ID KS6B1_HUMAN Reviewed; 525 AA.
AC P23443; B2R779; B4DLT4; B4DTG1; E7ESB8; F6UYM1; Q7Z721;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 2.
DT 27-MAR-2024, entry version 229.
DE RecName: Full=Ribosomal protein S6 kinase beta-1;
DE Short=S6K-beta-1;
DE Short=S6K1 {ECO:0000303|PubMed:22017876};
DE EC=2.7.11.1 {ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:28178239};
DE AltName: Full=70 kDa ribosomal protein S6 kinase 1;
DE Short=P70S6K1;
DE Short=p70-S6K 1;
DE AltName: Full=Ribosomal protein S6 kinase I;
DE AltName: Full=Serine/threonine-protein kinase 14A;
DE AltName: Full=p70 ribosomal S6 kinase alpha;
DE Short=p70 S6 kinase alpha;
DE Short=p70 S6K-alpha;
DE Short=p70 S6KA;
GN Name=RPS6KB1; Synonyms=STK14A;
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] (ISOFORMS ALPHA I AND ALPHA II), AND ALTERNATIVE
RP INITIATION.
RX PubMed=1922062; DOI=10.1128/mcb.11.11.5541-5550.1991;
RA Grove J., Bonerjee P., Balasubramanyam A., Coffer P., Price D.J.,
RA Avruch J., Woodgett J.R.;
RT "Cloning and expression of two human p70 S6 kinase polypeptides differing
RT only at their amino termini.";
RL Mol. Cell. Biol. 11:5541-5550(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA I; 2 AND 4).
RC TISSUE=Placenta, and Trachea;
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 GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Eye;
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 TISSUE SPECIFICITY.
RX PubMed=9804755; DOI=10.1074/jbc.273.46.30061;
RA Gout I., Minami T., Hara K., Tsujishita Y., Filonenko V., Waterfield M.D.,
RA Yonezawa K.;
RT "Molecular cloning and characterization of a novel p70 S6 kinase, p70 S6
RT kinase beta containing a proline-rich region.";
RL J. Biol. Chem. 273:30061-30064(1998).
RN [7]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT THR-252, AND MUTAGENESIS OF
RP THR-412; SER-434; SER-441; THR-444 AND SER-447.
RX PubMed=9445476; DOI=10.1126/science.279.5351.707;
RA Pullen N., Dennis P.B., Andjelkovic M., Dufner A., Kozma S.C.,
RA Hemmings B.A., Thomas G.;
RT "Phosphorylation and activation of p70s6k by PDK1.";
RL Science 279:707-710(1998).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF EEF2K, AND FUNCTION IN TRANSLATION
RP REGULATION.
RX PubMed=11500364; DOI=10.1093/emboj/20.16.4370;
RA Wang X., Li W., Williams M., Terada N., Alessi D.R., Proud C.G.;
RT "Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase.";
RL EMBO J. 20:4370-4379(2001).
RN [9]
RP INTERACTION WITH RPTOR.
RX PubMed=12150926; DOI=10.1016/s0092-8674(02)00833-4;
RA Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S.,
RA Tokunaga C., Avruch J., Yonezawa K.;
RT "Raptor, a binding partner of target of rapamycin (TOR), mediates TOR
RT action.";
RL Cell 110:177-189(2002).
RN [10]
RP FUNCTION, AND INTERACTION WITH TRAF4.
RX PubMed=12801526; DOI=10.1016/s0145-2126(02)00325-9;
RA Fleckenstein D.S., Dirks W.G., Drexler H.G., Quentmeier H.;
RT "Tumor necrosis factor receptor-associated factor (TRAF) 4 is a new binding
RT partner for the p70S6 serine/threonine kinase.";
RL Leuk. Res. 27:687-694(2003).
RN [11]
RP FUNCTION, AND INTERACTION WITH POLDIP3.
RX PubMed=15341740; DOI=10.1016/j.cub.2004.08.061;
RA Richardson C.J., Broenstrup M., Fingar D.C., Julich K., Ballif B.A.,
RA Gygi S., Blenis J.;
RT "SKAR is a specific target of S6 kinase 1 in cell growth control.";
RL Curr. Biol. 14:1540-1549(2004).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF EIF4B.
RX PubMed=15071500; DOI=10.1038/sj.emboj.7600193;
RA Raught B., Peiretti F., Gingras A.C., Livingstone M., Shahbazian D.,
RA Mayeur G.L., Polakiewicz R.D., Sonenberg N., Hershey J.W.;
RT "Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is
RT modulated by S6 kinases.";
RL EMBO J. 23:1761-1769(2004).
RN [13]
RP FUNCTION IN CELL CYCLE PROGRESSION.
RX PubMed=14673156; DOI=10.1128/mcb.24.1.200-216.2004;
RA Fingar D.C., Richardson C.J., Tee A.R., Cheatham L., Tsou C., Blenis J.;
RT "mTOR controls cell cycle progression through its cell growth effectors
RT S6K1 and 4E-BP1/eukaryotic translation initiation factor 4E.";
RL Mol. Cell. Biol. 24:200-216(2004).
RN [14]
RP FUNCTION IN TRANSLATION INITIATION, INTERACTION WITH EIF3B AND EIF3C, AND
RP MUTAGENESIS OF THR-412.
RX PubMed=16286006; DOI=10.1016/j.cell.2005.10.024;
RA Holz M.K., Ballif B.A., Gygi S.P., Blenis J.;
RT "mTOR and S6K1 mediate assembly of the translation preinitiation complex
RT through dynamic protein interchange and ordered phosphorylation events.";
RL Cell 123:569-580(2005).
RN [15]
RP FUNCTION IN PHOSPHORYLATION OF GSK3B.
RX PubMed=17052453; DOI=10.1016/j.molcel.2006.09.019;
RA Zhang H.H., Lipovsky A.I., Dibble C.C., Sahin M., Manning B.D.;
RT "S6K1 regulates GSK3 under conditions of mTOR-dependent feedback inhibition
RT of Akt.";
RL Mol. Cell 24:185-197(2006).
RN [16]
RP FUNCTION.
RX PubMed=17053147; DOI=10.1126/science.1130276;
RA Dorrello N.V., Peschiaroli A., Guardavaccaro D., Colburn N.H.,
RA Sherman N.E., Pagano M.;
RT "S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein
RT translation and cell growth.";
RL Science 314:467-471(2006).
RN [17]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF LYS-167 AND SER-394.
RX PubMed=17446865; DOI=10.1038/sj.emboj.7601682;
RA Hauge C., Antal T.L., Hirschberg D., Doehn U., Thorup K., Idrissova L.,
RA Hansen K., Jensen O.N., Jorgensen T.J., Biondi R.M., Frodin M.;
RT "Mechanism for activation of the growth factor-activated AGC kinases by
RT turn motif phosphorylation.";
RL EMBO J. 26:2251-2261(2007).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF URI1, CATALYTIC ACTIVITY, DEPHOSPHORYLATION
RP AT THR-412 BY PPP1CC, AND SUBCELLULAR LOCATION.
RX PubMed=17936702; DOI=10.1016/j.molcel.2007.08.010;
RA Djouder N., Metzler S.C., Schmidt A., Wirbelauer C., Gstaiger M.,
RA Aebersold R., Hess D., Krek W.;
RT "S6K1-mediated disassembly of mitochondrial URI/PP1gamma complexes
RT activates a negative feedback program that counters S6K1 survival
RT signaling.";
RL Mol. Cell 28:28-40(2007).
RN [19]
RP PHOSPHORYLATION AT THR-412.
RX PubMed=18925875; DOI=10.1042/bj20081668;
RA Garcia-Martinez J.M., Alessi D.R.;
RT "mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and
RT activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1).";
RL Biochem. J. 416:375-385(2008).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF IRS1, CATALYTIC ACTIVITY, FUNCTION IN
RP GLUCOSE HOMEOSTASIS, AND INTERACTION WITH IRS1.
RX PubMed=18952604; DOI=10.1074/jbc.m806480200;
RA Zhang J., Gao Z., Yin J., Quon M.J., Ye J.;
RT "S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance
RT in response to TNF-(alpha) signaling through IKK2.";
RL J. Biol. Chem. 283:35375-35382(2008).
RN [21]
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 [22]
RP FUNCTION, CATALYTIC ACTIVITY, ALTERNATIVE SPLICING, PHOSPHORYLATION AT
RP SER-394; THR-412; THR-444 AND SER-447, AND SUBCELLULAR LOCATION.
RX PubMed=19085255; DOI=10.1080/08977190802556986;
RA Kim D., Akcakanat A., Singh G., Sharma C., Meric-Bernstam F.;
RT "Regulation and localization of ribosomal protein S6 kinase 1 isoforms.";
RL Growth Factors 27:12-21(2009).
RN [23]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF THR-412.
RX PubMed=19570988; DOI=10.1074/jbc.m109.032177;
RA Keshwani M.M., Gao X., Harris T.K.;
RT "Mechanism of PDK1-catalyzed Thr-229 phosphorylation of the S6K1 protein
RT kinase.";
RL J. Biol. Chem. 284:22611-22624(2009).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF RICTOR.
RX PubMed=19720745; DOI=10.1128/mcb.00735-09;
RA Dibble C.C., Asara J.M., Manning B.D.;
RT "Characterization of Rictor phosphorylation sites reveals direct regulation
RT of mTOR complex 2 by S6K1.";
RL Mol. Cell. Biol. 29:5657-5670(2009).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-447, 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 [26]
RP FUNCTION IN PHOSPHORYLATION OF RICTOR.
RX PubMed=19995915; DOI=10.1128/mcb.00601-09;
RA Julien L.A., Carriere A., Moreau J., Roux P.P.;
RT "mTORC1-activated S6K1 phosphorylates Rictor on threonine 1135 and
RT regulates mTORC2 signaling.";
RL Mol. Cell. Biol. 30:908-921(2010).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF RICTOR.
RX PubMed=19935711; DOI=10.1038/onc.2009.401;
RA Treins C., Warne P.H., Magnuson M.A., Pende M., Downward J.;
RT "Rictor is a novel target of p70 S6 kinase-1.";
RL Oncogene 29:1003-1016(2010).
RN [28]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
RX PubMed=18092230; DOI=10.1080/08977190701779101;
RA Jastrzebski K., Hannan K.M., Tchoubrieva E.B., Hannan R.D., Pearson R.B.;
RT "Coordinate regulation of ribosome biogenesis and function by the ribosomal
RT protein S6 kinase, a key mediator of mTOR function.";
RL Growth Factors 25:209-226(2007).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441; THR-444; SER-447 AND
RP SER-452, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [30]
RP REVIEW ON FUNCTION, AND REVIEW ON ACTIVITY REGULATION.
RX PubMed=20932932; DOI=10.1016/j.biocel.2010.09.018;
RA Fenton T.R., Gout I.T.;
RT "Functions and regulation of the 70kDa ribosomal S6 kinases.";
RL Int. J. Biochem. Cell Biol. 43:47-59(2011).
RN [31]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=22017876; DOI=10.1016/j.molcel.2011.08.029;
RA Zhao Y., Xiong X., Sun Y.;
RT "DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(betaTrCP)
RT E3 ubiquitin ligase and regulates survival and autophagy.";
RL Mol. Cell 44:304-316(2011).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-444 AND SER-447, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [33]
RP FUNCTION, PHOSPHORYLATION OF CAD, AND PHOSPHORYLATION BY MTOR.
RX PubMed=23429703; DOI=10.1126/science.1228792;
RA Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.;
RT "Stimulation of de novo pyrimidine synthesis by growth signaling through
RT mTOR and S6K1.";
RL Science 339:1323-1328(2013).
RN [34]
RP INTERACTION WITH IER5.
RX PubMed=26496226; DOI=10.1016/j.febslet.2015.10.013;
RA Kawabata S., Ishita Y., Ishikawa Y., Sakurai H.;
RT "Immediate-early response 5 (IER5) interacts with protein phosphatase 2A
RT and regulates the phosphorylation of ribosomal protein S6 kinase and heat
RT shock factor 1.";
RL FEBS Lett. 589:3679-3685(2015).
RN [35]
RP FUNCTION IN PHOSPHORYLATION OF EPRS, CATALYTIC ACTIVITY, AND ACTIVITY
RP REGULATION.
RX PubMed=28178239; DOI=10.1038/nature21380;
RA Arif A., Terenzi F., Potdar A.A., Jia J., Sacks J., China A., Halawani D.,
RA Vasu K., Li X., Brown J.M., Chen J., Kozma S.C., Thomas G., Fox P.L.;
RT "EPRS is a critical mTORC1-S6K1 effector that influences adiposity in
RT mice.";
RL Nature 542:357-361(2017).
RN [36]
RP PHOSPHORYLATION AT THR-412.
RX PubMed=29750193; DOI=10.1126/sciadv.aao5838;
RA Nguyen J.T., Ray C., Fox A.L., Mendonca D.B., Kim J.K., Krebsbach P.H.;
RT "Mammalian EAK-7 activates alternative mTOR signaling to regulate cell
RT proliferation and migration.";
RL Sci. Adv. 4:EAAO5838-EAAO5838(2018).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 75-399, AND PHOSPHORYLATION AT
RP THR-252.
RX PubMed=19864428; DOI=10.1074/jbc.m109.040667;
RA Sunami T., Byrne N., Diehl R.E., Funabashi K., Hall D.L., Ikuta M.,
RA Patel S.B., Shipman J.M., Smith R.F., Takahashi I., Zugay-Murphy J.,
RA Iwasawa Y., Lumb K.J., Munshi S.K., Sharma S.;
RT "Structural basis of human p70 ribosomal S6 kinase-1 regulation by
RT activation loop phosphorylation.";
RL J. Biol. Chem. 285:4587-4594(2010).
RN [38] {ECO:0007744|PDB:5WBH, ECO:0007744|PDB:5WBK}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 412-437 IN COMPLEX WITH MTOR, AND
RP PHOSPHORYLATION AT THR-412.
RX PubMed=29236692; DOI=10.1038/nature25023;
RA Yang H., Jiang X., Li B., Yang H.J., Miller M., Yang A., Dhar A.,
RA Pavletich N.P.;
RT "Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.";
RL Nature 552:368-373(2017).
RN [39]
RP VARIANT [LARGE SCALE ANALYSIS] GLU-289.
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 [40]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-225; CYS-272; CYS-276 AND ALA-398.
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 mTOR
CC signaling in response to growth factors and nutrients to promote cell
CC proliferation, cell growth and cell cycle progression (PubMed:11500364,
CC PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740,
CC PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702,
CC PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711,
CC PubMed:19995915, PubMed:23429703, PubMed:28178239, PubMed:22017876).
CC Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and
CC EEF2K, and contributes to cell survival by repressing the pro-apoptotic
CC function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156,
CC PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453,
CC PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255,
CC PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703,
CC PubMed:28178239, PubMed:22017876). Under conditions of nutrient
CC depletion, the inactive form associates with the EIF3 translation
CC initiation complex (PubMed:16286006). Upon mitogenic stimulation,
CC phosphorylation by the mechanistic target of rapamycin complex 1
CC (mTORC1) leads to dissociation from the EIF3 complex and activation
CC (PubMed:16286006). The active form then phosphorylates and activates
CC several substrates in the pre-initiation complex, including the EIF2B
CC complex and the cap-binding complex component EIF4B (PubMed:16286006).
CC Also controls translation initiation by phosphorylating a negative
CC regulator of EIF4A, PDCD4, targeting it for ubiquitination and
CC subsequent proteolysis (PubMed:17053147). Promotes initiation of the
CC pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR
CC (PubMed:15341740). In response to IGF1, activates translation
CC elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its
CC inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a
CC role in feedback regulation of mTORC2 by mTORC1 by phosphorylating
CC RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling
CC (PubMed:19720745, PubMed:19935711, PubMed:19995915). Also involved in
CC feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR
CC (PubMed:22017876). Mediates cell survival by phosphorylating the pro-
CC apoptotic protein BAD and suppressing its pro-apoptotic function (By
CC similarity). Phosphorylates mitochondrial URI1 leading to dissociation
CC of a URI1-PPP1CC complex (PubMed:17936702). The free mitochondrial
CC PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed
CC to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic
CC function (PubMed:17936702). Mediates TNF-alpha-induced insulin
CC resistance by phosphorylating IRS1 at multiple serine residues,
CC resulting in accelerated degradation of IRS1 (PubMed:18952604). In
CC cells lacking functional TSC1-2 complex, constitutively phosphorylates
CC and inhibits GSK3B (PubMed:17052453). May be involved in cytoskeletal
CC rearrangement through binding to neurabin (By similarity).
CC Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD,
CC downstream of MTOR (PubMed:23429703). Following activation by mTORC1,
CC phosphorylates EPRS and thereby plays a key role in fatty acid uptake
CC by adipocytes and also most probably in interferon-gamma-induced
CC translation inhibition (PubMed:28178239).
CC {ECO:0000250|UniProtKB:P67999, ECO:0000250|UniProtKB:Q8BSK8,
CC ECO:0000269|PubMed:11500364, ECO:0000269|PubMed:12801526,
CC ECO:0000269|PubMed:14673156, ECO:0000269|PubMed:15071500,
CC ECO:0000269|PubMed:15341740, ECO:0000269|PubMed:16286006,
CC ECO:0000269|PubMed:17052453, ECO:0000269|PubMed:17053147,
CC ECO:0000269|PubMed:17936702, ECO:0000269|PubMed:18952604,
CC ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:19720745,
CC ECO:0000269|PubMed:19935711, ECO:0000269|PubMed:19995915,
CC ECO:0000269|PubMed:22017876, ECO:0000269|PubMed:23429703,
CC ECO:0000269|PubMed:28178239}.
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:17936702, ECO:0000269|PubMed:18952604,
CC ECO:0000269|PubMed:19085255, ECO:0000269|PubMed:28178239};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:17936702,
CC ECO:0000269|PubMed:18952604, ECO:0000269|PubMed:19085255,
CC ECO:0000269|PubMed:28178239};
CC -!- ACTIVITY REGULATION: Activation requires multiple phosphorylation
CC events on serine/threonine residues. Activation appears to be first
CC mediated by phosphorylation of multiple sites in the autoinhibitory
CC domain, which facilitates phosphorylation at Thr-412, disrupting the
CC autoinhibitory mechanism and allowing phosphorylation of Thr-252 by
CC PDPK1. The active conformation of the kinase is believed to be
CC stabilized by a mechanism involving three conserved phosphorylation
CC sites located in the kinase domain activation loop (Thr-252) and in the
CC AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker
CC region and Thr-412 within a hydrophobic motif at its end). Activated by
CC mTORC1; isoform Alpha I and isoform Alpha II are sensitive to
CC rapamycin, which inhibits activating phosphorylation at Thr-412.
CC Activated by PDPK1. {ECO:0000269|PubMed:17446865,
CC ECO:0000269|PubMed:19570988, ECO:0000269|PubMed:28178239,
CC ECO:0000269|PubMed:9445476}.
CC -!- SUBUNIT: Interacts with PPP1R9A/neurabin-1 (By similarity). Interacts
CC with RPTOR (PubMed:12150926). Interacts with IRS1 (PubMed:18952604).
CC Interacts with EIF3B and EIF3C (PubMed:16286006). Interacts with TRAF4
CC (PubMed:12801526). Interacts with POLDIP3 (PubMed:15341740). Interacts
CC (via N-terminus) with IER5 (PubMed:26496226).
CC {ECO:0000250|UniProtKB:P67999, ECO:0000269|PubMed:12150926,
CC ECO:0000269|PubMed:12801526, ECO:0000269|PubMed:15341740,
CC ECO:0000269|PubMed:16286006, ECO:0000269|PubMed:18952604,
CC ECO:0000269|PubMed:26496226}.
CC -!- INTERACTION:
CC P23443; Q06481-5: APLP2; NbExp=3; IntAct=EBI-1775921, EBI-25646567;
CC P23443; P55884: EIF3B; NbExp=3; IntAct=EBI-1775921, EBI-366696;
CC P23443; P08151: GLI1; NbExp=4; IntAct=EBI-1775921, EBI-308084;
CC P23443; Q5VY09: IER5; NbExp=2; IntAct=EBI-1775921, EBI-1774000;
CC P23443; Q00005: PPP2R2B; NbExp=2; IntAct=EBI-1775921, EBI-1052159;
CC P23443; P13051-2: UNG; NbExp=3; IntAct=EBI-1775921, EBI-25834258;
CC P23443-2; P08151: GLI1; NbExp=2; IntAct=EBI-6093204, EBI-308084;
CC P23443-4; P05067: APP; NbExp=3; IntAct=EBI-25882353, EBI-77613;
CC P23443-4; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-25882353, EBI-9090282;
CC -!- SUBCELLULAR LOCATION: Synapse, synaptosome {ECO:0000250}. Mitochondrion
CC outer membrane. Mitochondrion. Note=Colocalizes with URI1 at
CC mitochondrion.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha I]: Nucleus. Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform Alpha II]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=Alpha I; Synonyms=p80-S6K 1;
CC IsoId=P23443-1; Sequence=Displayed;
CC Name=Alpha II;
CC IsoId=P23443-2; Sequence=VSP_018839;
CC Name=2;
CC IsoId=P23443-3; Sequence=VSP_054613;
CC Name=4;
CC IsoId=P23443-5; Sequence=VSP_055026;
CC Name=3;
CC IsoId=P23443-4; Sequence=VSP_054614;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9804755}.
CC -!- DOMAIN: The autoinhibitory domain is believed to block phosphorylation
CC within the AGC-kinase C-terminal domain and the activation loop.
CC -!- DOMAIN: The TOS (TOR signaling) motif is essential for activation by
CC mTORC1. {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-412 is regulated by mTORC1. The
CC phosphorylation at this site is maintained by an agonist-dependent
CC autophosphorylation mechanism (PubMed:29236692, PubMed:18925875,
CC PubMed:19085255, PubMed:22017876, PubMed:23429703). Activated by
CC phosphorylation at Thr-252 by PDPK1 (PubMed:9445476, PubMed:19864428).
CC Dephosphorylation by PPP1CC at Thr-412 in mitochondrion
CC (PubMed:17936702). {ECO:0000269|PubMed:17936702,
CC ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:19085255,
CC ECO:0000269|PubMed:19864428, ECO:0000269|PubMed:22017876,
CC ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:29236692,
CC ECO:0000269|PubMed:9445476}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. S6 kinase subfamily. {ECO:0000305}.
CC ---------------------------------------------------------------------------
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DR EMBL; M60724; AAA36410.1; -; mRNA.
DR EMBL; M60725; AAA36411.1; -; mRNA.
DR EMBL; AK297147; BAG59646.1; -; mRNA.
DR EMBL; AK300202; BAG61973.1; -; mRNA.
DR EMBL; AK312875; BAG35726.1; -; mRNA.
DR EMBL; AC004686; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471109; EAW94384.1; -; Genomic_DNA.
DR EMBL; BC053365; AAH53365.1; -; mRNA.
DR CCDS; CCDS11621.1; -. [P23443-1]
DR CCDS; CCDS62271.1; -. [P23443-4]
DR CCDS; CCDS62272.1; -. [P23443-5]
DR CCDS; CCDS62273.1; -. [P23443-3]
DR PIR; A41687; A41687.
DR RefSeq; NP_001258971.1; NM_001272042.1. [P23443-5]
DR RefSeq; NP_001258972.1; NM_001272043.1. [P23443-4]
DR RefSeq; NP_001258973.1; NM_001272044.1. [P23443-3]
DR RefSeq; NP_001258989.1; NM_001272060.1. [P23443-2]
DR RefSeq; NP_003152.1; NM_003161.3. [P23443-1]
DR PDB; 3A60; X-ray; 2.80 A; A/B=75-399.
DR PDB; 3A61; X-ray; 3.43 A; A=75-399.
DR PDB; 3A62; X-ray; 2.35 A; A=75-399.
DR PDB; 3WE4; X-ray; 2.00 A; A=78-399.
DR PDB; 3WF5; X-ray; 2.10 A; A=78-399.
DR PDB; 3WF6; X-ray; 2.03 A; A=78-399.
DR PDB; 3WF7; X-ray; 1.85 A; A=78-399.
DR PDB; 3WF8; X-ray; 1.98 A; A=78-399.
DR PDB; 3WF9; X-ray; 2.04 A; A=78-399.
DR PDB; 4L3J; X-ray; 2.10 A; A=75-375.
DR PDB; 4L3L; X-ray; 2.10 A; A=75-375.
DR PDB; 4L42; X-ray; 2.80 A; A=75-417.
DR PDB; 4L43; X-ray; 3.00 A; A=75-417.
DR PDB; 4L44; X-ray; 2.90 A; A=75-417.
DR PDB; 4L45; X-ray; 2.90 A; A=75-417.
DR PDB; 4L46; X-ray; 3.01 A; A=75-417.
DR PDB; 4RLO; X-ray; 2.53 A; A/B=85-372.
DR PDB; 4RLP; X-ray; 2.79 A; A=85-372.
DR PDB; 5WBH; X-ray; 1.75 A; W=412-437.
DR PDB; 5WBK; X-ray; 3.11 A; T=24-37.
DR PDB; 7N91; X-ray; 3.00 A; A/B=82-421.
DR PDB; 7N93; X-ray; 2.74 A; A/B=82-421.
DR PDBsum; 3A60; -.
DR PDBsum; 3A61; -.
DR PDBsum; 3A62; -.
DR PDBsum; 3WE4; -.
DR PDBsum; 3WF5; -.
DR PDBsum; 3WF6; -.
DR PDBsum; 3WF7; -.
DR PDBsum; 3WF8; -.
DR PDBsum; 3WF9; -.
DR PDBsum; 4L3J; -.
DR PDBsum; 4L3L; -.
DR PDBsum; 4L42; -.
DR PDBsum; 4L43; -.
DR PDBsum; 4L44; -.
DR PDBsum; 4L45; -.
DR PDBsum; 4L46; -.
DR PDBsum; 4RLO; -.
DR PDBsum; 4RLP; -.
DR PDBsum; 5WBH; -.
DR PDBsum; 5WBK; -.
DR PDBsum; 7N91; -.
DR PDBsum; 7N93; -.
DR AlphaFoldDB; P23443; -.
DR SMR; P23443; -.
DR BioGRID; 112112; 133.
DR DIP; DIP-29986N; -.
DR ELM; P23443; -.
DR IntAct; P23443; 36.
DR MINT; P23443; -.
DR STRING; 9606.ENSP00000225577; -.
DR BindingDB; P23443; -.
DR ChEMBL; CHEMBL4501; -.
DR DrugCentral; P23443; -.
DR GuidetoPHARMACOLOGY; 1525; -.
DR GlyGen; P23443; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P23443; -.
DR PhosphoSitePlus; P23443; -.
DR BioMuta; RPS6KB1; -.
DR DMDM; 54041234; -.
DR CPTAC; CPTAC-3183; -.
DR CPTAC; CPTAC-3184; -.
DR EPD; P23443; -.
DR jPOST; P23443; -.
DR MassIVE; P23443; -.
DR MaxQB; P23443; -.
DR PaxDb; 9606-ENSP00000225577; -.
DR PeptideAtlas; P23443; -.
DR ProteomicsDB; 28050; -.
DR ProteomicsDB; 4559; -.
DR ProteomicsDB; 54095; -. [P23443-1]
DR ProteomicsDB; 54096; -. [P23443-2]
DR ProteomicsDB; 69478; -.
DR Pumba; P23443; -.
DR Antibodypedia; 3544; 3063 antibodies from 54 providers.
DR DNASU; 6198; -.
DR Ensembl; ENST00000225577.9; ENSP00000225577.4; ENSG00000108443.14. [P23443-1]
DR Ensembl; ENST00000393021.7; ENSP00000376744.3; ENSG00000108443.14. [P23443-3]
DR Ensembl; ENST00000406116.7; ENSP00000384335.3; ENSG00000108443.14. [P23443-4]
DR Ensembl; ENST00000443572.6; ENSP00000441993.1; ENSG00000108443.14. [P23443-5]
DR GeneID; 6198; -.
DR KEGG; hsa:6198; -.
DR MANE-Select; ENST00000225577.9; ENSP00000225577.4; NM_003161.4; NP_003152.1.
DR UCSC; uc002ixy.5; human. [P23443-1]
DR AGR; HGNC:10436; -.
DR CTD; 6198; -.
DR DisGeNET; 6198; -.
DR GeneCards; RPS6KB1; -.
DR HGNC; HGNC:10436; RPS6KB1.
DR HPA; ENSG00000108443; Low tissue specificity.
DR MIM; 608938; gene.
DR neXtProt; NX_P23443; -.
DR OpenTargets; ENSG00000108443; -.
DR PharmGKB; PA34851; -.
DR VEuPathDB; HostDB:ENSG00000108443; -.
DR eggNOG; KOG0598; Eukaryota.
DR GeneTree; ENSGT00940000154203; -.
DR HOGENOM; CLU_000288_63_5_1; -.
DR InParanoid; P23443; -.
DR OMA; CWTAMPP; -.
DR OrthoDB; 5489497at2759; -.
DR PhylomeDB; P23443; -.
DR TreeFam; TF313438; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P23443; -.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR SABIO-RK; P23443; -.
DR SignaLink; P23443; -.
DR SIGNOR; P23443; -.
DR BioGRID-ORCS; 6198; 48 hits in 1195 CRISPR screens.
DR ChiTaRS; RPS6KB1; human.
DR EvolutionaryTrace; P23443; -.
DR GeneWiki; P70-S6_Kinase_1; -.
DR GenomeRNAi; 6198; -.
DR Pharos; P23443; Tchem.
DR PRO; PR:P23443; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P23443; Protein.
DR Bgee; ENSG00000108443; Expressed in endothelial cell and 191 other cell types or tissues.
DR ExpressionAtlas; P23443; baseline and differential.
DR Genevisible; P23443; HS.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0098794; C:postsynapse; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0030165; F:PDZ domain binding; IEA:Ensembl.
DR GO; GO:0042277; F:peptide binding; IEA:Ensembl.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProt.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0004711; F:ribosomal protein S6 kinase activity; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl.
DR GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR GO; GO:0031670; P:cellular response to nutrient; IDA:UniProt.
DR GO; GO:0071346; P:cellular response to type II interferon; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0044539; P:long-chain fatty acid import into cell; ISS:UniProtKB.
DR GO; GO:0007616; P:long-term memory; IEA:Ensembl.
DR GO; GO:0050804; P:modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:UniProtKB.
DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0048633; P:positive regulation of skeletal muscle tissue growth; IEA:Ensembl.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IEA:Ensembl.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IDA:UniProt.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0045948; P:positive regulation of translational initiation; IDA:UniProt.
DR GO; GO:0046324; P:regulation of glucose import; IEA:Ensembl.
DR GO; GO:0014878; P:response to electrical stimulus involved in regulation of muscle adaptation; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0033762; P:response to glucagon; IEA:Ensembl.
DR GO; GO:0009749; P:response to glucose; IEA:Ensembl.
DR GO; GO:0043201; P:response to leucine; IEA:Ensembl.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0014732; P:skeletal muscle atrophy; IEA:Ensembl.
DR GO; GO:0003009; P:skeletal muscle contraction; IEA:Ensembl.
DR GO; GO:0031929; P:TOR signaling; IDA:UniProtKB.
DR CDD; cd05584; STKc_p70S6K; 1.
DR DisProt; DP01554; -.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; IPR016238; Ribosomal_S6_kinase.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1.
DR PANTHER; PTHR24351:SF48; RIBOSOMAL PROTEIN S6 KINASE BETA-1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000605; Ribsml_S6_kin_1; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation; Alternative splicing;
KW Apoptosis; ATP-binding; Cell cycle; Cytoplasm; Kinase; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Synaptosome; Transferase; Translation regulation.
FT CHAIN 1..525
FT /note="Ribosomal protein S6 kinase beta-1"
FT /id="PRO_0000024342"
FT DOMAIN 91..352
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 353..423
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 380..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 424..525
FT /note="Autoinhibitory domain"
FT MOTIF 28..32
FT /note="TOS motif"
FT COMPBIAS 8..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..48
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 218
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 97..105
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 123
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 252
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:19864428,
FT ECO:0000269|PubMed:9445476"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19085255"
FT MOD_RES 412
FT /note="Phosphothreonine; by MTOR, NEK6 and NEK7"
FT /evidence="ECO:0000269|PubMed:29236692,
FT ECO:0000269|PubMed:29750193"
FT MOD_RES 434
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P67999"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 444
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19085255,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19085255,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 516
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P67999"
FT VAR_SEQ 1..53
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054613"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform Alpha II)"
FT /evidence="ECO:0000303|PubMed:1922062"
FT /id="VSP_018839"
FT VAR_SEQ 104..126
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055026"
FT VAR_SEQ 448..525
FT /note="PVKFSPGDFWGRGASASTANPQTPVEYPMETSGIEQMDVTMSGEASAPLPIR
FT QPNSGPYKKQAFPMISKRPEHLRMNL -> TAMC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054614"
FT VARIANT 225
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040639"
FT VARIANT 272
FT /note="R -> C (in dbSNP:rs766645749)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040640"
FT VARIANT 276
FT /note="W -> C"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040641"
FT VARIANT 289
FT /note="G -> E (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035628"
FT VARIANT 398
FT /note="S -> A"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040642"
FT MUTAGEN 167
FT /note="K->N: Greatly reduces activity. Greatly reduces
FT phosphorylation at T-412 and moderately reduces
FT phosphorylation at T-252."
FT /evidence="ECO:0000269|PubMed:17446865"
FT MUTAGEN 394
FT /note="S->A: Loss of activity. Loss of phosphorylation at
FT T-412."
FT /evidence="ECO:0000269|PubMed:17446865"
FT MUTAGEN 412
FT /note="T->E: Mimics phosphorylation. Facilitates
FT phosphorylation of T-252 by PDPK1; when associated with E-
FT 434; E-441; E-444 and E-447. Mimics phosphorylation. No
FT effect on interaction with PDPK1 and phosphorylation of T-
FT 252. Impairs association with the eIF3 complex."
FT /evidence="ECO:0000269|PubMed:16286006,
FT ECO:0000269|PubMed:19570988, ECO:0000269|PubMed:9445476"
FT MUTAGEN 434
FT /note="S->E: Facilitates phosphorylation of T-252 by PDPK1;
FT when associated with E-412; E-441; E-444 and E-447."
FT /evidence="ECO:0000269|PubMed:9445476"
FT MUTAGEN 441
FT /note="S->E: Facilitates phosphorylation of T-252 by PDPK1;
FT when associated with E-412; E-434; E-444 and E-447."
FT /evidence="ECO:0000269|PubMed:9445476"
FT MUTAGEN 444
FT /note="T->E: Facilitates phosphorylation of T-252 by PDPK1;
FT when associated with E-412; E-434; E-441 and E-447."
FT /evidence="ECO:0000269|PubMed:9445476"
FT MUTAGEN 447
FT /note="S->E: Facilitates phosphorylation of T-252 by PDPK1;
FT when associated with E-412; E-434; E-441 and E-444."
FT /evidence="ECO:0000269|PubMed:9445476"
FT CONFLICT 222
FT /note="E -> V (in Ref. 2; BAG61973)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="F -> L (in Ref. 2; BAG35726)"
FT /evidence="ECO:0000305"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 91..99
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 101..110
FT /evidence="ECO:0007829|PDB:3WF7"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 119..126
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 127..132
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 137..149
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 158..164
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 167..173
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 180..187
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 192..212
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 221..223
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 246..249
FT /evidence="ECO:0007829|PDB:3WF8"
FT STRAND 252..255
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 262..265
FT /evidence="ECO:0007829|PDB:3WF7"
FT TURN 266..269
FT /evidence="ECO:0007829|PDB:4RLO"
FT HELIX 273..288
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 298..307
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:3A61"
FT HELIX 318..327
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:3WF7"
FT TURN 340..342
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 343..347
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 350..352
FT /evidence="ECO:0007829|PDB:3WF7"
FT HELIX 357..361
FT /evidence="ECO:0007829|PDB:3WF7"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:3WF7"
FT STRAND 374..377
FT /evidence="ECO:0007829|PDB:4L44"
FT TURN 380..382
FT /evidence="ECO:0007829|PDB:4L45"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:7N93"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:4L42"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:4L42"
FT HELIX 418..421
FT /evidence="ECO:0007829|PDB:5WBH"
FT HELIX 423..426
FT /evidence="ECO:0007829|PDB:5WBH"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:5WBH"
SQ SEQUENCE 525 AA; 59140 MW; 2C3BA13CCDAF4AB3 CRC64;
MRRRRRRDGF YPAPDFRDRE AEDMAGVFDI DLDQPEDAGS EDELEEGGQL NESMDHGGVG
PYELGMEHCE KFEISETSVN RGPEKIRPEC FELLRVLGKG GYGKVFQVRK VTGANTGKIF
AMKVLKKAMI VRNAKDTAHT KAERNILEEV KHPFIVDLIY AFQTGGKLYL ILEYLSGGEL
FMQLEREGIF MEDTACFYLA EISMALGHLH QKGIIYRDLK PENIMLNHQG HVKLTDFGLC
KESIHDGTVT HTFCGTIEYM APEILMRSGH NRAVDWWSLG ALMYDMLTGA PPFTGENRKK
TIDKILKCKL NLPPYLTQEA RDLLKKLLKR NAASRLGAGP GDAGEVQAHP FFRHINWEEL
LARKVEPPFK PLLQSEEDVS QFDSKFTRQT PVDSPDDSTL SESANQVFLG FTYVAPSVLE
SVKEKFSFEP KIRSPRRFIG SPRTPVSPVK FSPGDFWGRG ASASTANPQT PVEYPMETSG
IEQMDVTMSG EASAPLPIRQ PNSGPYKKQA FPMISKRPEH LRMNL
//
