EKS-MUM-00166

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00166

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/RSKb	497.8	1.5E-149	394	651	258

Status

Reviewed

Ensembl Protein

ENSMUSP00000108112

UniProt Accession

P18654; B1AXN4; Q03140; Q8K3J8;

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; 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; Mapkapk1b, Rps6ka-rs1, Rsk2;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000031309	ENSMUSP00000123059	ENSMUST00000148570
ENSMUSG00000031309	ENSMUSP00000115271	ENSMUST00000156648
ENSMUSG00000031309	ENSMUSP00000033671	ENSMUST00000033671
ENSMUSG00000031309	ENSMUSP00000108112	ENSMUST00000112493
ENSMUSG00000031309	ENSMUSP00000108111	ENSMUST00000112492
ENSMUSG00000031309	ENSMUSP00000108110	ENSMUST00000112491
ENSMUSG00000031309	ENSMUSP00000118007	ENSMUST00000126686

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 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 (By similarity).

Protein Length

712

Protein Sequence
(FASTA)

MDEPMGEEEI NPQTEEGSIK 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 QQLHRNSIQF TDGYEVKEDI GVGSYSVCKR CIHKATNMEF 420

AVKIIDKSKR DPTEEIEILL RYGQHPNIIT LKDVYDDGKY VYVVTELMKG GELLDKILRQ 480

KFFSEREASA VLFTITKTVE YLHAQGVVHR DLKPSNILYV DESGNPESIR ICDFGFAKQL 540

RAENGLLMTP CYTANFVAPE VLKRQGYDAA CDIWSLGVLL YTMLTGYTPF ANGPDDTPEE 600

ILARIGSGKF SLSGGYWNSV SDTAKDLVSK MLHVDPHQRL TAALVLRHPW IVHWDQLPQY 660

QLNRQDAPHL VKGAMAATYS ALNRNQSPVL EPVGRSTLAQ RRGIKKITST AL 712

Nucleotide Sequence
(FASTA)

ATGGATGAAC CTATGGGAGA GGAGGAGATT AACCCACAAA CTGAAGAAGG CAGTATCAAA 60

GAAATTGCAA TCACACATCA TGTGAAGGAA GGACATGAAA AGGCAGATCC TTCCCAGTTT 120

GAACTTTTAA AAGTATTAGG GCAGGGATCA TTTGGAAAGG TTTTCTTAGT TAAAAAAATC 180

TCAGGCTCTG ATGCTAGACA GCTTTATGCC ATGAAAGTAT TAAAGAAGGC CACGCTGAAA 240

GTTCGAGACC GTGTTCGGAC AAAAATGGAA CGTGATATCT TGGTAGAAGT CAATCACCCT 300

TTCATTGTCA AATTGCATTA CGCTTTTCAA ACGGAAGGGA AGTTGTATCT TATTTTGGAT 360

TTTCTCAGGG GCGGAGACTT GTTTACACGC TTATCCAAAG AGGTGATGTT CACAGAGGAA 420

GATGTCAAAT TCTACTTGGC TGAACTTGCA CTTGCTTTAG ACCATCTTCA TAGCCTGGGA 480

ATAATCTATA GAGACTTAAA ACCAGAAAAC ATACTTCTTG ATGAAGAAGG TCACATCAAG 540

TTAACTGATT TTGGCTTAAG TAAGGAATCT ATTGATCATG AGAAGAAGGC TTATTCTTTT 600

TGTGGCACTG TGGAATACAT GGCTCCAGAA GTAGTTAACC GCAGAGGTCA CACTCAGAGT 660

GCGGACTGGT GGTCCTTTGG TGTGTTGATG TTTGAAATGC TCACTGGTAC ACTACCTTTC 720

CAAGGAAAAG ATCGTAAAGA AACAATGACT ATGATTCTTA AAGCCAAACT CGGGATGCCA 780

CAGTTTCTGA GTCCTGAAGC CCAGAGTCTT TTACGAATGC TTTTCAAACG GAATCCTGCA 840

AACAGATTAG GTGCTGGACC AGATGGAGTT GAAGAAATTA AAAGACATTC ATTTTTCTCA 900

ACAATAGACT GGAATAAACT ATATAGAAGA GAGATTCACC CACCTTTTAA GCCTGCAACT 960

GGCAGACCTG AAGATACATT TTATTTTGAT CCTGAGTTTA CTGCAAAAAC TCCCAAAGAT 1020

TCACCGGGCA TTCCACCTAG TGCTAACGCA CATCAGCTTT TTCGGGGGTT TAGTTTTGTT 1080

GCTATTACCT CAGATGATGA AAGCCAAGCT ATGCAGACAG TTGGTGTGCA TTCAATTGTT 1140

CAGCAATTAC ACAGAAACAG TATTCAGTTT ACTGATGGAT ATGAAGTAAA AGAGGATATT 1200

GGCGTTGGCT CATACTCCGT TTGTAAGAGA TGTATACATA AAGCTACAAA CATGGAGTTT 1260

GCCGTGAAGA TTATTGATAA AAGCAAGAGA GACCCAACAG AAGAGATTGA AATTCTTCTT 1320

CGCTATGGAC AGCATCCAAA CATCATTACC CTAAAGGATG TGTATGATGA TGGAAAATAT 1380

GTGTATGTAG TAACAGAACT TATGAAAGGA GGTGAATTGC TGGATAAGAT TCTTAGACAG 1440

AAGTTTTTCT CAGAGCGAGA GGCCAGCGCT GTCCTGTTTA CTATAACCAA AACTGTTGAG 1500

TATCTTCATG CACAAGGGGT GGTTCACAGA GACTTGAAAC CTAGCAACAT TCTTTATGTG 1560

GATGAGTCTG GTAATCCAGA ATCTATTCGA ATTTGTGATT TTGGCTTTGC AAAACAACTG 1620

AGAGCAGAAA ATGGTCTTCT CATGACTCCT TGTTATACTG CAAATTTTGT TGCACCAGAG 1680

GTTTTAAAAC GGCAAGGTTA TGATGCTGCC TGTGATATAT GGAGTCTTGG CGTCCTCCTT 1740

TATACAATGC TTACTGGTTA CACTCCATTT GCAAATGGCC CTGATGATAC TCCAGAGGAA 1800

ATACTGGCAC GAATAGGTAG TGGAAAATTC TCACTCAGTG GTGGTTACTG GAATTCTGTT 1860

TCAGACACAG CAAAGGACCT GGTGTCAAAG ATGCTTCATG TAGATCCTCA TCAGAGACTG 1920

ACGGCTGCTC TGGTGCTCAG ACATCCTTGG ATTGTCCACT GGGACCAACT ACCACAATAC 1980

CAACTAAACA GACAGGATGC GCCGCATCTC GTAAAGGGTG CCATGGCAGC TACGTACTCT 2040

GCTTTAAACC GCAATCAGTC CCCAGTCTTG GAACCAGTGG GCCGCTCCAC TCTTGCTCAG 2100

CGGAGAGGGA TTAAAAAAAT CACCTCAACA GCCCTGTGA 2139

Domain Profile

S: 1     yevkedlGvGsysvckrcvhkatnqefavkiidkskrdtseeieillryeqhpnivtlkd  60

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

Q: 394   YEVKEDIGVGSYSVCKRCIHKATNMEFAVKIIDKSKRDPTEEIEILLRYGQHPNIITLKD  453

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

S: 61    vyddgkyvylvlellkGGelldrikkkkffsereasailrtlvkaveylheqGvvhrdlk  120

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

Q: 454   VYDDGKYVYVVTELMKGGELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLK  513

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

S: 121   penilyvdesdnaesikiidfGfaklkraengllktpcytlnfvapevlkrqGydeacdl  180

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

Q: 514   PSNILYVDESGNPESIRICDFGFAKQLRAENGLLMTPCYTANFVAPEVLKRQGYDAACDI  573

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

S: 181   wslGvllytmlaGyvpfangpedtaeeilakikeGkfslsGeawdsvseeakdlvskllt  240

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

Q: 574   WSLGVLLYTMLTGYTPFANGPDDTPEEILARIGSGKFSLSGGYWNSVSDTAKDLVSKMLH  633

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

S: 241   vdpakrlkleqllkhswl  258

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

Q: 634   VDPHQRLTAALVLRHPWI  651

         *****************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; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; 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"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>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"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Vicugna pacos"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005634	; C:nucleus
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:0007049	; P:cell cycle
GO:0007243	; P:intracellular protein kinase cascade
GO:0045944	; P:positive regulation of transcription from RNA polymerase II promoter
GO:0032496	; P:response to lipopolysaccharide
GO:0006950	; P:response to stress
GO:0002224	; P:toll-like receptor signaling pathway

KEGG

mmu:110651

;

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