EKS-MUM-00161
Eukaryotic Protein Kinase & Protein Phosphatase Database
TagContent
EKPD IDEKS-MUM-00161
Classification
Group/FamilyScoreE-ValueStartEndDomain Length
AGC/RSK351.86.7E-10548317270
StatusReviewed
Ensembl ProteinENSMUSP00000042987
UniProt AccessionQ8C050; Q8CI92;
Protein NameRibosomal 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; RLSK;
Gene NameRps6ka5
Gene Synonyms/Alias Rps6ka5; Msk1;
Ensembl Information
Ensembl Gene IDEnsembl Protein IDEnsembl Transcript ID
ENSMUSG00000021180ENSMUSP00000042987ENSMUST00000043599
OrganismMus musculus
Functional DescriptionSerine/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 Length863
Protein Sequence
(FASTA)
MEGEGGGSGG AGTSGDSGDG GEQLLTVKHE LRTANLTGHA EKVGIENFEL LKVLGTGAYG 60
KVFLVRKISG HDAGKLYAMK VLKKATIVQK AKTTEHTRTE RQVLEHIRQS PFLVTLHYAF 120
QTETKLHLIL DYINGGELFT HLSQRERFTE HEVQIYVGEI VLALEHLHKL GIIYRDIKLE 180
NILLDSNGHV VLTDFGLSKE FVADETERAY SFCGTIEYMA PDIVRGGDSG HDKAVDWWSL 240
GVLMYELLTG ASPFTVDGEK NSQAEISRRI LKSEPPYPQE MSTVAKDLLQ RLLMKDPKKR 300
LGCGPRDAEE IKEHLFFEKI KWDDLAAKKV PAPFKPVIRD ELDVSNFAEE FTEMDPTYSP 360
AALPQSSERL FQGYSFVAPS ILFKRNAAVI DPLQFHMGVD RPGVTNVARS AMMKDSPFYQ 420
HYDLDLKDKP LGEGSFSICR KCVHKKTNQA FAVKIISKRM EANTQKEITA LKLCEGHPNI 480
VKLHEVFHDQ VAASAQPPGQ VVLCSLLLLA LLFNRSLTRK PVTWTWLVHS TSQLPPLPPP 540
MPEIVLFILL SDNGQLHTFL VMELLNGGEL FERIKRKKHF SETEASYIMR KLVSAVSHMH 600
DVGVVHRDLK PENLLFTDEN DNLEIKVIDF GFARLKPPDN QPLKTPCFTL HYAAPELLTH 660
NGYDESCDLW SLGVILYTML SGQVPFQSHD RSLTCTSAVE IMKKIKKGDF SFEGEAWKNV 720
SQEAKDLIQG LLTVDPNKRL KMSGLRYNEW LQDGSQLSSN PLMTPDILGS SGAAVHTCVK 780
ATFHAFNKYK REGFCLQNVD KAPLAKRRKM KRTSTSTETR SSSSESSRSS SSQSHGKTTP 840
TKTLQPSNPT EGSNPDTLFQ FSD 863
Nucleotide Sequence
(FASTA)
ATGGAGGGGG AGGGCGGCGG CAGCGGCGGC GCGGGCACCA GCGGGGACAG CGGCGACGGC 60
GGCGAGCAGC TCCTTACTGT CAAGCACGAG CTGCGGACCG CCAACTTAAC AGGACACGCA 120
GAGAAGGTGG GGATTGAAAA CTTTGAGCTG CTGAAGGTCC TAGGAACTGG AGCTTATGGG 180
AAAGTATTTC TAGTTCGTAA AATAAGCGGC CATGATGCTG GAAAGCTGTA TGCTATGAAG 240
GTTTTAAAAA AGGCAACAAT AGTTCAGAAG GCTAAAACTA CAGAGCATAC AAGGACAGAA 300
CGACAGGTTC TGGAGCACAT TAGACAGTCG CCATTTTTGG TGACATTGCA CTATGCTTTC 360
CAGACAGAGA CCAAGCTTCA TCTCATCTTA GATTATATAA ATGGTGGAGA ACTTTTTACT 420
CATCTTTCTC AAAGAGAGCG TTTCACAGAG CACGAAGTGC AGATCTATGT TGGAGAGATT 480
GTGCTTGCCC TGGAACACCT GCACAAGTTG GGGATTATAT ACCGTGACAT TAAGCTTGAA 540
AATATTCTCC TGGATTCTAA CGGCCATGTG GTGCTGACAG ATTTCGGTCT GAGTAAGGAG 600
TTTGTGGCCG ATGAAACTGA AAGAGCATAT TCTTTTTGTG GAACTATTGA ATACATGGCT 660
CCAGATATTG TCAGAGGGGG TGATTCGGGA CACGACAAGG CAGTTGACTG GTGGAGCTTA 720
GGTGTTCTAA TGTATGAGCT ACTAACTGGA GCATCTCCTT TCACTGTCGA TGGAGAAAAA 780
AATTCCCAGG CTGAGATATC TAGGAGAATT TTAAAAAGTG AGCCTCCGTA TCCCCAGGAA 840
ATGAGCACAG TAGCTAAAGA CCTACTTCAG CGTCTCTTGA TGAAAGATCC CAAGAAGCGA 900
TTGGGATGTG GCCCACGGGA TGCAGAAGAA ATCAAAGAAC ATCTCTTCTT TGAGAAGATA 960
AAGTGGGATG ACTTAGCTGC CAAAAAAGTG CCTGCGCCAT TCAAGCCGGT GATCCGGGAT 1020
GAGTTAGATG TGAGTAACTT CGCTGAAGAG TTCACAGAGA TGGACCCCAC CTACTCTCCC 1080
GCTGCCTTGC CACAGAGCTC CGAGCGACTG TTTCAGGGCT ATTCCTTCGT TGCTCCATCT 1140
ATTCTCTTCA AGCGTAACGC AGCTGTCATA GATCCTCTTC AGTTCCATAT GGGAGTTGAC 1200
CGTCCTGGAG TGACAAATGT TGCCAGGAGT GCAATGATGA AGGACTCACC CTTCTATCAA 1260
CACTATGACC TAGATCTGAA GGACAAACCT TTGGGAGAAG GAAGTTTTTC AATTTGTCGC 1320
AAGTGTGTAC ACAAAAAAAC TAACCAAGCA TTTGCTGTCA AAATAATCAG CAAAAGGATG 1380
GAAGCCAATA CTCAGAAAGA AATAACAGCT CTGAAACTCT GCGAAGGACA CCCCAATATT 1440
GTGAAACTAC ATGAAGTTTT TCACGATCAG GTGGCAGCGT CTGCTCAGCC CCCAGGACAG 1500
GTTGTTCTAT GCTCTCTTCT ACTCTTAGCT CTGCTTTTCA ACAGAAGTCT CACACGGAAG 1560
CCTGTCACTT GGACATGGCT GGTCCATAGC ACCTCTCAGC TCCCTCCATT GCCACCTCCC 1620
ATGCCTGAAA TTGTGCTATT TATTCTTCTC TCTGATAATG GACAGCTTCA TACGTTTCTT 1680
GTGATGGAAC TTCTGAATGG CGGAGAGCTG TTCGAGCGCA TCAAGAGAAA GAAGCACTTC 1740
AGCGAGACTG AGGCCAGCTA CATCATGCGG AAGCTTGTGT CAGCTGTGAG CCACATGCAC 1800
GATGTAGGAG TGGTGCACAG AGATCTGAAG CCTGAGAATC TGTTGTTCAC TGATGAAAAC 1860
GACAATTTGG AAATTAAAGT GATTGACTTT GGGTTTGCAC GCCTCAAGCC ACCTGACAAT 1920
CAGCCCCTCA AGACCCCGTG CTTCACCCTC CACTACGCAG CACCGGAGCT CTTGACGCAC 1980
AATGGCTACG ATGAGTCCTG TGACCTGTGG AGCTTGGGTG TCATCCTGTA TACAATGCTG 2040
TCAGGGCAGG TGCCATTCCA GTCTCATGAC AGAAGTTTAA CATGCACCAG TGCAGTGGAA 2100
ATCATGAAGA AAATTAAAAA GGGAGACTTC TCCTTTGAAG GAGAAGCGTG GAAGAATGTA 2160
TCCCAAGAGG CTAAAGATTT GATTCAAGGG CTTCTTACAG TTGATCCAAA TAAAAGGCTG 2220
AAAATGTCTG GTTTGAGATA CAATGAATGG CTTCAGGATG GCAGTCAGCT GTCCTCCAAT 2280
CCTCTGATGA CTCCAGACAT TCTGGGATCG TCAGGAGCAG CTGTGCACAC CTGTGTGAAA 2340
GCAACCTTTC ATGCCTTTAA CAAGTATAAG AGAGAAGGAT TTTGCCTGCA GAATGTGGAT 2400
AAGGCCCCTT TGGCTAAGAG GAGGAAAATG AAGAGGACCA GCACCAGCAC AGAGACTCGC 2460
AGCAGCTCCA GCGAGAGCTC CCGCTCCTCC TCCTCCCAGT CCCACGGCAA GACAACGCCT 2520
ACCAAGACGC TGCAGCCCAG CAATCCCACC GAAGGCAGTA ACCCAGACAC CCTCTTCCAG 2580
TTCTCAGACT GA 2592
Domain Profile
S: 1     fellkvlgkGaygkvflvrkvekkdtgklyavKvlkkaelvk..kkkertkeereiLeev  58
         fellkvlg+Gaygkvflvrk++++d+gklya+Kvlkka++v+  k++e+t++er++Le++
Q: 48    FELLKVLGTGAYGKVFLVRKISGHDAGKLYAMKVLKKATIVQkaKTTEHTRTERQVLEHI  107
         89***************************************988999*************
S: 59    eh.pfivklheafqdekklylvlellkGgeLlerlkkkklfseeeasfilaelvlaleyl  117
         ++ pf+v+lh+afq+e+kl+l+l++++GgeL+++l+++++f+e+e++ ++ e+vlale+l
Q: 108   RQsPFLVTLHYAFQTETKLHLILDYINGGELFTHLSQRERFTEHEVQIYVGEIVLALEHL  167
         ************************************************************
S: 118   HskgvvyrDLkpeNilldeeghvkltDfglakekiaeneekaysfcgTleyvaPevl..k  175
         H+ g++yrD+k+eNilld++ghv+ltDfgl+ke +a+++e+aysfcgT+ey+aP+++   
Q: 168   HKLGIIYRDIKLENILLDSNGHVVLTDFGLSKEFVADETERAYSFCGTIEYMAPDIVrgG  227
         *********************************************************766
S: 176   rkgydeavDlwslGvllyemLtGktPftgeerketlarilkgkfslklpaweelseeakd  235
         ++g+d+avD+wslGvl+ye+LtG++Pft + +k+++a+i +  ++ + p  +e+s+ akd
Q: 228   DSGHDKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQEMSTVAKD  287
         79*******************************88887777776666777777*******
S: 236   lvkklLkkdpakRlga...taeeikehkfl  262
         l+++lL kdp+kRlg+   +aeeikeh f+
Q: 288   LLQRLLMKDPKKRLGCgprDAEEIKEHLFF  317
         ***************************997
Domain Sequence
(FASTA)
FELLKVLGTG AYGKVFLVRK ISGHDAGKLY AMKVLKKATI VQKAKTTEHT RTERQVLEHI 60
RQSPFLVTLH YAFQTETKLH LILDYINGGE LFTHLSQRER FTEHEVQIYV GEIVLALEHL 120
HKLGIIYRDI KLENILLDSN GHVVLTDFGL SKEFVADETE RAYSFCGTIE YMAPDIVRGG 180
DSGHDKAVDW WSLGVLMYEL LTGASPFTVD GEKNSQAEIS RRILKSEPPY PQEMSTVAKD 240
LLQRLLMKDP KKRLGCGPRD AEEIKEHLFF 270
KeywordAlternative splicing; ATP-binding; Complete proteome; Inflammatory response; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat; Serine/threonine-protein kinase; Stress response; Transferase.
Sequence SourceEnsembl
Orthology
Ortholog group
Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Drosophila melanogaster"; ?>Pelodiscus sinensis"; ?>Rattus norvegicus"; ?>
EKS-AIM-00149
EKS-ANC-00151
EKS-DRM-00077
EKS-PES-00139
EKS-RAN-00154
Gene Ontology
GO:0005737; C:cytoplasm
GO:0005634; C:nucleus
GO:0005524; F:ATP binding
GO:0000287; F:magnesium ion binding
GO:0004674; F:protein serine/threonine kinase activity
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:0070498; P:interleukin-1-mediated signaling pathway
GO:0007243; P:intracellular protein kinase cascade
GO:0045892; P:negative regulation of transcription, DNA-dependent
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:0009605; P:response to external stimulus
KEGG
mmu:73086;
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; 3.
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 Date20-Feb-2013