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 27-MAR-2024, entry version 204.
DE RecName: Full=Serine/threonine-protein kinase mTOR {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000269|PubMed:11792863, 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:0000303|PubMed:15545625, ECO:0000312|MGI:MGI:1928394};
GN 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, ACTIVITY REGULATION, MUTAGENESIS
RP 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 DISRUPTION PHENOTYPE.
RX PubMed=15485918; DOI=10.1128/mcb.24.21.9508-9516.2004;
RA Gangloff Y.G., Mueller M., Dann S.G., Svoboda P., Sticker M., Spetz J.F.,
RA Um S.H., Brown E.J., Cereghini S., Thomas G., Kozma S.C.;
RT "Disruption of the mouse mTOR gene leads to early postimplantation
RT lethality and prohibits embryonic stem cell development.";
RL Mol. Cell. Biol. 24:9508-9516(2004).
RN [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP FUNCTION.
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
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 [24]
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 [25]
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 [26]
RP PHOSPHORYLATION AT SER-2448.
RX PubMed=24187137; DOI=10.1074/jbc.m113.500736;
RA Seldin M.M., Lei X., Tan S.Y., Stanson K.P., Wei Z., Wong G.W.;
RT "Skeletal muscle-derived myonectin activates the mammalian target of
RT rapamycin (mTOR) pathway to suppress autophagy in liver.";
RL J. Biol. Chem. 288:36073-36082(2013).
RN [27]
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 [28]
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 [29]
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 [30]
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).
RN [31]
RP PHOSPHORYLATION AT SER-2159, AND MUTAGENESIS OF SER-2159.
RX PubMed=29150432; DOI=10.15252/embj.201696164;
RA Bodur C., Kazyken D., Huang K., Ekim Ustunel B., Siroky K.A., Tooley A.S.,
RA Gonzalez I.E., Foley D.H., Acosta-Jaquez H.A., Barnes T.M., Steinl G.K.,
RA Cho K.W., Lumeng C.N., Riddle S.M., Myers M.G. Jr., Fingar D.C.;
RT "The IKK-related kinase TBK1 activates mTORC1 directly in response to
RT growth factors and innate immune agonists.";
RL EMBO J. 37:19-38(2018).
RN [32]
RP FUNCTION.
RX PubMed=34289345; DOI=10.1016/j.cell.2021.06.028;
RA Evavold C.L., Hafner-Bratkovic I., Devant P., D'Andrea J.M., Ngwa E.M.,
RA Borsic E., Doench J.G., LaFleur M.W., Sharpe A.H., Thiagarajah J.R.,
RA Kagan J.C.;
RT "Control of gasdermin D oligomerization and pyroptosis by the Ragulator-
RT Rag-mTORC1 pathway.";
RL Cell 184:4495-4511(2021).
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:15485918, PubMed:16221682, PubMed:16915281,
CC PubMed:16962653, PubMed:18046414, PubMed:19440205, PubMed:21659604).
CC MTOR directly or indirectly regulates the phosphorylation of at least
CC 800 proteins (PubMed:15467718, PubMed:15545625, PubMed:16221682,
CC PubMed:16915281, PubMed:16962653, PubMed:18046414, PubMed:19440205,
CC PubMed:21659604). Functions as part of 2 structurally and functionally
CC distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2)
CC (PubMed:15467718, PubMed:16962653, PubMed:21659604). In response to
CC nutrients, growth factors or amino acids, mTORC1 is recruited to the
CC lysosome membrane and promotes protein, lipid and nucleotide synthesis
CC by phosphorylating key regulators of mRNA translation and ribosome
CC synthesis (PubMed:15485918). This includes phosphorylation of EIF4EBP1
CC and release of its inhibition toward the elongation initiation factor
CC 4E (eiF4E) (PubMed:15485918). Moreover, phosphorylates and activates
CC RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the
CC activity of their downstream targets including ribosomal protein S6,
CC eukaryotic translation initiation factor EIF4B, and the inhibitor of
CC translation initiation PDCD4 (PubMed:15485918). Stimulates the
CC pyrimidine biosynthesis pathway, both by acute regulation through
CC RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and
CC delayed regulation, through transcriptional enhancement of the pentose
CC phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate
CC (PRPP), an allosteric activator of CAD at a later step in synthesis,
CC this function is dependent on the mTORC1 complex (By similarity).
CC Regulates ribosome synthesis by activating RNA polymerase III-dependent
CC transcription through phosphorylation and inhibition of MAF1 an RNA
CC polymerase III-repressor (By similarity). Activates dormant ribosomes
CC by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation
CC and reactivation of translation (By similarity). In parallel to protein
CC synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and
CC LPIN1 (PubMed:11792863). To maintain energy homeostasis mTORC1 may also
CC regulate mitochondrial biogenesis through regulation of PPARGC1A
CC (PubMed:18046414). In the same time, mTORC1 inhibits catabolic
CC pathways: negatively regulates autophagy through phosphorylation of
CC ULK1 (PubMed:21258367). Under nutrient sufficiency, phosphorylates ULK1
CC at 'Ser-758', disrupting the interaction with AMPK and preventing
CC activation of ULK1 (PubMed:21258367). Also prevents autophagy through
CC phosphorylation of the autophagy inhibitor DAP (By similarity). Also
CC prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich
CC conditions (By similarity). Prevents autophagy by mediating
CC phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate
CC ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (By
CC similarity). mTORC1 exerts a feedback control on upstream growth factor
CC signaling that includes phosphorylation and activation of GRB10 a INSR-
CC dependent signaling suppressor (PubMed:21659604). Among other potential
CC targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (By
CC similarity). The mTORC1 complex is inhibited in response to starvation
CC and amino acid depletion (By similarity). The non-canonical mTORC1
CC complex, which acts independently of RHEB, specifically mediates
CC phosphorylation of MiT/TFE factors TFEB and TFE3 in the presence of
CC nutrients, 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 The mTORC1 complex regulates pyroptosis in macrophages by promoting
CC GSDMD oligomerization (PubMed:34289345). MTOR phosphorylates RPTOR
CC which in turn inhibits mTORC1 (PubMed:19346248). As part of the mTORC2
CC complex MTOR may regulate other cellular processes including survival
CC and organization of the cytoskeleton. mTORC2 plays a critical role in
CC the phosphorylation at 'Ser-473' of AKT1, a pro-survival effector of
CC phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2
CC may regulate the actin cytoskeleton, through phosphorylation of PRKCA,
CC PXN and activation of the Rho-type guanine nucleotide exchange factors
CC RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of
CC SGK1 at 'Ser-422' (By similarity). Regulates osteoclastogenesis by
CC adjusting the expression of CEBPB isoforms (PubMed:19440205). Plays an
CC important regulatory role in the circadian clock function; regulates
CC period length and rhythm amplitude of the suprachiasmatic nucleus (SCN)
CC and liver clocks (PubMed:29750810). {ECO:0000250|UniProtKB:P42345,
CC ECO:0000269|PubMed:11792863, ECO:0000269|PubMed:15467718,
CC ECO:0000269|PubMed:15485918, 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:19346248, ECO:0000269|PubMed:19440205,
CC ECO:0000269|PubMed:21258367, ECO:0000269|PubMed:21659604,
CC ECO:0000269|PubMed:27913603, ECO:0000269|PubMed:29750810,
CC ECO:0000269|PubMed:34289345}.
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: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: The mTORC1 complex is activated in response to
CC nutrients, growth factors or amino acids: activation requires
CC relocalization of the mTORC1 complex to lysosomes that is mediated by
CC the Ragulator complex, SLC38A9, and the Rag GTPases RagA/RRAGA,
CC RagB/RRAGB, RagC/RRAGC and RagD/RRAGD (By similarity). Activation of
CC mTORC1 by growth factors such as insulin involves AKT1-mediated
CC phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB
CC GTPase a potent activator of the protein kinase activity of mTORC1 (By
CC similarity). Insulin-stimulated and amino acid-dependent
CC phosphorylation at Ser-1261 promotes autophosphorylation and the
CC activation of mTORC1 (PubMed:19487463). On the other hand, low cellular
CC energy levels can inhibit mTORC1 through activation of PRKAA1 while
CC hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may
CC also require PRKAA1 (PubMed:15545625). The kinase activity of MTOR
CC within the mTORC1 complex is positively regulated by MLST8 (By
CC similarity). The kinase activity of MTOR is inhibited by DEPTOR and
CC AKT1S1 (By similarity). The non-canonical mTORC1 complex is independent
CC of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE
CC factors TFEB and TFE3 but not other mTORC1 substrates: it is activated
CC by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD (By
CC similarity). MTOR is the target of the immunosuppressive and anti-
CC cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and
CC specifically inhibits its kinase activity (PubMed:7809080). mTORC2 is
CC also activated by growth factors, but seems to be nutrient-insensitive
CC (By similarity). mTORC2 may also be regulated by RHEB but in an
CC indirect manner through the PI3K signaling pathway (By similarity).
CC {ECO:0000250|UniProtKB:P42345, ECO:0000269|PubMed:15545625,
CC ECO:0000269|PubMed:19487463, ECO:0000269|PubMed:7809080}.
CC -!- SUBUNIT: Part of the mechanistic target of rapamycin complex 1 (mTORC1)
CC which contains MTOR, MLST8 and RPTOR (PubMed:20801936). 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 (By similarity). It
CC has a rhomboid shape and a central cavity, the dimeric interfaces are
CC formed by interlocking interactions between the two MTOR and the two
CC RPTOR subunits (By similarity). The MLST8 subunit forms distal foot-
CC like protuberances, and contacts only one MTOR within the complex,
CC while the small AKT1S1/PRAS40 localizes to the midsection of the
CC central core, in close proximity to RPTOR (By similarity). mTORC1
CC associates with AKT1S1/PRAS40, which inhibits its activity by blocking
CC MTOR substrate-recruitment site (By similarity). Part of the
CC mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR,
CC MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15467718,
CC PubMed:16962653). Interacts with PLPP7 and PML (PubMed:16915281,
CC PubMed:19704009). 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:20801936).
CC mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity
CC (By similarity). 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 UBQLN1 (By similarity). Interacts with TTI1 and TELO2
CC (By similarity). Interacts with CLIP1; phosphorylates and regulates
CC CLIP1 (By similarity). Interacts with NBN (By similarity). Interacts
CC with HTR6 (PubMed:23027611). Interacts with BRAT1 (By similarity).
CC Interacts with MEAK7 (via C-terminal domain); the interaction increases
CC upon nutrient stimulation (By similarity). Interacts with TM4SF5; the
CC interaction is positively regulated by arginine and is negatively
CC regulated by leucine (By similarity). Interacts with GPR137B (By
CC similarity). Interacts with NCKAP1L (By similarity). Interacts with
CC TPCN1 and TPCN2; the interaction is required for TPCN1 and TPCN2
CC sensitivity to ATP (By similarity). Interacts with ATP6V1A and with
CC CRYAB, forming a ternary complex (PubMed:31786107). Interacts with
CC SLC38A7; this interaction mediates the recruitment of mTORC1 to the
CC lysosome and its subsequent activation (By similarity).
CC {ECO:0000250|UniProtKB:P42345, ECO:0000269|PubMed:15467718,
CC ECO:0000269|PubMed:16915281, ECO:0000269|PubMed:16962653,
CC ECO:0000269|PubMed:19704009, ECO:0000269|PubMed:20801936,
CC ECO:0000269|PubMed:23027611, ECO:0000269|PubMed:31786107}.
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: Lysosome membrane {ECO:0000250|UniProtKB:P42345};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:P42345}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:P42345}. 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:0000250|UniProtKB:P42345}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P42345}. Cytoplasm {ECO:0000269|PubMed:11930000,
CC ECO:0000269|PubMed:16915281}. Nucleus {ECO:0000269|PubMed:16915281}.
CC Nucleus, PML body {ECO:0000269|PubMed:16915281}. Microsome membrane
CC {ECO:0000250|UniProtKB:P42345}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:P42345}. Note=Shuttles between cytoplasm and
CC nucleus (PubMed:16915281). Accumulates in the nucleus in response to
CC hypoxia (PubMed:16915281). Targeting to lysosomes depends on amino acid
CC availability and RRAGA and RRAGB (By similarity). Lysosome targeting
CC also depends on interaction with MEAK7 (By similarity). Translocates to
CC the 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|UniProtKB:P42345}.
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|UniProtKB:P42345}.
CC -!- PTM: Autophosphorylates when part of mTORC1 or mTORC2 (By similarity).
CC Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes
CC autophosphorylation (PubMed:19487463). Phosphorylation in the kinase
CC domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40
CC and leads to increased intrinsic mTORC1 kinase activity (By
CC similarity). Phosphorylation at Ser-2159 by TBK1 in response to growth
CC factors and pathogen recognition receptors promotes mTORC1 activity
CC (PubMed:29150432). Phosphorylation at Thr-2173 in the ATP-binding
CC region by AKT1 strongly reduces kinase activity (By similarity).
CC {ECO:0000250|UniProtKB:P42345, ECO:0000269|PubMed:19487463,
CC ECO:0000269|PubMed:29150432}.
CC -!- DISRUPTION PHENOTYPE: Early embryonic lethality (PubMed:15485918).
CC Embryonic development stops at 5.5 dpc and embryos are severely runted
CC and display an aberrant developmental phenotype (PubMed:15485918).
CC Embryos are able to implant due to a maternal mRNA contribution, which
CC persists during preimplantation development (PubMed:15485918). Embryos
CC display a lesion in inner cell mass proliferation, due to the inability
CC to establish embryonic stem cells (PubMed:15485918).
CC {ECO:0000269|PubMed:15485918}.
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 GlyGen; Q9JLN9; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9JLN9; -.
DR PhosphoSitePlus; Q9JLN9; -.
DR SwissPalm; Q9JLN9; -.
DR EPD; Q9JLN9; -.
DR jPOST; Q9JLN9; -.
DR MaxQB; Q9JLN9; -.
DR PaxDb; 10090-ENSMUSP00000099510; -.
DR PeptideAtlas; Q9JLN9; -.
DR ProteomicsDB; 287515; -. [Q9JLN9-1]
DR ProteomicsDB; 287516; -. [Q9JLN9-2]
DR Pumba; Q9JLN9; -.
DR Antibodypedia; 3566; 2157 antibodies from 53 providers.
DR DNASU; 56717; -.
DR Ensembl; ENSMUST00000057580.8; ENSMUSP00000054164.8; ENSMUSG00000028991.16. [Q9JLN9-2]
DR Ensembl; ENSMUST00000103221.10; ENSMUSP00000099510.4; ENSMUSG00000028991.16. [Q9JLN9-1]
DR GeneID; 56717; -.
DR KEGG; mmu:56717; -.
DR UCSC; uc008vuq.3; mouse. [Q9JLN9-2]
DR UCSC; uc008vur.2; mouse. [Q9JLN9-1]
DR AGR; MGI:1928394; -.
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; MRQHSAK; -.
DR OrthoDB; 8448at2759; -.
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 118 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 99 other cell types or 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: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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
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: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:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
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:0031670; P:cellular response to nutrient; ISO:MGI.
DR GO; GO:0031669; P:cellular response to nutrient levels; IDA:UniProtKB.
DR GO; GO:0071470; P:cellular response to osmotic stress; NAS:ComplexPortal.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; NAS:ComplexPortal.
DR GO; GO:0006974; P:DNA damage response; NAS: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; NAS: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:1905672; P:negative regulation of lysosome organization; ISS:UniProtKB.
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:1900181; P:negative regulation of protein localization to nucleus; ISS:UniProtKB.
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:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IDA:MGI.
DR GO; GO:0030307; P:positive regulation of cell growth; NAS: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:1904037; P:positive regulation of epithelial cell apoptotic process; 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; NAS: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:0043525; P:positive regulation of neuron apoptotic process; 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; NAS:ComplexPortal.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:MGI.
DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP: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:0045948; P:positive regulation of translational initiation; 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:0031648; P:protein destabilization; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:2000785; P:regulation of autophagosome assembly; 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: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:0051896; P:regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; 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: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; IMP:UniProtKB.
DR GO; GO:0038202; P:TORC1 signaling; ISS:UniProtKB.
DR GO; GO:0038203; P:TORC2 signaling; ISO:MGI.
DR GO; GO:0008542; P:visual learning; ISO:MGI.
DR GO; GO:0050882; P:voluntary musculoskeletal movement; IMP:MGI.
DR CDD; cd05169; PIKKc_TOR; 1.
DR Gene3D; 1.20.120.150; FKBP12-rapamycin binding domain; 1.
DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 4.
DR Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR003152; FATC_dom.
DR InterPro; IPR009076; FRB_dom.
DR InterPro; IPR036738; FRB_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024585; mTOR_dom.
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_cat.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR PANTHER; PTHR11139; ATAXIA TELANGIECTASIA MUTATED ATM -RELATED; 1.
DR PANTHER; PTHR11139:SF9; SERINE_THREONINE-PROTEIN KINASE MTOR; 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 SMART; SM01345; Rapamycin_bind; 1.
DR SUPFAM; SSF48371; ARM repeat; 1.
DR SUPFAM; SSF47212; FKBP12-rapamycin-binding domain of FKBP-rapamycin-associated protein (FRAP); 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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; Magnesium;
KW Membrane; Metal-binding; Microsome; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; TPR repeat;
KW 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|UniProtKB:P42345"
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 /evidence="ECO:0000269|PubMed:7809080"
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|UniProtKB:P42345"
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 BINDING 2165
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2187
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2190
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2225
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2238
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2239
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2245
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2343
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2345
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2356
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P42345"
FT BINDING 2357
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P42345"
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; by TBK1"
FT /evidence="ECO:0000269|PubMed:29150432"
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:24187137,
FT 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 MUTAGEN 2159
FT /note="S->A: Knockin macrophages display reduced mTORC1
FT activity."
FT /evidence="ECO:0000269|PubMed:29150432"
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
//
