EKS-MUM-00165

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00165

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RSKb	498.5	9.1E-150	308	565	258

Status

Reviewed

Ensembl Protein

ENSMUSP00000134507

UniProt Accession

P18653;

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
ENSMUSG00000003644	ENSMUSP00000003741	ENSMUST00000003741
ENSMUSG00000003644	ENSMUSP00000119328	ENSMUST00000137486
ENSMUSG00000003644	ENSMUSP00000134507	ENSMUST00000174481
ENSMUSG00000003644	ENSMUSP00000121341	ENSMUST00000157067
ENSMUSG00000003644	ENSMUSP00000101514	ENSMUST00000105894
ENSMUSG00000003644	ENSMUSP00000126774	ENSMUST00000168974

Organism

Mus musculus

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 (By similarity).

Protein Length

625

Protein Sequence
(FASTA)

MERDILADVN HPFVVKLHYA FQTEGKLYLI LDFLRGGDLF TRLSKEVMFT EEDVKFYLAE 60

LALGLDHLHS LGIIYRDLKP ENILLDEEGH IKLTDFGLSK EAIDHEKKAY SFCGTVEYMA 120

PEVVNRQGHT HSADWWSYGV LMFEMLTGSL PFQGKDRKET MTLILKAKLG MPQFLSTEAQ 180

SLLRALFKRN PANRLGSGPD GAEEIKRHIF YSTIDWNKLY RREIKPPFKP AVAQPDDTFY 240

FDTEFTSRTP RDSPGIPPSA GAHQLFRGFS FVATGLMEDD GKPRTTQAPL HSVVQQLHGK 300

NLVFSDGYVV KETIGVGSYS VCKRCVHKAT NMEYAVKVID KSKRDPSEEI EILLRYGQHP 360

NIITLKDVYD DGKHVYLVTE LMRGGELLDK ILRQKFFSER EASFVLHTIS KTVEYLHSQG 420

VVHRDLKPSN ILYVDESGNP ECLRICDFGF AKQLRAENGL LMTPCYTANF VAPEVLKRQG 480

YDEGCDIWSL GILLYTMLAG YTPFANGPSD TPEEILTRIG SGKFTLSGGN WNTVSETAKD 540

LVSKMLHVDP HQRLTAKQVL QHPWITQKDK LPQSQLSHQD LQLVKGAMAA TYSALNSSKP 600

TPQLKPIESS ILAQRRVRKL PSTTL 625

Nucleotide Sequence
(FASTA)

ATGGAGAGAG ACATCCTCGC TGACGTGAAC CACCCGTTCG TGGTGAAGCT ACATTATGCC 60

TTCCAGACCG AGGGCAAGCT CTATCTTATT CTGGACTTCC TGCGTGGTGG AGACCTGTTC 120

ACACGGCTCT CAAAGGAGGT CATGTTTACA GAGGAGGATG TGAAGTTTTA CCTGGCTGAG 180

CTGGCACTGG GCCTGGACCA CCTGCACAGC TTGGGCATTA TTTACAGAGA CCTCAAGCCT 240

GAGAATATCC TTTTGGATGA GGAGGGCCAC ATCAAACTCA CTGACTTTGG CCTGAGCAAG 300

GAGGCCATAG ACCATGAGAA GAAGGCTTAC TCCTTCTGCG GGACAGTGGA GTACATGGCG 360

CCCGAGGTTG TCAACCGCCA GGGTCACACC CACAGTGCAG ACTGGTGGTC CTATGGGGTG 420

CTGATGTTTG AGATGCTGAC GGGCTCCCTG CCCTTCCAGG GGAAGGACCG GAAGGAGACC 480

ATGACCTTGA TTTTGAAGGC GAAGCTAGGC ATGCCCCAGT TTCTGAGCAC GGAAGCCCAG 540

AGCCTCCTGC GGGCCCTGTT CAAGAGGAAT CCTGCCAATC GGCTTGGCTC GGGCCCTGAT 600

GGGGCAGAGG AAATTAAGAG ACATATCTTC TACTCCACCA TTGACTGGAA TAAGCTCTAC 660

CGGCGTGAGA TCAAGCCCCC TTTCAAGCCG GCTGTGGCCC AGCCCGACGA CACCTTCTAC 720

TTTGATACCG AGTTCACGTC ACGCACACCC AGGGATTCGC CAGGCATCCC TCCCAGTGCT 780

GGTGCCCATC AGCTGTTCCG TGGCTTCAGC TTCGTGGCCA CTGGTCTGAT GGAGGACGAC 840

GGCAAGCCTC GGACCACTCA GGCCCCCCTA CACTCGGTGG TACAGCAACT CCACGGGAAG 900

AACTTGGTTT TCAGTGACGG CTACGTAGTA AAGGAGACGA TCGGCGTGGG CTCCTACTCT 960

GTGTGTAAGC GTTGTGTCCA CAAGGCCACC AACATGGAGT ATGCTGTCAA GGTCATCGAC 1020

AAGAGCAAAA GAGATCCCTC AGAAGAGATT GAGATTCTTC TGCGGTATGG CCAGCACCCC 1080

AACATCATCA CCCTGAAAGA TGTGTACGAT GATGGTAAGC ACGTGTACCT GGTGACAGAG 1140

CTGATGAGGG GCGGCGAGCT GCTGGATAAG ATCCTACGGC AGAAATTCTT CTCAGAGCGG 1200

GAGGCCAGCT TCGTCCTGCA CACGATCAGC AAGACTGTGG AATACTTGCA CTCTCAAGGG 1260

GTTGTCCACA GAGATCTCAA ACCCAGTAAC ATCCTCTATG TGGATGAGTC TGGGAACCCC 1320

GAGTGCCTGC GCATCTGCGA CTTTGGCTTT GCCAAGCAGC TACGGGCCGA GAACGGACTC 1380

CTCATGACAC CTTGCTACAC AGCCAACTTT GTGGCACCTG AGGTGCTGAA GCGCCAGGGC 1440

TACGATGAAG GCTGTGACAT ATGGAGCCTG GGCATTCTGC TGTACACGAT GCTGGCAGGA 1500

TACACTCCAT TTGCCAATGG GCCCAGTGAC ACCCCAGAGG AGATCCTCAC CCGGATCGGC 1560

AGCGGGAAGT TCACCCTCAG TGGGGGAAAC TGGAACACGG TTTCAGAGAC AGCCAAGGAC 1620

TTGGTATCTA AGATGCTGCA TGTGGACCCC CACCAGCGCC TCACAGCCAA GCAGGTCCTG 1680

CAGCACCCAT GGATCACCCA GAAAGACAAG CTTCCCCAGA GCCAGTTGTC CCACCAAGAC 1740

CTGCAGCTCG TGAAGGGAGC CATGGCGGCT ACATACTCTG CTCTCAATAG CTCCAAACCC 1800

ACCCCTCAGC TCAAGCCAAT TGAGTCGTCT ATCCTGGCCC AGCGGCGGGT GAGGAAGCTG 1860

CCATCCACCA CCCTGTGA 1878

Domain Profile

S: 1     yevkedlGvGsysvckrcvhkatnqefavkiidkskrdtseeieillryeqhpnivtlkd  60

         y+vke++GvGsysvckrcvhkatn+e+avk+idkskrd+seeieillry+qhpni+tlkd

Q: 308   YVVKETIGVGSYSVCKRCVHKATNMEYAVKVIDKSKRDPSEEIEILLRYGQHPNIITLKD  367

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

S: 61    vyddgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheqGvvhrdlk  120

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

Q: 368   VYDDGKHVYLVTELMRGGELLDKILRQKFFSEREASFVLHTISKTVEYLHSQGVVHRDLK  427

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

S: 121   penilyvdesdnaesikiidfGfaklkraengllktpcytlnfvapevlkrqGydeacdl  180

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

Q: 428   PSNILYVDESGNPECLRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDEGCDI  487

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

S: 181   wslGvllytmlaGyvpfangpedtaeeilakikeGkfslsGeawdsvseeakdlvskllt  240

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

Q: 488   WSLGILLYTMLAGYTPFANGPSDTPEEILTRIGSGKFTLSGGNWNTVSETAKDLVSKMLH  547

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

S: 241   vdpakrlkleqllkhswl  258

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

Q: 548   VDPHQRLTAKQVLQHPWI  565

         *****************8

Domain Sequence
(FASTA)

YVVKETIGVG SYSVCKRCVH KATNMEYAVK VIDKSKRDPS EEIEILLRYG QHPNIITLKD 60

VYDDGKHVYL VTELMRGGEL LDKILRQKFF SEREASFVLH TISKTVEYLH SQGVVHRDLK 120

PSNILYVDES GNPECLRICD FGFAKQLRAE NGLLMTPCYT ANFVAPEVLK RQGYDEGCDI 180

WSLGILLYTM LAGYTPFANG PSDTPEEILT RIGSGKFTLS GGNWNTVSET AKDLVSKMLH 240

VDPHQRLTAK QVLQHPWI 258

Keyword

ATP-binding; Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Equus caballus"; ?>Erinaceus europaeus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oryctolagus cuniculus"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Procavia capensis"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
GO:0005819	; C:spindle
GO:0005524	; F:ATP binding
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0007243	; P:intracellular protein kinase cascade
GO:0043066	; P:negative regulation of apoptotic process
GO:2000491	; P:positive regulation of hepatic stellate cell activation

KEGG

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