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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDaLLPPDT 137
Cdd:cd07852   189 RYTKGVDMWSVGCILGEMLLGKPLFPGTSTLNQLEKIIEVIGRPSAEDIESIQSPFAATMLESLPPSRPKSLD-ELFPKA 267

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQII 207
Cdd:cd07852   268 SPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQFHNPADEPSLPGPIVIPLDDNKKLTVDEYRNRLYEEI 337

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDaLLPPDT 137
Cdd:cd07852   189 RYTKGVDMWSVGCILGEMLLGKPLFPGTSTLNQLEKIIEVIGRPSAEDIESIQSPFAATMLESLPPSRPKSLD-ELFPKA 267

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQII 207
Cdd:cd07852   268 SPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQFHNPADEPSLPGPIVIPLDDNKKLTVDEYRNRLYEEI 337

glycogen synthase kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRpqqTLDALLPPDTP 138
Cdd:PTZ00036  248 YTTHIDLWSLGCIIAEMILGYPIFSGQSSVDQLVRIIQVLGTPTEDQLKEMNPNYADIKFPDVKPK---DLKKVFPKGTP 324

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1039749119 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCP 174
Cdd:PTZ00036  325 DDAINFISQFLKYEPLKRLNPIEALADPFFDDLRDP 360

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQ----NLGSRPQ--QTLDA 131
Cdd:COG0515   184 PVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPPPSELRPDLPPALDAIVLRalakDPEERYQsaAELAA 263

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 132 LLPPDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQIILEQS 211
Cdd:COG0515   264 ALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAPAAAAAAAAAAAALAAAAAAA 343

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 212 GNSRSPREEGLGVVASRAELRASPARTQSLKSGVLPQVPAETPARKRGPKPPRSPGHDPEHKFAGRAQTP 281
Cdd:COG0515   344 AAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAALAAAAAAAAAAAAA 413

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDaLLPPDT 137
Cdd:cd07852   189 RYTKGVDMWSVGCILGEMLLGKPLFPGTSTLNQLEKIIEVIGRPSAEDIESIQSPFAATMLESLPPSRPKSLD-ELFPKA 267

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQII 207
Cdd:cd07852   268 SPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQFHNPADEPSLPGPIVIPLDDNKKLTVDEYRNRLYEEI 337

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 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDTP 138
Cdd:cd07849   187 YTKAIDIWSVGCILAEMLSNRPLFPGKDYLHQLNLILGILGTPSQEDLNCIISLKARNYIKSLPFKPKVPWNKLF-PNAD 265

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVHEGDQLSAPEYRKRLYQIIL 208
Cdd:cd07849   266 PKALDLLDKMLTFNPHKRITVEEALAHPYLEQYHDPSDEPVAEEPFPFDMELFDDLPKEKLKELIFEEIM 335

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDT 137
Cdd:cd07855   190 EYTQAIDMWSVGCIFAEMLGRRQLFPGKNYVHQLQLILTVLGTPSQAVINAIGADRVRRYIQNLPNKQPVPWETLY-PKA 268

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDRE 177
Cdd:cd07855   269 DQQALDLLSQMLRFDPSERITVAEALQHPFLAKYHDPDDE 308

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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDT 137
Cdd:cd07857   186 SYTKAIDVWSVGCILAELLGRKPVFKGKDYVDQLNQILQVLGTPDEETLSRIGSPKAQNYIRSLPNIPKKPFESIF-PNA 264

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039749119 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 1039749119  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLPPD 136
Cdd:cd07851   191 MHYNQTVDIWSVGCIMAELLTGKTLFPGSDHIDQLKRIMNLVGTPDEELLKKISSESARNYIQSLPQMPKKDFKEVFSGA 270

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 137 TpPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARE------SDVRLPVHE 190
Cdd:cd07851   271 N-PLAIDLLEKMLVLDPDKRITAAEALAHPYLAEYHDPEDEPVAPpydqsfESRDLTVDE 329

Catalytic domain of the Serine/Threonine Kinases, Plant TDY 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 TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. 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 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY 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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDT 137
Cdd:cd07859   184 KYTPAIDIWSIGCIFAEVLTGKPLFPGKNVVHQLDLITDLLGTPSPETISRVRNEKARRYLSSMRKKQPVPFSQKF-PNA 262

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREWARESDVRLPVH-EGDQLSAPEYRKRLYQIILE 209
Cdd:cd07859   263 DPLALRLLERLLAFDPKDRPTAEEALADPYFKGLAKVEREPSAQPITKLEFEfERRRLTKEDVRELIYREILE 335

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 1039749119  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPD 136
Cdd:cd07878   191 MHYNQTVDIWSVGCIMAELLKGKALFPGNDYIDQLKRIMEVVGTPSPEVLKKISSEHARKYIQSLPHMPQQDLKKIF-RG 269

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1039749119 137 TPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDRE 177
Cdd:cd07878   270 ANPLAIDLLEKMLVLDSDKRISASEALAHPYFSQYHDPEDE 310

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 1039749119  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPD 136
Cdd:cd07879   190 MHYNQTVDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTGVPGPEFVQKLEDKAAKSYIKSLPKYPRKDFSTLF-PK 268

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1039749119 137 TPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDREwaRESDVRLPVHEGDQLSAPEYRKRLYQIIL 208
Cdd:cd07879   269 ASPQAVDLLEKMLELDVDKRLTATEALEHPYFDSFRDADEE--TEQQPYDDSLENEKLSVDEWKKHIYKEVK 338

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. 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 CDK4/6-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 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLgsdySALILQNLGSRPQQTLDALLpPDTP 138
Cdd:cd07838   183 YATPVDMWSVGCIFAELFNRRPLFRGSSEADQLGKIFDVIGLPSEEEWPRN----SALPRSSFPSYTPRPFKSFV-PEID 257

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039749119 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:cd07838   258 EEGLDLLKKMLTFNPHKRISAFEALQHPYF 287

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 1039749119  56 CLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLPP 135
Cdd:cd07853   179 SRHYTSAVDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRSACEGARAHILRGPHKPPSLPVLYTLSS 258

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119 136 DTPPEALDLLKRLLAFAPDKRLSAEQALQHPYVQ----RFH---C-------PDREWARESDVRLP-----VHEGDQLSA 196
Cdd:cd07853   259 QATHEAVHLLCRMLVFDPDKRISAADALAHPYLDegrlRYHtcmCkccyttsGGRVYTSDFEPSANppfddEYEKNLTSV 338

                         170       180
                  ....*....|....*....|.
gi 1039749119 197 PEYRKRLYQIILEQSGNSRSP 217
Cdd:cd07853   339 RQVKEELHQFILEQQQGNRVP 359

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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTiplpsmeelqdlgsdysalilqnLGsrpqqtldallppdt 137
Cdd:cd05118   177 PYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRL-----------------------LG--------------- 218

                          90       100       110
                  ....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd05118   219 TPEALDLLSKMLKYDPAKRITASQALAHPY 248

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 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGS--DYSAlilqnLGSRPQQTLDALLPPD 136
Cdd:cd07841   180 YGVGVDMWSVGCIFAELLLRVPFLPGDSDIDQLGKIFEALGTPTEENWPGVTSlpDYVE-----FKPFPPTPLKQIFPAA 254

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1039749119 137 tPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07841   255 -SDDALDLLQRLLTLNPNKRITARQALEHPY 284

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; 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 Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 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 1039749119  58 RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRPQQTLDALLpPDT 137
Cdd:cd07856   182 KYDVEVDIWSAGCIFAEMLEGKPLFPGKDHVNQFSIITELLGTPPDDVINTICSENTLRFVQSLPKRERVPFSEKF-KNA 260

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1039749119 138 PPEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCPDRE 177
Cdd:cd07856   261 DPDAIDLLEKMLVFDPKKRISAAEALAHPYLAPYHDPTDE 300

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 1039749119  54 PSCL----RYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLgsDYSALILQNLGSRPQQTL 129
Cdd:cd07831   167 PECLltdgYYGPKMDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKF--RKSRHMNYNFPSKKGTGL 244

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1039749119 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 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSmeELQDLGSDYSALILQNLGSRPQQTLDALLpPDTP 138
Cdd:cd07836   178 YSTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMGTPT--ESTWPGISQLPEYKPTFPRYPPQDLQQLF-PHAD 254

                          90       100
                  ....*....|....*....|....*....
gi 1039749119 139 PEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07836   255 PLGIDLLHRLLQLNPELRISAHDALQHPW 283

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; 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. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-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 1039749119  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALIlqnlgsrpqqtldallppd 136
Cdd:cd14133   176 LPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGTIGIPPAHMLDQGKADDELFV------------------- 236

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039749119 137 tppealDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:cd14133   237 ------DFLKKLLEIDPKERPTASQALSHPWL 262

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119   55 SCLRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEElqdlgsdysalilqnlgsrpqqtldallP 134
Cdd:smart00220 169 LGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKPKPPFPPP----------------------------E 220

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1039749119  135 PDTPPEALDLLKRLLAFAPDKRLSAEQALQHPYV 168
Cdd:smart00220 221 WDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

glycogen synthase kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKTIPLPSMEELQDLGSDYSALILQNLGSRpqqTLDALLPPDTP 138
Cdd:PTZ00036  248 YTTHIDLWSLGCIIAEMILGYPIFSGQSSVDQLVRIIQVLGTPTEDQLKEMNPNYADIKFPDVKPK---DLKKVFPKGTP 324

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1039749119 139 PEALDLLKRLLAFAPDKRLSAEQALQHPYVQRFHCP 174
Cdd:PTZ00036  325 DDAINFISQFLKYEPLKRLNPIEALADPFFDDLRDP 360

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. 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 CDK5 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 1039749119  59 YTPGVDMWSLGCILGEMLR-GQPLFPGTSTFHQLELILKTIPLPSMEELQDLG--SDYSALILQnlgsrPQQTLDALLPP 135
Cdd:cd07839   177 YSTSIDMWSAGCIFAELANaGRPLFPGNDVDDQLKRIFRLLGTPTEESWPGVSklPDYKPYPMY-----PATTSLVNVVP 251

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1039749119 136 DTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07839   252 KLNSTGRDLLQNLLVCNPVQRISAEEALQHPY 283

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 1039749119  59 YTPGVDMWSLGCILGEMLRGQPLFPG-------TSTFH--QLELILKTIPLPSMEELQDLGS--DYSALilqnLGSRPQQ 127
Cdd:cd07842   193 YTKAIDIWAIGCIFAELLTLEPIFKGreakikkSNPFQrdQLERIFEVLGTPTEKDWPDIKKmpEYDTL----KSDTKAS 268

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1039749119 128 TLDALLPPD-------TPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07842   269 TYPNSLLAKwmhkhkkPDSQGFDLLRKLLEYDPTKRITAEEALEHPY 315

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 1039749119  59 YTPGVDMWSLGCILGEML-RGQPLFPGTSTFHQLELILK---TIPLpsMEELQDLGSDYSALILQNLGSRPQQTLDALLP 134
Cdd:cd14132   190 YDYSLDMWSLGCMLASMIfRKEPFFHGHDNYDQLVKIAKvlgTDDL--YAYLDKYGIELPPRLNDILGRHSKKPWERFVN 267

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1039749119 135 PDT----PPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd14132   268 SENqhlvTPEALDLLDKLLRYDHQERITAKEAMQHPY 304

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 1039749119  57 LRYTPGVDMWSLGCILGEMLRGQPLFPGTSTFHQLELILKT----IP----------------LPSMEELQDLGSDYsal 116
Cdd:cd07847   176 TQYGPPVDVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTlgdlIPrhqqifstnqffkglsIPEPETREPLESKF--- 252

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1039749119 117 ilqnlgsrpqqtldallpPDTPPEALDLLKRLLAFAPDKRLSAEQALQHPY 167
Cdd:cd07847   253 ------------------PNISSPALSFLKGCLQMDPTERLSCEELLEHPY 285