MTOR_HUMAN
ID MTOR_HUMAN Reviewed; 2549 AA.
AC P42345; Q4LE76; Q5TER1; Q6LE87; Q96QG3; Q9Y4I3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Serine/threonine-protein kinase mTOR {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015, ECO:0000269|PubMed:22692423};
DE AltName: Full=FK506-binding protein 12-rapamycin complex-associated protein 1;
DE AltName: Full=FKBP12-rapamycin complex-associated protein;
DE AltName: Full=Mammalian target of rapamycin;
DE Short=mTOR;
DE AltName: Full=Mechanistic target of rapamycin;
DE AltName: Full=Rapamycin and FKBP12 target 1;
DE AltName: Full=Rapamycin target protein 1;
GN Name=MTOR {ECO:0000312|HGNC:HGNC:3942};
GN Synonyms=FRAP, FRAP1, FRAP2, RAFT1, RAPT1;
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=Brain;
RX PubMed=8008069; DOI=10.1038/369756a0;
RA Brown E.J., Albers M.W., Shin T.B., Ichikawa K., Keith C.T., Lane W.S.,
RA Schreiber S.L.;
RT "A mammalian protein targeted by G1-arresting rapamycin-receptor complex.";
RL Nature 369:756-758(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9653645; DOI=10.1006/geno.1997.5186;
RA Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.;
RT "Molecular cloning and expression analysis of five novel genes in
RT chromosome 1p36.";
RL Genomics 50:187-198(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R.,
RA Okazaki N., Koga H., Nagase T., Ohara O.;
RT "Preparation of a set of expression-ready clones of mammalian long cDNAs
RT encoding large proteins by the ORF trap cloning method.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1362-2549.
RX PubMed=11426320; DOI=10.1038/sj.gene.6363745;
RA Stover C., Endo Y., Takahashi M., Lynch N., Constantinescu C.,
RA Vorup-Jensen T., Thiel S., Friedl H., Hankeln T., Hall R., Gregory S.,
RA Fujita T., Schwaeble W.;
RT "The human gene for mannan-binding lectin-associated serine protease-2
RT (MASP-2), the effector component of the lectin route of complement
RT activation, is part of a tightly linked gene cluster on chromosome 1p36.2-
RT 3.";
RL Genes Immun. 2:119-127(2001).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2146, AND TISSUE SPECIFICITY.
RC TISSUE=B-cell;
RX PubMed=7809080; DOI=10.1073/pnas.91.26.12574;
RA Chiu M.I., Katz H., Berlin V.;
RT "RAPT1, a mammalian homolog of yeast Tor, interacts with the
RT FKBP12/rapamycin complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:12574-12578(1994).
RN [8]
RP SUBCELLULAR LOCATION, AND AUTOPHOSPHORYLATION.
RX PubMed=9434772; DOI=10.1006/bbrc.1997.7878;
RA Withers D.J., Ouwens D.M., Nave B.T., van der Zon G.C.M., Alarcon C.M.,
RA Cardenas M.E., Heitman J., Maassen J.A., Shepherd P.R.;
RT "Expression, enzyme activity, and subcellular localization of mammalian
RT target of rapamycin in insulin-responsive cells.";
RL Biochem. Biophys. Res. Commun. 241:704-709(1997).
RN [9]
RP INTERACTION WITH UBQLN1.
RX PubMed=11853878; DOI=10.1016/s0167-4889(01)00164-1;
RA Wu S., Mikhailov A., Kallo-Hosein H., Hara K., Yonezawa K., Avruch J.;
RT "Characterization of ubiquilin 1, an mTOR-interacting protein.";
RL Biochim. Biophys. Acta 1542:41-56(2002).
RN [10]
RP FUNCTION IN NUTRIENT-DEPENDENT CELL GROWTH, CATALYTIC ACTIVITY, FUNCTION IN
RP PHOSPHORYLATION OF RPS6KB1, AND INTERACTION WITH RPTOR.
RX PubMed=12150925; DOI=10.1016/s0092-8674(02)00808-5;
RA Kim D.-H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R.,
RA Erdjument-Bromage H., Tempst P., Sabatini D.M.;
RT "mTOR interacts with raptor to form a nutrient-sensitive complex that
RT signals to the growth machinery.";
RL Cell 110:163-175(2002).
RN [11]
RP FUNCTION, AND 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 [12]
RP INTERACTION WITH CLIP1, FUNCTION IN PHOSPHORYLATION OF CLIP1, AND CATALYTIC
RP ACTIVITY.
RX PubMed=12231510; DOI=10.1093/embo-reports/kvf197;
RA Choi J.H., Bertram P.G., Drenan R., Carvalho J., Zhou H.H., Zheng X.F.;
RT "The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase.";
RL EMBO Rep. 3:988-994(2002).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF RPS6KB2, AND CATALYTIC ACTIVITY.
RX PubMed=12087098; DOI=10.1074/jbc.m204080200;
RA Park I.H., Bachmann R., Shirazi H., Chen J.;
RT "Regulation of ribosomal S6 kinase 2 by mammalian target of rapamycin.";
RL J. Biol. Chem. 277:31423-31429(2002).
RN [14]
RP INTERACTION WITH MLST8 AND RPTOR, IDENTIFICATION IN THE MTORC1 COMPLEX, AND
RP TISSUE SPECIFICITY.
RX PubMed=12408816; DOI=10.1016/s1097-2765(02)00636-6;
RA Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L.,
RA Bonenfant D., Oppliger W., Jenoe P., Hall M.N.;
RT "Two TOR complexes, only one of which is rapamycin sensitive, have distinct
RT roles in cell growth control.";
RL Mol. Cell 10:457-468(2002).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=11930000; DOI=10.1073/pnas.261702698;
RA Desai B.N., Myers B.R., Schreiber S.L.;
RT "FKBP12-rapamycin-associated protein associates with mitochondria and
RT senses osmotic stress via mitochondrial dysfunction.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:4319-4324(2002).
RN [16]
RP ACTIVITY REGULATION, AND FUNCTION IN RESPONSE TO LOW CELLULAR ENERGY.
RX PubMed=14651849; DOI=10.1016/s0092-8674(03)00929-2;
RA Inoki K., Zhu T., Guan K.L.;
RT "TSC2 mediates cellular energy response to control cell growth and
RT survival.";
RL Cell 115:577-590(2003).
RN [17]
RP FUNCTION, AND INTERACTION WITH MLST8.
RX PubMed=12718876; DOI=10.1016/s1097-2765(03)00114-x;
RA Kim D.-H., Sarbassov D.D., Ali S.M., Latek R.R., Guntur K.V.P.,
RA Erdjument-Bromage H., Tempst P., Sabatini D.M.;
RT "GbetaL, a positive regulator of the rapamycin-sensitive pathway required
RT for the nutrient-sensitive interaction between raptor and mTOR.";
RL Mol. Cell 11:895-904(2003).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF PRKCA, CATALYTIC ACTIVITY, FUNCTION IN
RP REGULATION OF THE ACTIN CYTOSKELETON, IDENTIFICATION IN THE MTORC2 COMPLEX,
RP AND INTERACTION WITH RICTOR.
RX PubMed=15268862; DOI=10.1016/j.cub.2004.06.054;
RA Sarbassov D.D., Ali S.M., Kim D.-H., Guertin D.A., Latek R.R.,
RA Erdjument-Bromage H., Tempst P., Sabatini D.M.;
RT "Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive
RT and raptor-independent pathway that regulates the cytoskeleton.";
RL Curr. Biol. 14:1296-1302(2004).
RN [19]
RP ACTIVITY REGULATION, AND FUNCTION IN RESPONSE TO HYPOXIA.
RX PubMed=15545625; DOI=10.1101/gad.1256804;
RA Brugarolas J., Lei K., Hurley R.L., Manning B.D., Reiling J.H., Hafen E.,
RA Witters L.A., Ellisen L.W., Kaelin W.G. Jr.;
RT "Regulation of mTOR function in response to hypoxia by REDD1 and the
RT TSC1/TSC2 tumor suppressor complex.";
RL Genes Dev. 18:2893-2904(2004).
RN [20]
RP SUBCELLULAR LOCATION.
RX PubMed=14578359; DOI=10.1074/jbc.m305912200;
RA Drenan R.M., Liu X., Bertram P.G., Zheng X.F.S.;
RT "FKBP12-rapamycin-associated protein or mammalian target of rapamycin
RT (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi
RT apparatus.";
RL J. Biol. Chem. 279:772-778(2004).
RN [21]
RP FUNCTION IN REGULATION OF THE ACTIN CYTOSKELETON, CATALYTIC ACTIVITY,
RP FUNCTION IN PHOSPHORYLATION OF PXN, IDENTIFICATION IN THE MTORC2 COMPLEX,
RP INTERACTION WITH RICTOR, AND AUTOPHOSPHORYLATION.
RX PubMed=15467718; DOI=10.1038/ncb1183;
RA Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., Hall M.N.;
RT "Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin
RT insensitive.";
RL Nat. Cell Biol. 6:1122-1128(2004).
RN [22]
RP PHOSPHORYLATION AT THR-2446 AND SER-2448.
RX PubMed=15905173; DOI=10.1074/jbc.m504045200;
RA Holz M.K., Blenis J.;
RT "Identification of S6 kinase 1 as a novel mammalian target of rapamycin
RT (mTOR)-phosphorylating kinase.";
RL J. Biol. Chem. 280:26089-26093(2005).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF AKT1, AND CATALYTIC ACTIVITY.
RX PubMed=15718470; DOI=10.1126/science.1106148;
RA Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.;
RT "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.";
RL Science 307:1098-1101(2005).
RN [24]
RP IDENTIFICATION IN THE MTORC2 COMPLEX, AND INTERACTION WITH PRR5.
RX PubMed=17599906; DOI=10.1074/jbc.m704343200;
RA Woo S.-Y., Kim D.-H., Jun C.-B., Kim Y.-M., Haar E.V., Lee S.-I.,
RA Hegg J.W., Bandhakavi S., Griffin T.J., Kim D.-H.;
RT "PRR5, a novel component of mTOR complex 2, regulates platelet-derived
RT growth factor receptor beta expression and signaling.";
RL J. Biol. Chem. 282:25604-25612(2007).
RN [25]
RP INTERACTION WITH AKT1S1, AND ACTIVITY REGULATION.
RX PubMed=17386266; DOI=10.1016/j.molcel.2007.03.003;
RA Sancak Y., Thoreen C.C., Peterson T.R., Lindquist R.A., Kang S.A.,
RA Spooner E., Carr S.A., Sabatini D.M.;
RT "PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase.";
RL Mol. Cell 25:903-915(2007).
RN [26]
RP IDENTIFICATION IN THE MTORC1 AND MTORC2 COMPLEXES, CATALYTIC ACTIVITY, AND
RP FUNCTION IN PHOSPHORYLATION OF RPS6KB1 AND SGK1.
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 [27]
RP FUNCTION IN LIPID SYNTHESIS AND CELL GROWTH.
RX PubMed=18762023; DOI=10.1016/j.cmet.2008.07.007;
RA Porstmann T., Santos C.R., Griffiths B., Cully M., Wu M., Leevers S.,
RA Griffiths J.R., Chung Y.L., Schulze A.;
RT "SREBP activity is regulated by mTORC1 and contributes to Akt-dependent
RT cell growth.";
RL Cell Metab. 8:224-236(2008).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567, AND IDENTIFICATION BY
RP MASS 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 [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2478 AND SER-2481, 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 [30]
RP FUNCTION, ACTIVITY REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18497260; DOI=10.1126/science.1157535;
RA Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C.,
RA Bar-Peled L., Sabatini D.M.;
RT "The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1.";
RL Science 320:1496-1501(2008).
RN [31]
RP INTERACTION WITH DEPTOR, AND ACTIVITY REGULATION.
RX PubMed=19446321; DOI=10.1016/j.cell.2009.03.046;
RA Peterson T.R., Laplante M., Thoreen C.C., Sancak Y., Kang S.A., Kuehl W.M.,
RA Gray N.S., Sabatini D.M.;
RT "DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma
RT cells and required for their survival.";
RL Cell 137:873-886(2009).
RN [32]
RP PHOSPHORYLATION AT SER-1261.
RX PubMed=19487463; DOI=10.1128/mcb.01665-08;
RA Acosta-Jaquez H.A., Keller J.A., Foster K.G., Ekim B., Soliman G.A.,
RA Feener E.P., Ballif B.A., Fingar D.C.;
RT "Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and
RT cell growth.";
RL Mol. Cell. Biol. 29:4308-4324(2009).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [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 [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1218, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [35]
RP PHOSPHORYLATION AT SER-2448.
RX PubMed=19145465; DOI=10.1007/s00726-008-0230-7;
RA Rosner M., Siegel N., Valli A., Fuchs C., Hengstschlager M.;
RT "mTOR phosphorylated at S2448 binds to raptor and rictor.";
RL Amino Acids 38:223-228(2010).
RN [36]
RP SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=20381137; DOI=10.1016/j.cell.2010.02.024;
RA Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.;
RT "Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is
RT necessary for its activation by amino acids.";
RL Cell 141:290-303(2010).
RN [37]
RP FUNCTION IN PHOSPHORYLATION OF DAP, FUNCTION IN AUTOPHAGY, AND CATALYTIC
RP ACTIVITY.
RX PubMed=20537536; DOI=10.1016/j.cub.2010.04.041;
RA Koren I., Reem E., Kimchi A.;
RT "DAP1, a novel substrate of mTOR, negatively regulates autophagy.";
RL Curr. Biol. 20:1093-1098(2010).
RN [38]
RP INTERACTION WITH TTI1.
RX PubMed=20810650; DOI=10.1101/gad.1934210;
RA Hurov K.E., Cotta-Ramusino C., Elledge S.J.;
RT "A genetic screen identifies the Triple T complex required for DNA damage
RT signaling and ATM and ATR stability.";
RL Genes Dev. 24:1939-1950(2010).
RN [39]
RP INTERACTION WITH TELO2.
RX PubMed=20801936; DOI=10.1101/gad.1956410;
RA Takai H., Xie Y., de Lange T., Pavletich N.P.;
RT "Tel2 structure and function in the Hsp90-dependent maturation of mTOR and
RT ATR complexes.";
RL Genes Dev. 24:2019-2030(2010).
RN [40]
RP INTERACTION WITH TELO2 AND TTI1.
RX PubMed=20427287; DOI=10.1074/jbc.m110.121699;
RA Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K.,
RA Iemura S., Natsume T., Mizushima N.;
RT "Tti1 and Tel2 are critical factors in mammalian target of rapamycin
RT complex assembly.";
RL J. Biol. Chem. 285:20109-20116(2010).
RN [41]
RP FUNCTION IN REGULATION OF RNA POLYMERASE III TRANSCRIPTION, FUNCTION IN
RP PHOSPHORYLATION OF MAF1, AND CATALYTIC ACTIVITY.
RX PubMed=20516213; DOI=10.1128/mcb.00319-10;
RA Michels A.A., Robitaille A.M., Buczynski-Ruchonnet D., Hodroj W.,
RA Reina J.H., Hall M.N., Hernandez N.;
RT "mTORC1 directly phosphorylates and regulates human MAF1.";
RL Mol. Cell. Biol. 30:3749-3757(2010).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567 AND THR-1162, AND
RP 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 [43]
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 [44]
RP PHOSPHORYLATION AT SER-2159; THR-2164 AND SER-2481, AND MUTAGENESIS OF
RP SER-2159 AND THR-2164.
RX PubMed=21576368; DOI=10.1128/mcb.05437-11;
RA Ekim B., Magnuson B., Acosta-Jaquez H.A., Keller J.A., Feener E.P.,
RA Fingar D.C.;
RT "mTOR kinase domain phosphorylation promotes mTORC1 signaling, cell growth,
RT and cell cycle progression.";
RL Mol. Cell. Biol. 31:2787-2801(2011).
RN [45]
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 [46]
RP FUNCTION IN PHOSPHORYLATION OF GRB10, CATALYTIC ACTIVITY, AND FUNCTION IN
RP INSR-DEPENDENT SIGNALING.
RX PubMed=21659604; DOI=10.1126/science.1199498;
RA Hsu P.P., Kang S.A., Rameseder J., Zhang Y., Ottina K.A., Lim D.,
RA Peterson T.R., Choi Y., Gray N.S., Yaffe M.B., Marto J.A., Sabatini D.M.;
RT "The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated
RT inhibition of growth factor signaling.";
RL Science 332:1317-1322(2011).
RN [47]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22576015; DOI=10.4161/auto.19653;
RA Martina J.A., Chen Y., Gucek M., Puertollano R.;
RT "MTORC1 functions as a transcriptional regulator of autophagy by preventing
RT nuclear transport of TFEB.";
RL Autophagy 8:903-914(2012).
RN [48]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22343943; DOI=10.1038/emboj.2012.32;
RA Settembre C., Zoncu R., Medina D.L., Vetrini F., Erdin S., Erdin S.,
RA Huynh T., Ferron M., Karsenty G., Vellard M.C., Facchinetti V.,
RA Sabatini D.M., Ballabio A.;
RT "A lysosome-to-nucleus signalling mechanism senses and regulates the
RT lysosome via mTOR and TFEB.";
RL EMBO J. 31:1095-1108(2012).
RN [49]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22692423; DOI=10.1126/scisignal.2002790;
RA Roczniak-Ferguson A., Petit C.S., Froehlich F., Qian S., Ky J.,
RA Angarola B., Walther T.C., Ferguson S.M.;
RT "The transcription factor TFEB links mTORC1 signaling to transcriptional
RT control of lysosome homeostasis.";
RL Sci. Signal. 5:RA42-RA42(2012).
RN [50]
RP INTERACTION WITH HTR6.
RX PubMed=23027611; DOI=10.1002/emmm.201201410;
RA Meffre J., Chaumont-Dubel S., Mannoury la Cour C., Loiseau F., Watson D.J.,
RA Dekeyne A., Seveno M., Rivet J.M., Gaven F., Deleris P., Herve D.,
RA Fone K.C., Bockaert J., Millan M.J., Marin P.;
RT "5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed
RT cognition in schizophrenia.";
RL EMBO Mol. Med. 4:1043-1056(2012).
RN [51]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [52]
RP FUNCTION, AND INTERACTION WITH TPCN1 AND TPCN2.
RX PubMed=23394946; DOI=10.1016/j.cell.2013.01.023;
RA Cang C., Zhou Y., Navarro B., Seo Y.J., Aranda K., Shi L.,
RA Battaglia-Hsu S., Nissim I., Clapham D.E., Ren D.;
RT "mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to
RT metabolic state.";
RL Cell 152:778-790(2013).
RN [53]
RP INTERACTION WITH BRAT1.
RX PubMed=25657994;
RA So E.Y., Ouchi T.;
RT "The potential role of BRCA1-associated ATM activator-1 (BRAT1) in
RT regulation of mTOR.";
RL J. Cancer Biol. Res. 1:0-0(2013).
RN [54]
RP PHOSPHORYLATION AT THR-2173, AND MUTAGENESIS OF THR-2173.
RX PubMed=24247430; DOI=10.1083/jcb.201305103;
RA Halova L., Du W., Kirkham S., Smith D.L., Petersen J.;
RT "Phosphorylation of the TOR ATP binding domain by AGC kinase constitutes a
RT novel mode of TOR inhibition.";
RL J. Cell Biol. 203:595-604(2013).
RN [55]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1261, AND IDENTIFICATION BY
RP 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 [56]
RP FUNCTION IN PHOSPHORYLATION OF AMBRA1.
RX PubMed=23524951; DOI=10.1038/ncb2708;
RA Nazio F., Strappazzon F., Antonioli M., Bielli P., Cianfanelli V.,
RA Bordi M., Gretzmeier C., Dengjel J., Piacentini M., Fimia G.M., Cecconi F.;
RT "mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-
RT association and function through AMBRA1 and TRAF6.";
RL Nat. Cell Biol. 15:406-416(2013).
RN [57]
RP INTERACTION WITH NBN.
RX PubMed=23762398; DOI=10.1371/journal.pone.0065586;
RA Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C., Wu K.J.;
RT "Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific
RT domains.";
RL PLoS ONE 8:E65586-E65586(2013).
RN [58]
RP FUNCTION, PHOSPHORYLATION OF RPS6KB1, AND REGULATION OF PYRIMIDINE
RP SYNTHESIS.
RX PubMed=23429704; DOI=10.1126/science.1228771;
RA Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L.,
RA Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N.;
RT "Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine
RT synthesis.";
RL Science 339:1320-1323(2013).
RN [59]
RP FUNCTION, PHOSPHORYLATION OF RPS6KB1, AND REGULATION OF PYRIMIDINE
RP SYNTHESIS.
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 [60]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2448, AND IDENTIFICATION BY
RP 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 [61]
RP INVOLVEMENT IN SKS, VARIANT SKS LYS-1799, AND CHARACTERIZATION OF VARIANT
RP SKS LYS-1799.
RX PubMed=25851998; DOI=10.1002/ajmg.a.37070;
RA Baynam G., Overkov A., Davis M., Mina K., Schofield L., Allcock R.,
RA Laing N., Cook M., Dawkins H., Goldblatt J.;
RT "A germline MTOR mutation in Aboriginal Australian siblings with
RT intellectual disability, dysmorphism, macrocephaly, and small thoraces.";
RL Am. J. Med. Genet. A 167:1659-1667(2015).
RN [62]
RP FUNCTION, INVOLVEMENT IN FCORD2, VARIANTS FCORD2 ASP-1459; PRO-1460;
RP PHE-2215 AND TYR-2215, AND CHARACTERIZATION OF VARIANTS FCORD2 ASP-1459;
RP PRO-1460; PHE-2215 AND TYR-2215.
RX PubMed=26018084; DOI=10.1002/ana.24444;
RA Nakashima M., Saitsu H., Takei N., Tohyama J., Kato M., Kitaura H.,
RA Shiina M., Shirozu H., Masuda H., Watanabe K., Ohba C., Tsurusaki Y.,
RA Miyake N., Zheng Y., Sato T., Takebayashi H., Ogata K., Kameyama S.,
RA Kakita A., Matsumoto N.;
RT "Somatic mutations in the MTOR gene cause focal cortical dysplasia type
RT IIb.";
RL Ann. Neurol. 78:375-386(2015).
RN [63]
RP INVOLVEMENT IN SKS, VARIANT SKS LYS-1799, AND CHARACTERIZATION OF VARIANT
RP SKS LYS-1799.
RX PubMed=26542245; DOI=10.1186/s12881-015-0240-8;
RA Mroske C., Rasmussen K., Shinde D.N., Huether R., Powis Z., Lu H.M.,
RA Baxter R.M., McPherson E., Tang S.;
RT "Germline activating MTOR mutation arising through gonadal mosaicism in two
RT brothers with megalencephaly and neurodevelopmental abnormalities.";
RL BMC Med. Genet. 16:102-102(2015).
RN [64]
RP FUNCTION IN PHOSPHORYLATION OF AMBRA1.
RX PubMed=25438055; DOI=10.1038/ncb3072;
RA Cianfanelli V., Fuoco C., Lorente M., Salazar M., Quondamatteo F.,
RA Gherardini P.F., De Zio D., Nazio F., Antonioli M., D'Orazio M., Skobo T.,
RA Bordi M., Rohde M., Dalla Valle L., Helmer-Citterich M., Gretzmeier C.,
RA Dengjel J., Fimia G.M., Piacentini M., Di Bartolomeo S., Velasco G.,
RA Cecconi F.;
RT "AMBRA1 links autophagy to cell proliferation and tumorigenesis by
RT promoting c-Myc dephosphorylation and degradation.";
RL Nat. Cell Biol. 17:20-30(2015).
RN [65]
RP FUNCTION, INVOLVEMENT IN FCORD2, VARIANTS FCORD2 HIS-624; ASP-1450;
RP ARG-1483; HIS-1709; LYS-1977; CYS-2193; PHE-2215; GLN-2427 AND PRO-2427,
RP AND CHARACTERIZATION OF VARIANTS FCORD2 ARG-1483; GLN-2427 AND PRO-2427.
RX PubMed=25799227; DOI=10.1038/nm.3824;
RA Lim J.S., Kim W.I., Kang H.C., Kim S.H., Park A.H., Park E.K., Cho Y.W.,
RA Kim S., Kim H.M., Kim J.A., Kim J., Rhee H., Kang S.G., Kim H.D., Kim D.,
RA Kim D.S., Lee J.H.;
RT "Brain somatic mutations in MTOR cause focal cortical dysplasia type II
RT leading to intractable epilepsy.";
RL Nat. Med. 21:395-400(2015).
RN [66]
RP ACTIVITY REGULATION.
RX PubMed=25561175; DOI=10.1038/nature14107;
RA Rebsamen M., Pochini L., Stasyk T., de Araujo M.E., Galluccio M.,
RA Kandasamy R.K., Snijder B., Fauster A., Rudashevskaya E.L., Bruckner M.,
RA Scorzoni S., Filipek P.A., Huber K.V., Bigenzahn J.W., Heinz L.X.,
RA Kraft C., Bennett K.L., Indiveri C., Huber L.A., Superti-Furga G.;
RT "SLC38A9 is a component of the lysosomal amino acid sensing machinery that
RT controls mTORC1.";
RL Nature 519:477-481(2015).
RN [67]
RP INVOLVEMENT IN FCORD2, AND VARIANT FCORD2 GLY-1456.
RX PubMed=25878179; DOI=10.1212/wnl.0000000000001594;
RA Leventer R.J., Scerri T., Marsh A.P., Pope K., Gillies G., Maixner W.,
RA MacGregor D., Harvey A.S., Delatycki M.B., Amor D.J., Crino P., Bahlo M.,
RA Lockhart P.J.;
RT "Hemispheric cortical dysplasia secondary to a mosaic somatic mutation in
RT MTOR.";
RL Neurology 84:2029-2032(2015).
RN [68]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [69]
RP ACTIVITY REGULATION.
RX PubMed=25567906; DOI=10.1126/science.1257132;
RA Wang S., Tsun Z.Y., Wolfson R.L., Shen K., Wyant G.A., Plovanich M.E.,
RA Yuan E.D., Jones T.D., Chantranupong L., Comb W., Wang T., Bar-Peled L.,
RA Zoncu R., Straub C., Kim C., Park J., Sabatini B.L., Sabatini D.M.;
RT "Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine
RT sufficiency to mTORC1.";
RL Science 347:188-194(2015).
RN [70]
RP INTERACTION WITH WAC.
RX PubMed=26812014; DOI=10.1016/j.devcel.2015.12.019;
RA David-Morrison G., Xu Z., Rui Y.N., Charng W.L., Jaiswal M., Yamamoto S.,
RA Xiong B., Zhang K., Sandoval H., Duraine L., Zuo Z., Zhang S., Bellen H.J.;
RT "WAC regulates mTOR activity by acting as an adaptor for the TTT and
RT Pontin/Reptin complexes.";
RL Dev. Cell 36:139-151(2016).
RN [71]
RP SUBCELLULAR LOCATION.
RX PubMed=27623384; DOI=10.1016/j.devcel.2016.08.001;
RA Krishna S., Palm W., Lee Y., Yang W., Bandyopadhyay U., Xu H., Florey O.,
RA Thompson C.B., Overholtzer M.;
RT "PIKfyve Regulates Vacuole Maturation and Nutrient Recovery following
RT Engulfment.";
RL Dev. Cell 38:536-547(2016).
RN [72]
RP INVOLVEMENT IN FCORD2, VARIANTS GLU-1376 AND VAL-2501, VARIANTS FCORD2
RP SER-1459; PRO-1460; PHE-2215 AND TYR-2215, AND VARIANTS SKS ARG-1490;
RP ILE-1595; THR-1832; CYS-1888 AND ILE-2327.
RX PubMed=27830187; DOI=10.1212/nxg.0000000000000118;
RA Moeller R.S., Weckhuysen S., Chipaux M., Marsan E., Taly V., Bebin E.M.,
RA Hiatt S.M., Prokop J.W., Bowling K.M., Mei D., Conti V., de la Grange P.,
RA Ferrand-Sorbets S., Dorfmueller G., Lambrecq V., Larsen L.H., Leguern E.,
RA Guerrini R., Rubboli G., Cooper G.M., Baulac S.;
RT "Germline and somatic mutations in the MTOR gene in focal cortical
RT dysplasia and epilepsy.";
RL Neurol. Genet. 2:E118-E118(2016).
RN [73]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MEAK7.
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 [74]
RP INTERACTION WITH TM4SF5, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-2357
RP AND VAL-2364.
RX PubMed=30956113; DOI=10.1016/j.cmet.2019.03.005;
RA Jung J.W., Macalino S.J.Y., Cui M., Kim J.E., Kim H.J., Song D.G.,
RA Nam S.H., Kim S., Choi S., Lee J.W.;
RT "Transmembrane 4 L six family member 5 senses arginine for mTORC1
RT signaling.";
RL Cell Metab. 29:1306-1319(2019).
RN [75]
RP FUNCTION.
RX PubMed=30704899; DOI=10.1016/j.molcel.2018.12.017;
RA Cheng X., Ma X., Zhu Q., Song D., Ding X., Li L., Jiang X., Wang X.,
RA Tian R., Su H., Shen Z., Chen S., Liu T., Gong W., Liu W., Sun Q.;
RT "Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of
RT autophagosome maturation and lipid metabolism.";
RL Mol. Cell 73:1-15(2019).
RN [76]
RP INTERACTION WITH GPR137B.
RX PubMed=31036939; DOI=10.1038/s41556-019-0321-6;
RA Gan L., Seki A., Shen K., Iyer H., Han K., Hayer A., Wollman R., Ge X.,
RA Lin J.R., Dey G., Talbot W.S., Meyer T.;
RT "The lysosomal GPCR-like protein GPR137B regulates Rag and mTORC1
RT localization and activity.";
RL Nat. Cell Biol. 21:614-626(2019).
RN [77]
RP INTERACTION WITH RICTOR.
RX PubMed=33378666; DOI=10.1016/j.celrep.2020.108564;
RA Wrobel L., Siddiqi F.H., Hill S.M., Son S.M., Karabiyik C., Kim H.,
RA Rubinsztein D.C.;
RT "mTORC2 Assembly Is Regulated by USP9X-Mediated Deubiquitination of
RT RICTOR.";
RL Cell Rep. 33:108564-108564(2020).
RN [78]
RP INTERACTION WITH NCKAP1L.
RX PubMed=32647003; DOI=10.1126/science.aay5663;
RA Cook S.A., Comrie W.A., Poli M.C., Similuk M., Oler A.J., Faruqi A.J.,
RA Kuhns D.B., Yang S., Vargas-Hernandez A., Carisey A.F., Fournier B.,
RA Anderson D.E., Price S., Smelkinson M., Abou Chahla W., Forbes L.R.,
RA Mace E.M., Cao T.N., Coban-Akdemir Z.H., Jhangiani S.N., Muzny D.M.,
RA Gibbs R.A., Lupski J.R., Orange J.S., Cuvelier G.D.E., Al Hassani M.,
RA Al Kaabi N., Al Yafei Z., Jyonouchi S., Raje N., Caldwell J.W., Huang Y.,
RA Burkhardt J.K., Latour S., Chen B., ElGhazali G., Rao V.K., Chinn I.K.,
RA Lenardo M.J.;
RT "HEM1 deficiency disrupts mTORC2 and F-actin control in inherited
RT immunodysregulatory disease.";
RL Science 369:202-207(2020).
RN [79]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2018-2112 IN COMPLEX WITH FKBP1A
RP AND INHIBITOR RAPAMYCIN.
RX PubMed=8662507; DOI=10.1126/science.273.5272.239;
RA Choi J., Chen J., Schreiber S.L., Clardy J.;
RT "Structure of the FKBP12-rapamycin complex interacting with the binding
RT domain of human FRAP.";
RL Science 273:239-242(1996).
RN [80]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2018-2112 IN COMPLEX WITH FKBP1A
RP AND INHIBITOR RAPAMYCIN.
RX PubMed=10089303; DOI=10.1107/s0907444998014747;
RA Liang J., Choi J., Clardy J.;
RT "Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A
RT resolution.";
RL Acta Crystallogr. D 55:736-744(1999).
RN [81]
RP 3D-STRUCTURE MODELING, HEAT-REPEATS, AND TPR-REPEATS.
RX PubMed=20060908; DOI=10.1016/j.jsb.2010.01.002;
RA Knutson B.A.;
RT "Insights into the domain and repeat architecture of target of rapamycin.";
RL J. Struct. Biol. 170:354-363(2010).
RN [82]
RP STRUCTURE BY ELECTRON MICROSCOPY (26 ANGSTROMS) OF MTORC1 COMPLEX, AND
RP SUBUNIT.
RX PubMed=20542007; DOI=10.1016/j.molcel.2010.05.017;
RA Yip C.K., Murata K., Walz T., Sabatini D.M., Kang S.A.;
RT "Structure of the human mTOR complex I and its implications for rapamycin
RT inhibition.";
RL Mol. Cell 38:768-774(2010).
RN [83]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 1376-2549 IN COMPLEX WITH MLST8,
RP SUBUNIT, TPR-REPEATS, DOMAINS, AND MUTAGENESIS OF HIS-2340.
RX PubMed=23636326; DOI=10.1038/nature12122;
RA Yang H., Rudge D.G., Koos J.D., Vaidialingam B., Yang H.J., Pavletich N.P.;
RT "mTOR kinase structure, mechanism and regulation.";
RL Nature 497:217-223(2013).
RN [84]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-8; THR-135; VAL-1083; VAL-1134;
RP PHE-1178; VAL-2011; TYR-2215 AND LEU-2476.
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).
RN [85]
RP VARIANTS PHE-2220 AND ALA-2406.
RX PubMed=21248752; DOI=10.1038/nature09639;
RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H.,
RA Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J.,
RA Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M.,
RA Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L.,
RA Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J.,
RA Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A.,
RA Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K.,
RA Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.;
RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex gene
RT PBRM1 in renal carcinoma.";
RL Nature 469:539-542(2011).
CC -!- FUNCTION: Serine/threonine protein kinase which is a central regulator
CC of cellular metabolism, growth and survival in response to hormones,
CC growth factors, nutrients, energy and stress signals (PubMed:12087098,
CC PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876,
CC PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625,
CC PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875,
CC PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703,
CC PubMed:23429704, PubMed:25799227, PubMed:26018084). MTOR directly or
CC indirectly regulates the phosphorylation of at least 800 proteins.
CC Functions as part of 2 structurally and functionally distinct signaling
CC complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862,
CC PubMed:15467718, PubMed:18925875, PubMed:18497260, PubMed:20516213,
CC PubMed:21576368, PubMed:21659604, PubMed:23429704). Activated mTORC1
CC up-regulates protein synthesis by phosphorylating key regulators of
CC mRNA translation and ribosome synthesis (PubMed:12087098,
CC PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876,
CC PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625,
CC PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875,
CC PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703,
CC PubMed:23429704, PubMed:25799227, PubMed:26018084). This includes
CC phosphorylation of EIF4EBP1 and release of its inhibition toward the
CC elongation initiation factor 4E (eiF4E) (By similarity). Moreover,
CC phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein
CC synthesis by modulating the activity of their downstream targets
CC including ribosomal protein S6, eukaryotic translation initiation
CC factor EIF4B, and the inhibitor of translation initiation PDCD4
CC (PubMed:12150925, PubMed:12087098, PubMed:18925875). This also includes
CC mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3:
CC in the presence of nutrients, mediates phosphorylation of TFEB and
CC TFE3, promoting their cytosolic retention and inactivation
CC (PubMed:22576015, PubMed:22343943, PubMed:22692423). Upon starvation or
CC lysosomal stress, inhibition of mTORC1 induces dephosphorylation and
CC nuclear translocation of TFEB and TFE3, promoting their transcription
CC factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423).
CC Stimulates the pyrimidine biosynthesis pathway, both by acute
CC regulation through RPS6KB1-mediated phosphorylation of the biosynthetic
CC enzyme CAD, and delayed regulation, through transcriptional enhancement
CC of the pentose phosphate pathway which produces 5-phosphoribosyl-1-
CC pyrophosphate (PRPP), an allosteric activator of CAD at a later step in
CC synthesis, this function is dependent on the mTORC1 complex
CC (PubMed:23429704, PubMed:23429703). Regulates ribosome synthesis by
CC activating RNA polymerase III-dependent transcription through
CC phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor
CC (PubMed:20516213). In parallel to protein synthesis, also regulates
CC lipid synthesis through SREBF1/SREBP1 and LPIN1 (By similarity). To
CC maintain energy homeostasis mTORC1 may also regulate mitochondrial
CC biogenesis through regulation of PPARGC1A (By similarity). mTORC1 also
CC negatively regulates autophagy through phosphorylation of ULK1 (By
CC similarity). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-
CC 758', disrupting the interaction with AMPK and preventing activation of
CC ULK1 (By similarity). Also prevents autophagy through phosphorylation
CC of the autophagy inhibitor DAP (PubMed:20537536). Also prevents
CC autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich
CC conditions (PubMed:30704899). Prevents autophagy by mediating
CC phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate
CC ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA
CC (PubMed:23524951, PubMed:25438055). mTORC1 exerts a feedback control on
CC upstream growth factor signaling that includes phosphorylation and
CC activation of GRB10 a INSR-dependent signaling suppressor
CC (PubMed:21659604). Among other potential targets mTORC1 may
CC phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). As
CC part of the mTORC2 complex MTOR may regulate other cellular processes
CC including survival and organization of the cytoskeleton
CC (PubMed:15268862, PubMed:15467718). Plays a critical role in the
CC phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of
CC phosphoinositide 3-kinase, facilitating its activation by PDK1
CC (PubMed:15718470). mTORC2 may regulate the actin cytoskeleton, through
CC phosphorylation of PRKCA, PXN and activation of the Rho-type guanine
CC nucleotide exchange factors RHOA and RAC1A or RAC1B (PubMed:15268862).
CC mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'
CC (PubMed:18925875). Regulates osteoclastogenesis by adjusting the
CC expression of CEBPB isoforms (By similarity). Plays an important
CC regulatory role in the circadian clock function; regulates period
CC length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and
CC liver clocks (By similarity). Phosphorylates SQSTM1, promoting
CC interaction between SQSTM1 and KEAP1 and subsequent inactivation of the
CC BCR(KEAP1) complex (By similarity). {ECO:0000250|UniProtKB:P42346,
CC ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:12087098,
CC ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926,
CC ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12718876,
CC ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15268862,
CC ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:18497260,
CC ECO:0000269|PubMed:18762023, ECO:0000269|PubMed:18925875,
CC ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536,
CC ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:21659604,
CC ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015,
CC ECO:0000269|PubMed:22692423, ECO:0000269|PubMed:23429703,
CC ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:23524951,
CC ECO:0000269|PubMed:25438055, ECO:0000269|PubMed:25799227,
CC ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:30704899}.
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:12087098, ECO:0000269|PubMed:12150925,
CC ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:15268862,
CC ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15718470,
CC ECO:0000269|PubMed:18925875, ECO:0000269|PubMed:20516213,
CC ECO:0000269|PubMed:20537536, ECO:0000269|PubMed:21659604,
CC ECO:0000269|PubMed:22343943, ECO:0000269|PubMed:22576015,
CC ECO:0000269|PubMed:22692423};
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:12087098,
CC ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12231510,
CC ECO:0000269|PubMed:15268862, ECO:0000269|PubMed:15467718,
CC ECO:0000269|PubMed:15718470, ECO:0000269|PubMed:18925875,
CC ECO:0000269|PubMed:20516213, ECO:0000269|PubMed:20537536,
CC ECO:0000269|PubMed:21659604};
CC -!- ACTIVITY REGULATION: Activation of mTORC1 by growth factors such as
CC insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which
CC leads to the activation of the RHEB GTPase a potent activator of the
CC protein kinase activity of mTORC1. Insulin-stimulated and amino acid-
CC dependent phosphorylation at Ser-1261 promotes autophosphorylation and
CC the activation of mTORC1. Activation by amino acids requires
CC relocalization of the mTORC1 complex to lysosomes that is mediated by
CC the Ragulator complex, SLC38A9, and the Rag GTPases RRAGA, RRAGB, RRAGC
CC and RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175,
CC PubMed:25567906). On the other hand, low cellular energy levels can
CC inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits
CC mTORC1 through a REDD1-dependent mechanism which may also require
CC PRKAA1. The kinase activity of MTOR within the mTORC1 complex is
CC positively regulated by MLST8 and negatively regulated by DEPTOR and
CC AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. MTOR
CC is the target of the immunosuppressive and anti-cancer drug rapamycin
CC which acts in complex with FKBP1A/FKBP12, and specifically inhibits its
CC kinase activity. mTORC2 is also activated by growth factors, but seems
CC to be nutrient-insensitive. It may be regulated by RHEB but in an
CC indirect manner through the PI3K signaling pathway.
CC {ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:17386266, ECO:0000269|PubMed:18497260,
CC ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:20381137,
CC ECO:0000269|PubMed:25561175, ECO:0000269|PubMed:25567906}.
CC -!- SUBUNIT: Part of the mammalian target of rapamycin complex 1 (mTORC1)
CC which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. The mTORC1
CC complex is a 1 Md obligate dimer of two stoichiometric heterotetramers
CC with overall dimensions of 290 A x 210 A x 135 A. It has a rhomboid
CC shape and a central cavity, the dimeric interfaces are formed by
CC interlocking interactions between the two MTOR and the two RPTOR
CC subunits. The MLST8 subunit forms distal foot-like protuberances, and
CC contacts only one MTOR within the complex, while the small PRAS40
CC localizes to the midsection of the central core, in close proximity to
CC RPTOR. Part of the mammalian target of rapamycin complex 2 (mTORC2)
CC which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Interacts
CC with PLPP7 and PML. Interacts with PRR5 and RICTOR; the interaction is
CC direct within the mTORC2 complex and interaction with RICTOR is
CC enhanced by deubiquitination of RICTOR by USP9X (PubMed:33378666).
CC Interacts with WAC; WAC positively regulates MTOR activity by promoting
CC the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and
CC the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL
CC complex which leads to the dimerization of the mTORC1 complex and its
CC subsequent activation (PubMed:26812014). Interacts with UBQLN1.
CC Interacts with TTI1 and TELO2. Interacts with CLIP1; phosphorylates and
CC regulates CLIP1. Interacts with NBN. Interacts with HTR6
CC (PubMed:23027611). Interacts with BRAT1. Interacts with MEAK7 (via C-
CC terminal domain); the interaction increases upon nutrient stimulation
CC (PubMed:29750193). Interacts with TM4SF5; the interaction is positively
CC regulated by arginine and is negatively regulated by leucine
CC (PubMed:30956113). Interacts with GPR137B (PubMed:31036939). Interacts
CC with NCKAP1L (PubMed:32647003). Interacts with TPCN1 and TPCN2; the
CC interaction is required for TPCN1 and TPCN2 sensitivity to ATP
CC (PubMed:23394946). Interacts with ATP6V1A and with CRYAB, forming a
CC ternary complex (By similarity). {ECO:0000250|UniProtKB:Q9JLN9,
CC ECO:0000269|PubMed:10089303, ECO:0000269|PubMed:11853878,
CC ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926,
CC ECO:0000269|PubMed:12231510, ECO:0000269|PubMed:12408816,
CC ECO:0000269|PubMed:12718876, ECO:0000269|PubMed:15268862,
CC ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:17386266,
CC ECO:0000269|PubMed:17599906, ECO:0000269|PubMed:18925875,
CC ECO:0000269|PubMed:19446321, ECO:0000269|PubMed:20427287,
CC ECO:0000269|PubMed:20542007, ECO:0000269|PubMed:20801936,
CC ECO:0000269|PubMed:20810650, ECO:0000269|PubMed:23027611,
CC ECO:0000269|PubMed:23394946, ECO:0000269|PubMed:23636326,
CC ECO:0000269|PubMed:23762398, ECO:0000269|PubMed:25657994,
CC ECO:0000269|PubMed:26812014, ECO:0000269|PubMed:29750193,
CC ECO:0000269|PubMed:30956113, ECO:0000269|PubMed:31036939,
CC ECO:0000269|PubMed:32647003, ECO:0000269|PubMed:33378666,
CC ECO:0000269|PubMed:8662507}.
CC -!- INTERACTION:
CC P42345; P31749: AKT1; NbExp=4; IntAct=EBI-359260, EBI-296087;
CC P42345; Q07817-1: BCL2L1; NbExp=4; IntAct=EBI-359260, EBI-287195;
CC P42345; Q8TB45: DEPTOR; NbExp=5; IntAct=EBI-359260, EBI-2359040;
CC P42345; Q13541: EIF4EBP1; NbExp=2; IntAct=EBI-359260, EBI-74090;
CC P42345; P62942: FKBP1A; NbExp=5; IntAct=EBI-359260, EBI-1027571;
CC P42345; Q8WUA4: GTF3C2; NbExp=3; IntAct=EBI-359260, EBI-1237062;
CC P42345; Q9BVC4: MLST8; NbExp=5; IntAct=EBI-359260, EBI-1387471;
CC P42345; Q9BVC4-1: MLST8; NbExp=7; IntAct=EBI-359260, EBI-16056342;
CC P42345; Q13615: MTMR3; NbExp=3; IntAct=EBI-359260, EBI-371938;
CC P42345; P42345: MTOR; NbExp=2; IntAct=EBI-359260, EBI-359260;
CC P42345; Q8TCU6: PREX1; NbExp=11; IntAct=EBI-359260, EBI-1046542;
CC P42345; P62820: RAB1A; NbExp=4; IntAct=EBI-359260, EBI-716845;
CC P42345; Q15382: RHEB; NbExp=2; IntAct=EBI-359260, EBI-1055287;
CC P42345; Q6R327: RICTOR; NbExp=34; IntAct=EBI-359260, EBI-1387196;
CC P42345; Q8N122: RPTOR; NbExp=47; IntAct=EBI-359260, EBI-1567928;
CC P42345; Q96EB6: SIRT1; NbExp=2; IntAct=EBI-359260, EBI-1802965;
CC P42345; Q92544: TM9SF4; NbExp=4; IntAct=EBI-359260, EBI-6138615;
CC P42345; Q8NHX9: TPCN2; NbExp=2; IntAct=EBI-359260, EBI-5239949;
CC P42345; O75385: ULK1; NbExp=7; IntAct=EBI-359260, EBI-908831;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:14578359}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14578359}; Cytoplasmic side
CC {ECO:0000269|PubMed:14578359}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:14578359}; Peripheral membrane protein
CC {ECO:0000269|PubMed:14578359}; Cytoplasmic side
CC {ECO:0000269|PubMed:14578359}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}; Peripheral
CC membrane protein {ECO:0000269|PubMed:11930000,
CC ECO:0000269|PubMed:14578359}; Cytoplasmic side
CC {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:14578359}. Lysosome
CC {ECO:0000269|PubMed:18497260, ECO:0000269|PubMed:20381137,
CC ECO:0000269|PubMed:29750193}. Cytoplasm {ECO:0000269|PubMed:11930000,
CC ECO:0000269|PubMed:18497260}. Nucleus, PML body
CC {ECO:0000250|UniProtKB:Q9JLN9}. Microsome membrane
CC {ECO:0000269|PubMed:9434772}. Lysosome membrane
CC {ECO:0000269|PubMed:30956113}. Cytoplasmic vesicle, phagosome
CC {ECO:0000269|PubMed:27623384}. Note=Shuttles between cytoplasm and
CC nucleus. Accumulates in the nucleus in response to hypoxia (By
CC similarity). Targeting to lysosomes depends on amino acid availability
CC and RRAGA and RRAGB (PubMed:18497260, PubMed:20381137). Lysosome
CC targeting also depends on interaction with MEAK7. Translocates to the
CC lysosome membrane in the presence of TM4SF5 (PubMed:30956113).
CC {ECO:0000250|UniProtKB:Q9JLN9, ECO:0000269|PubMed:18497260,
CC ECO:0000269|PubMed:20381137, ECO:0000269|PubMed:29750193,
CC ECO:0000269|PubMed:30956113}.
CC -!- TISSUE SPECIFICITY: Expressed in numerous tissues, with highest levels
CC in testis. {ECO:0000269|PubMed:12408816, ECO:0000269|PubMed:7809080}.
CC -!- DOMAIN: The kinase domain (PI3K/PI4K) is intrinsically active but has a
CC highly restricted catalytic center. {ECO:0000269|PubMed:23636326}.
CC -!- DOMAIN: The FAT domain forms three discontinuous subdomains of alpha-
CC helical TPR repeats plus a single subdomain of HEAT repeats. The four
CC domains pack sequentially to form a C-shaped a-solenoid that clamps
CC onto the kinase domain (PubMed:23636326).
CC {ECO:0000269|PubMed:23636326}.
CC -!- PTM: Autophosphorylates when part of mTORC1 or mTORC2. Phosphorylation
CC at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation.
CC Phosphorylation in the kinase domain modulates the interactions of MTOR
CC with RPTOR and PRAS40 and leads to increased intrinsic mTORC1 kinase
CC activity. Phosphorylation at Thr-2173 in the ATP-binding region by AKT1
CC strongly reduces kinase activity. {ECO:0000269|PubMed:15905173,
CC ECO:0000269|PubMed:19145465, ECO:0000269|PubMed:19487463,
CC ECO:0000269|PubMed:21576368, ECO:0000269|PubMed:23429703,
CC ECO:0000269|PubMed:23429704, ECO:0000269|PubMed:24247430}.
CC -!- DISEASE: Smith-Kingsmore syndrome (SKS) [MIM:616638]: An autosomal
CC dominant syndrome characterized by intellectual disability,
CC macrocephaly, seizures, umbilical hernia, and facial dysmorphic
CC features. {ECO:0000269|PubMed:25851998, ECO:0000269|PubMed:26542245,
CC ECO:0000269|PubMed:27830187}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Focal cortical dysplasia 2 (FCORD2) [MIM:607341]: A form of
CC focal cortical dysplasia, a malformation of cortical development that
CC results in medically refractory epilepsy in the pediatric population
CC and in adults. FCORD2 is a severe form, with onset usually in
CC childhood, characterized by disrupted cortical lamination and specific
CC cytological abnormalities. It is classified in 2 subtypes: type IIA
CC characterized by dysmorphic neurons and lack of balloon cells; type IIB
CC with dysmorphic neurons and balloon cells.
CC {ECO:0000269|PubMed:25799227, ECO:0000269|PubMed:25878179,
CC ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC39933.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAE06077.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FRAP1ID40639ch1p36.html";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Mammalian target of rapamycin entry;
CC URL="https://en.wikipedia.org/wiki/Mammalian_target_of_rapamycin";
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DR EMBL; L34075; AAA58486.1; -; mRNA.
DR EMBL; U88966; AAC39933.1; ALT_FRAME; mRNA.
DR EMBL; AB209995; BAE06077.1; ALT_INIT; mRNA.
DR EMBL; AL109811; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL391561; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL049653; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC117166; AAI17167.1; -; mRNA.
DR EMBL; AJ300188; CAC15570.1; -; Genomic_DNA.
DR EMBL; L35478; AAC41713.1; -; mRNA.
DR CCDS; CCDS127.1; -.
DR PIR; S45340; S45340.
DR RefSeq; NP_004949.1; NM_004958.3.
DR RefSeq; XP_005263495.1; XM_005263438.2.
DR PDB; 1AUE; X-ray; 2.33 A; A/B=2015-2114.
DR PDB; 1FAP; X-ray; 2.70 A; B=2018-2112.
DR PDB; 1NSG; X-ray; 2.20 A; B=2019-2112.
DR PDB; 2FAP; X-ray; 2.20 A; B=2019-2112.
DR PDB; 2GAQ; NMR; -; A=2015-2114.
DR PDB; 2NPU; NMR; -; A=2015-2114.
DR PDB; 2RSE; NMR; -; B=2019-2112.
DR PDB; 3FAP; X-ray; 1.85 A; B=2019-2112.
DR PDB; 3JBZ; EM; 28.00 A; A=1385-2549.
DR PDB; 4DRH; X-ray; 2.30 A; B/E=2025-2114.
DR PDB; 4DRI; X-ray; 1.45 A; B=2025-2114.
DR PDB; 4DRJ; X-ray; 1.80 A; B=2025-2114.
DR PDB; 4FAP; X-ray; 2.80 A; B=2019-2112.
DR PDB; 4JSN; X-ray; 3.20 A; A/B=1376-2549.
DR PDB; 4JSP; X-ray; 3.30 A; A/B=1376-2549.
DR PDB; 4JSV; X-ray; 3.50 A; A/B=1376-2549.
DR PDB; 4JSX; X-ray; 3.50 A; A/B=1376-2549.
DR PDB; 4JT5; X-ray; 3.45 A; A/B=1376-2549.
DR PDB; 4JT6; X-ray; 3.60 A; A/B=1376-2549.
DR PDB; 5FLC; EM; 5.90 A; B/F=1382-2549.
DR PDB; 5GPG; X-ray; 1.67 A; B=2021-2112.
DR PDB; 5H64; EM; 4.40 A; A/a=1-2549.
DR PDB; 5WBH; X-ray; 1.75 A; A/B/C/D/E=2018-2114.
DR PDB; 5WBU; X-ray; 3.42 A; A/B=1376-2549.
DR PDB; 5WBY; X-ray; 3.10 A; A/B=1376-2549.
DR PDB; 5ZCS; EM; 4.90 A; A/B=1-2549.
DR PDB; 6BCU; EM; 3.43 A; A/B=1-2549.
DR PDB; 6BCX; EM; 3.00 A; A/B=1-2549.
DR PDB; 6M4U; X-ray; 2.20 A; B/F=2021-2113.
DR PDB; 6M4W; X-ray; 3.11 A; G/H/I=2021-2113.
DR PDB; 6SB0; EM; 5.50 A; A/B=60-2549.
DR PDB; 6SB2; EM; 6.20 A; A/B=54-2549.
DR PDB; 6ZWM; EM; 3.20 A; A/B=1-2549.
DR PDB; 6ZWO; EM; 3.00 A; B=1-2549.
DR PDB; 7EPD; EM; 3.90 A; B=2019-2114.
DR PDB; 7OWG; EM; 4.70 A; B=1-2549.
DR PDB; 7PE7; EM; 3.41 A; A/B=1-2549.
DR PDB; 7PE8; EM; 3.20 A; A=1-2549.
DR PDB; 7PE9; EM; 3.70 A; A=1-2549.
DR PDB; 7PEA; EM; 4.07 A; A/B=1-2549.
DR PDB; 7PEB; EM; 3.67 A; A=1-2549.
DR PDB; 7PEC; EM; 4.24 A; A=1-2549.
DR PDBsum; 1AUE; -.
DR PDBsum; 1FAP; -.
DR PDBsum; 1NSG; -.
DR PDBsum; 2FAP; -.
DR PDBsum; 2GAQ; -.
DR PDBsum; 2NPU; -.
DR PDBsum; 2RSE; -.
DR PDBsum; 3FAP; -.
DR PDBsum; 3JBZ; -.
DR PDBsum; 4DRH; -.
DR PDBsum; 4DRI; -.
DR PDBsum; 4DRJ; -.
DR PDBsum; 4FAP; -.
DR PDBsum; 4JSN; -.
DR PDBsum; 4JSP; -.
DR PDBsum; 4JSV; -.
DR PDBsum; 4JSX; -.
DR PDBsum; 4JT5; -.
DR PDBsum; 4JT6; -.
DR PDBsum; 5FLC; -.
DR PDBsum; 5GPG; -.
DR PDBsum; 5H64; -.
DR PDBsum; 5WBH; -.
DR PDBsum; 5WBU; -.
DR PDBsum; 5WBY; -.
DR PDBsum; 5ZCS; -.
DR PDBsum; 6BCU; -.
DR PDBsum; 6BCX; -.
DR PDBsum; 6M4U; -.
DR PDBsum; 6M4W; -.
DR PDBsum; 6SB0; -.
DR PDBsum; 6SB2; -.
DR PDBsum; 6ZWM; -.
DR PDBsum; 6ZWO; -.
DR PDBsum; 7EPD; -.
DR PDBsum; 7OWG; -.
DR PDBsum; 7PE7; -.
DR PDBsum; 7PE8; -.
DR PDBsum; 7PE9; -.
DR PDBsum; 7PEA; -.
DR PDBsum; 7PEB; -.
DR PDBsum; 7PEC; -.
DR AlphaFoldDB; P42345; -.
DR BMRB; P42345; -.
DR SMR; P42345; -.
DR BioGRID; 108757; 318.
DR ComplexPortal; CPX-4402; mTORC2 complex.
DR ComplexPortal; CPX-503; mTORC1 complex.
DR CORUM; P42345; -.
DR DIP; DIP-790N; -.
DR IntAct; P42345; 109.
DR MINT; P42345; -.
DR STRING; 9606.ENSP00000354558; -.
DR BindingDB; P42345; -.
DR ChEMBL; CHEMBL2842; -.
DR DrugBank; DB01590; Everolimus.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00337; Pimecrolimus.
DR DrugBank; DB06233; Ridaforolimus.
DR DrugBank; DB04974; Rimiducid.
DR DrugBank; DB05210; SF1126.
DR DrugBank; DB00877; Sirolimus.
DR DrugBank; DB06287; Temsirolimus.
DR DrugBank; DB05241; XL765.
DR DrugCentral; P42345; -.
DR GuidetoPHARMACOLOGY; 2109; -.
DR iPTMnet; P42345; -.
DR MetOSite; P42345; -.
DR PhosphoSitePlus; P42345; -.
DR SwissPalm; P42345; -.
DR BioMuta; MTOR; -.
DR DMDM; 1169735; -.
DR CPTAC; CPTAC-1360; -.
DR CPTAC; CPTAC-1361; -.
DR EPD; P42345; -.
DR jPOST; P42345; -.
DR MassIVE; P42345; -.
DR MaxQB; P42345; -.
DR PaxDb; P42345; -.
DR PeptideAtlas; P42345; -.
DR PRIDE; P42345; -.
DR ProteomicsDB; 55511; -.
DR Antibodypedia; 3566; 1855 antibodies from 53 providers.
DR CPTC; P42345; 10 antibodies.
DR DNASU; 2475; -.
DR Ensembl; ENST00000361445.9; ENSP00000354558.4; ENSG00000198793.13.
DR GeneID; 2475; -.
DR KEGG; hsa:2475; -.
DR MANE-Select; ENST00000361445.9; ENSP00000354558.4; NM_004958.4; NP_004949.1.
DR UCSC; uc001asd.4; human.
DR CTD; 2475; -.
DR DisGeNET; 2475; -.
DR GeneCards; MTOR; -.
DR HGNC; HGNC:3942; MTOR.
DR HPA; ENSG00000198793; Low tissue specificity.
DR MalaCards; MTOR; -.
DR MIM; 601231; gene.
DR MIM; 607341; phenotype.
DR MIM; 616638; phenotype.
DR neXtProt; NX_P42345; -.
DR OpenTargets; ENSG00000198793; -.
DR Orphanet; 269001; Isolated focal cortical dysplasia type IIa.
DR Orphanet; 269008; Isolated focal cortical dysplasia type IIb.
DR Orphanet; 457485; Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome.
DR PharmGKB; PA28360; -.
DR VEuPathDB; HostDB:ENSG00000198793; -.
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00930000151037; -.
DR HOGENOM; CLU_000178_7_1_1; -.
DR InParanoid; P42345; -.
DR OMA; DPYKHQQ; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; P42345; -.
DR TreeFam; TF105134; -.
DR PathwayCommons; P42345; -.
DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-165159; MTOR signalling.
DR Reactome; R-HSA-166208; mTORC1-mediated signalling.
DR Reactome; R-HSA-3371571; HSF1-dependent transactivation.
DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-HSA-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9639288; Amino acids regulate mTORC1.
DR SABIO-RK; P42345; -.
DR SignaLink; P42345; -.
DR SIGNOR; P42345; -.
DR BioGRID-ORCS; 2475; 770 hits in 1099 CRISPR screens.
DR ChiTaRS; MTOR; human.
DR EvolutionaryTrace; P42345; -.
DR GeneWiki; Mammalian_target_of_rapamycin; -.
DR GenomeRNAi; 2475; -.
DR Pharos; P42345; Tclin.
DR PRO; PR:P42345; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P42345; protein.
DR Bgee; ENSG00000198793; Expressed in right hemisphere of cerebellum and 130 other tissues.
DR ExpressionAtlas; P42345; baseline and differential.
DR Genevisible; P42345; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0012505; C:endomembrane system; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005635; C:nuclear envelope; IDA:CACAO.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0045335; C:phagocytic vesicle; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0031931; C:TORC1 complex; IDA:UniProtKB.
DR GO; GO:0031932; C:TORC2 complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IDA:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0043022; F:ribosome binding; IEA:Ensembl.
DR GO; GO:0001002; F:RNA polymerase III type 1 promoter sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001003; F:RNA polymerase III type 2 promoter sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001006; F:RNA polymerase III type 3 promoter sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0001156; F:TFIIIC-class transcription factor complex binding; IDA:UniProtKB.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IEA:Ensembl.
DR GO; GO:0032148; P:activation of protein kinase B activity; TAS:Reactome.
DR GO; GO:0043276; P:anoikis; NAS:ParkinsonsUK-UCL.
DR GO; GO:0048266; P:behavioral response to pain; IEA:Ensembl.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0055013; P:cardiac muscle cell development; IEA:Ensembl.
DR GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; IDA:CAFA.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0071233; P:cellular response to leucine; IDA:CAFA.
DR GO; GO:1990253; P:cellular response to leucine starvation; IDA:CAFA.
DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IC:ComplexPortal.
DR GO; GO:0009267; P:cellular response to starvation; IDA:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IC:ComplexPortal.
DR GO; GO:0006112; P:energy reserve metabolic process; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl.
DR GO; GO:0003179; P:heart valve morphogenesis; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IDA:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0010507; P:negative regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0045792; P:negative regulation of cell size; IEA:Ensembl.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IDA:MGI.
DR GO; GO:0019228; P:neuronal action potential; IEA:Ensembl.
DR GO; GO:0051647; P:nucleus localization; IDA:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Ensembl.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IEA:Ensembl.
DR GO; GO:0030307; P:positive regulation of cell growth; IC:ComplexPortal.
DR GO; GO:1904690; P:positive regulation of cytoplasmic translational initiation; TAS:ARUK-UCL.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IC:ComplexPortal.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; IMP:BHF-UCL.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Ensembl.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IEA:Ensembl.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:1905857; P:positive regulation of pentose-phosphate shunt; IC:ComplexPortal.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl.
DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; TAS:ARUK-UCL.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IMP:UniProtKB.
DR GO; GO:1901838; P:positive regulation of transcription of nucleolar large rRNA by RNA polymerase I; IMP:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
DR GO; GO:1903691; P:positive regulation of wound healing, spreading of epidermal cells; IMP:BHF-UCL.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:MGI.
DR GO; GO:0030163; P:protein catabolic process; TAS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0001558; P:regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0008361; P:regulation of cell size; IMP:CAFA.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:Ensembl.
DR GO; GO:1904059; P:regulation of locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:Reactome.
DR GO; GO:0090559; P:regulation of membrane permeability; IEA:Ensembl.
DR GO; GO:0031641; P:regulation of myelination; IEA:Ensembl.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; ISS:UniProtKB.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IEA:Ensembl.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0043200; P:response to amino acid; IDA:UniProtKB.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IMP:UniProtKB.
DR GO; GO:0031667; P:response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0031529; P:ruffle organization; IEA:Ensembl.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; IEA:Ensembl.
DR GO; GO:0031929; P:TOR signaling; IMP:UniProtKB.
DR GO; GO:0038202; P:TORC1 signaling; IDA:UniProtKB.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IEA:Ensembl.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.20.120.150; -; 1.
DR Gene3D; 1.25.10.10; -; 4.
DR Gene3D; 1.25.40.10; -; 1.
DR IDEAL; IID00598; -.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR024585; DUF3385_TOR.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR009076; FRB_dom.
DR InterPro; IPR036738; FRB_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR InterPro; IPR018936; PI3/4_kinase_CS.
DR InterPro; IPR003151; PIK-rel_kinase_FAT.
DR InterPro; IPR014009; PIK_FAT.
DR InterPro; IPR026683; TOR.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR11139:SF9; PTHR11139:SF9; 1.
DR Pfam; PF11865; DUF3385; 1.
DR Pfam; PF02259; FAT; 1.
DR Pfam; PF02260; FATC; 1.
DR Pfam; PF08771; FRB_dom; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR SMART; SM01346; DUF3385; 1.
DR SMART; SM01343; FATC; 1.
DR SMART; SM00146; PI3Kc; 1.
DR SUPFAM; SSF47212; SSF47212; 1.
DR SUPFAM; SSF48371; SSF48371; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51189; FAT; 1.
DR PROSITE; PS51190; FATC; 1.
DR PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR PROSITE; PS50290; PI3_4_KINASE_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Biological rhythms; Cytoplasm;
KW Cytoplasmic vesicle; Disease variant; Endoplasmic reticulum; Epilepsy;
KW Golgi apparatus; Intellectual disability; Kinase; Lysosome; Membrane;
KW Microsome; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; TPR repeat; Transferase.
FT CHAIN 1..2549
FT /note="Serine/threonine-protein kinase mTOR"
FT /id="PRO_0000088808"
FT REPEAT 16..53
FT /note="HEAT 1"
FT REPEAT 55..99
FT /note="HEAT 2"
FT REPEAT 100..137
FT /note="HEAT 3"
FT REPEAT 138..179
FT /note="HEAT 4"
FT REPEAT 180..220
FT /note="HEAT 5"
FT REPEAT 222..276
FT /note="HEAT 6"
FT REPEAT 277..313
FT /note="HEAT 7"
FT REPEAT 314..364
FT /note="HEAT 8"
FT REPEAT 365..409
FT /note="HEAT 9"
FT REPEAT 410..445
FT /note="HEAT 10"
FT REPEAT 446..494
FT /note="HEAT 11"
FT REPEAT 495..529
FT /note="HEAT 12"
FT REPEAT 530..563
FT /note="HEAT 13"
FT REPEAT 564..596
FT /note="HEAT 14"
FT REPEAT 597..636
FT /note="HEAT 15"
FT REPEAT 637..683
FT /note="HEAT 16"
FT REPEAT 686..724
FT /note="HEAT 17"
FT REPEAT 727..766
FT /note="HEAT 18"
FT REPEAT 769..811
FT /note="HEAT 19"
FT REPEAT 814..853
FT /note="HEAT 20"
FT REPEAT 857..893
FT /note="HEAT 21"
FT REPEAT 894..942
FT /note="HEAT 22"
FT REPEAT 943..988
FT /note="HEAT 23"
FT REPEAT 989..1027
FT /note="HEAT 24"
FT REPEAT 1029..1068
FT /note="HEAT 25"
FT REPEAT 1069..1105
FT /note="HEAT 26"
FT REPEAT 1106..1144
FT /note="HEAT 27"
FT REPEAT 1145..1188
FT /note="HEAT 28"
FT REPEAT 1189..1225
FT /note="HEAT 29"
FT REPEAT 1226..1273
FT /note="HEAT 30"
FT REPEAT 1274..1311
FT /note="HEAT 31"
FT REPEAT 1312..1345
FT /note="HEAT 32"
FT REPEAT 1346..1382
FT /note="TPR 1"
FT DOMAIN 1382..1982
FT /note="FAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534"
FT REPEAT 1383..1408
FT /note="TPR 2"
FT REPEAT 1409..1442
FT /note="TPR 3"
FT REPEAT 1443..1473
FT /note="TPR 4"
FT REPEAT 1474..1507
FT /note="TPR 5"
FT REPEAT 1508..1541
FT /note="TPR 6"
FT REPEAT 1542..1574
FT /note="TPR 7"
FT REPEAT 1575..1614
FT /note="TPR 8"
FT REPEAT 1615..1649
FT /note="TPR 9"
FT REPEAT 1650..1693
FT /note="TPR 10"
FT REPEAT 1694..1731
FT /note="TPR 11"
FT REPEAT 1732..1786
FT /note="TPR 12"
FT REPEAT 1787..1846
FT /note="TPR 13"
FT REPEAT 1898..1930
FT /note="TPR 14"
FT REPEAT 1931..1970
FT /note="TPR 15"
FT REPEAT 1971..2005
FT /note="TPR 16"
FT DOMAIN 2156..2469
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT DOMAIN 2517..2549
FT /note="FATC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00534,
FT ECO:0000255|PROSITE-ProRule:PRU00535"
FT REGION 1..651
FT /note="Interaction with NBN"
FT /evidence="ECO:0000269|PubMed:23762398"
FT REGION 1812..1867
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2012..2144
FT /note="Sufficient for interaction with the FKBP1A/rapamycin
FT complex"
FT /evidence="ECO:0000250"
FT REGION 2162..2168
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2258..2296
FT /note="Interaction with MLST8"
FT REGION 2335..2343
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2355..2380
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT COMPBIAS 1822..1867
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:20068231"
FT MOD_RES 1162
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1218
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 1261
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19487463,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 2159
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21576368"
FT MOD_RES 2164
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21576368"
FT MOD_RES 2173
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:24247430"
FT MOD_RES 2446
FT /note="Phosphothreonine; by RPS6KB1"
FT /evidence="ECO:0000269|PubMed:15905173"
FT MOD_RES 2448
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000269|PubMed:15905173,
FT ECO:0000269|PubMed:19145465, ECO:0007744|PubMed:24275569"
FT MOD_RES 2478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 2481
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:21576368,
FT ECO:0007744|PubMed:18669648"
FT VARIANT 8
FT /note="A -> S (in a lung large cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041537"
FT VARIANT 135
FT /note="M -> T (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041538"
FT VARIANT 624
FT /note="R -> H (in FCORD2; somatic mutation; unknown
FT pathological significance; dbSNP:rs913197212)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078824"
FT VARIANT 1083
FT /note="M -> V (in dbSNP:rs56164650)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041539"
FT VARIANT 1134
FT /note="A -> V (in dbSNP:rs28730685)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041540"
FT VARIANT 1178
FT /note="S -> F (in dbSNP:rs55975118)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041541"
FT VARIANT 1376
FT /note="D -> E (found in a patient with focal epilepsy;
FT unknown pathological significance; dbSNP:rs975577894)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078825"
FT VARIANT 1450
FT /note="Y -> D (in FCORD2; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078826"
FT VARIANT 1456
FT /note="W -> G (in FCORD2; somatic mutation;
FT dbSNP:rs1085307114)"
FT /evidence="ECO:0000269|PubMed:25878179"
FT /id="VAR_078827"
FT VARIANT 1459
FT /note="A -> D (in FCORD2; somatic mutation; increased TOR
FT signaling)"
FT /evidence="ECO:0000269|PubMed:26018084"
FT /id="VAR_078828"
FT VARIANT 1459
FT /note="A -> S (in FCORD2; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078829"
FT VARIANT 1460
FT /note="L -> P (in FCORD2; somatic mutation; increased TOR
FT signaling; dbSNP:rs1057519779)"
FT /evidence="ECO:0000269|PubMed:26018084,
FT ECO:0000269|PubMed:27830187"
FT /id="VAR_078830"
FT VARIANT 1483
FT /note="C -> R (in FCORD2; somatic mutation; increased TOR
FT signaling; increased kinase activity; dbSNP:rs1057519914)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078831"
FT VARIANT 1490
FT /note="W -> R (in SKS)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078832"
FT VARIANT 1595
FT /note="M -> I (in SKS; dbSNP:rs869312671)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078833"
FT VARIANT 1709
FT /note="R -> H (in FCORD2; somatic mutation; unknown
FT pathological significance; dbSNP:rs587777895)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078834"
FT VARIANT 1799
FT /note="E -> K (in SKS; results in increased mTOR signaling;
FT dbSNP:rs863225264)"
FT /evidence="ECO:0000269|PubMed:25851998,
FT ECO:0000269|PubMed:26542245"
FT /id="VAR_075072"
FT VARIANT 1832
FT /note="A -> T (in SKS; dbSNP:rs369088781)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078835"
FT VARIANT 1888
FT /note="F -> C (in SKS; dbSNP:rs869312666)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078836"
FT VARIANT 1977
FT /note="T -> K (in FCORD2; somatic mutation;
FT dbSNP:rs587777893)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078837"
FT VARIANT 2011
FT /note="M -> V (in an ovarian mucinous carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041542"
FT VARIANT 2193
FT /note="R -> C (in FCORD2; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078838"
FT VARIANT 2215
FT /note="S -> F (in FCORD2; somatic mutation; increased TOR
FT signaling; dbSNP:rs587777894)"
FT /evidence="ECO:0000269|PubMed:25799227,
FT ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187"
FT /id="VAR_078839"
FT VARIANT 2215
FT /note="S -> Y (in FCORD2; also found in a colorectal
FT adenocarcinoma sample; somatic mutation; increased TOR
FT signaling; dbSNP:rs587777894)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:26018084, ECO:0000269|PubMed:27830187"
FT /id="VAR_041543"
FT VARIANT 2220
FT /note="L -> F (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064733"
FT VARIANT 2327
FT /note="M -> I (in SKS; dbSNP:rs878855328)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078840"
FT VARIANT 2406
FT /note="V -> A (found in a renal cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:21248752"
FT /id="VAR_064734"
FT VARIANT 2427
FT /note="L -> P (in FCORD2; somatic mutation; increased TOR
FT signaling; increased kinase activity; dbSNP:rs1085307113)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078841"
FT VARIANT 2427
FT /note="L -> Q (in FCORD2; somatic mutation; increased TOR
FT signaling; increased kinase activity; dbSNP:rs1085307113)"
FT /evidence="ECO:0000269|PubMed:25799227"
FT /id="VAR_078842"
FT VARIANT 2476
FT /note="P -> L (in a glioblastoma multiforme sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041544"
FT VARIANT 2501
FT /note="I -> V (found in a patient with non-lesional
FT nocturnal frontal epilepsy; unknown pathological
FT significance; dbSNP:rs968817513)"
FT /evidence="ECO:0000269|PubMed:27830187"
FT /id="VAR_078843"
FT MUTAGEN 2159
FT /note="S->A: Reduces mTORC1-associated S-2481
FT autophosphorylation; when associated with A-2164."
FT /evidence="ECO:0000269|PubMed:21576368"
FT MUTAGEN 2159
FT /note="S->D: Stronger phosphorylation of RPS6KB1; when
FT associated with E-2164."
FT /evidence="ECO:0000269|PubMed:21576368"
FT MUTAGEN 2164
FT /note="T->A: Reduces mTORC1-associated S-2481
FT autophosphorylation; when associated with A-2159."
FT /evidence="ECO:0000269|PubMed:21576368"
FT MUTAGEN 2164
FT /note="T->E: Stronger phosphorylation of RPS6KB1; when
FT associated with D-2159."
FT /evidence="ECO:0000269|PubMed:21576368"
FT MUTAGEN 2173
FT /note="T->A: Increased mTOR kinase activity."
FT /evidence="ECO:0000269|PubMed:24247430"
FT MUTAGEN 2340
FT /note="H->A: Barely detectable kinase activity."
FT /evidence="ECO:0000269|PubMed:23636326"
FT MUTAGEN 2357
FT /note="D->E: Kinase-dead mutant, loss of interaction with
FT TM4SF5 and loss of lysosome membrane localization; when
FT associated with I-2364."
FT /evidence="ECO:0000269|PubMed:30956113"
FT MUTAGEN 2364
FT /note="V->I: Kinase-dead mutant, loss of interaction with
FT TM4SF5 and loss of lysosome membrane localization; when
FT associated with E-2357."
FT /evidence="ECO:0000269|PubMed:30956113"
FT CONFLICT 353
FT /note="K -> N (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="S -> N (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 364
FT /note="D -> N (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="M -> L (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="R -> L (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 455..457
FT /note="VLD -> GVE (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 461
FT /note="A -> G (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 482..484
FT /note="VFT -> FFN (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 489
FT /note="L -> V (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="L -> I (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="L -> V (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="R -> C (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT CONFLICT 857
FT /note="P -> L (in Ref. 3; BAE06077)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075
FT /note="I -> S (in Ref. 2; AAC39933)"
FT /evidence="ECO:0000305"
FT HELIX 19..29
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 38..52
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 61..73
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 83..92
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 102..114
FT /evidence="ECO:0007829|PDB:6ZWM"
FT STRAND 115..117
FT /evidence="ECO:0007829|PDB:7PE7"
FT HELIX 122..134
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 141..155
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 182..185
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 188..197
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 204..222
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 234..245
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 262..275
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 278..286
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 358..362
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 363..375
FT /evidence="ECO:0007829|PDB:6ZWM"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:7PE8"
FT HELIX 387..402
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 411..423
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:7PE8"
FT HELIX 430..443
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 448..451
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 452..460
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 461..465
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 480..490
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 501..511
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 515..527
FT /evidence="ECO:0007829|PDB:6ZWM"
FT STRAND 530..532
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 533..548
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 582..589
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 601..606
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 609..612
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 616..628
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 648..665
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 669..678
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 681..683
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 684..687
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 690..700
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 705..718
FT /evidence="ECO:0007829|PDB:6ZWM"
FT TURN 719..721
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 723..742
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 747..763
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 765..768
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 769..771
FT /evidence="ECO:0007829|PDB:7PE7"
FT HELIX 772..783
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 793..808
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 811..813
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 814..816
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 817..828
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 837..846
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 849..852
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 856..860
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 864..870
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 871..873
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 878..891
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 896..901
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 930..935
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 936..939
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 944..946
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 947..959
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 962..964
FT /evidence="ECO:0007829|PDB:7PE7"
FT HELIX 965..967
FT /evidence="ECO:0007829|PDB:7PE8"
FT HELIX 968..982
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 986..989
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 990..1003
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1006..1008
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1009..1022
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1023..1025
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1028..1030
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1031..1038
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1044..1046
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1049..1063
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1064..1066
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 1067..1069
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1072..1074
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1075..1083
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1088..1090
FT /evidence="ECO:0007829|PDB:7PE8"
FT HELIX 1091..1100
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1101..1105
FT /evidence="ECO:0007829|PDB:7PE8"
FT STRAND 1108..1110
FT /evidence="ECO:0007829|PDB:7PE8"
FT TURN 1111..1114
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1116..1122
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1129..1141
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1144..1146
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1150..1152
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1153..1164
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1167..1169
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1170..1181
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1186..1188
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1189..1191
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1192..1201
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1207..1217
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1222..1226
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1229..1237
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1266..1269
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1277..1293
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1298..1307
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1311..1316
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1318..1326
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1331..1347
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1351..1365
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1367..1369
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1377..1379
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1380..1388
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1389..1391
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1393..1406
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1410..1422
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1426..1439
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1447..1452
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1456..1467
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1474..1476
FT /evidence="ECO:0007829|PDB:6ZWM"
FT HELIX 1477..1487
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1490..1498
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1501..1504
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1506..1523
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1526..1533
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1538..1540
FT /evidence="ECO:0007829|PDB:5WBY"
FT HELIX 1541..1553
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1559..1578
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1579..1581
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1583..1597
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1599..1607
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1609..1611
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1612..1623
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1630..1640
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1641..1643
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1646..1648
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1651..1662
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1666..1677
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1681..1683
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1685..1687
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1694..1707
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1712..1728
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1736..1738
FT /evidence="ECO:0007829|PDB:7PE8"
FT HELIX 1740..1762
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1766..1768
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1769..1783
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1787..1808
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1876..1895
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 1896..1898
FT /evidence="ECO:0007829|PDB:5WBY"
FT HELIX 1900..1913
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1917..1929
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1933..1938
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1939..1943
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1944..1947
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1951..1967
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1970..1972
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1973..1980
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 1985..1998
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 1999..2001
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2004..2020
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2025..2039
FT /evidence="ECO:0007829|PDB:4DRI"
FT HELIX 2044..2058
FT /evidence="ECO:0007829|PDB:4DRI"
FT HELIX 2065..2091
FT /evidence="ECO:0007829|PDB:4DRI"
FT HELIX 2094..2111
FT /evidence="ECO:0007829|PDB:4DRI"
FT TURN 2115..2117
FT /evidence="ECO:0007829|PDB:5WBY"
FT STRAND 2120..2122
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2123..2126
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2128..2132
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2137..2139
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2141..2143
FT /evidence="ECO:0007829|PDB:5WBY"
FT STRAND 2146..2148
FT /evidence="ECO:0007829|PDB:5WBY"
FT STRAND 2152..2156
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2158..2162
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2165..2167
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2173..2176
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2181..2190
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2193..2210
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2213..2216
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2217..2219
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2227..2231
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2234..2238
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2241..2246
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2247..2256
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2263..2271
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2275..2277
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2280..2292
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2298..2305
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2310..2334
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2343..2347
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2348..2350
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2353..2355
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2362..2366
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2369..2371
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2381..2384
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2385..2387
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2392..2394
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2395..2409
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2411..2422
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2425..2429
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2430..2432
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2433..2435
FT /evidence="ECO:0007829|PDB:5WBY"
FT HELIX 2493..2507
FT /evidence="ECO:0007829|PDB:6ZWO"
FT TURN 2508..2510
FT /evidence="ECO:0007829|PDB:6ZWO"
FT STRAND 2512..2516
FT /evidence="ECO:0007829|PDB:4JT5"
FT HELIX 2521..2532
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2535..2538
FT /evidence="ECO:0007829|PDB:6ZWO"
FT HELIX 2543..2545
FT /evidence="ECO:0007829|PDB:6ZWO"
SQ SEQUENCE 2549 AA; 288892 MW; 7D9AD6E784882AB4 CRC64;
MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR
CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL
VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS
MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI
LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA
LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR
DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV
SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR
VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD
PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP
TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN
EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS
KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG
ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL
QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL
SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL
MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH
PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG
VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD
VPTQVELLIK QATSHENLCQ CYIGWCPFW
