EKS-HOS-00165

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00165

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RSKb	497.8	3.0E-149	393	650	258

Status

Reviewed

Ensembl Protein

ENSP00000444837

UniProt Accession

P51812; B2R9V4; Q4VAP3; Q59H26; Q5JPK8; Q7Z3Z7;

Protein Name

Ribosomal protein S6 kinase alpha-3

Protein Synonyms/Alias

S6K-alpha-3; 90 kDa ribosomal protein S6 kinase 3; p90-RSK 3; p90RSK3; Insulin-stimulated protein kinase 1; ISPK-1; MAP kinase-activated protein kinase 1b; MAPK-activated protein kinase 1b; MAPKAP kinase 1b; MAPKAPK-1b; Ribosomal S6 kinase 2; RSK-2; pp90RSK2;

Gene Name

RPS6KA3

Gene Synonyms/Alias

RPS6KA3; ISPK1, MAPKAPK1B, RSK2;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000177189	ENSP00000407655	ENST00000457145
ENSG00000177189	ENSP00000368884	ENST00000379565
ENSG00000177189	ENSP00000368865	ENST00000379548
ENSG00000177189	ENSP00000444837	ENST00000540702
ENSG00000177189	ENSP00000388512	ENST00000438357
ENSG00000177189	ENSP00000440220	ENST00000544447

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 and histone H3 at 'Ser-10', 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. In LPS-stimulated dendritic cells, is involved in TLR4-induced macropinocytosis, and in myeloma cells, acts as effector of FGFR3-mediated transformation signaling, after direct phosphorylation at Tyr-529 by FGFR3. Phosphorylates DAPK1.

Protein Length

711

Protein Sequence
(FASTA)

MDEPMGEEEI NPQTEEVSIK EIAITHHVKE GHEKADPSQF ELLKVLGQGS FGKVFLVKKI 60

SGSDARQLYA MKVLKKATLK VRDRVRTKME RDILVEVNHP FIVKLHYAFQ TEGKLYLILD 120

FLRGGDLFTR LSKEVMFTEE DVKFYLAELA LALDHLHSLG IIYRDLKPEN ILLDEEGHIK 180

LTDFGLSKES IDHEKKAYSF CGTVEYMAPE VVNRRGHTQS ADWWSFGVLM FEMLTGTLPF 240

QGKDRKETMT MILKAKLGMP QFLSPEAQSL LRMLFKRNPA NRLGAGPDGV EEIKRHSFFS 300

TIDWNKLYRR EIHPPFKPAT GRPEDTFYFD PEFTAKTPKD SPGIPPSANA HQLFRGFSFV 360

AITSDDESQA MQTVGVHSIV QLHRNSIQFT DGYEVKEDIG VGSYSVCKRC IHKATNMEFA 420

VKIIDKSKRD PTEEIEILLR YGQHPNIITL KDVYDDGKYV YVVTELMKGG ELLDKILRQK 480

FFSEREASAV LFTITKTVEY LHAQGVVHRD LKPSNILYVD ESGNPESIRI CDFGFAKQLR 540

AENGLLMTPC YTANFVAPEV LKRQGYDAAC DIWSLGVLLY TMLTGYTPFA NGPDDTPEEI 600

LARIGSGKFS LSGGYWNSVS DTAKDLVSKM LHVDPHQRLT AALVLRHPWI VHWDQLPQYQ 660

LNRQDAPHLV KGAMAATYSA LNRNQSPVLE PVGRSTLAQR RGIKKITSTA L 711

Nucleotide Sequence
(FASTA)

ATGGATGAAC CTATGGGAGA GGAGGAGATT AACCCACAAA CTGAAGAAGT CAGTATCAAA 60

GAAATTGCAA TCACACATCA TGTAAAGGAA GGACATGAAA AGGCAGATCC TTCCCAGTTT 120

GAACTTTTAA AAGTATTAGG GCAGGGATCA TTTGGAAAGG TTTTCTTAGT TAAAAAAATC 180

TCAGGCTCTG ATGCTAGGCA GCTTTATGCC ATGAAGGTAT TGAAGAAGGC CACACTGAAA 240

GTTCGAGACC GAGTTCGGAC AAAAATGGAA CGTGATATCT TGGTAGAGGT TAATCATCCT 300

TTTATTGTCA AGTTGCATTA TGCTTTTCAA ACTGAAGGGA AGTTGTATCT TATTTTGGAT 360

TTTCTCAGGG GAGGAGATTT GTTTACACGC TTATCCAAAG AGGTGATGTT CACAGAAGAA 420

GATGTCAAAT TCTACTTGGC TGAACTTGCA CTTGCTTTAG ACCATCTACA TAGCCTGGGA 480

ATAATTTATA GAGACTTAAA ACCAGAAAAT ATACTTCTTG ATGAAGAAGG TCACATCAAG 540

TTAACAGATT TCGGCCTAAG TAAAGAGTCT ATTGACCATG AAAAGAAGGC ATATTCTTTT 600

TGTGGAACTG TGGAGTATAT GGCTCCAGAA GTAGTTAATC GTCGAGGTCA TACTCAGAGT 660

GCTGACTGGT GGTCTTTTGG TGTGTTAATG TTTGAAATGC TTACTGGTAC ACTCCCTTTC 720

CAAGGAAAAG ATCGAAAAGA AACAATGACT ATGATTCTTA AAGCCAAACT TGGAATGCCA 780

CAGTTTTTGA GTCCTGAAGC GCAGAGTCTT TTACGAATGC TTTTCAAGCG AAATCCTGCA 840

AACAGATTAG GTGCAGGACC AGATGGAGTT GAAGAAATTA AAAGACATTC ATTTTTCTCA 900

ACGATAGACT GGAATAAACT GTATAGAAGA GAAATTCATC CGCCATTTAA ACCTGCAACG 960

GGCAGGCCTG AAGATACATT CTATTTTGAT CCTGAGTTTA CTGCAAAAAC TCCCAAAGAT 1020

TCACCTGGCA TTCCACCTAG TGCTAATGCA CATCAGCTTT TTCGGGGGTT TAGTTTTGTT 1080

GCTATTACCT CAGATGATGA AAGCCAAGCT ATGCAGACAG TTGGTGTACA TTCAATTGTT 1140

CAGTTACACA GGAACAGTAT TCAGTTTACT GATGGATATG AAGTAAAAGA AGATATTGGA 1200

GTTGGCTCCT ACTCTGTTTG CAAGAGATGT ATACATAAAG CTACAAACAT GGAGTTTGCA 1260

GTGAAGATTA TTGATAAAAG CAAGAGAGAC CCAACAGAAG AAATTGAAAT TCTTCTTCGT 1320

TATGGACAGC ATCCAAACAT TATCACTCTA AAGGATGTAT ATGATGATGG AAAGTATGTG 1380

TATGTAGTAA CAGAACTTAT GAAAGGAGGT GAATTGCTGG ATAAAATTCT TAGACAAAAA 1440

TTTTTCTCTG AACGAGAGGC CAGTGCTGTC CTGTTCACTA TAACTAAAAC CGTTGAATAT 1500

CTTCACGCAC AAGGGGTGGT TCATAGAGAC TTGAAACCTA GCAACATTCT TTATGTGGAT 1560

GAATCTGGTA ATCCGGAATC TATTCGAATT TGTGATTTTG GCTTTGCAAA ACAGCTGAGA 1620

GCGGAAAATG GTCTTCTCAT GACTCCTTGT TACACTGCAA ATTTTGTTGC ACCAGAGGTT 1680

TTAAAAAGAC AAGGCTATGA TGCTGCTTGT GATATATGGA GTCTTGGTGT CCTACTCTAT 1740

ACAATGCTTA CCGGTTACAC TCCATTTGCA AATGGTCCTG ATGATACACC AGAGGAAATA 1800

TTGGCACGAA TAGGTAGCGG AAAATTCTCA CTCAGTGGTG GTTACTGGAA TTCTGTTTCA 1860

GACACAGCAA AGGACCTGGT GTCAAAGATG CTTCATGTAG ACCCTCATCA GAGACTGACT 1920

GCTGCTCTTG TGCTCAGACA TCCTTGGATC GTCCACTGGG ACCAACTGCC ACAATACCAA 1980

CTAAACAGAC AGGATGCACC ACATCTAGTA AAGGGTGCCA TGGCAGCTAC ATATTCTGCT 2040

TTGAACCGTA ATCAGTCACC AGTTTTGGAA CCAGTAGGCC GCTCTACTCT TGCTCAGCGG 2100

AGAGGTATTA AAAAAATCAC CTCAACAGCC CTGTGA 2136

Domain Profile

S: 1     yevkedlGvGsysvckrcvhkatnqefavkiidkskrdtseeieillryeqhpnivtlkd  60

         yevked+GvGsysvckrc+hkatn+efavkiidkskrd++eeieillry+qhpni+tlkd

Q: 393   YEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKD  452

         789*********************************************************

S: 61    vyddgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheqGvvhrdlk  120

         vyddgkyvy+v+el+kGGelld+i+++kffsereasa+l+t++k+veylh+qGvvhrdlk

Q: 453   VYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLK  512

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

S: 121   penilyvdesdnaesikiidfGfaklkraengllktpcytlnfvapevlkrqGydeacdl  180

         p+nilyvdes+n+esi+i+dfGfak++raengll+tpcyt+nfvapevlkrqGyd+acd+

Q: 513   PSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDI  572

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

S: 181   wslGvllytmlaGyvpfangpedtaeeilakikeGkfslsGeawdsvseeakdlvskllt  240

         wslGvllytml+Gy+pfangp+dt+eeila+i++GkfslsG++w+svs++akdlvsk+l+

Q: 573   WSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLH  632

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

S: 241   vdpakrlkleqllkhswl  258

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

Q: 633   VDPHQRLTAALVLRHPWI  650

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

Domain Sequence
(FASTA)

YEVKEDIGVG SYSVCKRCIH KATNMEFAVK IIDKSKRDPT EEIEILLRYG QHPNIITLKD 60

VYDDGKYVYV VTELMKGGEL LDKILRQKFF SEREASAVLF TITKTVEYLH AQGVVHRDLK 120

PSNILYVDES GNPESIRICD FGFAKQLRAE NGLLMTPCYT ANFVAPEVLK RQGYDAACDI 180

WSLGVLLYTM LTGYTPFANG PDDTPEEILA RIGSGKFSLS GGYWNSVSDT AKDLVSKMLH 240

VDPHQRLTAA LVLRHPWI 258

Keyword

3D-structure; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Disease mutation; Kinase; Magnesium; Mental retardation; 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"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Ciona savignyi"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005829	; C:cytosol
GO:0005654	; C:nucleoplasm
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:0007417	; P:central nervous system development
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: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:0032496	; P:response to lipopolysaccharide
GO:0001501	; P:skeletal system development
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:6197

;

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