EKS-HOS-00170
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-HOS-00170
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
CAMK/RSKb431.74.8E-129393652260
StatusReviewed
Ensembl ProteinENSP00000432945
UniProt AccessionO75676; A8K7Z8; O75585; Q53ES8;
Protein NameRibosomal protein S6 kinase alpha-4
Protein Synonyms/Alias S6K-alpha-4; 90 kDa ribosomal protein S6 kinase 4; Nuclear mitogen- and stress-activated protein kinase 2; Ribosomal protein kinase B; RSKB;
Gene NameRPS6KA4
Gene Synonyms/Alias RPS6KA4; MSK2;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSG00000162302ENSP00000294261ENST00000294261
ENSG00000162302ENSP00000333896ENST00000334205
ENSG00000162302ENSP00000432945ENST00000530504
ENSG00000162302ENSP00000435580ENST00000528057
ENSG00000162302ENSP00000435314ENST00000528355
OrganismHomo sapiens
Functional DescriptionSerine/threonine-protein kinase that is required for themitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and for the regulation of the transcription factor RELA, and that contributes to gene activation by histone phosphorylation and functions in the regulation of inflammatory genes. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Plays an essential role in the control of RELA transcriptional activity in response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In lipopolysaccharide- stimulated primary macrophages, acts downstream of the Toll-like receptor TLR4 to limit the production of pro-inflammatory cytokines. Functions probably by inducing transcription of the MAP kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin 10 (IL10), via CREB1 and ATF1 transcription factors.
Protein Length705
Protein Sequence
(FASTA)
TEANLTGHEE KVSVENFELL KVLGTGAYGK VFLVRKAGGH DAGKLYAMKV LRKAALVQRA 60
KTQEHTRTER SVLELVRQAP FLVTLHYAFQ TDAKLHLILD YVSGGEMFTH LYQRQYFKEA 120
EVRVYGGEIV LALEHLHKLG IIYRDLKLEN VLLDSEGHIV LTDFGLSKEF LTEEKERTFS 180
FCGTIEYMAP EIIRSKTGHG KAVDWWSLGI LLFELLTGAS PFTLEGERNT QAEVSRRILK 240
CSPPFPPRIG PVAQDLLQRL LCKDPKKRLG AGPQGAQEVR NHPFFQGLDW VALAARKIPA 300
PFRPQIRSEL DVGNFAEEFT RLEPVYSPPG SPPPGDPRIF QGYSFVAPSI LFDHNNAVMT 360
DGLEAPGAGD RPGRAAVARS AMMQQYELDL REPALGQGSF SVCRRCRQRQ SGQEFAVKIL 420
SRRLEANTQR EVAALRLCQS HPNVVNLHEV HHDQLHTYLV LELLRGGELL EHIRKKRHFS 480
ESEASQILRS LVSAVSFMHE EAGVVHRDLK PENILYADDT PGAPVKIIDF GFARLRPQSP 540
GVPMQTPCFT LQYAAPELLA QQGYDESCDL WSLGVILYMM LSGQVPFQGA SGQGGQSQAA 600
EIMCKIREGR FSLDGEAWQG VSEEAKELVR GLLTVDPAKR LKLEGLRGSS WLQDGSARSS 660
PPLRTPDVLE SSGPAVRSGL NATFMAFNRG KREGFFLKSV ENAPL 705
Nucleotide Sequence
(FASTA)
ACAGAAGCCA ACCTGACCGG GCACGAGGAG AAGGTGAGCG TGGAGAACTT CGAGCTGCTC 60
AAGGTGCTGG GCACGGGAGC CTACGGCAAG GTGTTCCTGG TGCGGAAGGC GGGCGGGCAC 120
GACGCGGGGA AGCTGTACGC CATGAAGGTG CTGCGCAAGG CGGCGCTGGT GCAGCGCGCC 180
AAGACGCAAG AGCACACGCG CACCGAGCGC TCGGTGCTGG AGCTGGTGCG CCAGGCGCCC 240
TTCCTGGTCA CGCTGCACTA CGCTTTCCAG ACGGATGCCA AGCTGCACCT CATCCTGGAC 300
TATGTGAGCG GCGGGGAGAT GTTCACCCAC CTCTACCAGC GCCAGTACTT CAAGGAGGCT 360
GAGGTGCGCG TGTATGGGGG TGAGATCGTG CTGGCCCTGG AACACCTGCA CAAGCTCGGC 420
ATCATTTACC GAGACCTGAA ACTGGAGAAT GTGCTGCTGG ACTCCGAGGG CCACATTGTC 480
CTCACGGACT TCGGGCTGAG CAAGGAGTTC CTGACGGAGG AGAAAGAGCG GACCTTCTCC 540
TTCTGTGGCA CCATCGAGTA CATGGCCCCC GAAATCATCC GTAGCAAGAC GGGGCATGGC 600
AAGGCTGTGG ACTGGTGGAG CCTGGGCATC TTGCTCTTCG AGCTGCTGAC GGGGGCCTCG 660
CCCTTCACCC TGGAGGGCGA GAGGAACACG CAGGCTGAGG TGTCTCGACG GATCCTGAAG 720
TGCTCCCCTC CCTTCCCCCC TCGGATCGGG CCCGTGGCGC AGGACCTGCT GCAGCGGCTG 780
CTTTGTAAGG ATCCTAAGAA GCGATTGGGC GCGGGGCCCC AGGGGGCACA AGAAGTCCGG 840
AACCATCCCT TCTTCCAGGG CCTCGATTGG GTGGCTCTGG CTGCCAGGAA GATTCCAGCC 900
CCATTCCGGC CCCAAATCCG CTCAGAGCTG GATGTGGGCA ACTTTGCGGA GGAATTCACT 960
CGGCTGGAGC CTGTCTACTC ACCCCCTGGC AGCCCCCCAC CTGGGGACCC CCGAATCTTT 1020
CAGGGATACT CCTTTGTGGC ACCCTCCATT CTCTTTGACC ACAACAACGC GGTGATGACC 1080
GATGGGCTGG AAGCGCCTGG TGCTGGAGAC CGGCCAGGTC GGGCAGCGGT GGCCAGGAGC 1140
GCTATGATGC AGCAGTACGA GCTGGACCTG CGGGAGCCTG CGCTGGGCCA GGGCAGCTTT 1200
TCTGTGTGTC GCCGCTGCCG CCAGCGCCAG AGCGGCCAGG AGTTCGCAGT CAAGATCCTC 1260
AGTCGCAGGC TGGAGGCGAA CACGCAGCGC GAAGTGGCTG CCCTGCGCCT GTGCCAGTCA 1320
CACCCCAACG TGGTGAATCT GCACGAGGTG CATCACGACC AGCTGCACAC GTACCTGGTC 1380
CTGGAGCTGC TGCGGGGCGG GGAGCTGCTG GAGCACATCC GCAAGAAGCG GCACTTCAGC 1440
GAGTCGGAAG CAAGCCAGAT CCTGCGCAGC CTCGTGTCGG CCGTGAGCTT CATGCACGAG 1500
GAGGCGGGCG TGGTGCACCG CGACCTCAAG CCGGAGAACA TCCTGTACGC CGACGACACG 1560
CCCGGGGCCC CGGTGAAAAT CATCGACTTC GGGTTCGCGC GGTTGCGGCC GCAGAGTCCC 1620
GGGGTGCCCA TGCAGACGCC CTGCTTCACG CTGCAGTACG CTGCCCCCGA GCTGCTGGCG 1680
CAGCAGGGCT ACGACGAGTC CTGCGACCTC TGGAGCCTGG GCGTCATTCT GTACATGATG 1740
CTGTCGGGGC AGGTCCCCTT CCAGGGGGCC TCTGGCCAGG GCGGGCAGAG CCAGGCGGCC 1800
GAGATCATGT GCAAAATCCG CGAGGGGCGC TTCTCCCTTG ACGGGGAGGC CTGGCAGGGT 1860
GTATCCGAGG AAGCCAAGGA GCTGGTCCGA GGGCTCCTGA CCGTGGACCC CGCCAAGCGG 1920
CTGAAGCTCG AGGGACTGCG GGGCAGCTCG TGGCTGCAGG ACGGCAGCGC GCGCTCCTCG 1980
CCCCCGCTCC GGACGCCCGA CGTGCTCGAG TCCTCTGGGC CCGCAGTGCG CTCGGGTCTC 2040
AACGCCACCT TCATGGCATT CAACCGGGGC AAGCGGGAGG GCTTCTTCCT GAAGAGCGTG 2100
GAGAATGCAC CCCT 2114
Domain Profile
S: 5     edlGvGsysvckrcvhkatnqefavkiidks.krdtseeieillryeqhpnivtlkdvyd  63
           lG+Gs+svc+rc++++++qefavki++++ +++t++e+++l+++++hpn+v+l++v++
Q: 393   PALGQGSFSVCRRCRQRQSGQEFAVKILSRRlEANTQREVAALRLCQSHPNVVNLHEVHH  452
         579*********************************************************
S: 64    dgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheq.Gvvhrdlkpe  122
         d++++ylvlell+GGell++i+kk++fse+eas+ilr+lv+av+++he+ Gvvhrdlkpe
Q: 453   DQLHTYLVLELLRGGELLEHIRKKRHFSESEASQILRSLVSAVSFMHEEaGVVHRDLKPE  512
         ***********************************************999**********
S: 123   nilyvdesdnaesikiidfGfaklkraeng.llktpcytlnfvapevlkrqGydeacdlw  181
         nily+d++++a+ +kiidfGfa+l+++++g +++tpc+tl+++ape+l++qGyde+cdlw
Q: 513   NILYADDTPGAP-VKIIDFGFARLRPQSPGvPMQTPCFTLQYAAPELLAQQGYDESCDLW  571
         ************.*****************99****************************
S: 182   slGvllytmlaGyvpf....angpedtaeeilakikeGkfslsGeawdsvseeakdlvsk  237
         slGv+ly+ml+G+vpf    ++g++++a+ei++ki+eG+fsl+Geaw++vseeak+lv++
Q: 572   SLGVILYMMLSGQVPFqgasGQGGQSQAAEIMCKIREGRFSLDGEAWQGVSEEAKELVRG  631
         ****************999889**************************************
S: 238   lltvdpakrlkleqllkhswl  258
         lltvdpakrlkle+l+ +swl
Q: 632   LLTVDPAKRLKLEGLRGSSWL  652
         ********************7
Domain Sequence
(FASTA)
PALGQGSFSV CRRCRQRQSG QEFAVKILSR RLEANTQREV AALRLCQSHP NVVNLHEVHH 60
DQLHTYLVLE LLRGGELLEH IRKKRHFSES EASQILRSLV SAVSFMHEEA GVVHRDLKPE 120
NILYADDTPG APVKIIDFGF ARLRPQSPGV PMQTPCFTLQ YAAPELLAQQ GYDESCDLWS 180
LGVILYMMLS GQVPFQGASG QGGQSQAAEI MCKIREGRFS LDGEAWQGVS EEAKELVRGL 240
LTVDPAKRLK LEGLRGSSWL 260
KeywordAlternative splicing; ATP-binding; Complete proteome; Inflammatory response; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Stress response; Transferase.
Sequence SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Equus caballus"; ?>Felis catus"; ?>Gasterosteus aculeatus"; ?>Ictidomys tridecemlineatus"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xiphophorus maculatus"; ?>
EKS-AIM-00156
EKS-ANC-00159
EKS-BOT-00164
EKS-CAE-00125
EKS-CAJ-00168
EKS-CAF-00171
EKS-CAP-00163
EKS-CIS-00194
EKS-DAR-00453
EKS-EQC-00155
EKS-FEC-00154
EKS-GAA-00194
EKS-ICT-00159
EKS-LOA-00163
EKS-MAM-00162
EKS-MAE-00060
EKS-MUM-00169
EKS-MUP-00168
EKS-NOL-00157
EKS-ORN-00204
EKS-OTG-00168
EKS-PAT-00154
EKS-PES-00145
EKS-RAN-00161
EKS-SAH-00158
EKS-SUS-00141
EKS-TAR-00211
EKS-TEN-00204
EKS-XIM-00199
Gene Ontology
GO:0005737; C:cytoplasm
GO:0005634; C:nucleus
GO:0005524; F:ATP binding
GO:0000287; F:magnesium ion binding
GO:0048273; F:mitogen-activated protein kinase p38 binding
GO:0004711; F:ribosomal protein S6 kinase activity
GO:0007411; P:axon guidance
GO:0043987; P:histone H3-S10 phosphorylation
GO:0043988; P:histone H3-S28 phosphorylation
GO:0006954; P:inflammatory response
GO:0070498; P:interleukin-1-mediated signaling pathway
GO:0007243; P:intracellular protein kinase cascade
GO:0001818; P:negative regulation of cytokine production
GO:0032793; P:positive regulation of CREB transcription factor activity
GO:0035066; P:positive regulation of histone acetylation
GO:0033129; P:positive regulation of histone phosphorylation
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter
KEGG
hsa:8986;
InterPros
IPR000961; AGC-kinase_C.
IPR011009; Kinase-like_dom.
IPR017892; Pkinase_C.
IPR000719; Prot_kinase_cat_dom.
IPR017441; Protein_kinase_ATP_BS.
IPR016239; Ribosomal_S6_kinase_II.
IPR002290; Ser/Thr_dual-sp_kinase_dom.
IPR008271; Ser/Thr_kinase_AS.
Pfam
PF00069; Pkinase; 2.
PF00433; Pkinase_C; 1.
SMARTs
SM00133; S_TK_X; 1.
SM00220; S_TKc; 2.
Prosites
PS51285; AGC_KINASE_CTER; 1.
PS00107; PROTEIN_KINASE_ATP; 2.
PS50011; PROTEIN_KINASE_DOM; 2.
PS00108; PROTEIN_KINASE_ST; 2.
Prints
Created Date20-Feb-2013