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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; P23443; HS. 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 FT E-434; E-441; E-444 and E-447. Mimics phosphorylation. No FT effect on interaction with PDPK1 and phosphorylation of FT T-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 //