwkpQDLSRAV-P 260

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1907113201 136 DTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07837   261 DLEPEGVDLLTKMLAYDPAKRISAKAALQHPY 292

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK 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 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDySALILQNLGSRPQQTL-----DALL 133
Cdd:cd07850   178 YKENVDIWSVGCIMGEMIRGTVLFPGTDHIDQWNKIIEQLGTPSDEFMSRLQPT-VRNYVENRPKYAGYSFeelfpDVLF 256

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907113201 134 PPD-------TPPEALDLLKRLLAFAPDKRLSAEQALQHPYVqrfhcpdREWARESDVRLP 187
Cdd:cd07850   257 PPDseehnklKASQARDLLSKMLVIDPEKRISVDDALQHPYI-------NVWYDPSEVEAP 310

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMeelqdlgsdysalilqnlgsrpqqtldalLPPDTP 138
Cdd:pfam00069 137 YGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPE-----------------------------LPSNLS 187

                          90       100       110
                  ....*....|....*....|....*....|
gi 1907113201 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:pfam00069 188 EEAKDLLKKLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907113201  59 YTPGVDMWSLGCILGEMLRGQPLFPG-------TSTFH--QLELILKTIPLPSMEELQDLGS--DYSALilqnLGSRPQQ 127
Cdd:cd07842   193 YTKAIDIWAIGCIFAELLTLEPIFKGreakikkSNPFQrdQLERIFEVLGTPTEKDWPDIKKmpEYDTL----KSDTKAS 268

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1907113201 128 TLDALLPPD-------TPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07842   269 TYPNSLLAKwmhkhkkPDSQGFDLLRKLLEYDPTKRITAEEALEHPY 315

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 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 1907113201  56 CLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSmeelQDLGSDYSALILQNLGSRPQQTLDALLP- 134
Cdd:cd07845   183 CTTYTTAIDMWAVGCILAELLAHKPLLPGKSEIEQLDLIIQLLGTPN----ESIWPGFSDLPLVGKFTLPKQPYNNLKHk 258

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1907113201 135 -PDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQ 169
Cdd:cd07845   259 fPWLSEAGLRLLNFLLMYDPKKRATAEEALESSYFK 294

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 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 1907113201  59 YTPGVDMWSLGCILGEML-RGQPLFPGTSTFHQLELILK---TIPLpsMEELQDLGSDYSALILQNLGSRPQQTLDALLP 134
Cdd:cd14132   190 YDYSLDMWSLGCMLASMIfRKEPFFHGHDNYDQLVKIAKvlgTDDL--YAYLDKYGIELPPRLNDILGRHSKKPWERFVN 267

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1907113201 135 PDT----PPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd14132   268 SENqhlvTPEALDLLDKLLRYDHQERITAKEAMQHPY 304