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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELLRVMPSFVS-STWEVKRPLRKLLPDVNREAIDFLE 79
Cdd:cd07854   202 MWAAGCIFAEMLTGKPLFAGAHELEQMQLILESVPVVREEDRNELLNVIPSFVRnDGGEPRRPLRDLLPGVNPEALDFLE 281

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958743601  80 KILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQHPFRIEDEIDDLVLMAASQSQLSNWD 140
Cdd:cd07854   282 QILTFNPMDRLTAEEALMHPYMSCYSCPFDEPVSLHPFHIEDELDDILLMTEIHSIIYNWD 342

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELLRVMPSFVS-STWEVKRPLRKLLPDVNREAIDFLE 79
Cdd:cd07854   202 MWAAGCIFAEMLTGKPLFAGAHELEQMQLILESVPVVREEDRNELLNVIPSFVRnDGGEPRRPLRDLLPGVNPEALDFLE 281

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958743601  80 KILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQHPFRIEDEIDDLVLMAASQSQLSNWD 140
Cdd:cd07854   282 QILTFNPMDRLTAEEALMHPYMSCYSCPFDEPVSLHPFHIEDELDDILLMTEIHSIIYNWD 342

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958743601    1 MWAAGCILAEMLTGKMLFAGAHELEQM-QLILDTIPVVREEDkeellrvmpsfvsstwevkrplrkllPDVNREAIDFLE 79
Cdd:smart00220 179 IWSLGVILYELLTGKPPFPGDDQLLELfKKIGKPKPPFPPPE--------------------------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1958743601   80 KILTFNPMDRLTAEMGLQHPYM 101
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958743601   2 WAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVvreedkeellrvmpsfvsstwevkrPLRKLLPDVNREAIDFLEKI 81
Cdd:COG0515   192 YSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPP-------------------------PPSELRPDLPPALDAIVLRA 246

                  ....*...
gi 1958743601  82 LTFNPMDR 89
Cdd:COG0515   247 LAKDPEER 254

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELLRVMPSFVS-STWEVKRPLRKLLPDVNREAIDFLE 79
Cdd:cd07854   202 MWAAGCIFAEMLTGKPLFAGAHELEQMQLILESVPVVREEDRNELLNVIPSFVRnDGGEPRRPLRDLLPGVNPEALDFLE 281

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1958743601  80 KILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQHPFRIEDEIDDLVLMAASQSQLSNWD 140
Cdd:cd07854   282 QILTFNPMDRLTAEEALMHPYMSCYSCPFDEPVSLHPFHIEDELDDILLMTEIHSIIYNWD 342

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-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 the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKE--------ELLRVMPsfvsstWEVKRPLRKLLPDVNR 72
Cdd:cd07849   193 IWSVGCILAEMLSNRPLFPGKDYLHQLNLILGILGTPSQEDLNciislkarNYIKSLP------FKPKVPWNKLFPNADP 266

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958743601  73 EAIDFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQHPFRIE-DEIDDL 126
Cdd:cd07849   267 KALDLLDKMLTFNPHKRITVEEALAHPYLEQYHDPSDEPVAEEPFPFDmELFDDL 321

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEEL--------LRVMPSFVsstwevKRPLRKLLPDVNR 72
Cdd:cd07858   192 VWSVGCIFAELLGRKPLFPGKDYVHQLKLITELLGSPSEEDLGFIrnekarryIRSLPYTP------RQSFARLFPHANP 265

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958743601  73 EAIDFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQHPFRIEDEIDDL 126
Cdd:cd07858   266 LAIDLLEKMLVFDPSKRITVEEALAHPYLASLHDPSDEPVCQTPFSFDFEEDAL 319

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDtipVVREEDkEELLRVMPS-----FVSS-TWEVKRPLRKLLPDVNREA 74
Cdd:cd07851   199 IWSVGCIMAELLTGKTLFPGSDHIDQLKRIMN---LVGTPD-EELLKKISSesarnYIQSlPQMPKKDFKEVFSGANPLA 274

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1958743601  75 IDFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTsQHPFRIEDEIDDL 126
Cdd:cd07851   275 IDLLEKMLVLDPDKRITAAEALAHPYLAEYHDPEDEPV-APPYDQSFESRDL 325

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELLRvMPSFVSS--TWEvKRPLRKLLPDVNREAIDFL 78
Cdd:cd07829   182 IWSVGCIFAELITGKPLFPGDSEIDQLFKIFQILGTPTEESWPGVTK-LPDYKPTfpKWP-KNDLEKVLPRLDPEGIDLL 259

                          90       100
                  ....*....|....*....|..
gi 1958743601  79 EKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07829   260 SKMLQYNPAKRISAKEALKHPY 281

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELLRV-------MPSFVSStwevkrPLRKLLPDVNRE 73
Cdd:cd07830   182 IWALGCIMAELYTLRPLFPGSSEIDQLYKICSVLGTPTKQDWPEGYKLasklgfrFPQFAPT------SLHQLIPNASPE 255

                          90       100
                  ....*....|....*....|....*...
gi 1958743601  74 AIDFLEKILTFNPMDRLTAEMGLQHPYM 101
Cdd:cd07830   256 AIDLIKDMLRWDPKKRPTASQALQHPYF 283

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTI--PvvreeDKEELLRVMPSFVSSTW-EVKR-PLRKLLP-DVNREAI 75
Cdd:cd14137   190 IWSAGCVLAELLLGQPLFPGESSVDQLVEIIKVLgtP-----TREQIKAMNPNYTEFKFpQIKPhPWEKVFPkRTPPDAI 264

                          90       100
                  ....*....|....*....|....*
gi 1958743601  76 DFLEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd14137   265 DLLSKILVYNPSKRLTALEALAHPF 289

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. 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 p38gamma 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLIL--------DTIPVVREEDKEELLRVMPSFVsstwevKRPLRKLLPDVNR 72
Cdd:cd07880   199 IWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMkvtgtpskEFVQKLQSEDAKNYVKKLPRFR------KKDFRSLLPNANP 272

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1958743601  73 EAIDFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQhPFriEDEIDDlvlmaASQSqLSNWDR 141
Cdd:cd07880   273 LAVNVLEKMLVLDAESRITAAEALAHPYFEEFHDPEDETEAP-PY--DDSFDE-----VDQS-LEEWKR 332

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVvreeDKEELLRVMPS-----FVSS-TWEVKRPLRKLLPDVNREA 74
Cdd:cd07877   201 IWSVGCIMAELLTGRTLFPGTDHIDQLKLILRLVGT----PGAELLKKISSesarnYIQSlTQMPKMNFANVFIGANPLA 276

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1958743601  75 IDFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQhPFRIEDEIDDLVL 128
Cdd:cd07877   277 VDLLEKMLVLDSDKRITAAQALAHAYFAQYHDPDDEPVAD-PYDQSFESRDLLI 329

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDtipVVREEDKEELLRVMPSFVSS-TWEVKRP--LRKLLPDVNREAIDF 77
Cdd:cd07831   182 IWAVGCVFFEILSLFPLFPGTNELDQIAKIHD---VLGTPDAEVLKKFRKSRHMNyNFPSKKGtgLRKLLPNASAEGLDL 258

                          90       100
                  ....*....|....*....|...
gi 1958743601  78 LEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07831   259 LKKLLAYDPDERITAKQALRHPY 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEELL-RVMPSFVSSTWEV-KRPLRKLLPDVNREAIDFL 78
Cdd:cd07879   198 IWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTGVPGPEFVQKLEdKAAKSYIKSLPKYpRKDFSTLFPKASPQAVDLL 277

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958743601  79 EKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEpTSQHPF 117
Cdd:cd07879   278 EKMLELDVDKRLTATEALEHPYFDSFRDADEE-TEQQPY 315

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958743601    1 MWAAGCILAEMLTGKMLFAGAHELEQM-QLILDTIPVVREEDkeellrvmpsfvsstwevkrplrkllPDVNREAIDFLE 79
Cdd:smart00220 179 IWSLGVILYELLTGKPPFPGDDQLLELfKKIGKPKPPFPPPE--------------------------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1958743601   80 KILTFNPMDRLTAEMGLQHPYM 101
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. 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 BUR1 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREEDKEElLRVMP------SFVSSTWEVKRPLRKLLPDVnrea 74
Cdd:cd07866   210 IWGIGCVFAEMFTRRPILQGKSDIDQLHLIFKLCGTPTEETWPG-WRSLPgcegvhSFTNYPRTLEERFGKLGPEG---- 284

                          90       100
                  ....*....|....*....|....*.
gi 1958743601  75 IDFLEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07866   285 LDLLSKLLSLDPYKRLTASDALEHPY 310

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein 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 p38beta 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDtipVVREEDKEELLRVMPSFVSSTWEV-----KRPLRKLLPDVNREAI 75
Cdd:cd07878   199 IWSVGCIMAELLKGKALFPGNDYIDQLKRIME---VVGTPSPEVLKKISSEHARKYIQSlphmpQQDLKKIFRGANPLAI 275

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958743601  76 DFLEKILTFNPMDRLTAEMGLQHPYMSPYSCPEDEPTSQ 114
Cdd:cd07878   276 DLLEKMLVLDSDKRISASEALAHPYFSQYHDPEDEPEAE 314

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of 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. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. 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 CDK1 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTI--PvvrEEDKEELLRVMPSFVSS--TWEvKRPLRKLLPDVNREAID 76
Cdd:cd07835   183 IWSVGCIFAEMVTRRPLFPGDSEIDQLFRIFRTLgtP---DEDVWPGVTSLPDYKPTfpKWA-RQDLSKVVPSLDEDGLD 258

                          90       100
                  ....*....|....*....|....
gi 1958743601  77 FLEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07835   259 LLSQMLVYDPAKRISAKAALQHPY 282

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. 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. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPvvreedkeellrvmpsfvsstwevkrplrkllpdvNREAIDFLEK 80
Cdd:cd05118   184 IWSLGCILAELLTGRPLFPGDSEVDQLAKIVRLLG-----------------------------------TPEALDLLSK 228

                          90       100
                  ....*....|....*....|
gi 1958743601  81 ILTFNPMDRLTAEMGLQHPY 100
Cdd:cd05118   229 MLKYDPAKRITASQALAHPY 248

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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPV----------VREEDKEELLRvmPSFVSSTWEVKRP-----LRK 65
Cdd:cd14210   198 MWSLGCILAELYTGYPLFPGENEEEQLACIMEVLGVppkslidkasRRKKFFDSNGK--PRPTTNSKGKKRRpgsksLAQ 275

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958743601  66 LLPDVNREAIDFLEKILTFNPMDRLTAEMGLQHPYM 101
Cdd:cd14210   276 VLKCDDPSFLDFLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. 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 CDK2/3 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPvVREEDKEELLRVMPSFVSS--TWEVKrPLRKLLPDVNREAIDFL 78
Cdd:cd07860   184 IWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLG-TPDEVVWPGVTSMPDYKPSfpKWARQ-DFSKVVPPLDEDGRDLL 261

                          90       100
                  ....*....|....*....|..
gi 1958743601  79 EKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07860   262 SQMLHYDPNKRISAKAALAHPF 283

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. 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 CDK1 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDTIPVVREE---DKEELLRVMPSFvsSTWEvKRPLRKLLPDVNREAIDF 77
Cdd:cd07861   185 IWSIGTIFAEMATKKPLFHGDSEIDQLFRIFRILGTPTEDiwpGVTSLPDYKNTF--PKWK-KGSLRTAVKNLDEDGLDL 261

                          90       100
                  ....*....|....*....|...
gi 1958743601  78 LEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07861   262 LEKMLIYDPAKRISAKKALVHPY 284

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILD---TIPV-----VREEDKEELLRV---MPSFVSstwevkrpLRKLLPD 69
Cdd:cd07853   188 IWSVGCIFAELLGRRILFQAQSPIQQLDLITDllgTPSLeamrsACEGARAHILRGphkPPSLPV--------LYTLSSQ 259

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1958743601  70 VNREAIDFLEKILTFNPMDRLTAEMGLQHPYM--------------------SPYSCPEDEPTSQHPFRIEDE 122
Cdd:cd07853   260 ATHEAVHLLCRMLVFDPDKRISAADALAHPYLdegrlryhtcmckccyttsgGRVYTSDFEPSANPPFDDEYE 332

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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 1958743601   2 WAAGCILAEMLTGKMLFAGAHELEQMQLILDTIpvvreedKEELLRVMPSFVSSTW---------EVKRPLRKLLPDVNR 72
Cdd:cd07847   185 WAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTL-------GDLIPRHQQIFSTNQFfkglsipepETREPLESKFPNISS 257

                          90       100
                  ....*....|....*....|....*....
gi 1958743601  73 EAIDFLEKILTFNPMDRLTAEMGLQHPYM 101
Cdd:cd07847   258 PALSFLKGCLQMDPTERLSCEELLEHPYF 286

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHE-LEQMQLILDTIPVVREEDKEELLRvMPSFV--SSTWEVKRPLRKLLPDVNR--EAI 75
Cdd:cd07844   182 MWGVGCIFYEMATGRPLFPGSTDvEDQLHKIFRVLGTPTEETWPGVSS-NPEFKpySFPFYPPRPLINHAPRLDRipHGE 260

                          90       100
                  ....*....|....*....|....*
gi 1958743601  76 DFLEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd07844   261 ELALKFLQYEPKKRISAAEAMKHPY 285

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 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 1958743601   1 MWAAGCILAEMLTGKMLFAGAHELEQMQLILDT---IP--------------------VVREEDK--EELLRVMPSFVSS 55
Cdd:cd14135   187 MWSVGCTLYELYTGKILFPGKTNNHMLKLMMDLkgkFPkkmlrkgqfkdqhfdenlnfIYREVDKvtKKEVRRVMSDIKP 266

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1958743601  56 TwevkRPLRKLLPDVNR----------EAIDFLEKILTFNPMDRLTAEMGLQHPY 100
Cdd:cd14135   267 T----KDLKTLLIGKQRlpdedrkkllQLKDLLDKCLMLDPEKRITPNEALQHPF 317