KS6A2_HUMAN
ID KS6A2_HUMAN Reviewed; 733 AA.
AC Q15349; B3KTK9; Q15419; Q59GJ3; Q5TI68; Q96J38; Q9UJN5;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Ribosomal protein S6 kinase alpha-2;
DE Short=S6K-alpha-2;
DE EC=2.7.11.1;
DE AltName: Full=90 kDa ribosomal protein S6 kinase 2;
DE Short=p90-RSK 2;
DE Short=p90RSK2;
DE AltName: Full=MAP kinase-activated protein kinase 1c;
DE Short=MAPK-activated protein kinase 1c;
DE Short=MAPKAP kinase 1c;
DE Short=MAPKAPK-1c;
DE AltName: Full=Ribosomal S6 kinase 3;
DE Short=RSK-3;
DE AltName: Full=pp90RSK3;
GN Name=RPS6KA2; Synonyms=MAPKAPK1C, RSK3;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=7623830; DOI=10.1128/mcb.15.8.4353;
RA Zhao Y., Bjoerbaek C., Weremowicz S., Morton C.C., Moller D.E.;
RT "RSK3 encodes a novel pp90rsk isoform with a unique N-terminal sequence:
RT growth factor-stimulated kinase function and nuclear translocation.";
RL Mol. Cell. Biol. 15:4353-4363(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-540 (ISOFORM 1).
RX PubMed=8141249; DOI=10.1152/ajpcell.1994.266.2.c351;
RA Moller D.E., Xia C.-H., Tang W., Zhu A.X., Jakubowski M.;
RT "Human rsk isoforms: cloning and characterization of tissue-specific
RT expression.";
RL Am. J. Physiol. 266:C351-C359(1994).
RN [7]
RP ACTIVITY REGULATION, AND PHOSPHORYLATION AT SER-218.
RX PubMed=10480933; DOI=10.1074/jbc.274.38.27168;
RA Jensen C.J., Buch M.-B., Krag T.O., Hemmings B.A., Gammeltoft S.,
RA Froedin M.;
RT "90-kDa ribosomal S6 kinase is phosphorylated and activated by 3-
RT phosphoinositide-dependent protein kinase-1.";
RL J. Biol. Chem. 274:27168-27176(1999).
RN [8]
RP FUNCTION IN TUMORIGENESIS, AND TISSUE SPECIFICITY.
RX PubMed=16878154; DOI=10.1038/sj.onc.1209827;
RA Bignone P.A., Lee K.Y., Liu Y., Emilion G., Finch J., Soosay A.E.,
RA Charnock F.M., Beck S., Dunham I., Mungall A.J., Ganesan T.S.;
RT "RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial
RT ovarian cancer.";
RL Oncogene 26:683-700(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 REVIEW ON FUNCTION.
RX PubMed=18813292; DOI=10.1038/nrm2509;
RA Anjum R., Blenis J.;
RT "The RSK family of kinases: emerging roles in cellular signalling.";
RL Nat. Rev. Mol. Cell Biol. 9:747-758(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND IDENTIFICATION BY
RP 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 VARIANTS [LARGE SCALE ANALYSIS] LYS-311 AND GLN-732.
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 acts downstream of ERK
CC (MAPK1/ERK2 and MAPK3/ERK1) signaling and mediates mitogenic and
CC stress-induced activation of transcription factors, regulates
CC translation, and mediates cellular proliferation, survival, and
CC differentiation. May function as tumor suppressor in epithelial ovarian
CC cancer cells. {ECO:0000269|PubMed:16878154,
CC ECO:0000269|PubMed:7623830}.
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Upon extracellular signal or mitogen stimulation,
CC phosphorylated at Thr-570 in the C-terminal kinase domain (CTKD) by
CC MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates
CC Ser-377, allowing binding of PDPK1, which in turn phosphorylates Ser-
CC 218 in the N-terminal kinase domain (NTDK) leading to the full
CC activation of the protein and subsequent phosphorylation of the
CC substrates by the NTKD. {ECO:0000269|PubMed:10480933}.
CC -!- SUBUNIT: Forms a complex with either MAPK1/ERK2 or MAPK3/ERK1 in
CC quiescent cells. Transiently dissociates following mitogenic
CC stimulation (By similarity). Interacts with FBXO5; cooperate to induce
CC the metaphase arrest of early blastomeres; increases and stabilizes
CC interaction of FBXO5 with CDC20 (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:Q9WUT3}.
CC -!- INTERACTION:
CC Q15349; P05067: APP; NbExp=3; IntAct=EBI-1384149, EBI-77613;
CC Q15349; P15056: BRAF; NbExp=2; IntAct=EBI-1384149, EBI-365980;
CC Q15349; O14901: KLF11; NbExp=3; IntAct=EBI-1384149, EBI-948266;
CC Q15349; P28482: MAPK1; NbExp=9; IntAct=EBI-1384149, EBI-959949;
CC Q15349; Q02156: PRKCE; NbExp=2; IntAct=EBI-1384149, EBI-706254;
CC Q15349; Q14160: SCRIB; NbExp=9; IntAct=EBI-1384149, EBI-357345;
CC Q15349; Q9Y566: SHANK1; NbExp=2; IntAct=EBI-1384149, EBI-3442234;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:7623830}. Cytoplasm
CC {ECO:0000269|PubMed:7623830}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q15349-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15349-2; Sequence=VSP_017732;
CC Name=3;
CC IsoId=Q15349-3; Sequence=VSP_041836;
CC -!- TISSUE SPECIFICITY: Widely expressed with higher expression in lung,
CC skeletal muscle, brain, uterus, ovary, thyroid and prostate.
CC {ECO:0000269|PubMed:16878154, ECO:0000269|PubMed:7623830}.
CC -!- PTM: Activated by phosphorylation at Ser-218 by PDPK1.
CC Autophosphorylated on Ser-377, as part of the activation process. May
CC be phosphorylated at Thr-356 and Ser-360 by MAPK1/ERK2 and MAPK3/ERK1
CC (By similarity). {ECO:0000250}.
CC -!- PTM: N-terminal myristoylation results in an activated kinase in the
CC absence of added growth factors. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC82496.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD92353.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAG53121.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X85106; CAA59427.1; -; mRNA.
DR EMBL; AB209116; BAD92353.1; ALT_INIT; mRNA.
DR EMBL; AK095751; BAG53121.1; ALT_FRAME; mRNA.
DR EMBL; AL022069; CAI19651.1; -; Genomic_DNA.
DR EMBL; Z98049; CAI19651.1; JOINED; Genomic_DNA.
DR EMBL; AL023775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL159163; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; Z98049; CAI20579.1; -; Genomic_DNA.
DR EMBL; AL022069; CAI20579.1; JOINED; Genomic_DNA.
DR EMBL; BC002363; AAH02363.1; -; mRNA.
DR EMBL; L07598; AAC82496.1; ALT_INIT; mRNA.
DR CCDS; CCDS34570.1; -. [Q15349-3]
DR CCDS; CCDS5294.1; -. [Q15349-1]
DR CCDS; CCDS83148.1; -. [Q15349-2]
DR PIR; A57459; A57459.
DR RefSeq; NP_001006933.2; NM_001006932.2. [Q15349-3]
DR RefSeq; NP_001305865.1; NM_001318936.1.
DR RefSeq; NP_001305866.1; NM_001318937.1.
DR RefSeq; NP_001305867.1; NM_001318938.1.
DR RefSeq; NP_066958.2; NM_021135.5. [Q15349-1]
DR AlphaFoldDB; Q15349; -.
DR SMR; Q15349; -.
DR BioGRID; 112110; 176.
DR DIP; DIP-295N; -.
DR IntAct; Q15349; 46.
DR MINT; Q15349; -.
DR STRING; 9606.ENSP00000427015; -.
DR BindingDB; Q15349; -.
DR ChEMBL; CHEMBL3906; -.
DR DrugCentral; Q15349; -.
DR GuidetoPHARMACOLOGY; 1529; -.
DR iPTMnet; Q15349; -.
DR PhosphoSitePlus; Q15349; -.
DR BioMuta; RPS6KA2; -.
DR DMDM; 90110031; -.
DR REPRODUCTION-2DPAGE; Q15349; -.
DR EPD; Q15349; -.
DR jPOST; Q15349; -.
DR MassIVE; Q15349; -.
DR MaxQB; Q15349; -.
DR PaxDb; Q15349; -.
DR PeptideAtlas; Q15349; -.
DR PRIDE; Q15349; -.
DR ProteomicsDB; 60536; -. [Q15349-1]
DR ProteomicsDB; 60537; -. [Q15349-2]
DR ProteomicsDB; 60538; -. [Q15349-3]
DR Antibodypedia; 33522; 567 antibodies from 42 providers.
DR DNASU; 6196; -.
DR Ensembl; ENST00000265678.9; ENSP00000265678.4; ENSG00000071242.12. [Q15349-1]
DR Ensembl; ENST00000503859.5; ENSP00000427015.1; ENSG00000071242.12. [Q15349-3]
DR GeneID; 6196; -.
DR KEGG; hsa:6196; -.
DR MANE-Select; ENST00000265678.9; ENSP00000265678.4; NM_021135.6; NP_066958.2.
DR UCSC; uc003qvb.2; human. [Q15349-1]
DR CTD; 6196; -.
DR DisGeNET; 6196; -.
DR GeneCards; RPS6KA2; -.
DR HGNC; HGNC:10431; RPS6KA2.
DR HPA; ENSG00000071242; Low tissue specificity.
DR MIM; 601685; gene.
DR neXtProt; NX_Q15349; -.
DR OpenTargets; ENSG00000071242; -.
DR PharmGKB; PA34846; -.
DR VEuPathDB; HostDB:ENSG00000071242; -.
DR eggNOG; KOG0603; Eukaryota.
DR GeneTree; ENSGT00940000159956; -.
DR InParanoid; Q15349; -.
DR OMA; NMKKFTV; -.
DR OrthoDB; 1132245at2759; -.
DR PhylomeDB; Q15349; -.
DR TreeFam; TF313438; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; Q15349; -.
DR Reactome; R-HSA-198753; ERK/MAPK targets.
DR Reactome; R-HSA-199920; CREB phosphorylation.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-442742; CREB1 phosphorylation through NMDA receptor-mediated activation of RAS signaling.
DR Reactome; R-HSA-444257; RSK activation.
DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR SignaLink; Q15349; -.
DR SIGNOR; Q15349; -.
DR BioGRID-ORCS; 6196; 18 hits in 1101 CRISPR screens.
DR ChiTaRS; RPS6KA2; human.
DR GeneWiki; RPS6KA2; -.
DR GenomeRNAi; 6196; -.
DR Pharos; Q15349; Tchem.
DR PRO; PR:Q15349; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q15349; protein.
DR Bgee; ENSG00000071242; Expressed in inferior olivary complex and 213 other tissues.
DR ExpressionAtlas; Q15349; baseline and differential.
DR Genevisible; Q15349; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0072687; C:meiotic spindle; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IBA:GO_Central.
DR GO; GO:0002035; P:brain renin-angiotensin system; IEA:Ensembl.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:Reactome.
DR GO; GO:0060047; P:heart contraction; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045835; P:negative regulation of meiotic nuclear division; IEA:Ensembl.
DR GO; GO:0001556; P:oocyte maturation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0070613; P:regulation of protein processing; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR CDD; cd14178; STKc_RSK3_C; 1.
DR CDD; cd05582; STKc_RSK_N; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; IPR042766; RSK3_STKc.
DR InterPro; IPR041906; RSK_N.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
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; SSF56112; 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; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Tumor suppressor.
FT CHAIN 1..733
FT /note="Ribosomal protein S6 kinase alpha-2"
FT /id="PRO_0000086201"
FT DOMAIN 59..318
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 319..388
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 415..672
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 184
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 532
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 65..73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 421..429
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 444
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 218
FT /note="Phosphoserine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:10480933"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 1..32
FT /note="MDLSMKKFAVRRFFSVYLRRKSRSKSSSLSRL -> MPIAQLLELWKKIEVE
FT PMEIETTEEDLNLDVGPATEDTAEEGKSDSAACKTKVAGSV (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_017732"
FT VAR_SEQ 1..32
FT /note="MDLSMKKFAVRRFFSVYLRRKSRSKSSSLSRL -> MPIAQLLELWKKIEVE
FT PMEIETTEEDLNLDVEPTTEDTAE (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041836"
FT VARIANT 311
FT /note="E -> K (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs267600891)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040627"
FT VARIANT 732
FT /note="R -> Q (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs376029388)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040628"
FT CONFLICT 256
FT /note="S -> A (in Ref. 6; AAC82496)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="A -> S (in Ref. 6; AAC82496)"
FT /evidence="ECO:0000305"
FT CONFLICT 339
FT /note="V -> L (in Ref. 1; CAA59427 and 6; AAC82496)"
FT /evidence="ECO:0000305"
FT CONFLICT 447
FT /note="D -> G (in Ref. 6; AAC82496)"
FT /evidence="ECO:0000305"
FT CONFLICT Q15349-3:32
FT /note="E -> G (in Ref. 3; BAG53121)"
FT /evidence="ECO:0000305"
FT CONFLICT Q15349-3:34
FT /note="T -> A (in Ref. 3; BAG53121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 733 AA; 83239 MW; 087CFB819A313760 CRC64;
MDLSMKKFAV RRFFSVYLRR KSRSKSSSLS RLEEEGVVKE IDISHHVKEG FEKADPSQFE
LLKVLGQGSY GKVFLVRKVK GSDAGQLYAM KVLKKATLKV RDRVRSKMER DILAEVNHPF
IVKLHYAFQT EGKLYLILDF LRGGDLFTRL SKEVMFTEED VKFYLAELAL ALDHLHSLGI
IYRDLKPENI LLDEEGHIKI TDFGLSKEAI DHDKRAYSFC GTIEYMAPEV VNRRGHTQSA
DWWSFGVLMF EMLTGSLPFQ GKDRKETMAL ILKAKLGMPQ FLSGEAQSLL RALFKRNPCN
RLGAGIDGVE EIKRHPFFVT IDWNTLYRKE IKPPFKPAVG RPEDTFHFDP EFTARTPTDS
PGVPPSANAH HLFRGFSFVA SSLIQEPSQQ DLHKVPVHPI VQQLHGNNIH FTDGYEIKED
IGVGSYSVCK RCVHKATDTE YAVKIIDKSK RDPSEEIEIL LRYGQHPNII TLKDVYDDGK
FVYLVMELMR GGELLDRILR QRYFSEREAS DVLCTITKTM DYLHSQGVVH RDLKPSNILY
RDESGSPESI RVCDFGFAKQ LRAGNGLLMT PCYTANFVAP EVLKRQGYDA ACDIWSLGIL
LYTMLAGFTP FANGPDDTPE EILARIGSGK YALSGGNWDS ISDAAKDVVS KMLHVDPHQR
LTAMQVLKHP WVVNREYLSP NQLSRQDVHL VKGAMAATYF ALNRTPQAPR LEPVLSSNLA
QRRGMKRLTS TRL
