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P42345 (MTOR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase mTOR

EC=2.7.11.1
Alternative name(s):
FK506-binding protein 12-rapamycin complex-associated protein 1
FKBP12-rapamycin complex-associated protein
Mammalian target of rapamycin
Short name=mTOR
Mechanistic target of rapamycin
Rapamycin and FKBP12 target 1
Rapamycin target protein 1
Gene names
Name:MTOR
Synonyms:FRAP, FRAP1, FRAP2, RAFT1, RAPT1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length2549 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins. 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. Stimulates the pyrimidine biosynthesis pathway, both by acute regulation through RPS6KB1-mediated phosphorylation of the biosynthetic enzyme CAD, and delayed regulation, through transcriptional enhancement of the pentose phosphate pathway which produces 5-phosphoribosyl-1-pyrophosphate (PRPP), an allosteric activator of CAD at a later step in synthesis, this function is dependent on the mTORC1 complex. Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an 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'. Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.17 Ref.18 Ref.19 Ref.21 Ref.23 Ref.26 Ref.27 Ref.30 Ref.37 Ref.41 Ref.46 Ref.49 Ref.50

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. Activation by amino acids requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD. On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. MTOR phosphorylates RPTOR which in turn inhibits mTORC1. MTOR is the target of the immunosuppressive and anti-cancer drug rapamycin which acts in complex with FKBP1A/FKBP12, and specifically inhibits its kinase activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. It may be regulated by RHEB but in an indirect manner through the PI3K signaling pathway. Ref.16 Ref.19 Ref.25 Ref.30 Ref.31

Subunit structure

Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. The mTORC1 complex is a 1 Md obligate dimer of two stoichiometric heterotetramers with overall dimensions of 290 A x 210 A x 135 A. It has a rhomboid shape and a central cavity, the dimeric interfaces are formed by interlocking interactions between the two MTOR and the two RPTOR subunits. the MLST8 subunits forms distal foot-like protuberances, and contacts only one MTOR within the complex, while the small PRAS40 localizes to the midsection of the central core, in close proximity to RPTOR. Part of the mammalian target of rapamycin COmplex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Interacts with PPAPDC3 and PML. Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex. Interacts with UBQLN1. Interacts with TTI1 and TELO2. Interacts with CLIP1; phosphorylates and regulates CLIP1. Interacts with NBN. Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.17 Ref.18 Ref.21 Ref.24 Ref.25 Ref.26 Ref.31 Ref.38 Ref.39 Ref.40 Ref.48 Ref.54 Ref.55

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome. Cytoplasm By similarity. NucleusPML body By similarity. Note: Shuttles between cytoplasm and nucleus. Accumulates in the nucleus in response to hypoxia By similarity. Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB. Ref.8 Ref.15 Ref.20 Ref.30 Ref.36

Tissue specificity

Expressed in numerous tissues, with highest levels in testis. Ref.7 Ref.14

Domain

The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center (Ref.55). Ref.55

The FAT domain forms three discontinuous subdomains of alpha-helical TPR repeats plus a single subdomain of HEAT repeats. The four domains pack sequentially to form a C-shaped a-solenoid that clamps onto the kinase domain (Ref.55). Ref.55

Post-translational modification

Autophosphorylates when part of mTORC1 or mTORC2. Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation. Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and PRAS40 and leads to increased intrinsic mTORC1 kinase activity.

Sequence similarities

Belongs to the PI3/PI4-kinase family.

Contains 1 FAT domain.

Contains 1 FATC domain.

Contains 32 HEAT repeats.

Contains 1 PI3K/PI4K domain.

Contains 16 TPR repeats.

Sequence caution

The sequence AAC39933.1 differs from that shown. Reason: Frameshift at positions 956 and 999.

The sequence BAE06077.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCytoplasm
Endoplasmic reticulum
Golgi apparatus
Lysosome
Membrane
Mitochondrion
Mitochondrion outer membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
TPR repeat
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

T cell costimulation

Traceable author statement. Source: Reactome

TOR signaling

Inferred from mutant phenotype Ref.21PubMed 17028174Ref.27. Source: UniProtKB

cell growth

Inferred from direct assay Ref.27. Source: UniProtKB

cellular response to hypoxia

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to nutrient levels

Inferred from sequence or structural similarity. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

germ cell development

Inferred from electronic annotation. Source: Ensembl

growth

Non-traceable author statement PubMed 15539461. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

negative regulation of NFAT protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

negative regulation of autophagy

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell size

Inferred from electronic annotation. Source: Ensembl

negative regulation of macroautophagy

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

peptidyl-serine phosphorylation

Inferred from mutant phenotype Ref.37. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from electronic annotation. Source: Ensembl

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

phosphorylation

Inferred from direct assay Ref.9. Source: UniProtKB

positive regulation of actin filament polymerization

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from mutant phenotype PubMed 17028174. Source: UniProtKB

positive regulation of lamellipodium assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of lipid biosynthetic process

Inferred from mutant phenotype Ref.27. Source: UniProtKB

positive regulation of myotube differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from direct assay PubMed 20233713. Source: UniProtKB

positive regulation of stress fiber assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase III promoter

Inferred from mutant phenotype PubMed 20233713. Source: UniProtKB

positive regulation of translation

Inferred from direct assay Ref.27. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.21. Source: MGI

protein catabolic process

Traceable author statement Ref.9. Source: UniProtKB

protein phosphorylation

Inferred from direct assay Ref.26. Source: UniProtKB

regulation of Rac GTPase activity

Inferred from electronic annotation. Source: Ensembl

regulation of actin cytoskeleton organization

Inferred from mutant phenotype Ref.21. Source: UniProtKB

regulation of carbohydrate utilization

Inferred from electronic annotation. Source: Ensembl

regulation of fatty acid beta-oxidation

Inferred from electronic annotation. Source: Ensembl

regulation of glycogen biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

regulation of response to food

Inferred from electronic annotation. Source: Ensembl

response to amino acid

Inferred from direct assay Ref.30. Source: UniProtKB

response to nutrient

Non-traceable author statement PubMed 15539461. Source: UniProtKB

response to stress

Inferred from mutant phenotype PubMed 17028174. Source: UniProtKB

ruffle organization

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement PubMed 15539461. Source: UniProtKB

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

PML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

TORC1 complex

Inferred from direct assay Ref.26. Source: UniProtKB

TORC2 complex

Inferred from direct assay Ref.26. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.9Ref.36. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

endomembrane system

Inferred from direct assay Ref.30. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

lysosome

Inferred from direct assay Ref.36. Source: UniProtKB

mTOR-FKBP12-rapamycin complex

Inferred from electronic annotation. Source: Ensembl

membrane

Inferred from direct assay Ref.9. Source: UniProtKB

mitochondrial outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

phosphatidylinositol 3-kinase complex

Non-traceable author statement PubMed 15539461. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

RNA polymerase III type 1 promoter DNA binding

Inferred from direct assay PubMed 20233713. Source: UniProtKB

RNA polymerase III type 2 promoter DNA binding

Inferred from direct assay PubMed 20233713. Source: UniProtKB

RNA polymerase III type 3 promoter DNA binding

Inferred from direct assay PubMed 20233713. Source: UniProtKB

TFIIIC-class transcription factor binding

Inferred from direct assay PubMed 20543138. Source: UniProtKB

drug binding

Inferred from electronic annotation. Source: InterPro

kinase activity

Traceable author statement Ref.9. Source: UniProtKB

phosphoprotein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.21. Source: UniProtKB

ribosome binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 25492549Serine/threonine-protein kinase mTOR
PRO_0000088808

Regions

Repeat16 – 5338HEAT 1
Repeat55 – 9945HEAT 2
Repeat100 – 13738HEAT 3
Repeat138 – 17942HEAT 4
Repeat180 – 22041HEAT 5
Repeat222 – 27655HEAT 6
Repeat277 – 31337HEAT 7
Repeat314 – 36451HEAT 8
Repeat365 – 40945HEAT 9
Repeat410 – 44536HEAT 10
Repeat446 – 49449HEAT 11
Repeat495 – 52935HEAT 12
Repeat530 – 56334HEAT 13
Repeat564 – 59633HEAT 14
Repeat597 – 63640HEAT 15
Repeat637 – 68347HEAT 16
Repeat686 – 72439HEAT 17
Repeat727 – 76640HEAT 18
Repeat769 – 81143HEAT 19
Repeat814 – 85340HEAT 20
Repeat857 – 89337HEAT 21
Repeat894 – 94249HEAT 22
Repeat943 – 98846HEAT 23
Repeat989 – 102739HEAT 24
Repeat1029 – 106840HEAT 25
Repeat1069 – 110537HEAT 26
Repeat1106 – 114439HEAT 27
Repeat1145 – 118844HEAT 28
Repeat1189 – 122537HEAT 29
Repeat1226 – 127348HEAT 30
Repeat1274 – 131138HEAT 31
Repeat1312 – 134534HEAT 32
Repeat1346 – 138237TPR 1
Domain1382 – 1982601FAT
Repeat1383 – 140826TPR 2
Repeat1409 – 144234TPR 3
Repeat1443 – 147331TPR 4
Repeat1474 – 150734TPR 5
Repeat1508 – 154134TPR 6
Repeat1542 – 157433TPR 7
Repeat1575 – 161440TPR 8
Repeat1615 – 164935TPR 9
Repeat1650 – 169344TPR 10
Repeat1694 – 173138TPR 11
Repeat1732 – 178655TPR 12
Repeat1787 – 184660TPR 13
Repeat1898 – 193033TPR 14
Repeat1931 – 197040TPR 15
Repeat1971 – 200535TPR 16
Domain2182 – 2516335PI3K/PI4K
Domain2517 – 254933FATC
Region1 – 651651Interaction with NBN
Region2012 – 2144133Sufficient for interaction with the FKBP1A/rapamycin complex By similarity
Region2258 – 229639Interaction with MLST8

Amino acid modifications

Modified residue11N-acetylmethionine Ref.47
Modified residue5671Phosphoserine Ref.28 Ref.33 Ref.42
Modified residue11621Phosphothreonine Ref.42
Modified residue12181N6-acetyllysine Ref.34
Modified residue12611Phosphoserine Ref.32
Modified residue21591Phosphoserine Ref.44
Modified residue21641Phosphothreonine Ref.44
Modified residue24461Phosphothreonine; by RPS6KB1 Ref.22
Modified residue24481Phosphoserine; by RPS6KB1 Ref.22 Ref.35
Modified residue24781Phosphoserine Ref.29
Modified residue24811Phosphoserine; by autocatalysis Ref.29 Ref.44

Natural variations

Natural variant81A → S in a lung large cell carcinoma sample; somatic mutation. Ref.56
VAR_041537
Natural variant1351M → T in a metastatic melanoma sample; somatic mutation. Ref.56
VAR_041538
Natural variant10831M → V. Ref.56
Corresponds to variant rs56164650 [ dbSNP | Ensembl ].
VAR_041539
Natural variant11341A → V. Ref.56
Corresponds to variant rs28730685 [ dbSNP | Ensembl ].
VAR_041540
Natural variant11781S → F. Ref.56
Corresponds to variant rs55975118 [ dbSNP | Ensembl ].
VAR_041541
Natural variant20111M → V in an ovarian mucinous carcinoma sample; somatic mutation. Ref.56
VAR_041542
Natural variant22151S → Y in a colorectal adenocarcinoma sample; somatic mutation. Ref.56
VAR_041543
Natural variant22201L → F Found in a renal cell carcinoma sample; somatic mutation. Ref.57
VAR_064733
Natural variant24061V → A Found in a renal cell carcinoma sample; somatic mutation. Ref.57
VAR_064734
Natural variant24761P → L in a glioblastoma multiforme sample; somatic mutation. Ref.56
VAR_041544

Experimental info

Mutagenesis21591S → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2164. Ref.44
Mutagenesis21591S → D: Stronger phosphorylation of RPS6KB1; when associated with E-2164. Ref.44
Mutagenesis21641T → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2159. Ref.44
Mutagenesis21641T → E: Stronger phosphorylation of RPS6KB1; when associated with D-2159. Ref.44
Mutagenesis23401H → A: Barely detectable kinase activity. Ref.55
Sequence conflict3531K → N in AAC39933. Ref.2
Sequence conflict3591S → N in AAC39933. Ref.2
Sequence conflict3641D → N in AAC39933. Ref.2
Sequence conflict3901M → L in AAC39933. Ref.2
Sequence conflict4301R → L in AAC39933. Ref.2
Sequence conflict455 – 4573VLD → GVE in AAC39933. Ref.2
Sequence conflict4611A → G in AAC39933. Ref.2
Sequence conflict482 – 4843VFT → FFN in AAC39933. Ref.2
Sequence conflict4891L → V in AAC39933. Ref.2
Sequence conflict5131L → I in AAC39933. Ref.2
Sequence conflict5391L → V in AAC39933. Ref.2
Sequence conflict5531R → C in AAC39933. Ref.2
Sequence conflict8571P → L in BAE06077. Ref.3
Sequence conflict10751I → S in AAC39933. Ref.2

Secondary structure

........................................................................................................................................................... 2549
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42345 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 7D9AD6E784882AB4

FASTA2,549288,892
        10         20         30         40         50         60 
MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM ELREMSQEES 

        70         80         90        100        110        120 
TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN ATRIGRFANY LRNLLPSNDP 

       130        140        150        160        170        180 
VVMEMASKAI GRLAMAGDTF TAEYVEFEVK RALEWLGADR NEGRRHAAVL VLRELAISVP 

       190        200        210        220        230        240 
TFFFQQVQPF FDNIFVAVWD PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE 

       250        260        270        280        290        300 
AEKGFDETLA KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC 

       310        320        330        340        350        360 
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS PAKSTLVESR 

       370        380        390        400        410        420 
CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA AFRPSAFTDT QYLQDTMNHV 

       430        440        450        460        470        480 
LSCVKKEKER TAAFQALGLL SVAVRSEFKV YLPRVLDIIR AALPPKDFAH KRQKAMQVDA 

       490        500        510        520        530        540 
TVFTCISMLA RAMGPGIQQD IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL 

       550        560        570        580        590        600 
KMLSLVLMHK PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT 

       610        620        630        640        650        660 
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ VVADVLSKLL 

       670        680        690        700        710        720 
VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL NDQVFEIREL AICTVGRLSS 

       730        740        750        760        770        780 
MNPAFVMPFL RKMLIQILTE LEHSGIGRIK EQSARMLGHL VSNAPRLIRP YMEPILKALI 

       790        800        810        820        830        840 
LKLKDPDPDP NPGVINNVLA TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA 

       850        860        870        880        890        900 
LWTLGQLVAS TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK 

       910        920        930        940        950        960 
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV SMVALMRIFR 

       970        980        990       1000       1010       1020 
DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV IRVCDGAIRE FLFQQLGMLV 

      1030       1040       1050       1060       1070       1080 
SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS TIILLIEQIV VALGGEFKLY LPQLIPHMLR 

      1090       1100       1110       1120       1130       1140 
VFMHDNSPGR IVSIKLLAAI QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD 

      1150       1160       1170       1180       1190       1200 
RLTESLDFTD YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 

      1210       1220       1230       1240       1250       1260 
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV ETGPMKKLHV 

      1270       1280       1290       1300       1310       1320 
STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL RSCWALAQAY NPMARDLFNA 

      1330       1340       1350       1360       1370       1380 
AFVSCWSELN EDQQDELIRS IELALTSQDI AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI 

      1390       1400       1410       1420       1430       1440 
VLLGERAAKC RAYAKALHYK ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF 

      1450       1460       1470       1480       1490       1500 
GELEIQATWY EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK 

      1510       1520       1530       1540       1550       1560 
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL ALHQDLFSLA 

      1570       1580       1590       1600       1610       1620 
QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE EVIQYKLVPE RREIIRQIWW 

      1630       1640       1650       1660       1670       1680 
ERLQGCQRIV EDWQKILMVR SLVVSPHEDM RTWLKYASLC GKSGRLALAH KTLVLLLGVD 

      1690       1700       1710       1720       1730       1740 
PSRQLDHPLP TVHPQVTYAY MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK 

      1750       1760       1770       1780       1790       1800 
QELHKLMARC FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA 

      1810       1820       1830       1840       1850       1860 
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE SEAESTENSP 

      1870       1880       1890       1900       1910       1920 
TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL QDTLRVLTLW FDYGHWPDVN 

      1930       1940       1950       1960       1970       1980 
EALVEGVKAI QIDTWLQVIP QLIARIDTPR PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS 

      1990       2000       2010       2020       2030       2040 
KSTTTARHNA ANKILKNMCE HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG 

      2050       2060       2070       2080       2090       2100 
ERNVKGMFEV LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA 

      2110       2120       2130       2140       2150       2160 
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI IRIQSIAPSL 

      2170       2180       2190       2200       2210       2220 
QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ LFGLVNTLLA NDPTSLRKNL 

      2230       2240       2250       2260       2270       2280 
SIQRYAVIPL STNSGLIGWV PHCDTLHALI RDYREKKKIL LNIEHRIMLR MAPDYDHLTL 

      2290       2300       2310       2320       2330       2340 
MQKVEVFEHA VNNTAGDDLA KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH 

      2350       2360       2370       2380       2390       2400 
PSNLMLDRLS GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC 

      2410       2420       2430       2440       2450       2460 
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS AGQSVEILDG 

      2470       2480       2490       2500       2510       2520 
VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI INRVRDKLTG RDFSHDDTLD 

      2530       2540 
VPTQVELLIK QATSHENLCQ CYIGWCPFW 

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References

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[1]"A mammalian protein targeted by G1-arresting rapamycin-receptor complex."
Brown E.J., Albers M.W., Shin T.B., Ichikawa K., Keith C.T., Lane W.S., Schreiber S.L.
Nature 369:756-758(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Molecular cloning and expression analysis of five novel genes in chromosome 1p36."
Onyango P., Lubyova B., Gardellin P., Kurzbauer R., Weith A.
Genomics 50:187-198(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"Preparation of a set of expression-ready clones of mammalian long cDNAs encoding large proteins by the ORF trap cloning method."
Nakajima D., Saito K., Yamakawa H., Kikuno R.F., Nakayama M., Ohara R., Okazaki N., Koga H., Nagase T., Ohara O.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Cerebellum.
[6]"The human gene for mannan-binding lectin-associated serine protease-2 (MASP-2), the effector component of the lectin route of complement activation, is part of a tightly linked gene cluster on chromosome 1p36.2-3."
Stover C., Endo Y., Takahashi M., Lynch N., Constantinescu C., Vorup-Jensen T., Thiel S., Friedl H., Hankeln T., Hall R., Gregory S., Fujita T., Schwaeble W.
Genes Immun. 2:119-127(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1362-2549.
[7]"RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex."
Chiu M.I., Katz H., Berlin V.
Proc. Natl. Acad. Sci. U.S.A. 91:12574-12578(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1987-2146, TISSUE SPECIFICITY.
Tissue: B-cell.
[8]"Expression, enzyme activity, and subcellular localization of mammalian target of rapamycin in insulin-responsive cells."
Withers D.J., Ouwens D.M., Nave B.T., van der Zon G.C.M., Alarcon C.M., Cardenas M.E., Heitman J., Maassen J.A., Shepherd P.R.
Biochem. Biophys. Res. Commun. 241:704-709(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION.
[9]"Characterization of ubiquilin 1, an mTOR-interacting protein."
Wu S., Mikhailov A., Kallo-Hosein H., Hara K., Yonezawa K., Avruch J.
Biochim. Biophys. Acta 1542:41-56(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UBQLN1.
[10]"mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the growth machinery."
Kim D.-H., Sarbassov D.D., Ali S.M., King J.E., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M.
Cell 110:163-175(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NUTRIENT-DEPENDENT CELL GROWTH, FUNCTION IN PHOSPHORYLATION OF RPS6KB1, INTERACTION WITH RPTOR.
[11]"Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action."
Hara K., Maruki Y., Long X., Yoshino K., Oshiro N., Hidayat S., Tokunaga C., Avruch J., Yonezawa K.
Cell 110:177-189(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RPTOR.
[12]"The FKBP12-rapamycin-associated protein (FRAP) is a CLIP-170 kinase."
Choi J.H., Bertram P.G., Drenan R., Carvalho J., Zhou H.H., Zheng X.F.
EMBO Rep. 3:988-994(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CLIP1, FUNCTION IN PHOSPHORYLATION OF CLIP1.
[13]"Regulation of ribosomal S6 kinase 2 by mammalian target of rapamycin."
Park I.H., Bachmann R., Shirazi H., Chen J.
J. Biol. Chem. 277:31423-31429(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RPS6KB2.
[14]"Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control."
Loewith R., Jacinto E., Wullschleger S., Lorberg A., Crespo J.L., Bonenfant D., Oppliger W., Jenoe P., Hall M.N.
Mol. Cell 10:457-468(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MLST8 AND RPTOR, IDENTIFICATION IN THE MTORC1 COMPLEX, TISSUE SPECIFICITY.
[15]"FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction."
Desai B.N., Myers B.R., Schreiber S.L.
Proc. Natl. Acad. Sci. U.S.A. 99:4319-4324(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[16]"TSC2 mediates cellular energy response to control cell growth and survival."
Inoki K., Zhu T., Guan K.L.
Cell 115:577-590(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, FUNCTION IN RESPONSE TO LOW CELLULAR ENERGY.
[17]"GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR."
Kim D.-H., Sarbassov D.D., Ali S.M., Latek R.R., Guntur K.V.P., Erdjument-Bromage H., Tempst P., Sabatini D.M.
Mol. Cell 11:895-904(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MLST8.
[18]"Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton."
Sarbassov D.D., Ali S.M., Kim D.-H., Guertin D.A., Latek R.R., Erdjument-Bromage H., Tempst P., Sabatini D.M.
Curr. Biol. 14:1296-1302(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PRKCA, FUNCTION IN REGULATION OF THE ACTIN CYTOSKELETON, IDENTIFICATION IN THE MTORC2 COMPLEX, INTERACTION WITH RICTOR.
[19]"Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex."
Brugarolas J., Lei K., Hurley R.L., Manning B.D., Reiling J.H., Hafen E., Witters L.A., Ellisen L.W., Kaelin W.G. Jr.
Genes Dev. 18:2893-2904(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, FUNCTION IN RESPONSE TO HYPOXIA.
[20]"FKBP12-rapamycin-associated protein or mammalian target of rapamycin (FRAP/mTOR) localization in the endoplasmic reticulum and the Golgi apparatus."
Drenan R.M., Liu X., Bertram P.G., Zheng X.F.S.
J. Biol. Chem. 279:772-778(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[21]"Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive."
Jacinto E., Loewith R., Schmidt A., Lin S., Ruegg M.A., Hall A., Hall M.N.
Nat. Cell Biol. 6:1122-1128(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF THE ACTIN CYTOSKELETON, FUNCTION IN PHOSPHORYLATION OF PXN, IDENTIFICATION IN THE MTORC2 COMPLEX, INTERACTION WITH RICTOR, AUTOPHOSPHORYLATION.
[22]"Identification of S6 kinase 1 as a novel mammalian target of rapamycin (mTOR)-phosphorylating kinase."
Holz M.K., Blenis J.
J. Biol. Chem. 280:26089-26093(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-2446 AND SER-2448.
[23]"Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex."
Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.
Science 307:1098-1101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF AKT1.
[24]"PRR5, a novel component of mTOR complex 2, regulates platelet-derived growth factor receptor beta expression and signaling."
Woo S.-Y., Kim D.-H., Jun C.-B., Kim Y.-M., Haar E.V., Lee S.-I., Hegg J.W., Bandhakavi S., Griffin T.J., Kim D.-H.
J. Biol. Chem. 282:25604-25612(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MTORC2 COMPLEX, INTERACTION WITH PRR5.
[25]"PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase."
Sancak Y., Thoreen C.C., Peterson T.R., Lindquist R.A., Kang S.A., Spooner E., Carr S.A., Sabatini D.M.
Mol. Cell 25:903-915(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKT1S1, ENZYME REGULATION.
[26]"mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)."
Garcia-Martinez J.M., Alessi D.R.
Biochem. J. 416:375-385(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE MTORC1 AND MTORC2 COMPLEXES, FUNCTION IN PHOSPHORYLATION OF RPS6KB1 AND SGK1.
[27]"SREBP activity is regulated by mTORC1 and contributes to Akt-dependent cell growth."
Porstmann T., Santos C.R., Griffiths B., Cully M., Wu M., Leevers S., Griffiths J.R., Chung Y.L., Schulze A.
Cell Metab. 8:224-236(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN LIPID SYNTHESIS AND CELL GROWTH.
[28]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[29]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2478 AND SER-2481, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[30]"The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1."
Sancak Y., Peterson T.R., Shaul Y.D., Lindquist R.A., Thoreen C.C., Bar-Peled L., Sabatini D.M.
Science 320:1496-1501(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, SUBCELLULAR LOCATION.
[31]"DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival."
Peterson T.R., Laplante M., Thoreen C.C., Sancak Y., Kang S.A., Kuehl W.M., Gray N.S., Sabatini D.M.
Cell 137:873-886(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DEPTOR, ENZYME REGULATION.
[32]"Site-specific mTOR phosphorylation promotes mTORC1-mediated signaling and cell growth."
Acosta-Jaquez H.A., Keller J.A., Foster K.G., Ekim B., Soliman G.A., Feener E.P., Ballif B.A., Fingar D.C.
Mol. Cell. Biol. 29:4308-4324(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1261.
[33]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1218, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[35]"mTOR phosphorylated at S2448 binds to raptor and rictor."
Rosner M., Siegel N., Valli A., Fuchs C., Hengstschlager M.
Amino Acids 38:223-228(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-2448.
[36]"Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids."
Sancak Y., Bar-Peled L., Zoncu R., Markhard A.L., Nada S., Sabatini D.M.
Cell 141:290-303(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[37]"DAP1, a novel substrate of mTOR, negatively regulates autophagy."
Koren I., Reem E., Kimchi A.
Curr. Biol. 20:1093-1098(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF DAP, FUNCTION IN AUTOPHAGY.
[38]"A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability."
Hurov K.E., Cotta-Ramusino C., Elledge S.J.
Genes Dev. 24:1939-1950(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TTI1.
[39]"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
Takai H., Xie Y., de Lange T., Pavletich N.P.
Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TELO2.
[40]"Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly."
Kaizuka T., Hara T., Oshiro N., Kikkawa U., Yonezawa K., Takehana K., Iemura S., Natsume T., Mizushima N.
J. Biol. Chem. 285:20109-20116(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TELO2 AND TTI1.
[41]"mTORC1 directly phosphorylates and regulates human MAF1."
Michels A.A., Robitaille A.M., Buczynski-Ruchonnet D., Hodroj W., Reina J.H., Hall M.N., Hernandez N.
Mol. Cell. Biol. 30:3749-3757(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN REGULATION OF RNA POLYMERASE III TRANSCRIPTION, FUNCTION IN PHOSPHORYLATION OF MAF1.
[42]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-567 AND THR-1162, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[43]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[44]"mTOR kinase domain phosphorylation promotes mTORC1 signaling, cell growth, and cell cycle progression."
Ekim B., Magnuson B., Acosta-Jaquez H.A., Keller J.A., Feener E.P., Fingar D.C.
Mol. Cell. Biol. 31:2787-2801(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-2159; THR-2164 AND SER-2481, MUTAGENESIS OF SER-2159 AND THR-2164.
[45]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[46]"The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling."
Hsu P.P., Kang S.A., Rameseder J., Zhang Y., Ottina K.A., Lim D., Peterson T.R., Choi Y., Gray N.S., Yaffe M.B., Marto J.A., Sabatini D.M.
Science 332:1317-1322(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF GRB10, FUNCTION IN INSR-DEPENDENT SIGNALING.
[47]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[48]"Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains."
Wang J.Q., Chen J.H., Chen Y.C., Chen M.Y., Hsieh C.Y., Teng S.C., Wu K.J.
PLoS ONE 8:E65586-E65586(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NBN.
[49]"Quantitative phosphoproteomics reveal mTORC1 activates de novo pyrimidine synthesis."
Robitaille A.M., Christen S., Shimobayashi M., Cornu M., Fava L.L., Moes S., Prescianotto-Baschong C., Sauer U., Jenoe P., Hall M.N.
Science 339:1320-1323(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION OF RPS6KB1, REGULATION OF PYRIMIDINE SYNTHESIS.
[50]"Stimulation of de novo pyrimidine synthesis by growth signaling through mTOR and S6K1."
Ben-Sahra I., Howell J.J., Asara J.M., Manning B.D.
Science 339:1323-1328(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION OF RPS6KB1, REGULATION OF PYRIMIDINE SYNTHESIS.
[51]"Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP."
Choi J., Chen J., Schreiber S.L., Clardy J.
Science 273:239-242(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2018-2112 IN COMPLEX WITH FKBP1A AND INHIBITOR RAPAMYCIN.
[52]"Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution."
Liang J., Choi J., Clardy J.
Acta Crystallogr. D 55:736-744(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 2018-2112 IN COMPLEX WITH FKBP1A AND INHIBITOR RAPAMYCIN.
[53]"Insights into the domain and repeat architecture of target of rapamycin."
Knutson B.A.
J. Struct. Biol. 170:354-363(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING, HEAT-REPEATS, TPR-REPEATS.
[54]"Structure of the human mTOR complex I and its implications for rapamycin inhibition."
Yip C.K., Murata K., Walz T., Sabatini D.M., Kang S.A.
Mol. Cell 38:768-774(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CRYO-ELECTRON MICROSCOPY (26 ANGSTROMS) OF MTORC1 COMPLEX, SUBUNIT.
[55]"mTOR kinase structure, mechanism and regulation."
Yang H., Rudge D.G., Koos J.D., Vaidialingam B., Yang H.J., Pavletich N.P.
Nature 497:217-223(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 1376-2549 IN COMPLEX WITH MLST8, SUBUNIT, TPR-REPEATS, DOMAINS, MUTAGENESIS OF HIS-2340.
[56]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-8; THR-135; VAL-1083; VAL-1134; PHE-1178; VAL-2011; TYR-2215 AND LEU-2476.
[57]"Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma."
Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., Jia M. expand/collapse author list , Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., Futreal P.A.
Nature 469:539-542(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PHE-2220 AND ALA-2406.
+Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

Mammalian target of rapamycin entry

Target mTOR

mTOR signaling pathway and mTOR inhibition resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L34075 mRNA. Translation: AAA58486.1.
U88966 mRNA. Translation: AAC39933.1. Frameshift.
AB209995 mRNA. Translation: BAE06077.1. Different initiation.
AL109811, AL049653, AL391561 Genomic DNA. Translation: CAI22105.1.
AL391561, AL049653, AL109811 Genomic DNA. Translation: CAI17228.1.
AL049653, AL109811, AL391561 Genomic DNA. Translation: CAI22145.1.
BC117166 mRNA. Translation: AAI17167.1.
AJ300188 Genomic DNA. Translation: CAC15570.1.
L35478 mRNA. Translation: AAC41713.1.
PIRS45340.
RefSeqNP_004949.1. NM_004958.3.
XP_005263495.1. XM_005263438.1.
UniGeneHs.338207.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AUEX-ray2.33A/B2015-2114[»]
1FAPX-ray2.70B2018-2112[»]
1NSGX-ray2.20B2019-2112[»]
2FAPX-ray2.20B2019-2112[»]
2GAQNMR-A2015-2114[»]
2NPUNMR-A2015-2114[»]
2RSENMR-B2019-2112[»]
3FAPX-ray1.85B2019-2112[»]
4DRHX-ray2.30B/E2025-2114[»]
4DRIX-ray1.45B2025-2114[»]
4DRJX-ray1.80B2025-2114[»]
4FAPX-ray2.80B2019-2112[»]
4JSNX-ray3.20A/B1376-2549[»]
4JSPX-ray3.30A/B1376-2549[»]
4JSVX-ray3.50A/B1376-2549[»]
4JSXX-ray3.50A/B1376-2549[»]
4JT5X-ray3.45A/B1376-2549[»]
4JT6X-ray3.60A/B1376-2549[»]
ProteinModelPortalP42345.
SMRP42345. Positions 108-218, 692-728, 770-892, 951-1081, 2025-2422, 2517-2549.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108757. 83 interactions.
DIPDIP-790N.
IntActP42345. 48 interactions.
MINTMINT-121301.
STRING9606.ENSP00000354558.

Chemistry

BindingDBP42345.
ChEMBLCHEMBL2221341.
GuidetoPHARMACOLOGY2109.

PTM databases

PhosphoSiteP42345.

Polymorphism databases

DMDM1169735.

Proteomic databases

PaxDbP42345.
PRIDEP42345.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361445; ENSP00000354558; ENSG00000198793.
GeneID2475.
KEGGhsa:2475.
UCSCuc001asd.3. human.

Organism-specific databases

CTD2475.
GeneCardsGC01M011166.
HGNCHGNC:3942. MTOR.
HPACAB005057.
MIM601231. gene.
neXtProtNX_P42345.
PharmGKBPA28360.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5032.
HOGENOMHOG000163215.
HOVERGENHBG005744.
InParanoidP42345.
KOK07203.
OMADPYKHKM.
PhylomeDBP42345.
TreeFamTF105134.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkP42345.

Gene expression databases

ArrayExpressP42345.
BgeeP42345.
CleanExHS_FRAP1.
GenevestigatorP42345.

Family and domain databases

Gene3D1.10.1070.11. 3 hits.
1.20.120.150. 1 hit.
1.25.10.10. 4 hits.
1.25.40.10. 2 hits.
InterProIPR011989. 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.
IPR011990. TPR-like_helical.
[Graphical view]
PANTHERPTHR11139:SF9. PTHR11139:SF9. 1 hit.
PfamPF11865. DUF3385. 1 hit.
PF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
PF08771. Rapamycin_bind. 1 hit.
[Graphical view]
SMARTSM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMSSF47212. SSF47212. 1 hit.
SSF48371. SSF48371. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEPS51189. FAT. 1 hit.
PS51190. FATC. 1 hit.
PS00915. PI3_4_KINASE_1. 1 hit.
PS00916. PI3_4_KINASE_2. 1 hit.
PS50290. PI3_4_KINASE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSMTOR. human.
EvolutionaryTraceP42345.
GeneWikiMammalian_target_of_rapamycin.
GenomeRNAi2475.
NextBio9805.
PROP42345.
SOURCESearch...

Entry information

Entry nameMTOR_HUMAN
AccessionPrimary (citable) accession number: P42345
Secondary accession number(s): Q4LE76 expand/collapse secondary AC list , Q5TER1, Q6LE87, Q96QG3, Q9Y4I3
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM