KS6A3_HUMAN
ID KS6A3_HUMAN Reviewed; 740 AA.
AC P51812; B2R9V4; Q4VAP3; Q59H26; Q5JPK8; Q7Z3Z7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Ribosomal protein S6 kinase alpha-3;
DE Short=S6K-alpha-3;
DE EC=2.7.11.1 {ECO:0000269|PubMed:17213202};
DE AltName: Full=90 kDa ribosomal protein S6 kinase 3;
DE Short=p90-RSK 3;
DE Short=p90RSK3;
DE AltName: Full=Insulin-stimulated protein kinase 1;
DE Short=ISPK-1;
DE AltName: Full=MAP kinase-activated protein kinase 1b;
DE Short=MAPK-activated protein kinase 1b;
DE Short=MAPKAP kinase 1b;
DE Short=MAPKAPK-1b;
DE AltName: Full=Ribosomal S6 kinase 2;
DE Short=RSK-2;
DE AltName: Full=pp90RSK2;
GN Name=RPS6KA3; Synonyms=ISPK1, MAPKAPK1B, RSK2;
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].
RC TISSUE=Placenta, and T-cell;
RX PubMed=7813820; DOI=10.2337/diab.44.1.90;
RA Bjoerbaek C., Vik T.A., Echwald S.M., Webb G.C., Wang J.P., Yang P.-Y.,
RA Vestergaard H., Richmond K., Hansen T., Erikson R.L., Miklos G.L.G.,
RA Cohen P.T.W., Pedersen O.;
RT "Cloning of a human insulin-stimulated protein kinase (ISPK-1) gene and
RT analysis of coding regions and mRNA levels of the ISPK-1 and the protein
RT phosphatase-1 genes in muscle from NIDDM patients.";
RL Diabetes 44:90-97(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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].
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].
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 MRNA].
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 2-582.
RC TISSUE=Skeletal muscle;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 15-735.
RX PubMed=12777533; DOI=10.1093/molbev/msg134;
RA Kitano T., Schwarz C., Nickel B., Paeaebo S.;
RT "Gene diversity patterns at 10 X-chromosomal loci in humans and
RT chimpanzees.";
RL Mol. Biol. Evol. 20:1281-1289(2003).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF GSK3B.
RX PubMed=8250835; DOI=10.1042/bj2960015;
RA Sutherland C., Leighton I.A., Cohen P.;
RT "Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new
RT kinase connections in insulin and growth-factor signalling.";
RL Biochem. J. 296:15-19(1993).
RN [9]
RP FUNCTION IN PHOSPHORYLATION OF CREB1.
RX PubMed=9770464; DOI=10.1073/pnas.95.21.12202;
RA De Cesare D., Jacquot S., Hanauer A., Sassone-Corsi P.;
RT "Rsk-2 activity is necessary for epidermal growth factor-induced
RT phosphorylation of CREB protein and transcription of c-fos gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12202-12207(1998).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF HISTONE H3.
RX PubMed=10436156; DOI=10.1126/science.285.5429.886;
RA Sassone-Corsi P., Mizzen C.A., Cheung P., Crosio C., Monaco L., Jacquot S.,
RA Hanauer A., Allis C.D.;
RT "Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation
RT of histone H3.";
RL Science 285:886-891(1999).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF DAPK1.
RX PubMed=16213824; DOI=10.1016/j.cub.2005.08.050;
RA Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.;
RT "The tumor suppressor DAP kinase is a target of RSK-mediated survival
RT signaling.";
RL Curr. Biol. 15:1762-1767(2005).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF NR4A1/NUR77.
RX PubMed=16223362; DOI=10.1042/bj20050967;
RA Wingate A.D., Campbell D.G., Peggie M., Arthur J.S.;
RT "Nur77 is phosphorylated in cells by RSK in response to mitogenic
RT stimulation.";
RL Biochem. J. 393:715-724(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-715, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [14]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, INTERACTION WITH NFATC4,
RP AND SUBCELLULAR LOCATION.
RX PubMed=17213202; DOI=10.1074/jbc.m611322200;
RA Cho Y.-Y., Yao K., Bode A.M., Bergen H.R. III, Madden B.J., Oh S.-M.,
RA Ermakova S., Kang B.S., Choi H.S., Shim J.-H., Dong Z.;
RT "RSK2 mediates muscle cell differentiation through regulation of NFAT3.";
RL J. Biol. Chem. 282:8380-8392(2007).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF RPS6.
RX PubMed=17360704; DOI=10.1074/jbc.m700906200;
RA Roux P.P., Shahbazian D., Vu H., Holz M.K., Cohen M.S., Taunton J.,
RA Sonenberg N., Blenis J.;
RT "RAS/ERK signaling promotes site-specific ribosomal protein S6
RT phosphorylation via RSK and stimulates cap-dependent translation.";
RL J. Biol. Chem. 282:14056-14064(2007).
RN [16]
RP FUNCTION IN MTOR SIGNALING.
RX PubMed=18722121; DOI=10.1016/j.cub.2008.07.078;
RA Carriere A., Cargnello M., Julien L.A., Gao H., Bonneil E., Thibault P.,
RA Roux P.P.;
RT "Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-
RT mediated raptor phosphorylation.";
RL Curr. Biol. 18:1269-1277(2008).
RN [17]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
RX PubMed=18508509; DOI=10.2741/3003;
RA Carriere A., Ray H., Blenis J., Roux P.P.;
RT "The RSK factors of activating the Ras/MAPK signaling cascade.";
RL Front. Biosci. 13:4258-4275(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365; SER-369; SER-375;
RP SER-386; SER-415; SER-556 AND SER-715, AND IDENTIFICATION BY MASS
RP 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 [19]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365; SER-369 AND SER-375, AND
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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365; SER-369; SER-375;
RP SER-386; SER-415 AND SER-715, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-715, AND IDENTIFICATION BY
RP 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 [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365 AND SER-369, AND
RP IDENTIFICATION BY 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-365; SER-369; SER-415 AND
RP SER-715, AND 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 [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-369; SER-386; SER-415 AND
RP SER-715, AND 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 [28]
RP FUNCTION IN PHOSPHORYLATION OF EPHA2.
RX PubMed=26158630; DOI=10.1038/ncomms8679;
RA Zhou Y., Yamada N., Tanaka T., Hori T., Yokoyama S., Hayakawa Y., Yano S.,
RA Fukuoka J., Koizumi K., Saiki I., Sakurai H.;
RT "Crucial roles of RSK in cell motility by catalysing serine phosphorylation
RT of EphA2.";
RL Nat. Commun. 6:7679-7679(2015).
RN [29]
RP VARIANTS CLS VAL-75 AND ALA-227.
RX PubMed=8955270; DOI=10.1038/384567a0;
RA Trivier E., de Cesare D., Jacquot S., Pannetier S., Zackai E., Young I.,
RA Mandel J.-L., Sassone-Corsi P., Hanauer A.;
RT "Mutations in the kinase Rsk-2 associated with Coffin-Lowry syndrome.";
RL Nature 384:567-570(1996).
RN [30]
RP VARIANTS CLS PHE-82; GLN-127; TYR-154; VAL-225 AND ASP-431, AND VARIANT
RP SER-38.
RX PubMed=9837815; DOI=10.1086/302153;
RA Jacquot S., Merienne K., de Cesare D., Pannetier S., Mandel J.-L.,
RA Sassone-Corsi P., Hanauer A.;
RT "Mutation analysis of the RSK2 gene in Coffin-Lowry patients: extensive
RT allelic heterogeneity and a high rate of De novo mutations.";
RL Am. J. Hum. Genet. 63:1631-1640(1998).
RN [31]
RP VARIANTS CLS TRP-114 AND GLN-729.
RX PubMed=10094187; DOI=10.1038/sj.ejhg.5200231;
RA Abidi F., Jacquot S., Lassiter C., Trivier E., Hanauer A., Schwartz C.E.;
RT "Novel mutations in Rsk-2, the gene for Coffin-Lowry syndrome (CLS).";
RL Eur. J. Hum. Genet. 7:20-26(1999).
RN [32]
RP VARIANT CLS LYS-189.
RX PubMed=10528858; DOI=10.1136/jmg.36.10.775;
RA Manouvrier-Hanu S., Amiel J., Jacquot S., Merienne K., Moerman A.,
RA Coeslier A., Labarriere F., Vallee L., Croquette M.F., Hanauer A.;
RT "Unreported RSK2 missense mutation in two male sibs with an unusually mild
RT form of Coffin-Lowry syndrome.";
RL J. Med. Genet. 36:775-778(1999).
RN [33]
RP VARIANT XLID19 TRP-383, AND CHARACTERIZATION OF VARIANT XLID19 TRP-383.
RX PubMed=10319851; DOI=10.1038/8719;
RA Merienne K., Jacquot S., Pannetier S., Zeniou M., Bankier A., Gecz J.,
RA Mandel J.L., Mulley J., Sassone-Corsi P., Hanauer A.;
RT "A missense mutation in RPS6KA3 (RSK2) responsible for non-specific mental
RT retardation.";
RL Nat. Genet. 22:13-14(1999).
RN [34]
RP VARIANT CLS SER-268.
RX PubMed=14986828; DOI=10.1046/j.1399-0004.2003.00166.x;
RA Martinez-Garay I., Ballesta M.J., Oltra S., Orellana C., Palomeque A.,
RA Molto M.D., Prieto F., Martinez F.;
RT "Intronic L1 insertion and F268S, novel mutations in RPS6KA3 (RSK2) causing
RT Coffin-Lowry syndrome.";
RL Clin. Genet. 64:491-496(2003).
RN [35]
RP VARIANT CLS ILE-477 DEL.
RX PubMed=15214012; DOI=10.1002/ajmg.a.30056;
RA Facher J.J., Regier E.J., Jacobs G.H., Siwik E., Delaunoy J.P., Robin N.H.;
RT "Cardiomyopathy in Coffin-Lowry syndrome.";
RL Am. J. Med. Genet. A 128:176-178(2004).
RN [36]
RP VARIANTS XLID19 SER-115; GLY-152 DEL AND ASP-202 DEL.
RX PubMed=17100996; DOI=10.1111/j.1399-0004.2006.00723.x;
RA Field M., Tarpey P., Boyle J., Edkins S., Goodship J., Luo Y., Moon J.,
RA Teague J., Stratton M.R., Futreal P.A., Wooster R., Raymond F.L.,
RA Turner G.;
RT "Mutations in the RSK2(RPS6KA3) gene cause Coffin-Lowry syndrome and
RT nonsyndromic X-linked mental retardation.";
RL Clin. Genet. 70:509-515(2006).
RN [37]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-416.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [38]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-38; CYS-483; PHE-608 AND CYS-723.
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 the transcription factors CREB1, ETV1/ER81
CC and NR4A1/NUR77, regulates translation through RPS6 and EIF4B
CC phosphorylation, and mediates cellular proliferation, survival, and
CC differentiation by modulating mTOR signaling and repressing pro-
CC apoptotic function of BAD and DAPK1 (PubMed:9770464, PubMed:16223362,
CC PubMed:17360704, PubMed:16213824). In fibroblast, is required for EGF-
CC stimulated phosphorylation of CREB1 and histone H3 at 'Ser-10', which
CC results in the subsequent transcriptional activation of several
CC immediate-early genes (PubMed:9770464, PubMed:10436156). In response to
CC mitogenic stimulation (EGF and PMA), phosphorylates and activates
CC NR4A1/NUR77 and ETV1/ER81 transcription factors and the cofactor CREBBP
CC (PubMed:16223362). Upon insulin-derived signal, acts indirectly on the
CC transcription regulation of several genes by phosphorylating GSK3B at
CC 'Ser-9' and inhibiting its activity (PubMed:8250835). Phosphorylates
CC RPS6 in response to serum or EGF via an mTOR-independent mechanism and
CC promotes translation initiation by facilitating assembly of the
CC preinitiation complex (PubMed:17360704). In response to insulin,
CC phosphorylates EIF4B, enhancing EIF4B affinity for the EIF3 complex and
CC stimulating cap-dependent translation (PubMed:18508509,
CC PubMed:18813292). Is involved in the mTOR nutrient-sensing pathway by
CC directly phosphorylating TSC2 at 'Ser-1798', which potently inhibits
CC TSC2 ability to suppress mTOR signaling, and mediates phosphorylation
CC of RPTOR, which regulates mTORC1 activity and may promote rapamycin-
CC sensitive signaling independently of the PI3K/AKT pathway
CC (PubMed:18722121). Mediates cell survival by phosphorylating the pro-
CC apoptotic proteins BAD and DAPK1 and suppressing their pro-apoptotic
CC function (PubMed:16213824). Promotes the survival of hepatic stellate
CC cells by phosphorylating CEBPB in response to the hepatotoxin carbon
CC tetrachloride (CCl4) (PubMed:18508509, PubMed:18813292). Is involved in
CC cell cycle regulation by phosphorylating the CDK inhibitor CDKN1B,
CC which promotes CDKN1B association with 14-3-3 proteins and prevents its
CC translocation to the nucleus and inhibition of G1 progression (By
CC similarity). In LPS-stimulated dendritic cells, is involved in TLR4-
CC induced macropinocytosis, and in myeloma cells, acts as effector of
CC FGFR3-mediated transformation signaling, after direct phosphorylation
CC at Tyr-529 by FGFR3 (By similarity). Negatively regulates EGF-induced
CC MAPK1/3 phosphorylation via phosphorylation of SOS1 (By similarity).
CC Phosphorylates SOS1 at 'Ser-1134' and 'Ser-1161' that create YWHAB and
CC YWHAE binding sites and which contribute to the negative regulation of
CC MAPK1/3 phosphorylation (By similarity). Phosphorylates EPHA2 at 'Ser-
CC 897', the RPS6KA-EPHA2 signaling pathway controls cell migration
CC (PubMed:26158630). Acts as a regulator of osteoblast differentiation by
CC mediating phosphorylation of ATF4, thereby promoting ATF4
CC transactivation activity (By similarity).
CC {ECO:0000250|UniProtKB:P18654, ECO:0000269|PubMed:10436156,
CC ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:16223362,
CC ECO:0000269|PubMed:17360704, ECO:0000269|PubMed:18722121,
CC ECO:0000269|PubMed:26158630, ECO:0000269|PubMed:8250835,
CC ECO:0000269|PubMed:9770464, ECO:0000303|PubMed:18508509,
CC ECO:0000303|PubMed:18813292}.
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:17213202};
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: Upon extracellular signal or mitogen stimulation,
CC phosphorylated at Thr-577 in the C-terminal kinase domain (CTKD) by
CC MAPK1/ERK2 and MAPK3/ERK1. The activated CTKD then autophosphorylates
CC Ser-386, allowing binding of PDPK1, which in turn phosphorylates Ser-
CC 227 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.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.56 uM for NFATC4 {ECO:0000269|PubMed:17213202};
CC Vmax=11.5 umol/min/ug enzyme toward ATP
CC {ECO:0000269|PubMed:17213202};
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 NFATC4, ETV1/ER81 and
CC FGFR1. {ECO:0000250, ECO:0000269|PubMed:17213202}.
CC -!- INTERACTION:
CC P51812; P46379-2: BAG6; NbExp=3; IntAct=EBI-1046616, EBI-10988864;
CC P51812; P67870: CSNK2B; NbExp=4; IntAct=EBI-1046616, EBI-348169;
CC P51812; P09471: GNAO1; NbExp=3; IntAct=EBI-1046616, EBI-715087;
CC P51812; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1046616, EBI-352572;
CC P51812; O14901: KLF11; NbExp=3; IntAct=EBI-1046616, EBI-948266;
CC P51812; P28482: MAPK1; NbExp=7; IntAct=EBI-1046616, EBI-959949;
CC P51812; Q9HC98-4: NEK6; NbExp=3; IntAct=EBI-1046616, EBI-11750983;
CC P51812; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-1046616, EBI-9091052;
CC P51812; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-1046616, EBI-9090282;
CC P51812; Q7Z698: SPRED2; NbExp=4; IntAct=EBI-1046616, EBI-7082156;
CC P51812; A1JU68: yopM; Xeno; NbExp=2; IntAct=EBI-1046616, EBI-26365850;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17213202}. Cytoplasm
CC {ECO:0000269|PubMed:17213202}.
CC -!- TISSUE SPECIFICITY: Expressed in many tissues, highest levels in
CC skeletal muscle.
CC -!- PTM: Activated by phosphorylation at Ser-227 by PDPK1.
CC Autophosphorylated on Ser-386, as part of the activation process. May
CC be phosphorylated at Thr-365 and Ser-369 by MAPK1/ERK2 and MAPK3/ERK1.
CC Can also be activated via phosphorylation at Ser-386 by MAPKAPK2.
CC -!- PTM: N-terminal myristoylation results in an activated kinase in the
CC absence of added growth factors.
CC -!- DISEASE: Coffin-Lowry syndrome (CLS) [MIM:303600]: An X-linked disorder
CC characterized by intellectual disability associated with facial and
CC digital dysmorphisms, progressive skeletal malformations, growth
CC retardation, hearing deficit and paroxysmal movement disorders.
CC {ECO:0000269|PubMed:10094187, ECO:0000269|PubMed:10528858,
CC ECO:0000269|PubMed:14986828, ECO:0000269|PubMed:15214012,
CC ECO:0000269|PubMed:8955270, ECO:0000269|PubMed:9837815}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Intellectual developmental disorder, X-linked 19 (XLID19)
CC [MIM:300844]: A disorder characterized by significantly below average
CC general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:10319851, ECO:0000269|PubMed:17100996}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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=BAD92170.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; U08316; AAA81952.1; -; mRNA.
DR EMBL; AK313932; BAG36651.1; -; mRNA.
DR EMBL; AB208933; BAD92170.1; ALT_INIT; mRNA.
DR EMBL; AL732366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL807772; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096301; AAH96301.1; -; mRNA.
DR EMBL; BC096302; AAH96302.1; -; mRNA.
DR EMBL; BC096303; AAH96303.1; -; mRNA.
DR EMBL; L07599; AAC82495.1; -; mRNA.
DR EMBL; AB102662; BAC81131.1; -; mRNA.
DR CCDS; CCDS14197.1; -.
DR PIR; I38556; I38556.
DR RefSeq; NP_004577.1; NM_004586.2.
DR PDB; 4D9T; X-ray; 2.40 A; A=399-740.
DR PDB; 4D9U; X-ray; 2.40 A; A=399-740.
DR PDB; 4JG6; X-ray; 2.60 A; A=399-740.
DR PDB; 4JG7; X-ray; 3.00 A; A=399-740.
DR PDB; 4JG8; X-ray; 3.10 A; A=399-740.
DR PDB; 4NUS; X-ray; 2.39 A; A=39-359.
DR PDB; 4NW5; X-ray; 1.94 A; A=39-359.
DR PDB; 4NW6; X-ray; 1.74 A; A=39-359.
DR PDB; 5D9K; X-ray; 2.55 A; A/B=39-366.
DR PDB; 5D9L; X-ray; 2.15 A; A=39-359.
DR PDB; 7OPO; X-ray; 2.75 A; A/C/E/G/I/K=39-351.
DR PDBsum; 4D9T; -.
DR PDBsum; 4D9U; -.
DR PDBsum; 4JG6; -.
DR PDBsum; 4JG7; -.
DR PDBsum; 4JG8; -.
DR PDBsum; 4NUS; -.
DR PDBsum; 4NW5; -.
DR PDBsum; 4NW6; -.
DR PDBsum; 5D9K; -.
DR PDBsum; 5D9L; -.
DR PDBsum; 7OPO; -.
DR AlphaFoldDB; P51812; -.
DR SMR; P51812; -.
DR BioGRID; 112111; 159.
DR DIP; DIP-38247N; -.
DR IntAct; P51812; 96.
DR MINT; P51812; -.
DR STRING; 9606.ENSP00000368884; -.
DR BindingDB; P51812; -.
DR ChEMBL; CHEMBL2345; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P51812; -.
DR GuidetoPHARMACOLOGY; 1528; -.
DR GlyGen; P51812; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P51812; -.
DR MetOSite; P51812; -.
DR PhosphoSitePlus; P51812; -.
DR BioMuta; RPS6KA3; -.
DR DMDM; 1730070; -.
DR EPD; P51812; -.
DR jPOST; P51812; -.
DR MassIVE; P51812; -.
DR MaxQB; P51812; -.
DR PaxDb; P51812; -.
DR PeptideAtlas; P51812; -.
DR PRIDE; P51812; -.
DR ProteomicsDB; 56408; -.
DR Antibodypedia; 1004; 612 antibodies from 36 providers.
DR DNASU; 6197; -.
DR Ensembl; ENST00000379565.9; ENSP00000368884.3; ENSG00000177189.14.
DR GeneID; 6197; -.
DR KEGG; hsa:6197; -.
DR MANE-Select; ENST00000379565.9; ENSP00000368884.3; NM_004586.3; NP_004577.1.
DR UCSC; uc004czu.4; human.
DR CTD; 6197; -.
DR DisGeNET; 6197; -.
DR GeneCards; RPS6KA3; -.
DR GeneReviews; RPS6KA3; -.
DR HGNC; HGNC:10432; RPS6KA3.
DR HPA; ENSG00000177189; Low tissue specificity.
DR MalaCards; RPS6KA3; -.
DR MIM; 300075; gene.
DR MIM; 300844; phenotype.
DR MIM; 303600; phenotype.
DR neXtProt; NX_P51812; -.
DR OpenTargets; ENSG00000177189; -.
DR Orphanet; 192; Coffin-Lowry syndrome.
DR Orphanet; 276630; Symptomatic form of Coffin-Lowry syndrome in female carriers.
DR Orphanet; 777; X-linked non-syndromic intellectual disability.
DR PharmGKB; PA34847; -.
DR VEuPathDB; HostDB:ENSG00000177189; -.
DR eggNOG; KOG0603; Eukaryota.
DR GeneTree; ENSGT00940000159370; -.
DR HOGENOM; CLU_000288_58_3_1; -.
DR InParanoid; P51812; -.
DR OMA; VINCCEA; -.
DR OrthoDB; 1132245at2759; -.
DR PhylomeDB; P51812; -.
DR TreeFam; TF313438; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P51812; -.
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; P51812; -.
DR SIGNOR; P51812; -.
DR BioGRID-ORCS; 6197; 22 hits in 738 CRISPR screens.
DR ChiTaRS; RPS6KA3; human.
DR GeneWiki; RPS6KA3; -.
DR GenomeRNAi; 6197; -.
DR Pharos; P51812; Tchem.
DR PRO; PR:P51812; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P51812; protein.
DR Bgee; ENSG00000177189; Expressed in cartilage tissue and 202 other tissues.
DR ExpressionAtlas; P51812; baseline and differential.
DR Genevisible; P51812; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0043027; F:cysteine-type endopeptidase inhibitor activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0045597; P:positive regulation of cell differentiation; TAS:UniProtKB.
DR GO; GO:0030307; P:positive regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; TAS:UniProtKB.
DR GO; GO:0043555; P:regulation of translation in response to stress; TAS:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR CDD; cd14176; STKc_RSK2_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; IPR041905; RPS6KA3_C.
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; ATP-binding; Cell cycle; Cytoplasm; Disease variant;
KW Intellectual disability; Kinase; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Stress response; Transferase.
FT CHAIN 1..740
FT /note="Ribosomal protein S6 kinase alpha-3"
FT /id="PRO_0000086203"
FT DOMAIN 68..327
FT /note="Protein kinase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 328..397
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT DOMAIN 422..679
FT /note="Protein kinase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT ACT_SITE 539
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 74..82
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 428..436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 451
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 227
FT /note="Phosphoserine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P18654, ECO:0000305"
FT MOD_RES 365
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195"
FT MOD_RES 386
FT /note="Phosphoserine; by autocatalysis and MAPKAPK2"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:24275569"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 529
FT /note="Phosphotyrosine; by FGFR3"
FT /evidence="ECO:0000250|UniProtKB:P18654"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 715
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 38
FT /note="I -> S (in dbSNP:rs56218010)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:9837815"
FT /id="VAR_006188"
FT VARIANT 75
FT /note="G -> V (in CLS; dbSNP:rs122454124)"
FT /evidence="ECO:0000269|PubMed:8955270"
FT /id="VAR_006189"
FT VARIANT 82
FT /note="V -> F (in CLS; dbSNP:rs122454126)"
FT /evidence="ECO:0000269|PubMed:9837815"
FT /id="VAR_006190"
FT VARIANT 114
FT /note="R -> W (in CLS; dbSNP:rs122454127)"
FT /evidence="ECO:0000269|PubMed:10094187"
FT /id="VAR_006191"
FT VARIANT 115
FT /note="T -> S (in XLID19; dbSNP:rs387906703)"
FT /evidence="ECO:0000269|PubMed:17100996"
FT /id="VAR_065892"
FT VARIANT 127
FT /note="H -> Q (in CLS)"
FT /evidence="ECO:0000269|PubMed:9837815"
FT /id="VAR_006192"
FT VARIANT 152
FT /note="Missing (in XLID19; dbSNP:rs398122813)"
FT /evidence="ECO:0000269|PubMed:17100996"
FT /id="VAR_065893"
FT VARIANT 154
FT /note="D -> Y (in CLS)"
FT /evidence="ECO:0000269|PubMed:9837815"
FT /id="VAR_006193"
FT VARIANT 189
FT /note="I -> K (in CLS; dbSNP:rs122454130)"
FT /evidence="ECO:0000269|PubMed:10528858"
FT /id="VAR_065894"
FT VARIANT 202
FT /note="Missing (in XLID19)"
FT /evidence="ECO:0000269|PubMed:17100996"
FT /id="VAR_065895"
FT VARIANT 225
FT /note="A -> V (in CLS; dbSNP:rs879027948)"
FT /evidence="ECO:0000269|PubMed:9837815"
FT /id="VAR_006194"
FT VARIANT 227
FT /note="S -> A (in CLS; dbSNP:rs122454125)"
FT /evidence="ECO:0000269|PubMed:8955270"
FT /id="VAR_006195"
FT VARIANT 268
FT /note="F -> S (in CLS; dbSNP:rs122454131)"
FT /evidence="ECO:0000269|PubMed:14986828"
FT /id="VAR_065896"
FT VARIANT 383
FT /note="R -> W (in XLID19; kinase activity is decreased but
FT not abolished; dbSNP:rs122454129)"
FT /evidence="ECO:0000269|PubMed:10319851"
FT /id="VAR_065897"
FT VARIANT 416
FT /note="I -> V (in a breast cancer sample; somatic mutation;
FT dbSNP:rs148050184)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035627"
FT VARIANT 431
FT /note="G -> D (in CLS)"
FT /evidence="ECO:0000269|PubMed:9837815"
FT /id="VAR_006196"
FT VARIANT 477
FT /note="Missing (in CLS)"
FT /evidence="ECO:0000269|PubMed:15214012"
FT /id="VAR_065898"
FT VARIANT 483
FT /note="Y -> C (in a gastric adenocarcinoma sample; somatic
FT mutation; dbSNP:rs1271090915)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040629"
FT VARIANT 608
FT /note="L -> F (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040630"
FT VARIANT 723
FT /note="R -> C (in dbSNP:rs35026425)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040631"
FT VARIANT 729
FT /note="R -> Q (in CLS; dbSNP:rs28935171)"
FT /evidence="ECO:0000269|PubMed:10094187"
FT /id="VAR_006197"
FT CONFLICT 89
FT /note="S -> L (in Ref. 5; AAH96303)"
FT /evidence="ECO:0000305"
FT CONFLICT 410
FT /note="Missing (in Ref. 3; BAD92170)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="V -> L (in Ref. 6; AAC82495)"
FT /evidence="ECO:0000305"
FT CONFLICT 480
FT /note="K -> N (in Ref. 6; AAC82495)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="Missing (in Ref. 6; AAC82495)"
FT /evidence="ECO:0000305"
FT HELIX 50..54
FT /evidence="ECO:0007829|PDB:5D9L"
FT HELIX 65..67
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 68..76
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 78..87
FT /evidence="ECO:0007829|PDB:4NW6"
FT TURN 91..94
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:4NW6"
FT TURN 105..107
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 109..124
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 142..148
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:5D9K"
FT HELIX 155..162
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 167..186
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:5D9L"
FT HELIX 196..198
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:4NUS"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:4NW6"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:5D9L"
FT HELIX 217..223
FT /evidence="ECO:0007829|PDB:4NUS"
FT TURN 224..226
FT /evidence="ECO:0007829|PDB:4NUS"
FT HELIX 232..234
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 249..263
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 273..282
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 293..302
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4NW6"
FT TURN 315..318
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 319..322
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 332..336
FT /evidence="ECO:0007829|PDB:4NW6"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:5D9L"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:4JG7"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:4D9U"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 422..430
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 432..441
FT /evidence="ECO:0007829|PDB:4D9T"
FT TURN 442..445
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 446..454
FT /evidence="ECO:0007829|PDB:4D9T"
FT TURN 455..457
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 461..470
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 479..484
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 486..494
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 501..506
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 513..532
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 542..544
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 545..551
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 554..556
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 557..559
FT /evidence="ECO:0007829|PDB:4D9T"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:4JG8"
FT HELIX 587..613
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 626..635
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 643..645
FT /evidence="ECO:0007829|PDB:4D9U"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:4JG6"
FT HELIX 650..659
FT /evidence="ECO:0007829|PDB:4D9T"
FT TURN 664..666
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 670..673
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 677..680
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 682..684
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 696..710
FT /evidence="ECO:0007829|PDB:4D9T"
FT HELIX 711..713
FT /evidence="ECO:0007829|PDB:4JG8"
SQ SEQUENCE 740 AA; 83736 MW; 486AE8357CEAB6C8 CRC64;
MPLAQLADPW QKMAVESPSD SAENGQQIMD EPMGEEEINP QTEEVSIKEI AITHHVKEGH
EKADPSQFEL LKVLGQGSFG KVFLVKKISG SDARQLYAMK VLKKATLKVR DRVRTKMERD
ILVEVNHPFI VKLHYAFQTE GKLYLILDFL RGGDLFTRLS KEVMFTEEDV KFYLAELALA
LDHLHSLGII YRDLKPENIL LDEEGHIKLT DFGLSKESID HEKKAYSFCG TVEYMAPEVV
NRRGHTQSAD WWSFGVLMFE MLTGTLPFQG KDRKETMTMI LKAKLGMPQF LSPEAQSLLR
MLFKRNPANR LGAGPDGVEE IKRHSFFSTI DWNKLYRREI HPPFKPATGR PEDTFYFDPE
FTAKTPKDSP GIPPSANAHQ LFRGFSFVAI TSDDESQAMQ TVGVHSIVQQ LHRNSIQFTD
GYEVKEDIGV GSYSVCKRCI HKATNMEFAV KIIDKSKRDP TEEIEILLRY GQHPNIITLK
DVYDDGKYVY VVTELMKGGE LLDKILRQKF FSEREASAVL FTITKTVEYL HAQGVVHRDL
KPSNILYVDE SGNPESIRIC DFGFAKQLRA ENGLLMTPCY TANFVAPEVL KRQGYDAACD
IWSLGVLLYT MLTGYTPFAN GPDDTPEEIL ARIGSGKFSL SGGYWNSVSD TAKDLVSKML
HVDPHQRLTA ALVLRHPWIV HWDQLPQYQL NRQDAPHLVK GAMAATYSAL NRNQSPVLEP
VGRSTLAQRR GIKKITSTAL
