CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007559
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase mTOR 
Protein Synonyms/Alias
 FK506-binding protein 12-rapamycin complex-associated protein 1; FKBP12-rapamycin complex-associated protein; Mammalian target of rapamycin; mTOR; Mechanistic target of rapamycin; Rapamycin and FKBP12 target 1; Rapamycin target protein 1 
Gene Name
 MTOR 
Gene Synonyms/Alias
 FRAP; FRAP1; FRAP2; RAFT1; RAPT1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
42ETRAKAAKELQHYVTubiquitination[1]
84SSDANERKGGILAIAubiquitination[1]
128VVMEMASKAIGRLAMubiquitination[1, 2]
243HTFEEAEKGFDETLAubiquitination[2]
251GFDETLAKEKGMNRDubiquitination[1, 2]
298QQQLVHDKYCKDLMGubiquitination[1]
301LVHDKYCKDLMGFGTubiquitination[1]
309DLMGFGTKPRHITPFubiquitination[1, 3]
369CRDLMEEKFDQVCQWubiquitination[1]
379QVCQWVLKCRNSKNSubiquitination[1]
384VLKCRNSKNSLIQMTubiquitination[1]
426HVLSCVKKEKERTAAubiquitination[1]
449VAVRSEFKVYLPRVLubiquitination[1]
616HFLNSEHKEIRMEAAubiquitination[1]
777PYMEPILKALILKLKubiquitination[1, 2]
898LGALDPYKHKVNIGMubiquitination[2, 3, 4, 5, 6]
900ALDPYKHKVNIGMIDubiquitination[1, 2, 3]
1133EAPLPSRKAALETVDubiquitination[1]
1186SLVFQLGKKYQIFIPubiquitination[2, 7]
1187LVFQLGKKYQIFIPMubiquitination[1]
1197IFIPMVNKVLVRHRIubiquitination[1]
1218VLICRIVKGYTLADEacetylation[8, 9]
1218VLICRIVKGYTLADEubiquitination[1, 2]
1256PVETGPMKKLHVSTIubiquitination[1, 2, 5, 7]
1257VETGPMKKLHVSTINubiquitination[1, 3]
1267VSTINLQKAWGAARRubiquitination[1]
1293RLSLELLKDSSSPSLubiquitination[1, 2, 4, 6]
1395AKCRAYAKALHYKELubiquitination[1]
1400YAKALHYKELEFQKGubiquitination[1, 3]
1406YKELEFQKGPTPAILubiquitination[1, 2, 7]
1471DKKMDTNKDDPELMLubiquitination[1]
1511VNDETQAKMARMAAAubiquitination[1, 2, 7]
1566LAQQCIDKARDLLDAubiquitination[1]
1635RIVEDWQKILMVRSLubiquitination[1]
1655EDMRTWLKYASLCGKubiquitination[1, 4, 6]
1662KYASLCGKSGRLALAubiquitination[1]
2045YFGERNVKGMFEVLEubiquitination[1]
2066ERGPQTLKETSFNQAubiquitination[1, 2, 7]
2166SLQVITSKQRPRKLTubiquitination[1]
2218NDPTSLRKNLSIQRYubiquitination[1]
2283DHLTLMQKVEVFEHAubiquitination[7]
2301TAGDDLAKLLWLKSPubiquitination[7]
2306LAKLLWLKSPSSEVWubiquitination[7]
2370EVAMTREKFPEKIPFubiquitination[1]
2374TREKFPEKIPFRLTRubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [4] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [5] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [6] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [7] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [8] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E). Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A. mTORC1 also negatively regulates autophagy through phosphorylation of ULK1. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1. Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP. mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules. As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton. Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro- survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. mTORC2 may regulate the actin cytoskeleton, through phosphorylation of PRKCA, PXN and activation of the Rho- type guanine nucleotide exchange factors RHOA and RAC1A or RAC1B. mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422'. 
Sequence Annotation
 REPEAT 16 53 HEAT 1.
 REPEAT 650 688 HEAT 2.
 REPEAT 859 897 HEAT 3.
 REPEAT 988 1025 HEAT 4.
 REPEAT 1069 1106 HEAT 5.
 REPEAT 1109 1148 HEAT 6.
 REPEAT 1150 1186 HEAT 7.
 DOMAIN 1382 1982 FAT.
 DOMAIN 2182 2516 PI3K/PI4K.
 DOMAIN 2517 2549 FATC.
 REGION 2012 2144 Sufficient for interaction with the
 MOD_RES 567 567 Phosphoserine.
 MOD_RES 1162 1162 Phosphothreonine.
 MOD_RES 1218 1218 N6-acetyllysine.
 MOD_RES 1261 1261 Phosphoserine.
 MOD_RES 2159 2159 Phosphoserine; by autocatalysis.
 MOD_RES 2164 2164 Phosphothreonine; by autocatalysis (By
 MOD_RES 2446 2446 Phosphothreonine; by autocatalysis.
 MOD_RES 2478 2478 Phosphoserine.
 MOD_RES 2481 2481 Phosphoserine.  
Keyword
 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Kinase; Lysosome; Membrane; Mitochondrion; Mitochondrion outer membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 2549 AA 
Protein Sequence
MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES 60
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP 120
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP 180
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE 240
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC 300
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR 360
CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV 420
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA 480
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL 540
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT 600
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL 660
VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS 720
MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI 780
LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA 840
LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK 900
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR 960
DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV 1020
SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR 1080
VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD 1140
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 1200
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV 1260
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA 1320
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI 1380
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF 1440
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK 1500
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA 1560
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW 1620
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD 1680
PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK 1740
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA 1800
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP 1860
TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN 1920
EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS 1980
KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG 2040
ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA 2100
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL 2160
QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL 2220
SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL 2280
MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH 2340
PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC 2400
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG 2460
VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD 2520
VPTQVELLIK QATSHENLCQ CYIGWCPFW 2549 
Gene Ontology
 GO:0012505; C:endomembrane system; IDA:UniProtKB.
 GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
 GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
 GO:0005764; C:lysosome; IDA:UniProtKB.
 GO:0016020; C:membrane; IDA:UniProtKB.
 GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell.
 GO:0070438; C:mTOR-FKBP12-rapamycin complex; IEA:Compara.
 GO:0005942; C:phosphatidylinositol 3-kinase complex; NAS:UniProtKB.
 GO:0016605; C:PML body; IEA:UniProtKB-SubCell.
 GO:0031931; C:TORC1 complex; IDA:UniProtKB.
 GO:0031932; C:TORC2 complex; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0008144; F:drug binding; IEA:InterPro.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0043022; F:ribosome binding; IEA:Compara.
 GO:0001030; F:RNA polymerase III type 1 promoter DNA binding; IDA:UniProtKB.
 GO:0001031; F:RNA polymerase III type 2 promoter DNA binding; IDA:UniProtKB.
 GO:0001032; F:RNA polymerase III type 3 promoter DNA binding; IDA:UniProtKB.
 GO:0001156; F:TFIIIC-class transcription factor binding; IDA:UniProtKB.
 GO:0016049; P:cell growth; IDA:UniProtKB.
 GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
 GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0007281; P:germ cell development; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome.
 GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
 GO:0045792; P:negative regulation of cell size; IEA:Compara.
 GO:0016242; P:negative regulation of macroautophagy; IEA:Compara.
 GO:0051534; P:negative regulation of NFAT protein import into nucleus; IEA:Compara.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018105; P:peptidyl-serine phosphorylation; IMP:UniProtKB.
 GO:0018107; P:peptidyl-threonine phosphorylation; IEA:Compara.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0030838; P:positive regulation of actin filament polymerization; IEA:Compara.
 GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Compara.
 GO:0010592; P:positive regulation of lamellipodium assembly; IEA:Compara.
 GO:0046889; P:positive regulation of lipid biosynthetic process; IMP:UniProtKB.
 GO:0010831; P:positive regulation of myotube differentiation; IEA:Compara.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Compara.
 GO:0051897; P:positive regulation of protein kinase B signaling cascade; IEA:Compara.
 GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
 GO:0051496; P:positive regulation of stress fiber assembly; IEA:Compara.
 GO:0045945; P:positive regulation of transcription from RNA polymerase III promoter; IMP:UniProtKB.
 GO:0045727; P:positive regulation of translation; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:MGI.
 GO:0030163; P:protein catabolic process; TAS:UniProtKB.
 GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
 GO:0043610; P:regulation of carbohydrate utilization; IEA:Compara.
 GO:0031998; P:regulation of fatty acid beta-oxidation; IEA:Compara.
 GO:0005979; P:regulation of glycogen biosynthetic process; IEA:Compara.
 GO:0045859; P:regulation of protein kinase activity; IEA:Compara.
 GO:0032314; P:regulation of Rac GTPase activity; IEA:Compara.
 GO:0032095; P:regulation of response to food; IEA:Compara.
 GO:0043200; P:response to amino acid stimulus; IDA:UniProtKB.
 GO:0007584; P:response to nutrient; NAS:UniProtKB.
 GO:0031529; P:ruffle organization; IEA:Compara.
 GO:0031295; P:T cell costimulation; TAS:Reactome.
 GO:0031929; P:TOR signaling cascade; IMP:UniProtKB. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR024585; DUF3385_TOR.
 IPR003152; FATC.
 IPR011009; Kinase-like_dom.
 IPR000403; PI3/4_kinase_cat_dom.
 IPR018936; PI3/4_kinase_CS.
 IPR003151; PIK-rel_kinase_FAT.
 IPR014009; PIK_FAT.
 IPR009076; Rapamycin-bd_dom.
 IPR026683; TOR/Smg1.
 IPR011990; TPR-like_helical. 
Pfam
 PF11865; DUF3385
 PF02259; FAT
 PF02260; FATC
 PF00454; PI3_PI4_kinase
 PF08771; Rapamycin_bind 
SMART
 SM00146; PI3Kc 
PROSITE
 PS51189; FAT
 PS51190; FATC
 PS50077; HEAT_REPEAT
 PS00915; PI3_4_KINASE_1
 PS00916; PI3_4_KINASE_2
 PS50290; PI3_4_KINASE_3 
PRINTS