EKS-HOS-00169

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00169

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RSKb	448.9	2.5E-134	348	608	261

Status

Reviewed

Ensembl Protein

ENSP00000442803

UniProt Accession

O75582; O95316; Q96AF7;

Protein Name

Ribosomal protein S6 kinase alpha-5

Protein Synonyms/Alias

S6K-alpha-5; 90 kDa ribosomal protein S6 kinase 5; Nuclear mitogen- and stress-activated protein kinase 1; RSK-like protein kinase; RSKL;

Gene Name

RPS6KA5

Gene Synonyms/Alias

RPS6KA5; MSK1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000100784	ENSP00000451305	ENST00000556178
ENSG00000100784	ENSP00000261991	ENST00000261991
ENSG00000100784	ENSP00000450591	ENST00000554206
ENSG00000100784	ENSP00000442803	ENST00000536315
ENSG00000100784	ENSP00000451736	ENST00000556594
ENSG00000100784	ENSP00000402787	ENST00000418736

Organism

Homo sapiens

Functional Description

Serine/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 factors RELA, STAT3 and ETV1/ER81, 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 and upon glucocorticoid, associates in the cytoplasm with the glucocorticoid receptor NR3C1 and contributes to RELA inhibition and repression of inflammatory gene expression. In skeletal myoblasts is required for phosphorylation of RELA at 'Ser-276' during oxidative stress. In erythropoietin-stimulated cells, is necessary for the 'Ser-727' phosphorylation of STAT3 and regulation of its transcriptional potential. Phosphorylates ETV1/ER81 at 'Ser-191' and 'Ser-216', and thereby regulates its ability to stimulate transcription, which may be important during development and breast tumor formation. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. 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. Plays a role in neuronal cell death by mediating the downstream effects of excitotoxic injury.

Protein Length

723

Protein Sequence
(FASTA)

MKVLKKATIV QKAKTTEHTR TERQVLEHIR QSPFLVTLHY AFQTETKLHL ILDYINGGEL 60

FTHLSQRERF TEHEVQIYVG EIVLALEHLH KLGIIYRDIK LENILLDSNG HVVLTDFGLS 120

KEFVADETER AYSFCGTIEY MAPDIVRGGD SGHDKAVDWW SLGVLMYELL TGASPFTVDG 180

EKNSQAEISR RILKSEPPYP QEMSALAKDL IQRLLMKDPK KRLGCGPRDA DEIKEHLFFQ 240

KINWDDLAAK KVPAPFKPVI RDELDVSNFA EEFTEMDPTY SPAALPQSSE KLFQGYSFVA 300

PSILFKRNAA VIDPLQFHMG VERPGVTNVA RSAMMKDSPF YQHYDLDLKD KPLGEGSFSI 360

CRKCVHKKSN QAFAVKIISK RMEANTQKEI TALKLCEGHP NIVKLHEVFH DQLHTFLVME 420

LLNGGELFER IKKKKHFSET EASYIMRKLV SAVSHMHDVG VVHRDLKPEN LLFTDENDNL 480

EIKIIDFGFA RLKPPDNQPL KTPCFTLHYA APELLNQNGY DESCDLWSLG VILYTMLSGQ 540

VPFQSHDRSL TCTSAVEIMK KIKKGDFSFE GEAWKNVSQE AKDLIQGLLT VDPNKRLKMS 600

GLRYNEWLQD GSQLSSNPLM TPDILGSSGA AVHTCVKATF HAFNKYKREG FCLQNVDKAP 660

LAKRRKMKKT STSTETRSSS SESSHSSSSH SHGKTTPTKT LQPSNPADSN NPETLFQFSD 720

SVA 723

Nucleotide Sequence
(FASTA)

ATGAAAGTTT TGAAAAAGGC AACAATCGTT CAAAAGGCCA AAACCACAGA GCATACAAGG 60

ACAGAACGAC AAGTCCTGGA ACACATTAGG CAGTCGCCAT TTTTGGTAAC ATTACATTAT 120

GCTTTCCAGA CAGAAACCAA ACTTCATCTC ATTTTAGATT ATATAAATGG TGGTGAACTT 180

TTTACTCATC TTTCTCAAAG AGAGCGTTTC ACAGAGCATG AGGTGCAGAT TTATGTTGGA 240

GAGATTGTGC TTGCCCTCGA ACATCTCCAC AAGTTGGGGA TTATATATCG TGATATTAAG 300

CTTGAGAATA TTCTACTTGA TTCTAATGGC CATGTGGTGC TGACAGATTT TGGTCTGAGT 360

AAGGAGTTTG TGGCTGATGA AACTGAAAGA GCATATTCCT TTTGTGGAAC TATTGAATAC 420

ATGGCACCAG ATATTGTCAG AGGGGGAGAT TCAGGACATG ACAAGGCAGT TGACTGGTGG 480

AGTTTGGGTG TTCTAATGTA TGAATTACTA ACTGGAGCAT CTCCTTTCAC TGTTGATGGA 540

GAAAAAAATT CCCAAGCTGA GATATCTAGG AGAATATTAA AAAGTGAGCC TCCATATCCC 600

CAAGAAATGA GTGCTTTAGC GAAAGACCTA ATTCAGCGTC TTTTGATGAA AGATCCCAAG 660

AAGAGATTGG GATGTGGTCC ACGTGATGCA GATGAAATCA AAGAACATCT CTTCTTTCAG 720

AAAATAAATT GGGATGATTT AGCCGCCAAA AAAGTGCCTG CACCATTTAA GCCAGTCATT 780

CGAGATGAAT TAGATGTGAG TAACTTTGCA GAAGAGTTCA CAGAAATGGA TCCCACTTAT 840

TCTCCCGCAG CCCTGCCCCA GAGTTCTGAG AAGCTGTTTC AGGGCTATTC CTTTGTTGCT 900

CCTTCCATCC TATTCAAGCG TAATGCAGCT GTCATAGACC CTCTTCAGTT TCACATGGGA 960

GTTGAACGTC CTGGAGTGAC AAATGTTGCC AGGAGTGCAA TGATGAAGGA CTCTCCATTC 1020

TATCAACACT ATGACCTAGA TTTGAAGGAC AAACCCCTGG GAGAAGGTAG TTTTTCAATT 1080

TGTCGAAAGT GTGTGCATAA AAAAAGTAAC CAAGCTTTTG CAGTCAAAAT AATCAGCAAA 1140

AGGATGGAAG CCAATACTCA AAAGGAAATA ACAGCTCTGA AACTCTGTGA AGGACACCCC 1200

AATATTGTGA AGTTGCATGA AGTTTTTCAT GATCAGCTTC ACACGTTTCT AGTGATGGAA 1260

CTTCTGAATG GAGGAGAACT GTTTGAGCGC ATTAAGAAAA AGAAGCACTT CAGTGAGACG 1320

GAAGCCAGCT ACATCATGAG GAAGCTTGTT TCAGCTGTAA GCCACATGCA TGATGTTGGA 1380

GTGGTGCACA GGGATCTGAA ACCTGAGAAT TTATTGTTCA CCGATGAAAA TGACAATTTG 1440

GAAATTAAAA TAATTGATTT TGGATTTGCA CGGCTAAAGC CACCGGATAA TCAGCCCCTG 1500

AAGACTCCAT GCTTCACCCT TCATTATGCC GCCCCAGAGC TCTTGAATCA GAACGGCTAC 1560

GATGAGTCCT GTGACCTGTG GAGCTTGGGC GTCATTTTGT ACACAATGTT GTCAGGACAG 1620

GTTCCCTTCC AATCTCATGA CCGAAGTTTG ACGTGTACCA GCGCGGTGGA AATCATGAAG 1680

AAAATTAAAA AGGGAGATTT CTCCTTTGAA GGAGAAGCCT GGAAGAATGT ATCCCAAGAG 1740

GCTAAAGATT TGATCCAAGG ACTTCTCACA GTAGATCCAA ACAAAAGGCT TAAAATGTCT 1800

GGCTTGAGGT ACAATGAATG GCTACAAGAT GGAAGTCAGC TGTCCTCCAA TCCTCTGATG 1860

ACTCCGGATA TTCTAGGATC TTCCGGAGCT GCCGTGCATA CCTGTGTGAA AGCAACCTTC 1920

CACGCCTTTA ACAAATACAA GAGAGAGGGG TTTTGCCTTC AGAATGTTGA TAAGGCCCCT 1980

TTGGCTAAGA GAAGAAAAAT GAAAAAGACT AGCACCAGTA CCGAGACGCG CAGCAGTTCC 2040

AGTGAGAGTT CCCATTCTTC TTCCTCTCAT TCTCACGGTA AAACTACACC CACCAAGACA 2100

CTGCAGCCCA GCAATCCTGC CGACAGCAAT AACCCGGAGA CCCTCTTCCA GTTCTCGGAC 2160

TCAGTAGCTT AG 2172

Domain Profile

S: 2     evkedlGvGsysvckrcvhkatnqefavkiidks.krdtseeieillryeqhpnivtlkd  60

         +++++lG+Gs+s+c++cvhk++nq+favkii+k+ +++t++ei++l+++e+hpniv+l++

Q: 348   LKDKPLGEGSFSICRKCVHKKSNQAFAVKIISKRmEANTQKEITALKLCEGHPNIVKLHE  407

         5789******************************9*************************

S: 61    vyddgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheqGvvhrdlk  120

         v++d+++++lv+ell+GGel++rikkkk+fse+eas+i+r+lv+av+++h++Gvvhrdlk

Q: 408   VFHDQLHTFLVMELLNGGELFERIKKKKHFSETEASYIMRKLVSAVSHMHDVGVVHRDLK  467

         ************************************************************

S: 121   penilyvdesdnaesikiidfGfaklkraengllktpcytlnfvapevlkrqGydeacdl  180

         pen+l++de+dn+e ikiidfGfa+lk+++n++lktpc+tl+++ape+l+++Gyde+cdl

Q: 468   PENLLFTDENDNLE-IKIIDFGFARLKPPDNQPLKTPCFTLHYAAPELLNQNGYDESCDL  526

         **************.*********************************************

S: 181   wslGvllytmlaGyvpf....angpedtaeeilakikeGkfslsGeawdsvseeakdlvs  236

         wslGv+lytml+G+vpf    +++++++a+ei++kik+G+fs++Geaw++vs+eakdl++

Q: 527   WSLGVILYTMLSGQVPFqshdRSLTCTSAVEIMKKIKKGDFSFEGEAWKNVSQEAKDLIQ  586

         *****************9998899************************************

S: 237   klltvdpakrlkleqllkhswl  258

         +lltvdp+krlk+++l++++wl

Q: 587   GLLTVDPNKRLKMSGLRYNEWL  608

         *********************7

Domain Sequence
(FASTA)

LKDKPLGEGS FSICRKCVHK KSNQAFAVKI ISKRMEANTQ KEITALKLCE GHPNIVKLHE 60

VFHDQLHTFL VMELLNGGEL FERIKKKKHF SETEASYIMR KLVSAVSHMH DVGVVHRDLK 120

PENLLFTDEN DNLEIKIIDF GFARLKPPDN QPLKTPCFTL HYAAPELLNQ NGYDESCDLW 180

SLGVILYTML SGQVPFQSHD RSLTCTSAVE IMKKIKKGDF SFEGEAWKNV SQEAKDLIQG 240

LLTVDPNKRL KMSGLRYNEW L 261

Keyword

3D-structure; Alternative splicing; ATP-binding; Complete proteome; Cytoplasm; Inflammatory response; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Stress response; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Danio rerio"; ?>Dipodomys ordii"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Sarcophilus harrisii"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005654	; C:nucleoplasm
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0007411	; P:axon guidance
GO:0007173	; P:epidermal growth factor receptor signaling pathway
GO:0043990	; P:histone H2A-S1 phosphorylation
GO:0043987	; P:histone H3-S10 phosphorylation
GO:0043988	; P:histone H3-S28 phosphorylation
GO:0006954	; P:inflammatory response
GO:0045087	; P:innate immune response
GO:0070498	; P:interleukin-1-mediated signaling pathway
GO:0002755	; P:MyD88-dependent toll-like receptor signaling pathway
GO:0001818	; P:negative regulation of cytokine production
GO:0045892	; P:negative regulation of transcription, DNA-dependent
GO:0048011	; P:nerve growth factor receptor signaling pathway
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
GO:0051403	; P:stress-activated MAPK cascade
GO:0008063	; P:Toll signaling pathway
GO:0034130	; P:toll-like receptor 1 signaling pathway
GO:0034134	; P:toll-like receptor 2 signaling pathway
GO:0034138	; P:toll-like receptor 3 signaling pathway
GO:0034142	; P:toll-like receptor 4 signaling pathway
GO:0035666	; P:TRIF-dependent toll-like receptor signaling pathway

KEGG

hsa:9252

;

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 Date

20-Feb-2013