KS6A6_HUMAN
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 03-AUG-2022, entry version 190.
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; 48.
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 iPTMnet; Q9UK32; -.
DR PhosphoSitePlus; Q9UK32; -.
DR BioMuta; RPS6KA6; -.
DR DMDM; 11133131; -.
DR EPD; Q9UK32; -.
DR jPOST; Q9UK32; -.
DR MassIVE; Q9UK32; -.
DR MaxQB; Q9UK32; -.
DR PaxDb; Q9UK32; -.
DR PeptideAtlas; Q9UK32; -.
DR PRIDE; Q9UK32; -.
DR ProteomicsDB; 7217; -.
DR ProteomicsDB; 84712; -. [Q9UK32-1]
DR Antibodypedia; 489; 247 antibodies from 31 providers.
DR DNASU; 27330; -.
DR Ensembl; ENST00000262752.5; ENSP00000262752.2; ENSG00000072133.11. [Q9UK32-1]
DR Ensembl; ENST00000620340.4; ENSP00000483896.1; ENSG00000072133.11. [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 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; FVITKTV; -.
DR OrthoDB; 1132245at2759; -.
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; 14 hits in 729 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 143 other tissues.
DR Genevisible; Q9UK32; HS.
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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
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:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
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; 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 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
