MTOR_MOUSE
ID MTOR_MOUSE Reviewed; 2549 AA.
AC Q9JLN9; Q2KHT0; Q811J5; Q9CST1;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 15-JUN-2010, sequence version 2.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Serine/threonine-protein kinase mTOR {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:11792863, ECO:0000269|PubMed:24011591, ECO:0000269|PubMed:27913603};
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 target protein 1;
DE Short=RAPT1;
GN Name=Mtor {ECO:0000312|MGI:MGI:1928394}; Synonyms=Frap, Frap1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=BALB/cJ;
RA Bliskovsky V., Mock B.;
RT "Positional cloning of mouse plasmacytoma susceptibility gene.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and FVB/N; TISSUE=Kidney, and Retina;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1155-1334.
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP PROTEIN SEQUENCE OF 1287-1293, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2146, INTERACTION WITH THE
RP FKBP1A-RAPAMYCIN COMPLEX, MUTAGENESIS OF SER-2035, AND TISSUE SPECIFICITY.
RC TISSUE=Embryo;
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 [7]
RP FUNCTION IN PHOSPHORYLATION OF LPIN1, AND CATALYTIC ACTIVITY.
RX PubMed=11792863; DOI=10.1073/pnas.022634399;
RA Huffman T.A., Mothe-Satney I., Lawrence J.C. Jr.;
RT "Insulin-stimulated phosphorylation of lipin mediated by the mammalian
RT target of rapamycin.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1047-1052(2002).
RN [8]
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 [9]
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 [10]
RP FUNCTION, AND IDENTIFICATION IN MTORC2 COMPLEX.
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 [11]
RP FUNCTION.
RX PubMed=16221682; DOI=10.1074/jbc.m508361200;
RA Hresko R.C., Mueckler M.;
RT "mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1
RT adipocytes.";
RL J. Biol. Chem. 280:40406-40416(2005).
RN [12]
RP FUNCTION, AND IDENTIFICATION IN MTORC2 COMPLEX.
RX PubMed=16962653; DOI=10.1016/j.cell.2006.08.033;
RA Jacinto E., Facchinetti V., Liu D., Soto N., Wei S., Jung S.Y., Huang Q.,
RA Qin J., Su B.;
RT "SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt
RT phosphorylation and substrate specificity.";
RL Cell 127:125-137(2006).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=16915281; DOI=10.1038/nature05029;
RA Bernardi R., Guernah I., Jin D., Grisendi S., Alimonti A.,
RA Teruya-Feldstein J., Cordon-Cardo C., Simon M.C., Rafii S., Pandolfi P.P.;
RT "PML inhibits HIF-1alpha translation and neoangiogenesis through repression
RT of mTOR.";
RL Nature 442:779-785(2006).
RN [14]
RP FUNCTION IN MITOCHONDRIAL BIOGENESIS.
RX PubMed=18046414; DOI=10.1038/nature06322;
RA Cunningham J.T., Rodgers J.T., Arlow D.H., Vazquez F., Mootha V.K.,
RA Puigserver P.;
RT "mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha
RT transcriptional complex.";
RL Nature 450:736-740(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2478 AND SER-2481, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [16]
RP FUNCTION.
RX PubMed=19440205; DOI=10.1038/emboj.2009.127;
RA Smink J.J., Begay V., Schoenmaker T., Sterneck E., de Vries T.J., Leutz A.;
RT "Transcription factor C/EBPbeta isoform ratio regulates osteoclastogenesis
RT through MafB.";
RL EMBO J. 28:1769-1781(2009).
RN [17]
RP PHOSPHORYLATION OF RPTOR.
RX PubMed=19346248; DOI=10.1074/jbc.c109.002907;
RA Wang L., Lawrence J.C. Jr., Sturgill T.W., Harris T.E.;
RT "Mammalian target of rapamycin complex 1 (mTORC1) activity is associated
RT with phosphorylation of raptor by mTOR.";
RL J. Biol. Chem. 284:14693-14697(2009).
RN [18]
RP PHOSPHORYLATION AT SER-1261, AND ACTIVITY REGULATION.
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 [19]
RP INTERACTION WITH PLPP7.
RX PubMed=19704009; DOI=10.1128/mcb.00684-09;
RA Liu G.H., Guan T., Datta K., Coppinger J., Yates J. III, Gerace L.;
RT "Regulation of myoblast differentiation by the nuclear envelope protein
RT NET39.";
RL Mol. Cell. Biol. 29:5800-5812(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1261; SER-2478 AND SER-2481,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [21]
RP INTERACTION WITH MLST8; PRR5 AND RPTOR.
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 [22]
RP FUNCTION IN AUTOPHAGY, AND FUNCTION IN PHOSPHORYLATION OF ULK1.
RX PubMed=21258367; DOI=10.1038/ncb2152;
RA Kim J., Kundu M., Viollet B., Guan K.L.;
RT "AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.";
RL Nat. Cell Biol. 13:132-141(2011).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF GRB10.
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 [24]
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 [25]
RP PHOSPHORYLATION AT SER-2448.
RX PubMed=26359501; DOI=10.1074/jbc.m115.678433;
RA Cattin M.E., Wang J., Weldrick J.J., Roeske C.L., Mak E., Thorn S.L.,
RA DaSilva J.N., Wang Y., Lusis A.J., Burgon P.G.;
RT "Deletion of MLIP (muscle-enriched A-type lamin-interacting protein) leads
RT to cardiac hyperactivation of Akt/mammalian target of rapamycin (mTOR) and
RT impaired cardiac adaptation.";
RL J. Biol. Chem. 290:26699-26714(2015).
RN [26]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24011591; DOI=10.1016/j.molcel.2013.08.003;
RA Ichimura Y., Waguri S., Sou Y.S., Kageyama S., Hasegawa J., Ishimura R.,
RA Saito T., Yang Y., Kouno T., Fukutomi T., Hoshii T., Hirao A., Takagi K.,
RA Mizushima T., Motohashi H., Lee M.S., Yoshimori T., Tanaka K., Yamamoto M.,
RA Komatsu M.;
RT "Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective
RT autophagy.";
RL Mol. Cell 51:618-631(2013).
RN [27]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=27913603; DOI=10.1101/gad.287953.116;
RA Wada S., Neinast M., Jang C., Ibrahim Y.H., Lee G., Babu A., Li J.,
RA Hoshino A., Rowe G.C., Rhee J., Martina J.A., Puertollano R., Blenis J.,
RA Morley M., Baur J.A., Seale P., Arany Z.;
RT "The tumor suppressor FLCN mediates an alternate mTOR pathway to regulate
RT browning of adipose tissue.";
RL Genes Dev. 30:2551-2564(2016).
RN [28]
RP FUNCTION.
RX PubMed=29750810; DOI=10.1371/journal.pgen.1007369;
RA Ramanathan C., Kathale N.D., Liu D., Lee C., Freeman D.A., Hogenesch J.B.,
RA Cao R., Liu A.C.;
RT "mTOR signaling regulates central and peripheral circadian clock
RT function.";
RL PLoS Genet. 14:E1007369-E1007369(2018).
RN [29]
RP INTERACTION WITH ATP6V1A AND CRYAB.
RX PubMed=31786107; DOI=10.1016/j.bbagen.2019.129496;
RA Cui X., Feng R., Wang J., Du C., Pi X., Chen D., Li J., Li H., Zhang J.,
RA Zhang J., Mu H., Zhang F., Liu M., Hu Y.;
RT "Heat shock factor 4 regulates lysosome activity by modulating the alphaB-
RT crystallin-ATP6V1A-mTOR complex in ocular lens.";
RL Biochim. Biophys. Acta 1864:129496-129496(2020).
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:15467718,
CC PubMed:15545625, PubMed:16221682, PubMed:16915281, PubMed:16962653,
CC PubMed:18046414, PubMed:19440205, PubMed:21659604). MTOR directly or
CC indirectly regulates the phosphorylation of at least 800 proteins
CC (PubMed:15467718, PubMed:15545625, PubMed:16221682, PubMed:16915281,
CC PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604).
CC Functions as part of 2 structurally and functionally distinct signaling
CC complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15467718,
CC PubMed:16962653, PubMed:21659604). Activated mTORC1 up-regulates
CC protein synthesis by phosphorylating key regulators of mRNA translation
CC and ribosome synthesis (By similarity). This includes phosphorylation
CC of EIF4EBP1 and release of its inhibition toward the elongation
CC initiation factor 4E (eiF4E) (By similarity). Moreover, phosphorylates
CC and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by
CC modulating the activity of their downstream targets including ribosomal
CC protein S6, eukaryotic translation initiation factor EIF4B, and the
CC inhibitor of translation initiation PDCD4 (By similarity). This also
CC includes mTORC1 signaling cascade controlling the MiT/TFE factors TFEB
CC and TFE3: in the presence of nutrients, mediates phosphorylation of
CC TFEB and TFE3, promoting their cytosolic retention and inactivation
CC (PubMed:27913603). Upon starvation or lysosomal stress, inhibition of
CC mTORC1 induces dephosphorylation and nuclear translocation of TFEB and
CC TFE3, promoting their transcription factor activity (PubMed:27913603).
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 (By
CC similarity). Regulates ribosome synthesis by activating RNA polymerase
CC III-dependent transcription through phosphorylation and inhibition of
CC MAF1 an RNA polymerase III-repressor (By similarity). In parallel to
CC protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1
CC and LPIN1 (PubMed:11792863). To maintain energy homeostasis mTORC1 may
CC also regulate mitochondrial biogenesis through regulation of PPARGC1A
CC (PubMed:18046414). mTORC1 also negatively regulates autophagy through
CC phosphorylation of ULK1 (PubMed:21258367). Under nutrient sufficiency,
CC phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK
CC and preventing activation of ULK1 (PubMed:21258367). Also prevents
CC autophagy through phosphorylation of the autophagy inhibitor DAP (By
CC similarity). Also prevents autophagy by phosphorylating RUBCNL/Pacer
CC under nutrient-rich conditions (By similarity). Prevents autophagy by
CC mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability
CC to mediate ubiquitination of ULK1 and interaction between AMBRA1 and
CC PPP2CA (By similarity). mTORC1 exerts a feedback control on upstream
CC growth factor signaling that includes phosphorylation and activation of
CC GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among
CC other potential targets mTORC1 may phosphorylate CLIP1 and regulate
CC microtubules (By similarity). As part of the mTORC2 complex MTOR may
CC regulate other cellular processes including survival and organization
CC of the cytoskeleton (By similarity). 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 (By
CC similarity). 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 (By similarity).
CC mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (By
CC similarity). Regulates osteoclastogenesis by adjusting the expression
CC of CEBPB isoforms (PubMed:19440205). Plays an important regulatory role
CC in the circadian clock function; regulates period length and rhythm
CC amplitude of the suprachiasmatic nucleus (SCN) and liver clocks
CC (PubMed:29750810). Phosphorylates SQSTM1, promoting interaction between
CC SQSTM1 and KEAP1 and subsequent inactivation of the BCR(KEAP1) complex
CC (PubMed:24011591). {ECO:0000250|UniProtKB:P42345,
CC ECO:0000250|UniProtKB:P42346, ECO:0000269|PubMed:11792863,
CC ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:16221682, ECO:0000269|PubMed:16915281,
CC ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:18046414,
CC ECO:0000269|PubMed:19440205, ECO:0000269|PubMed:21258367,
CC ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:24011591,
CC ECO:0000269|PubMed:27913603, ECO:0000269|PubMed:29750810}.
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:11792863, ECO:0000269|PubMed:24011591,
CC ECO:0000269|PubMed:27913603};
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:11792863};
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. On the other hand, low cellular energy levels can inhibit
CC mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1
CC through a REDD1-dependent mechanism which may also require PRKAA1. The
CC kinase activity of MTOR within the mTORC1 complex is positively
CC regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR
CC phosphorylates RPTOR which in turn inhibits mTORC1. MTOR is the target
CC of the immunosuppressive and anti-cancer drug rapamycin which acts in
CC complex with FKBP1A/FKBP12, and specifically inhibits its kinase
CC activity. mTORC2 is also activated by growth factors, but seems to be
CC nutrient-insensitive. It may be regulated by RHEB but in an indirect
CC manner through the PI3K signaling pathway.
CC {ECO:0000250|UniProtKB:P42345, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:19487463}.
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 PRR5 and RICTOR; the interaction is direct within the mTORC2
CC complex and interaction with RICTOR is enhanced by deubiquitination of
CC RICTOR by USP9X. Interacts with WAC; WAC positively regulates MTOR
CC activity by promoting the assembly of the TTT complex composed of
CC TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and
CC RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of
CC the mTORC1 complex and its subsequent activation (By similarity).
CC Interacts with PLPP7 and PML. Interacts with UBQLN1. Interacts with
CC TTI1 and TELO2. Interacts with CLIP1; phosphorylates and regulates
CC CLIP1. Interacts with NBN. Interacts with HTR6 (PubMed:23027611).
CC Interacts with BRAT1 (By similarity). Interacts with MEAK7 (via C-
CC terminal domain); the interaction increases upon nutrient stimulation
CC (By similarity). Interacts with TM4SF5; the interaction is positively
CC regulated by arginine and is negatively regulated by leucine (By
CC similarity). Interacts with GPR137B (By similarity). Interacts with
CC NCKAP1L (By similarity). Interacts with TPCN1 and TPCN2; the
CC interaction is required for TPCN1 and TPCN2 sensitivity to ATP (By
CC similarity). Interacts with ATP6V1A and with CRYAB, forming a ternary
CC complex (PubMed:31786107). {ECO:0000250|UniProtKB:P42345,
CC ECO:0000269|PubMed:15467718, ECO:0000269|PubMed:16915281,
CC ECO:0000269|PubMed:16962653, ECO:0000269|PubMed:19704009,
CC ECO:0000269|PubMed:20801936, ECO:0000269|PubMed:23027611,
CC ECO:0000269|PubMed:31786107, ECO:0000269|PubMed:7809080}.
CC -!- INTERACTION:
CC Q9JLN9; Q9DCH4: Eif3f; NbExp=5; IntAct=EBI-1571628, EBI-1634316;
CC Q9JLN9; Q6QI06: Rictor; NbExp=12; IntAct=EBI-1571628, EBI-4286572;
CC Q9JLN9; Q8K4Q0: Rptor; NbExp=9; IntAct=EBI-1571628, EBI-4567273;
CC Q9JLN9; O70405: Ulk1; NbExp=3; IntAct=EBI-1571628, EBI-8390771;
CC Q9JLN9; Q00899: Yy1; NbExp=4; IntAct=EBI-1571628, EBI-6921536;
CC Q9JLN9; Q13541: EIF4EBP1; Xeno; NbExp=2; IntAct=EBI-1571628, EBI-74090;
CC Q9JLN9; Q8N122: RPTOR; Xeno; NbExp=5; IntAct=EBI-1571628, EBI-1567928;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P42345}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P42345}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P42345}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:P42345}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P42345}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P42345}. Mitochondrion outer membrane
CC {ECO:0000269|PubMed:11930000}; Peripheral membrane protein
CC {ECO:0000269|PubMed:11930000}; Cytoplasmic side
CC {ECO:0000269|PubMed:11930000}. Lysosome {ECO:0000250|UniProtKB:P42345}.
CC Cytoplasm {ECO:0000269|PubMed:11930000, ECO:0000269|PubMed:16915281}.
CC Nucleus, PML body {ECO:0000269|PubMed:16915281}. Lysosome membrane
CC {ECO:0000250|UniProtKB:P42345}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:P42345}. Note=Shuttles between cytoplasm and
CC nucleus. Accumulates in the nucleus in response to hypoxia
CC (PubMed:16915281). Targeting to lysosomes depends on amino acid
CC availability and RRAGA and RRAGB (By similarity). Translocates to the
CC lysosome membrane in the presence of TM4SF5 (By similarity).
CC {ECO:0000250|UniProtKB:P42345, ECO:0000269|PubMed:16915281}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9JLN9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9JLN9-2; Sequence=VSP_011909, VSP_011910;
CC -!- DOMAIN: The kinase domain (PI3K/PI4K) is intrinsically active but has a
CC highly restricted catalytic center. {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-2173 in the ATP-binding region by AKT1
CC strongly reduces kinase activity (By similarity). Autophosphorylates
CC when part of mTORC1 or mTORC2. Phosphorylation at Ser-1261, Ser-2159
CC and Thr-2164 promotes autophosphorylation. Phosphorylation in the
CC kinase domain modulates the interactions of MTOR with RPTOR and PRAS40
CC and leads to increased intrinsic mTORC1 kinase activity. {ECO:0000250,
CC ECO:0000269|PubMed:19346248, ECO:0000269|PubMed:19487463}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000305}.
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DR EMBL; AF152838; AAF73196.1; -; mRNA.
DR EMBL; AL713995; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL731654; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU210865; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043920; AAH43920.1; -; mRNA.
DR EMBL; BC112904; AAI12905.1; -; mRNA.
DR EMBL; AK012031; BAB27985.2; -; mRNA.
DR CCDS; CCDS18937.1; -. [Q9JLN9-1]
DR RefSeq; NP_064393.2; NM_020009.2. [Q9JLN9-1]
DR AlphaFoldDB; Q9JLN9; -.
DR BMRB; Q9JLN9; -.
DR SMR; Q9JLN9; -.
DR BioGRID; 208142; 34.
DR ComplexPortal; CPX-4472; mTORC2 complex.
DR ComplexPortal; CPX-4473; mTORC1 complex.
DR CORUM; Q9JLN9; -.
DR DIP; DIP-40570N; -.
DR IntAct; Q9JLN9; 24.
DR MINT; Q9JLN9; -.
DR STRING; 10090.ENSMUSP00000099510; -.
DR BindingDB; Q9JLN9; -.
DR ChEMBL; CHEMBL1255165; -.
DR iPTMnet; Q9JLN9; -.
DR PhosphoSitePlus; Q9JLN9; -.
DR SwissPalm; Q9JLN9; -.
DR EPD; Q9JLN9; -.
DR jPOST; Q9JLN9; -.
DR MaxQB; Q9JLN9; -.
DR PaxDb; Q9JLN9; -.
DR PeptideAtlas; Q9JLN9; -.
DR PRIDE; Q9JLN9; -.
DR ProteomicsDB; 287515; -. [Q9JLN9-1]
DR ProteomicsDB; 287516; -. [Q9JLN9-2]
DR Antibodypedia; 3566; 1855 antibodies from 53 providers.
DR DNASU; 56717; -.
DR Ensembl; ENSMUST00000057580; ENSMUSP00000054164; ENSMUSG00000028991. [Q9JLN9-2]
DR Ensembl; ENSMUST00000103221; ENSMUSP00000099510; ENSMUSG00000028991. [Q9JLN9-1]
DR GeneID; 56717; -.
DR KEGG; mmu:56717; -.
DR UCSC; uc008vuq.3; mouse. [Q9JLN9-2]
DR UCSC; uc008vur.2; mouse. [Q9JLN9-1]
DR CTD; 2475; -.
DR MGI; MGI:1928394; Mtor.
DR VEuPathDB; HostDB:ENSMUSG00000028991; -.
DR eggNOG; KOG0891; Eukaryota.
DR GeneTree; ENSGT00930000151037; -.
DR HOGENOM; CLU_000178_7_1_1; -.
DR InParanoid; Q9JLN9; -.
DR OMA; DPYKHQQ; -.
DR OrthoDB; 26975at2759; -.
DR PhylomeDB; Q9JLN9; -.
DR TreeFam; TF105134; -.
DR Reactome; R-MMU-1257604; PIP3 activates AKT signaling.
DR Reactome; R-MMU-1632852; Macroautophagy.
DR Reactome; R-MMU-165159; MTOR signalling.
DR Reactome; R-MMU-166208; mTORC1-mediated signalling.
DR Reactome; R-MMU-3371571; HSF1-dependent transactivation.
DR Reactome; R-MMU-380972; Energy dependent regulation of mTOR by LKB1-AMPK.
DR Reactome; R-MMU-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-MMU-5218920; VEGFR2 mediated vascular permeability.
DR Reactome; R-MMU-5628897; TP53 Regulates Metabolic Genes.
DR Reactome; R-MMU-6804757; Regulation of TP53 Degradation.
DR Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-MMU-9639288; Amino acids regulate mTORC1.
DR BioGRID-ORCS; 56717; 39 hits in 113 CRISPR screens.
DR ChiTaRS; Mtor; mouse.
DR PRO; PR:Q9JLN9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9JLN9; protein.
DR Bgee; ENSMUSG00000028991; Expressed in spermatid and 96 other tissues.
DR Genevisible; Q9JLN9; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0012505; C:endomembrane system; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:MGI.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031931; C:TORC1 complex; IDA:WormBase.
DR GO; GO:0031932; C:TORC2 complex; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0016301; F:kinase activity; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0001002; F:RNA polymerase III type 1 promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0001003; F:RNA polymerase III type 2 promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0001006; F:RNA polymerase III type 3 promoter sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0001156; F:TFIIIC-class transcription factor complex binding; ISO:MGI.
DR GO; GO:0045182; F:translation regulator activity; ISO:MGI.
DR GO; GO:0006207; P:'de novo' pyrimidine nucleobase biosynthetic process; IDA:CACAO.
DR GO; GO:0048266; P:behavioral response to pain; IGI:MGI.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IMP:MGI.
DR GO; GO:0055006; P:cardiac cell development; IMP:CACAO.
DR GO; GO:0055013; P:cardiac muscle cell development; IMP:MGI.
DR GO; GO:0060048; P:cardiac muscle contraction; IMP:MGI.
DR GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
DR GO; GO:0030030; P:cell projection organization; IMP:MGI.
DR GO; GO:0034198; P:cellular response to amino acid starvation; ISS:UniProtKB.
DR GO; GO:0071230; P:cellular response to amino acid stimulus; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IC:ComplexPortal.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0071233; P:cellular response to leucine; ISO:MGI.
DR GO; GO:1990253; P:cellular response to leucine starvation; ISO:MGI.
DR GO; GO:0031669; P:cellular response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; IC:ComplexPortal.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; IC:ComplexPortal.
DR GO; GO:0006112; P:energy reserve metabolic process; IMP:MGI.
DR GO; GO:0007281; P:germ cell development; IDA:MGI.
DR GO; GO:0003007; P:heart morphogenesis; IMP:MGI.
DR GO; GO:0003179; P:heart valve morphogenesis; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IGI:MGI.
DR GO; GO:0007616; P:long-term memory; ISO:MGI.
DR GO; GO:0007040; P:lysosome organization; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; IMP:MGI.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; ISO:MGI.
DR GO; GO:0048255; P:mRNA stabilization; ISO:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IC:ComplexPortal.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IMP:MGI.
DR GO; GO:0045792; P:negative regulation of cell size; IGI:MGI.
DR GO; GO:1904193; P:negative regulation of cholangiocyte apoptotic process; ISO:MGI.
DR GO; GO:1904213; P:negative regulation of iodide transmembrane transport; ISO:MGI.
DR GO; GO:0016242; P:negative regulation of macroautophagy; IMP:MGI.
DR GO; GO:0014736; P:negative regulation of muscle atrophy; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0019228; P:neuronal action potential; IGI:MGI.
DR GO; GO:0051647; P:nucleus localization; ISS:UniProtKB.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:MGI.
DR GO; GO:0010942; P:positive regulation of cell death; ISO:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; IC:ComplexPortal.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISO:MGI.
DR GO; GO:1904056; P:positive regulation of cholangiocyte proliferation; ISO:MGI.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISO:MGI.
DR GO; GO:1904000; P:positive regulation of eating behavior; ISO:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISO:MGI.
DR GO; GO:0045821; P:positive regulation of glycolytic process; IC:ComplexPortal.
DR GO; GO:1904197; P:positive regulation of granulosa cell proliferation; ISO:MGI.
DR GO; GO:0051549; P:positive regulation of keratinocyte migration; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; IDA:MGI.
DR GO; GO:0046889; P:positive regulation of lipid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0010831; P:positive regulation of myotube differentiation; IGI:MGI.
DR GO; GO:0050769; P:positive regulation of neurogenesis; ISO:MGI.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:MGI.
DR GO; GO:0014042; P:positive regulation of neuron maturation; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:1905857; P:positive regulation of pentose-phosphate shunt; IC:ComplexPortal.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:1904058; P:positive regulation of sensory perception of pain; ISO:MGI.
DR GO; GO:1904206; P:positive regulation of skeletal muscle hypertrophy; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:MGI.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; ISO:MGI.
DR GO; GO:1901838; P:positive regulation of transcription of nucleolar large rRNA by RNA polymerase I; ISO:MGI.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:1903691; P:positive regulation of wound healing, spreading of epidermal cells; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IDA:UniProtKB.
DR GO; GO:0090335; P:regulation of brown fat cell differentiation; ISO:MGI.
DR GO; GO:0006109; P:regulation of carbohydrate metabolic process; ISO:MGI.
DR GO; GO:0043610; P:regulation of carbohydrate utilization; ISO:MGI.
DR GO; GO:0001558; P:regulation of cell growth; ISO:MGI.
DR GO; GO:0008361; P:regulation of cell size; ISO:MGI.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0031998; P:regulation of fatty acid beta-oxidation; ISO:MGI.
DR GO; GO:0005979; P:regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IMP:MGI.
DR GO; GO:1904059; P:regulation of locomotor rhythm; IMP:UniProtKB.
DR GO; GO:0090559; P:regulation of membrane permeability; IMP:MGI.
DR GO; GO:0031641; P:regulation of myelination; IMP:MGI.
DR GO; GO:0045670; P:regulation of osteoclast differentiation; IDA:UniProtKB.
DR GO; GO:0045859; P:regulation of protein kinase activity; IGI:MGI.
DR GO; GO:0051896; P:regulation of protein kinase B signaling; IMP:MGI.
DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI.
DR GO; GO:0032095; P:regulation of response to food; ISO:MGI.
DR GO; GO:0099547; P:regulation of translation at synapse, modulating synaptic transmission; ISO:MGI.
DR GO; GO:0043200; P:response to amino acid; IDA:MGI.
DR GO; GO:0042220; P:response to cocaine; ISO:MGI.
DR GO; GO:0009408; P:response to heat; IGI:MGI.
DR GO; GO:0032868; P:response to insulin; IDA:MGI.
DR GO; GO:0043278; P:response to morphine; ISO:MGI.
DR GO; GO:0007584; P:response to nutrient; ISO:MGI.
DR GO; GO:0031667; P:response to nutrient levels; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0031529; P:ruffle organization; IDA:MGI.
DR GO; GO:0035176; P:social behavior; ISO:MGI.
DR GO; GO:0021510; P:spinal cord development; ISO:MGI.
DR GO; GO:0002296; P:T-helper 1 cell lineage commitment; IMP:MGI.
DR GO; GO:0031929; P:TOR signaling; IGI:BHF-UCL.
DR GO; GO:0038202; P:TORC1 signaling; ISO:MGI.
DR GO; GO:0008542; P:visual learning; ISO:MGI.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI.
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 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; 1.
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 Acetylation; Alternative splicing; ATP-binding; Biological rhythms;
KW Cytoplasm; Cytoplasmic vesicle; Direct protein sequencing;
KW Endoplasmic reticulum; Golgi apparatus; Kinase; Lysosome; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus;
KW 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_0000088809"
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:0000250"
FT REGION 1825..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 REGION 2162..2168
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 2258..2296
FT /note="Interaction with MLST8"
FT /evidence="ECO:0000250"
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 MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 1162
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 1218
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 1261
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19487463,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 2159
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 2164
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 2173
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 2446
FT /note="Phosphothreonine; by RPS6KB1"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT MOD_RES 2448
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000269|PubMed:26359501"
FT MOD_RES 2478
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 2481
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 236..256
FT /note="HTFEEAEKGFDETLAKEKGMN -> VRDGSTQPLAKHFGLESCSWP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011909"
FT VAR_SEQ 257..2549
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_011910"
FT MUTAGEN 2035
FT /note="S->R: Abolishes interaction with the FKBP1A-
FT rapamycin complex."
FT /evidence="ECO:0000269|PubMed:7809080"
FT CONFLICT 33
FT /note="N -> K (in Ref. 3; AAH43920)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="R -> C (in Ref. 1; AAF73196)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2549 AA; 288789 MW; 56302E5171FB6DBD CRC64;
MLGTGPAVAT ASAATSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN STRIGRFANY LRNLLPSSDP
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC
KDLMGFGTKP RHITPFTSFQ AVQPQQPNAL VGLLGYSSPQ GLMGFGTSPS PAKSTLVESR
CCRDLMEEKF DQVCQWVLKC RSSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKTVQVDA
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVA 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
VFMHDNSQGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEVPLP SRKAALETVD
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSS QGDALASGPV ETGPMKKLHV
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAS GVLEYAMKHF
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KEDPELMLGR MRCLEALGEW GQLHQQCCEK
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD
PSRQLDHPLP TAHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAASAAA ATSTEGSNSE SEAESNENSP
TPSPLQKKVT EDLSKTLLLY 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 GLDGNYRTTC
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG
VELGEPAHKK AGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD
VPTQVELLIK QATSHENLCQ CYIGWCPFW
