EKS-HOS-00166

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00166

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RSKb	495.6	1.4E-148	326	583	258

Status

Reviewed

Ensembl Protein

ENSP00000363277

UniProt Accession

Q15418; A6NGG4; A8K9K7; B2RDY8; B7Z5J0; Q5SVM5; Q5SVM8; Q5SVM9; Q96C05; Q9BQK2;

Protein Name

Ribosomal protein S6 kinase alpha-1

Protein Synonyms/Alias

S6K-alpha-1; 90 kDa ribosomal protein S6 kinase 1; p90-RSK 1; p90RSK1; p90S6K; MAP kinase-activated protein kinase 1a; MAPK-activated protein kinase 1a; MAPKAP kinase 1a; MAPKAPK-1a; Ribosomal S6 kinase 1; RSK-1;

Gene Name

RPS6KA1

Gene Synonyms/Alias

RPS6KA1; MAPKAPK1A, RSK1;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000117676	ENSP00000383967	ENST00000403732
ENSG00000117676	ENSP00000403548	ENST00000438977
ENSG00000117676	ENSP00000433039	ENST00000529454
ENSG00000117676	ENSP00000434616	ENST00000525525
ENSG00000117676	ENSP00000435412	ENST00000531382
ENSG00000117676	ENSP00000363281	ENST00000374166
ENSG00000117676	ENSP00000363283	ENST00000374168
ENSG00000117676	ENSP00000436990	ENST00000526040
ENSG00000117676	ENSP00000431651	ENST00000526792
ENSG00000117676	ENSP00000355831	ENST00000366866
ENSG00000117676	ENSP00000432281	ENST00000530003
ENSG00000117676	ENSP00000363278	ENST00000374163
ENSG00000117676	ENSP00000363277	ENST00000374162

Organism

Homo sapiens

Functional Description

Serine/threonine-protein kinase that acts downstream ofERK (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and stress-induced activation of the transcription factors CREB1, ETV1/ER81 and NR4A1/NUR77, regulates translation through RPS6 and EIF4B phosphorylation, and mediates cellular proliferation, survival, and differentiation by modulating mTOR signaling and repressing pro-apoptotic function of BAD and DAPK1. In fibroblast, is required for EGF-stimulated phosphorylation of CREB1, which results in the subsequent transcriptional activation of several immediate-early genes. In response to mitogenic stimulation (EGF and PMA), phosphorylates and activates NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP. Upon insulin- derived signal, acts indirectly on the transcription regulation of several genes by phosphorylating GSK3B at 'Ser-9' and inhibiting its activity. Phosphorylates RPS6 in response to serum or EGF via an mTOR-independent mechanism and promotes translation initiation by facilitating assembly of the preinitiation complex. In response to insulin, phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and stimulating cap-dependent translation. Is involved in the mTOR nutrient-sensing pathway by directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits TSC2 ability to suppress mTOR signaling, and mediates phosphorylation of RPTOR, which regulates mTORC1 activity and may promote rapamycin-sensitive signaling independently of the PI3K/AKT pathway. Mediates cell survival by phosphorylating the pro- apoptotic proteins BAD and DAPK1 and suppressing their pro- apoptotic function. Promotes the survival of hepatic stellate cells by phosphorylating CEBPB in response to the hepatotoxin carbon tetrachloride (CCl4). Is involved in cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B, which promotes CDKN1B association with 14-3-3 proteins and prevents its translocation to the nucleus and inhibition of G1 progression.

Protein Length

643

Protein Sequence
(FASTA)

MKVLKKATLK VRDRVRTKME RDILADVNHP FVVKLHYAFQ TEGKLYLILD FLRGGDLFTR 60

LSKEVMFTEE DVKFYLAELA LGLDHLHSLG IIYRDLKPEN ILLDEEGHIK LTDFGLSKEA 120

IDHEKKAYSF CGTVEYMAPE VVNRQGHSHS ADWWSYGVLM FEMLTGSLPF QGKDRKETMT 180

LILKAKLGMP QFLSTEAQSL LRALFKRNPA NRLGSGPDGA EEIKRHVFYS TIDWNKLYRR 240

EIKPPFKPAV AQPDDTFYFD TEFTSRTPKD SPGIPPSAGA HQLFRGFSFV ATGLMEDDGK 300

PRAPQAPLHS VVQQLHGKNL VFSDGYVVKE TIGVGSYSEC KRCVHKATNM EYAVKVIDKS 360

KRDPSEEIEI LLRYGQHPNI ITLKDVYDDG KHVYLVTELM RGGELLDKIL RQKFFSEREA 420

SFVLHTIGKT VEYLHSQGVV HRDLKPSNIL YVDESGNPEC LRICDFGFAK QLRAENGLLM 480

TPCYTANFVA PEVLKRQGYD EGCDIWSLGI LLYTMLAGYT PFANGPSDTP EEILTRIGSG 540

KFTLSGGNWN TVSETAKDLV SKMLHVDPHQ RLTAKQVLQH PWVTQKDKLP QSQLSHQDLQ 600

LVKGAMAATY SALNSSKPTP QLKPIESSIL AQRRVRKLPS TTL 643

Nucleotide Sequence
(FASTA)

ATGAAGGTGC TGAAGAAGGC AACGCTGAAA GTACGTGACC GCGTCCGGAC CAAGATGGAG 60

AGAGACATCC TGGCTGATGT AAATCACCCA TTCGTGGTGA AGCTGCACTA TGCCTTCCAG 120

ACCGAGGGCA AGCTCTATCT CATTCTGGAC TTCCTGCGTG GTGGGGACCT CTTCACCCGG 180

CTCTCAAAAG AGGTGATGTT CACGGAGGAG GATGTGAAGT TTTACCTGGC TGAGCTGGCT 240

CTGGGCCTGG ATCACCTGCA CAGCCTGGGT ATCATTTACA GAGACCTCAA GCCTGAGAAC 300

ATCCTTCTGG ATGAGGAGGG CCACATCAAA CTCACTGACT TTGGCCTGAG CAAAGAGGCC 360

ATTGACCACG AGAAGAAGGC CTATTCTTTC TGCGGGACAG TGGAGTACAT GGCCCCTGAG 420

GTCGTCAACC GCCAGGGCCA CTCCCATAGT GCGGACTGGT GGTCCTATGG GGTGTTGATG 480

TTTGAGATGC TGACGGGCTC CCTGCCCTTC CAGGGGAAGG ACCGGAAGGA GACCATGACA 540

CTGATTCTGA AGGCGAAGCT AGGCATGCCC CAGTTTCTGA GCACTGAAGC CCAGAGCCTC 600

TTGCGGGCCC TGTTCAAGCG GAATCCTGCC AACCGGCTCG GCTCCGGCCC TGATGGGGCA 660

GAGGAAATCA AGCGGCATGT CTTCTACTCC ACCATTGACT GGAATAAGCT ATACCGTCGT 720

GAGATCAAGC CACCCTTCAA GCCAGCAGTG GCTCAGCCTG ATGACACCTT CTACTTTGAC 780

ACCGAGTTCA CGTCCCGCAC ACCCAAGGAT TCCCCAGGCA TCCCCCCCAG CGCTGGGGCC 840

CATCAGCTGT TCCGGGGCTT CAGCTTCGTG GCCACCGGCC TGATGGAAGA CGACGGCAAG 900

CCTCGTGCCC CGCAGGCACC CCTGCACTCG GTGGTACAGC AACTCCATGG GAAGAACCTG 960

GTTTTTAGTG ACGGCTACGT GGTAAAGGAG ACAATTGGTG TGGGCTCCTA CTCTGAGTGC 1020

AAGCGCTGTG TCCACAAGGC CACCAACATG GAGTATGCTG TCAAGGTCAT TGATAAGAGC 1080

AAGCGGGATC CTTCAGAAGA GATTGAGATT CTTCTGCGGT ATGGCCAGCA CCCCAACATC 1140

ATCACTCTGA AAGATGTGTA TGATGATGGC AAACACGTGT ACCTGGTGAC AGAGCTGATG 1200

CGGGGTGGGG AGCTGCTGGA CAAGATCCTG CGGCAGAAGT TCTTCTCAGA GCGGGAGGCC 1260

AGCTTTGTCC TGCACACCAT TGGCAAAACT GTGGAGTATC TGCACTCACA GGGGGTTGTG 1320

CACAGGGACC TGAAGCCCAG CAACATCCTG TATGTGGACG AGTCCGGGAA TCCCGAGTGC 1380

CTGCGCATCT GTGACTTTGG TTTTGCCAAA CAGCTGCGGG CTGAGAATGG GCTCCTCATG 1440

ACACCTTGCT ACACAGCCAA CTTTGTGGCG CCTGAGGTGC TGAAGCGCCA GGGCTACGAT 1500

GAAGGCTGCG ACATCTGGAG CCTGGGCATT CTGCTGTACA CCATGCTGGC AGGATATACT 1560

CCATTTGCCA ACGGTCCCAG TGACACACCA GAGGAAATCC TAACCCGGAT CGGCAGTGGG 1620

AAGTTTACCC TCAGTGGGGG AAATTGGAAC ACAGTTTCAG AGACAGCCAA GGACCTGGTG 1680

TCCAAGATGC TACACGTGGA TCCCCACCAG CGCCTCACAG CTAAGCAGGT TCTGCAGCAT 1740

CCATGGGTCA CCCAGAAAGA CAAGCTTCCC CAAAGCCAGC TGTCCCACCA GGACCTACAG 1800

CTTGTGAAGG GAGCCATGGC TGCCACGTAC TCCGCACTCA ACAGCTCCAA GCCCACCCCC 1860

CAGCTGAAGC CCATCGAGTC ATCCATCCTG GCCCAGCGGC GAGTGAGGAA GTTGCCATCC 1920

ACCACCCTGT GA 1932

Domain Profile

S: 1     yevkedlGvGsysvckrcvhkatnqefavkiidkskrdtseeieillryeqhpnivtlkd  60

         y+vke++GvGsys ckrcvhkatn+e+avk+idkskrd+seeieillry+qhpni+tlkd

Q: 326   YVVKETIGVGSYSECKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKD  385

         689*********************************************************

S: 61    vyddgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheqGvvhrdlk  120

         vyddgk+vylv+el++GGelld+i+++kffsereas +l+t+ k+veylh+qGvvhrdlk

Q: 386   VYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTIGKTVEYLHSQGVVHRDLK  445

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

S: 121   penilyvdesdnaesikiidfGfaklkraengllktpcytlnfvapevlkrqGydeacdl  180

         p+nilyvdes+n+e+++i+dfGfak++raengll+tpcyt+nfvapevlkrqGyde+cd+

Q: 446   PSNILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDI  505

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

S: 181   wslGvllytmlaGyvpfangpedtaeeilakikeGkfslsGeawdsvseeakdlvskllt  240

         wslG+llytmlaGy+pfangp+dt+eeil++i++Gkf+lsG++w++vse+akdlvsk+l+

Q: 506   WSLGILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLH  565

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

S: 241   vdpakrlkleqllkhswl  258

         vdp++rl+++q+l+h+w+

Q: 566   VDPHQRLTAKQVLQHPWV  583

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

Domain Sequence
(FASTA)

YVVKETIGVG SYSECKRCVH KATNMEYAVK VIDKSKRDPS EEIEILLRYG QHPNIITLKD 60

VYDDGKHVYL VTELMRGGEL LDKILRQKFF SEREASFVLH TIGKTVEYLH SQGVVHRDLK 120

PSNILYVDES GNPECLRICD FGFAKQLRAE NGLLMTPCYT ANFVAPEVLK RQGYDEGCDI 180

WSLGILLYTM LAGYTPFANG PSDTPEEILT RIGSGKFTLS GGNWNTVSET AKDLVSKMLH 240

VDPHQRLTAK QVLQHPWV 258

Keyword

3D-structure; Alternative splicing; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; 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

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Procavia capensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005654	; C:nucleoplasm
GO:0005819	; C:spindle
GO:0005524	; F:ATP binding
GO:0043027	; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0007411	; P:axon guidance
GO:0007049	; P:cell cycle
GO:0045087	; P:innate immune response
GO:0002755	; P:MyD88-dependent toll-like receptor signaling pathway
GO:0043066	; P:negative regulation of apoptotic process
GO:0048011	; P:nerve growth factor receptor signaling pathway
GO:0045597	; P:positive regulation of cell differentiation
GO:0030307	; P:positive regulation of cell growth
GO:2000491	; P:positive regulation of hepatic stellate cell activation
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0043620	; P:regulation of DNA-dependent transcription in response to stress
GO:0043555	; P:regulation of translation in response to stress
GO:0051403	; P:stress-activated MAPK cascade
GO:0007268	; P:synaptic transmission
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:6195

;

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