ID KS6A4_HUMAN Reviewed; 772 AA.
AC O75676; A8K7Z8; O75585; Q53ES8;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 27-MAR-2024, entry version 211.
DE RecName: Full=Ribosomal protein S6 kinase alpha-4;
DE Short=S6K-alpha-4;
DE EC=2.7.11.1;
DE AltName: Full=90 kDa ribosomal protein S6 kinase 4;
DE AltName: Full=Nuclear mitogen- and stress-activated protein kinase 2;
DE AltName: Full=Ribosomal protein kinase B;
DE Short=RSKB;
GN Name=RPS6KA4; Synonyms=MSK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606 {ECO:0000312|EMBL:CAA09009.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ACTIVITY REGULATION,
RP INTERACTION WITH MAPK14; MAPK1 AND MAPK3, AND SUBCELLULAR LOCATION.
RC TISSUE=Placenta {ECO:0000312|EMBL:CAA09009.1};
RX PubMed=9792677; DOI=10.1074/jbc.273.45.29661;
RA Pierrat B., Correia J.D.S., Mary J.L., Tomas-Zuber M., Lesslauer W.;
RT "RSK-B, a novel ribosomal S6 kinase family member, is a CREB kinase under
RT dominant control of p38alpha mitogen-activated protein kinase
RT (p38alphaMAPK).";
RL J. Biol. Chem. 273:29661-29671(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ALA-758.
RC TISSUE=Brain;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 17-727 (ISOFORM 2).
RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426;
RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.;
RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly
RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB.";
RL EMBO J. 17:4426-4441(1998).
RN [6]
RP FUNCTION, INTERACTION WITH MAPK14, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP PHE-709.
RX PubMed=11035004; DOI=10.1074/jbc.m005822200;
RA Tomas-Zuber M., Mary J.L., Lamour F., Bur D., Lesslauer W.;
RT "C-terminal elements control location, activation threshold, and p38
RT docking of ribosomal S6 kinase B (RSKB).";
RL J. Biol. Chem. 276:5892-5899(2001).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3 AND HMGN1/HMG14.
RX PubMed=12773393; DOI=10.1093/emboj/cdg273;
RA Soloaga A., Thomson S., Wiggin G.R., Rampersaud N., Dyson M.H.,
RA Hazzalin C.A., Mahadevan L.C., Arthur J.S.;
RT "MSK2 and MSK1 mediate the mitogen- and stress-induced phosphorylation of
RT histone H3 and HMG-14.";
RL EMBO J. 22:2788-2797(2003).
RN [8]
RP REVIEW ON FUNCTION.
RX PubMed=18508628; DOI=10.2741/3122;
RA Arthur J.S.;
RT "MSK activation and physiological roles.";
RL Front. Biosci. 13:5866-5879(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347; SER-634; SER-678;
RP THR-687 AND SER-745, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347; THR-542 AND THR-687, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [12]
RP REVIEW ON FUNCTION.
RX PubMed=19464896; DOI=10.1016/j.tibs.2009.02.007;
RA Vermeulen L., Vanden Berghe W., Beck I.M., De Bosscher K., Haegeman G.;
RT "The versatile role of MSKs in transcriptional regulation.";
RL Trends Biochem. Sci. 34:311-318(2009).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347; THR-542 AND THR-687, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-678 AND SER-745, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-236 AND ALA-758.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine-protein kinase that is required for the
CC mitogen or stress-induced phosphorylation of the transcription factors
CC CREB1 and ATF1 and for the regulation of the transcription factor RELA,
CC and that contributes to gene activation by histone phosphorylation and
CC functions in the regulation of inflammatory genes. Phosphorylates CREB1
CC and ATF1 in response to mitogenic or stress stimuli such as UV-C
CC irradiation, epidermal growth factor (EGF) and anisomycin. Plays an
CC essential role in the control of RELA transcriptional activity in
CC response to TNF. Phosphorylates 'Ser-10' of histone H3 in response to
CC mitogenics, stress stimuli and EGF, which results in the
CC transcriptional activation of several immediate early genes, including
CC proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-
CC 28' of histone H3. Mediates the mitogen- and stress-induced
CC phosphorylation of high mobility group protein 1 (HMGN1/HMG14). In
CC lipopolysaccharide-stimulated primary macrophages, acts downstream of
CC the Toll-like receptor TLR4 to limit the production of pro-inflammatory
CC cytokines. Functions probably by inducing transcription of the MAP
CC kinase phosphatase DUSP1 and the anti-inflammatory cytokine interleukin
CC 10 (IL10), via CREB1 and ATF1 transcription factors.
CC {ECO:0000269|PubMed:11035004, ECO:0000269|PubMed:12773393,
CC ECO:0000269|PubMed:9792677}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:9792677};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:9792677};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:9792677};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Ser-343, Thr-568
CC and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha, and by
CC further autophosphorylation of Ser-196, Ser-360 and Ser-365 by the
CC activated C-terminal kinase domain. {ECO:0000250}.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells which transiently dissociates following mitogenic
CC stimulation. Also associates with MAPK14/p38-alpha. Activated RPS6KA4
CC associates with and phosphorylates the NF-kappa-B p65 subunit RELA.
CC -!- INTERACTION:
CC O75676; Q16539: MAPK14; NbExp=6; IntAct=EBI-73933, EBI-73946;
CC O75676-2; O14901: KLF11; NbExp=3; IntAct=EBI-21622593, EBI-948266;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11035004,
CC ECO:0000269|PubMed:9792677}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O75676-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O75676-2; Sequence=VSP_017733;
CC -!- PTM: Ser-343 and Thr-568 phosphorylation is required for kinase
CC activity. Ser-343 and Ser-196 are autophosphorylated by the C-terminal
CC kinase domain, and their phosphorylation is essential for the catalytic
CC activity of the N-terminal kinase domain. Phosphorylated at Ser-343,
CC Thr-568 and Thr-687 by MAPK1/ERK2, MAPK3/ERK1 and MAPK14/p38-alpha.
CC Autophosphorylated at Ser-737 and Ser-745 by the N-terminal kinase
CC domain (By similarity). {ECO:0000250}.
CC -!- MISCELLANEOUS: Enzyme activity requires the presence of both kinase
CC domains. {ECO:0000250|UniProtKB:O75582}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
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DR EMBL; AJ010119; CAA09009.1; -; mRNA.
DR EMBL; AK223561; BAD97281.1; -; mRNA.
DR EMBL; AK292163; BAF84852.1; -; mRNA.
DR EMBL; CH471076; EAW74260.1; -; Genomic_DNA.
DR EMBL; AF074715; AAC67395.1; -; mRNA.
DR CCDS; CCDS8073.1; -. [O75676-1]
DR RefSeq; NP_001006945.1; NM_001006944.1. [O75676-2]
DR RefSeq; NP_001287731.1; NM_001300802.1.
DR RefSeq; NP_001305290.1; NM_001318361.1.
DR RefSeq; NP_003933.1; NM_003942.2. [O75676-1]
DR AlphaFoldDB; O75676; -.
DR SMR; O75676; -.
DR BioGRID; 114468; 128.
DR ELM; O75676; -.
DR IntAct; O75676; 25.
DR MINT; O75676; -.
DR STRING; 9606.ENSP00000333896; -.
DR BindingDB; O75676; -.
DR ChEMBL; CHEMBL3125; -.
DR DrugBank; DB03247; Flavin mononucleotide.
DR DrugCentral; O75676; -.
DR GuidetoPHARMACOLOGY; 1524; -.
DR GlyGen; O75676; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75676; -.
DR PhosphoSitePlus; O75676; -.
DR BioMuta; RPS6KA4; -.
DR CPTAC; CPTAC-3104; -.
DR EPD; O75676; -.
DR jPOST; O75676; -.
DR MassIVE; O75676; -.
DR MaxQB; O75676; -.
DR PaxDb; 9606-ENSP00000333896; -.
DR PeptideAtlas; O75676; -.
DR ProteomicsDB; 50149; -. [O75676-1]
DR ProteomicsDB; 50150; -. [O75676-2]
DR Pumba; O75676; -.
DR Antibodypedia; 3272; 324 antibodies from 32 providers.
DR DNASU; 8986; -.
DR Ensembl; ENST00000334205.9; ENSP00000333896.4; ENSG00000162302.13. [O75676-1]
DR GeneID; 8986; -.
DR KEGG; hsa:8986; -.
DR MANE-Select; ENST00000334205.9; ENSP00000333896.4; NM_003942.3; NP_003933.1.
DR UCSC; uc001oae.4; human. [O75676-1]
DR AGR; HGNC:10433; -.
DR CTD; 8986; -.
DR DisGeNET; 8986; -.
DR GeneCards; RPS6KA4; -.
DR HGNC; HGNC:10433; RPS6KA4.
DR HPA; ENSG00000162302; Tissue enhanced (brain).
DR MIM; 603606; gene.
DR neXtProt; NX_O75676; -.
DR OpenTargets; ENSG00000162302; -.
DR PharmGKB; PA34848; -.
DR VEuPathDB; HostDB:ENSG00000162302; -.
DR eggNOG; KOG0603; Eukaryota.
DR GeneTree; ENSGT00940000161083; -.
DR InParanoid; O75676; -.
DR OMA; CKDPRKR; -.
DR OrthoDB; 5489497at2759; -.
DR PhylomeDB; O75676; -.
DR TreeFam; TF313438; -.
DR PathwayCommons; O75676; -.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR SignaLink; O75676; -.
DR SIGNOR; O75676; -.
DR BioGRID-ORCS; 8986; 23 hits in 1197 CRISPR screens.
DR ChiTaRS; RPS6KA4; human.
DR GeneWiki; RPS6KA4; -.
DR GenomeRNAi; 8986; -.
DR Pharos; O75676; Tchem.
DR PRO; PR:O75676; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75676; Protein.
DR Bgee; ENSG00000162302; Expressed in right hemisphere of cerebellum and 144 other cell types or tissues.
DR ExpressionAtlas; O75676; baseline and differential.
DR Genevisible; O75676; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0035175; F:histone H3S10 kinase activity; IMP:UniProtKB.
DR GO; GO:0044022; F:histone H3S28 kinase activity; IMP:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; NAS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0001818; P:negative regulation of cytokine production; TAS:UniProtKB.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043687; P:post-translational protein modification; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:UniProtKB.
DR CDD; cd05614; STKc_MSK2_N; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 2.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR037714; MSK2_N_dom.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR016239; Ribosomal_S6_kinase_II.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR PANTHER; PTHR24351:SF41; RIBOSOMAL PROTEIN S6 KINASE ALPHA-4; 1.
DR Pfam; PF00069; Pkinase; 2.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000606; Ribsml_S6_kin_2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 2.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 2.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Inflammatory response; Kinase;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase;
KW Stress response; Transferase.
FT CHAIN 1..772
FT /note="Ribosomal protein S6 kinase alpha-4"
FT /id="PRO_0000086205"
FT DOMAIN 33..301
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 302..371
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 411..674
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 673..696
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 725..772
FT /note="Required for nuclear targeting and association with
FT MAPK14"
FT REGION 728..772
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 161
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 530
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 39..47
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 65
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 417..425
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 440
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 196
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 343
FT /note="Phosphoserine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000305"
FT MOD_RES 347
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 360
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 365
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 542
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 568
FT /note="Phosphothreonine; by MAPK1, MAPK3 and MAPK14"
FT /evidence="ECO:0000250"
FT MOD_RES 634
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 678
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 687
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163"
FT MOD_RES 737
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305"
FT MOD_RES 745
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 401..406
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9687510, ECO:0000303|Ref.3"
FT /id="VSP_017733"
FT VARIANT 236
FT /note="S -> L (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation; dbSNP:rs746466314)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040632"
FT VARIANT 758
FT /note="S -> A (in dbSNP:rs17857342)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.3"
FT /id="VAR_040633"
FT MUTAGEN 709
FT /note="F->A: Strongly elevates basal activity."
FT /evidence="ECO:0000269|PubMed:11035004"
FT CONFLICT 477
FT /note="L -> P (in Ref. 3; BAD97281)"
FT /evidence="ECO:0000305"
FT CONFLICT O75676-2:400..401
FT /note="QQ -> Q (in Ref. 3; BAD97281)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 772 AA; 85606 MW; 3606209693D0B5F3 CRC64;
MGDEDDDESC AVELRITEAN LTGHEEKVSV ENFELLKVLG TGAYGKVFLV RKAGGHDAGK
LYAMKVLRKA ALVQRAKTQE HTRTERSVLE LVRQAPFLVT LHYAFQTDAK LHLILDYVSG
GEMFTHLYQR QYFKEAEVRV YGGEIVLALE HLHKLGIIYR DLKLENVLLD SEGHIVLTDF
GLSKEFLTEE KERTFSFCGT IEYMAPEIIR SKTGHGKAVD WWSLGILLFE LLTGASPFTL
EGERNTQAEV SRRILKCSPP FPPRIGPVAQ DLLQRLLCKD PKKRLGAGPQ GAQEVRNHPF
FQGLDWVALA ARKIPAPFRP QIRSELDVGN FAEEFTRLEP VYSPPGSPPP GDPRIFQGYS
FVAPSILFDH NNAVMTDGLE APGAGDRPGR AAVARSAMMQ DSPFFQQYEL DLREPALGQG
SFSVCRRCRQ RQSGQEFAVK ILSRRLEANT QREVAALRLC QSHPNVVNLH EVHHDQLHTY
LVLELLRGGE LLEHIRKKRH FSESEASQIL RSLVSAVSFM HEEAGVVHRD LKPENILYAD
DTPGAPVKII DFGFARLRPQ SPGVPMQTPC FTLQYAAPEL LAQQGYDESC DLWSLGVILY
MMLSGQVPFQ GASGQGGQSQ AAEIMCKIRE GRFSLDGEAW QGVSEEAKEL VRGLLTVDPA
KRLKLEGLRG SSWLQDGSAR SSPPLRTPDV LESSGPAVRS GLNATFMAFN RGKREGFFLK
SVENAPLAKR RKQKLRSATA SRRGSPAPAN PGRAPVASKG APRRANGPLP PS
//
