ID   KS6A6_HUMAN             Reviewed;         745 AA.
AC   Q9UK32; B2R854; B7ZL90; Q6FHX2; Q8WX28; Q9H4S6;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 199.
DE   RecName: Full=Ribosomal protein S6 kinase alpha-6;
DE            Short=S6K-alpha-6;
DE            EC=2.7.11.1;
DE   AltName: Full=90 kDa ribosomal protein S6 kinase 6;
DE            Short=p90-RSK 6;
DE            Short=p90RSK6;
DE   AltName: Full=Ribosomal S6 kinase 4;
DE            Short=RSK-4;
DE   AltName: Full=pp90RSK4;
GN   Name=RPS6KA6; Synonyms=RSK4;
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).
RX   PubMed=10644430; DOI=10.1006/geno.1999.6004;
RA   Yntema H.G., van den Helm B., Kissing J., van Duijnhoven G., Poppelaars F.,
RA   Chelly J., Moraine C., Fryns J.-P., Hamel B.C.J., Heilbronner H.,
RA   Pander H.-J., Brunner H.G., Ropers H.-H., Cremers F.P.M., van Bokhoven H.;
RT   "A novel ribosomal S6-kinase (RSK4; RPS6KA6) is commonly deleted in
RT   patients with complex X-linked mental retardation.";
RL   Genomics 62:332-343(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA   Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT   "Cloning of human full open reading frames in Gateway(TM) system entry
RT   vector (pDONR201).";
RL   Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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=15772651; DOI=10.1038/nature03440;
RA   Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA   Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA   Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA   Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA   Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA   Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA   Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA   Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA   Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA   Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA   Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA   Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA   Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA   Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA   Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA   Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA   Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA   Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA   Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA   Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA   Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA   Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA   Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA   Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA   Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA   Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA   Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA   Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA   Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA   Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA   McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA   Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA   Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA   Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA   Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA   Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA   Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA   Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA   Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA   Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA   d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA   Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA   Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA   Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA   Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA   Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA   Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA   Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA   Rogers J., Bentley D.R.;
RT   "The DNA sequence of the human X chromosome.";
RL   Nature 434:325-337(2005).
RN   [5]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Cerebellum;
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   [7]
RP   FUNCTION IN P53/TP53 SIGNALING.
RX   PubMed=15042092; DOI=10.1038/nature02371;
RA   Berns K., Hijmans E.M., Mullenders J., Brummelkamp T.R., Velds A.,
RA   Heimerikx M., Kerkhoven R.M., Madiredjo M., Nijkamp W., Weigelt B.,
RA   Agami R., Ge W., Cavet G., Linsley P.S., Beijersbergen R.L., Bernards R.;
RT   "A large-scale RNAi screen in human cells identifies new components of the
RT   p53 pathway.";
RL   Nature 428:431-437(2004).
RN   [8]
RP   FUNCTION, ACTIVITY REGULATION, INTERACTION WITH MAPK3, SUBCELLULAR
RP   LOCATION, PHOSPHORYLATION AT SER-232; SER-372; SER-389 AND THR-581, AND
RP   MUTAGENESIS OF SER-372; SER-389 AND THR-581.
RX   PubMed=15632195; DOI=10.1074/jbc.m408194200;
RA   Duemmler B.A., Hauge C., Silber J., Yntema H.G., Kruse L.S., Kofoed B.,
RA   Hemmings B.A., Alessi D.R., Froedin M.;
RT   "Functional characterization of human RSK4, a new 90-kDa ribosomal S6
RT   kinase, reveals constitutive activation in most cell types.";
RL   J. Biol. Chem. 280:13304-13314(2005).
RN   [9]
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   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [11]
RP   VARIANTS [LARGE SCALE ANALYSIS] CYS-140; THR-258 AND ASN-692.
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: Constitutively active serine/threonine-protein kinase that
CC       exhibits growth-factor-independent kinase activity and that may
CC       participate in p53/TP53-dependent cell growth arrest signaling and play
CC       an inhibitory role during embryogenesis. {ECO:0000269|PubMed:15042092,
CC       ECO:0000269|PubMed:15632195}.
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; Evidence={ECO:0000250};
CC   -!- ACTIVITY REGULATION: Constitutively activated by phosphorylation at
CC       Ser-232, Ser-372, and Ser-389 in serum-starved cells. Does not require
CC       growth factor stimulation for significant kinase activity.
CC       {ECO:0000269|PubMed:15632195}.
CC   -!- SUBUNIT: Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14
CC       in serum-starved cells.
CC   -!- INTERACTION:
CC       Q9UK32; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-722467, EBI-7082156;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15632195}.
CC       Nucleus {ECO:0000269|PubMed:15632195}. Note=Predominantly cytosolic.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q9UK32-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q9UK32-2; Sequence=VSP_056181;
CC   -!- PTM: Phosphorylated at Ser-232, Ser-372, and Ser-389 in serum-starved
CC       cells. {ECO:0000269|PubMed:15632195}.
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; AF184965; AAF13190.1; -; mRNA.
DR   EMBL; CR536566; CAG38803.1; -; mRNA.
DR   EMBL; AK313240; BAG36051.1; -; mRNA.
DR   EMBL; AL389887; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL354653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471104; EAW98575.1; -; Genomic_DNA.
DR   EMBL; BC143648; AAI43649.1; -; mRNA.
DR   CCDS; CCDS14451.1; -. [Q9UK32-1]
DR   CCDS; CCDS83480.1; -. [Q9UK32-2]
DR   RefSeq; NP_001317441.1; NM_001330512.1. [Q9UK32-2]
DR   RefSeq; NP_055311.1; NM_014496.4. [Q9UK32-1]
DR   RefSeq; XP_011529219.1; XM_011530917.2. [Q9UK32-2]
DR   PDB; 6G76; X-ray; 3.00 A; A/B=48-349.
DR   PDB; 6G77; X-ray; 2.50 A; A/B=48-349.
DR   PDB; 6G78; X-ray; 2.50 A; A/B=48-349.
DR   PDBsum; 6G76; -.
DR   PDBsum; 6G77; -.
DR   PDBsum; 6G78; -.
DR   AlphaFoldDB; Q9UK32; -.
DR   SMR; Q9UK32; -.
DR   BioGRID; 118144; 64.
DR   IntAct; Q9UK32; 44.
DR   MINT; Q9UK32; -.
DR   STRING; 9606.ENSP00000262752; -.
DR   BindingDB; Q9UK32; -.
DR   ChEMBL; CHEMBL4924; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; Q9UK32; -.
DR   GuidetoPHARMACOLOGY; 1530; -.
DR   GlyGen; Q9UK32; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9UK32; -.
DR   PhosphoSitePlus; Q9UK32; -.
DR   BioMuta; RPS6KA6; -.
DR   DMDM; 11133131; -.
DR   CPTAC; CPTAC-2974; -.
DR   CPTAC; CPTAC-2975; -.
DR   EPD; Q9UK32; -.
DR   jPOST; Q9UK32; -.
DR   MassIVE; Q9UK32; -.
DR   MaxQB; Q9UK32; -.
DR   PaxDb; 9606-ENSP00000262752; -.
DR   PeptideAtlas; Q9UK32; -.
DR   ProteomicsDB; 7217; -.
DR   ProteomicsDB; 84712; -. [Q9UK32-1]
DR   Antibodypedia; 489; 278 antibodies from 31 providers.
DR   DNASU; 27330; -.
DR   Ensembl; ENST00000262752.5; ENSP00000262752.2; ENSG00000072133.12. [Q9UK32-1]
DR   Ensembl; ENST00000620340.4; ENSP00000483896.1; ENSG00000072133.12. [Q9UK32-2]
DR   GeneID; 27330; -.
DR   KEGG; hsa:27330; -.
DR   MANE-Select; ENST00000262752.5; ENSP00000262752.2; NM_014496.5; NP_055311.1.
DR   UCSC; uc004eej.3; human. [Q9UK32-1]
DR   AGR; HGNC:10435; -.
DR   CTD; 27330; -.
DR   DisGeNET; 27330; -.
DR   GeneCards; RPS6KA6; -.
DR   HGNC; HGNC:10435; RPS6KA6.
DR   HPA; ENSG00000072133; Low tissue specificity.
DR   MIM; 300303; gene.
DR   neXtProt; NX_Q9UK32; -.
DR   OpenTargets; ENSG00000072133; -.
DR   PharmGKB; PA34850; -.
DR   VEuPathDB; HostDB:ENSG00000072133; -.
DR   eggNOG; KOG0603; Eukaryota.
DR   GeneTree; ENSGT00940000159242; -.
DR   HOGENOM; CLU_000288_58_3_1; -.
DR   InParanoid; Q9UK32; -.
DR   OMA; HSWITCK; -.
DR   OrthoDB; 5489497at2759; -.
DR   PhylomeDB; Q9UK32; -.
DR   TreeFam; TF313438; -.
DR   BRENDA; 2.7.11.1; 2681.
DR   PathwayCommons; Q9UK32; -.
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   SignaLink; Q9UK32; -.
DR   BioGRID-ORCS; 27330; 15 hits in 802 CRISPR screens.
DR   ChiTaRS; RPS6KA6; human.
DR   GenomeRNAi; 27330; -.
DR   Pharos; Q9UK32; Tchem.
DR   PRO; PR:Q9UK32; -.
DR   Proteomes; UP000005640; Chromosome X.
DR   RNAct; Q9UK32; Protein.
DR   Bgee; ENSG00000072133; Expressed in buccal mucosa cell and 145 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR   GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR   GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR   GO; GO:0004711; F:ribosomal protein S6 kinase activity; IBA:GO_Central.
DR   GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR   GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; IMP:UniProtKB.
DR   GO; GO:0045992; P:negative regulation of embryonic development; ISS:UniProtKB.
DR   GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:2000381; P:negative regulation of mesoderm development; ISS:UniProtKB.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd14177; STKc_RSK4_C; 1.
DR   CDD; cd05582; STKc_RSK_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; 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; IPR041906; RSK_N.
DR   InterPro; IPR008271; Ser/Thr_kinase_AS.
DR   PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR   PANTHER; PTHR24351:SF246; RIBOSOMAL PROTEIN S6 KINASE ALPHA-6; 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.
DR   Genevisible; Q9UK32; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW   Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase.
FT   CHAIN           1..745
FT                   /note="Ribosomal protein S6 kinase alpha-6"
FT                   /id="PRO_0000086209"
FT   DOMAIN          73..330
FT                   /note="Protein kinase 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   DOMAIN          331..400
FT                   /note="AGC-kinase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT   DOMAIN          426..683
FT                   /note="Protein kinase 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   REGION          1..28
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        198
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        543
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250"
FT   BINDING         79..87
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         105
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         432..440
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         455
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         232
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   MOD_RES         372
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   MOD_RES         389
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:15632195,
FT                   ECO:0007744|PubMed:21406692"
FT   MOD_RES         581
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   VAR_SEQ         1..27
FT                   /note="MLPFAPQDEPWDREMEVFSGGGASSGE -> MGLSTSAIWKNTRVEIVNPYE
FT                   VKRKVK (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_056181"
FT   VARIANT         140
FT                   /note="Y -> C (in a lung large cell carcinoma sample;
FT                   somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040637"
FT   VARIANT         258
FT                   /note="S -> T (in a lung adenocarcinoma sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_040638"
FT   VARIANT         692
FT                   /note="D -> N (in dbSNP:rs6616890)"
FT                   /evidence="ECO:0000269|PubMed:17344846"
FT                   /id="VAR_030670"
FT   MUTAGEN         372
FT                   /note="S->A: No effect on activity."
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   MUTAGEN         389
FT                   /note="S->A: Strongly decreases activity."
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   MUTAGEN         581
FT                   /note="T->A: No effect on activity."
FT                   /evidence="ECO:0000269|PubMed:15632195"
FT   CONFLICT        116
FT                   /note="D -> G (in Ref. 2; CAG38803)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        295
FT                   /note="F -> L (in Ref. 2; CAG38803)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        341
FT                   /note="R -> G (in Ref. 2; CAG38803)"
FT                   /evidence="ECO:0000305"
FT   STRAND          52..56
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           70..72
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          73..81
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          86..92
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   TURN            96..99
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          101..115
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           126..129
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          138..144
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          147..152
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           160..165
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           172..191
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           201..203
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          204..206
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          208..210
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          212..215
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   STRAND          220..222
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           226..230
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           237..239
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           242..245
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           252..268
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           278..287
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           298..307
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   TURN            312..314
FT                   /evidence="ECO:0007829|PDB:6G78"
FT   TURN            316..319
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           322..325
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           328..330
FT                   /evidence="ECO:0007829|PDB:6G77"
FT   HELIX           335..339
FT                   /evidence="ECO:0007829|PDB:6G77"
SQ   SEQUENCE   745 AA;  83872 MW;  5EC5AB2FA1C19DE8 CRC64;
     MLPFAPQDEP WDREMEVFSG GGASSGEVNG LKMVDEPMEE GEADSCHDEG VVKEIPITHH
     VKEGYEKADP AQFELLKVLG QGSFGKVFLV RKKTGPDAGQ LYAMKVLKKA SLKVRDRVRT
     KMERDILVEV NHPFIVKLHY AFQTEGKLYL ILDFLRGGDV FTRLSKEVLF TEEDVKFYLA
     ELALALDHLH QLGIVYRDLK PENILLDEIG HIKLTDFGLS KESVDQEKKA YSFCGTVEYM
     APEVVNRRGH SQSADWWSYG VLMFEMLTGT LPFQGKDRNE TMNMILKAKL GMPQFLSAEA
     QSLLRMLFKR NPANRLGSEG VEEIKRHLFF ANIDWDKLYK REVQPPFKPA SGKPDDTFCF
     DPEFTAKTPK DSPGLPASAN AHQLFKGFSF VATSIAEEYK ITPITSANVL PIVQINGNAA
     QFGEVYELKE DIGVGSYSVC KRCIHATTNM EFAVKIIDKS KRDPSEEIEI LMRYGQHPNI
     ITLKDVFDDG RYVYLVTDLM KGGELLDRIL KQKCFSEREA SDILYVISKT VDYLHCQGVV
     HRDLKPSNIL YMDESASADS IRICDFGFAK QLRGENGLLL TPCYTANFVA PEVLMQQGYD
     AACDIWSLGV LFYTMLAGYT PFANGPNDTP EEILLRIGNG KFSLSGGNWD NISDGAKDLL
     SHMLHMDPHQ RYTAEQILKH SWITHRDQLP NDQPKRNDVS HVVKGAMVAT YSALTHKTFQ
     PVLEPVAASS LAQRRSMKKR TSTGL
//