Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase mTOR

Gene

MTOR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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'. Regulates osteoclastogensis by adjusting the expression of CEBPB isoforms (By similarity).By similarity18 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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, SLC38A9, and the Rag GTPases RRAGA, RRAGB, RRAGC and RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175, PubMed:25567906). 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.8 Publications

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB
  • phosphoprotein binding Source: UniProtKB
  • protein kinase activity Source: WormBase
  • protein serine/threonine kinase activity Source: UniProtKB
  • ribosome binding Source: Ensembl
  • RNA polymerase III type 1 promoter DNA binding Source: UniProtKB
  • RNA polymerase III type 2 promoter DNA binding Source: UniProtKB
  • RNA polymerase III type 3 promoter DNA binding Source: UniProtKB
  • TFIIIC-class transcription factor binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS01439-MONOMER.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-3371571. HSF1-dependent transactivation.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-5218920. VEGFR2 mediated vascular permeability.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
R-HSA-6804757. Regulation of TP53 Degradation.
SignaLinkiP42345.
SIGNORiP42345.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:MTOR
Synonyms:FRAP, FRAP1, FRAP2, RAFT1, RAPT1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:3942. MTOR.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • dendrite Source: Ensembl
  • endomembrane system Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • Golgi membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • lysosome Source: UniProtKB
  • membrane Source: UniProtKB
  • mitochondrial outer membrane Source: UniProtKB-SubCell
  • neuronal cell body Source: Ensembl
  • nucleoplasm Source: Reactome
  • nucleus Source: GO_Central
  • phosphatidylinositol 3-kinase complex Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • TORC1 complex Source: UniProtKB
  • TORC2 complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Lysosome, Membrane, Microsome, Mitochondrion, Mitochondrion outer membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Smith-Kingsmore syndrome (SKS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features.
See also OMIM:616638
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0750721799E → K in SKS; results in increased mTOR signaling. 2 Publications1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2159S → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2164. 1 Publication1
Mutagenesisi2159S → D: Stronger phosphorylation of RPS6KB1; when associated with E-2164. 1 Publication1
Mutagenesisi2164T → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2159. 1 Publication1
Mutagenesisi2164T → E: Stronger phosphorylation of RPS6KB1; when associated with D-2159. 1 Publication1
Mutagenesisi2173T → A: Increased mTOR kinase activity. 1 Publication1
Mutagenesisi2340H → A: Barely detectable kinase activity. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy, Mental retardation

Organism-specific databases

DisGeNETi2475.
MIMi616638. phenotype.
OpenTargetsiENSG00000198793.
PharmGKBiPA28360.

Chemistry databases

ChEMBLiCHEMBL2842.
DrugBankiDB01590. Everolimus.
DB00337. Pimecrolimus.
DB00877. Sirolimus.
DB06287. Temsirolimus.
GuidetoPHARMACOLOGYi2109.

Polymorphism and mutation databases

BioMutaiMTOR.
DMDMi1169735.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000888081 – 2549Serine/threonine-protein kinase mTORAdd BLAST2549

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei567PhosphoserineCombined sources1
Modified residuei1162PhosphothreonineCombined sources1
Modified residuei1218N6-acetyllysineCombined sources1
Modified residuei1261PhosphoserineCombined sources1 Publication1
Modified residuei2159Phosphoserine1 Publication1
Modified residuei2164Phosphothreonine1 Publication1
Modified residuei2173Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei2446Phosphothreonine; by RPS6KB11 Publication1
Modified residuei2448Phosphoserine; by RPS6KB1Combined sources2 Publications1
Modified residuei2478PhosphoserineCombined sources1
Modified residuei2481Phosphoserine; by autocatalysisCombined sources1 Publication1

Post-translational modificationi

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. Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity.7 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP42345.
MaxQBiP42345.
PaxDbiP42345.
PeptideAtlasiP42345.
PRIDEiP42345.

PTM databases

iPTMnetiP42345.
PhosphoSitePlusiP42345.

Expressioni

Tissue specificityi

Expressed in numerous tissues, with highest levels in testis.2 Publications

Gene expression databases

BgeeiENSG00000198793.
CleanExiHS_FRAP1.
ExpressionAtlasiP42345. baseline and differential.
GenevisibleiP42345. HS.

Organism-specific databases

HPAiCAB005057.

Interactioni

Subunit structurei

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 PLPP7 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. Interacts with HTR6 (PubMed:23027611). Interacts with BRAT1.22 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AKT1P317492EBI-359260,EBI-296087
DEPTORQ8TB455EBI-359260,EBI-2359040
EIF4EBP1Q135412EBI-359260,EBI-74090
FKBP1AP629422EBI-359260,EBI-1027571
MLST8Q9BVC44EBI-359260,EBI-1387471
MTMR3Q136153EBI-359260,EBI-371938
PREX1Q8TCU611EBI-359260,EBI-1046542
RAB1AP628204EBI-359260,EBI-716845
RICTORQ6R32731EBI-359260,EBI-1387196
RPTORQ8N12232EBI-359260,EBI-1567928
SIRT1Q96EB62EBI-359260,EBI-1802965
TPCN2Q8NHX92EBI-359260,EBI-5239949

GO - Molecular functioni

  • phosphoprotein binding Source: UniProtKB
  • TFIIIC-class transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108757. 161 interactors.
DIPiDIP-790N.
IntActiP42345. 70 interactors.
MINTiMINT-121301.
STRINGi9606.ENSP00000354558.

Chemistry databases

BindingDBiP42345.

Structurei

Secondary structure

12549
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1387 – 1406Combined sources20
Helixi1410 – 1422Combined sources13
Helixi1426 – 1439Combined sources14
Helixi1446 – 1452Combined sources7
Helixi1456 – 1469Combined sources14
Helixi1474 – 1486Combined sources13
Helixi1490 – 1498Combined sources9
Beta strandi1501 – 1503Combined sources3
Helixi1506 – 1521Combined sources16
Turni1522 – 1524Combined sources3
Helixi1526 – 1533Combined sources8
Helixi1541 – 1553Combined sources13
Helixi1557 – 1572Combined sources16
Turni1573 – 1577Combined sources5
Turni1584 – 1586Combined sources3
Helixi1587 – 1605Combined sources19
Beta strandi1606 – 1608Combined sources3
Helixi1609 – 1611Combined sources3
Helixi1612 – 1624Combined sources13
Helixi1630 – 1640Combined sources11
Turni1641 – 1643Combined sources3
Turni1646 – 1648Combined sources3
Helixi1650 – 1663Combined sources14
Helixi1666 – 1677Combined sources12
Beta strandi1681 – 1684Combined sources4
Helixi1694 – 1706Combined sources13
Helixi1710 – 1729Combined sources20
Helixi1737 – 1762Combined sources26
Turni1766 – 1768Combined sources3
Helixi1769 – 1782Combined sources14
Turni1783 – 1785Combined sources3
Helixi1787 – 1813Combined sources27
Helixi1868 – 1893Combined sources26
Beta strandi1896 – 1898Combined sources3
Helixi1900 – 1913Combined sources14
Helixi1917 – 1929Combined sources13
Helixi1933 – 1938Combined sources6
Helixi1939 – 1943Combined sources5
Turni1944 – 1947Combined sources4
Helixi1951 – 1966Combined sources16
Helixi1970 – 1980Combined sources11
Helixi1985 – 2020Combined sources36
Helixi2025 – 2039Combined sources15
Helixi2044 – 2058Combined sources15
Helixi2065 – 2091Combined sources27
Helixi2094 – 2111Combined sources18
Helixi2115 – 2117Combined sources3
Beta strandi2119 – 2122Combined sources4
Helixi2123 – 2126Combined sources4
Helixi2128 – 2132Combined sources5
Beta strandi2137 – 2139Combined sources3
Beta strandi2152 – 2156Combined sources5
Beta strandi2158 – 2162Combined sources5
Beta strandi2165 – 2167Combined sources3
Beta strandi2170 – 2176Combined sources7
Beta strandi2181 – 2189Combined sources9
Helixi2193 – 2211Combined sources19
Helixi2213 – 2217Combined sources5
Beta strandi2227 – 2229Combined sources3
Beta strandi2231 – 2233Combined sources3
Beta strandi2235 – 2238Combined sources4
Beta strandi2243 – 2245Combined sources3
Helixi2246 – 2256Combined sources11
Helixi2263 – 2271Combined sources9
Helixi2275 – 2277Combined sources3
Helixi2280 – 2291Combined sources12
Helixi2298 – 2306Combined sources9
Helixi2310 – 2334Combined sources25
Turni2341 – 2343Combined sources3
Beta strandi2344 – 2347Combined sources4
Turni2348 – 2350Combined sources3
Beta strandi2353 – 2355Combined sources3
Helixi2364 – 2367Combined sources4
Beta strandi2369 – 2371Combined sources3
Helixi2381 – 2386Combined sources6
Turni2389 – 2394Combined sources6
Helixi2395 – 2409Combined sources15
Helixi2411 – 2422Combined sources12
Turni2425 – 2427Combined sources3
Helixi2428 – 2435Combined sources8
Helixi2493 – 2507Combined sources15
Turni2508 – 2510Combined sources3
Beta strandi2512 – 2516Combined sources5
Helixi2521 – 2533Combined sources13
Helixi2535 – 2538Combined sources4
Helixi2543 – 2545Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5FLCelectron microscopy5.90B/F1382-2549[»]
5GPGX-ray1.67B2021-2112[»]
ProteinModelPortaliP42345.
SMRiP42345.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP42345.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati16 – 53HEAT 1Add BLAST38
Repeati55 – 99HEAT 2Add BLAST45
Repeati100 – 137HEAT 3Add BLAST38
Repeati138 – 179HEAT 4Add BLAST42
Repeati180 – 220HEAT 5Add BLAST41
Repeati222 – 276HEAT 6Add BLAST55
Repeati277 – 313HEAT 7Add BLAST37
Repeati314 – 364HEAT 8Add BLAST51
Repeati365 – 409HEAT 9Add BLAST45
Repeati410 – 445HEAT 10Add BLAST36
Repeati446 – 494HEAT 11Add BLAST49
Repeati495 – 529HEAT 12Add BLAST35
Repeati530 – 563HEAT 13Add BLAST34
Repeati564 – 596HEAT 14Add BLAST33
Repeati597 – 636HEAT 15Add BLAST40
Repeati637 – 683HEAT 16Add BLAST47
Repeati686 – 724HEAT 17Add BLAST39
Repeati727 – 766HEAT 18Add BLAST40
Repeati769 – 811HEAT 19Add BLAST43
Repeati814 – 853HEAT 20Add BLAST40
Repeati857 – 893HEAT 21Add BLAST37
Repeati894 – 942HEAT 22Add BLAST49
Repeati943 – 988HEAT 23Add BLAST46
Repeati989 – 1027HEAT 24Add BLAST39
Repeati1029 – 1068HEAT 25Add BLAST40
Repeati1069 – 1105HEAT 26Add BLAST37
Repeati1106 – 1144HEAT 27Add BLAST39
Repeati1145 – 1188HEAT 28Add BLAST44
Repeati1189 – 1225HEAT 29Add BLAST37
Repeati1226 – 1273HEAT 30Add BLAST48
Repeati1274 – 1311HEAT 31Add BLAST38
Repeati1312 – 1345HEAT 32Add BLAST34
Repeati1346 – 1382TPR 1Add BLAST37
Domaini1382 – 1982FATPROSITE-ProRule annotationAdd BLAST601
Repeati1383 – 1408TPR 2Add BLAST26
Repeati1409 – 1442TPR 3Add BLAST34
Repeati1443 – 1473TPR 4Add BLAST31
Repeati1474 – 1507TPR 5Add BLAST34
Repeati1508 – 1541TPR 6Add BLAST34
Repeati1542 – 1574TPR 7Add BLAST33
Repeati1575 – 1614TPR 8Add BLAST40
Repeati1615 – 1649TPR 9Add BLAST35
Repeati1650 – 1693TPR 10Add BLAST44
Repeati1694 – 1731TPR 11Add BLAST38
Repeati1732 – 1786TPR 12Add BLAST55
Repeati1787 – 1846TPR 13Add BLAST60
Repeati1898 – 1930TPR 14Add BLAST33
Repeati1931 – 1970TPR 15Add BLAST40
Repeati1971 – 2005TPR 16Add BLAST35
Domaini2182 – 2516PI3K/PI4KPROSITE-ProRule annotationAdd BLAST335
Domaini2517 – 2549FATCPROSITE-ProRule annotationAdd BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 651Interaction with NBN1 PublicationAdd BLAST651
Regioni2012 – 2144Sufficient for interaction with the FKBP1A/rapamycin complexBy similarityAdd BLAST133
Regioni2258 – 2296Interaction with MLST8Add BLAST39

Domaini

The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center.1 Publication
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 (PubMed:23636326).1 Publication

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.Curated
Contains 1 FAT domain.PROSITE-ProRule annotation
Contains 1 FATC domain.PROSITE-ProRule annotation
Contains 32 HEAT repeats.Curated
Contains 1 PI3K/PI4K domain.PROSITE-ProRule annotation
Contains 16 TPR repeats.Curated

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0891. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00860000133856.
HOGENOMiHOG000163215.
HOVERGENiHBG005744.
InParanoidiP42345.
KOiK07203.
OMAiCCKLVAH.
OrthoDBiEOG091G0046.
PhylomeDBiP42345.
TreeFamiTF105134.

Family and domain databases

Gene3Di1.10.1070.11. 3 hits.
1.20.120.150. 1 hit.
1.25.10.10. 4 hits.
1.25.40.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR024585. DUF3385_TOR.
IPR003152. FATC_dom.
IPR009076. FRB_dom.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003151. PIK-rel_kinase_FAT.
IPR014009. PIK_FAT.
IPR026683. TOR.
IPR011990. TPR-like_helical_dom.
[Graphical view]
PANTHERiPTHR11139:SF9. PTHR11139:SF9. 2 hits.
PfamiPF11865. DUF3385. 1 hit.
PF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF08771. FRB_dom. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
[Graphical view]
SMARTiSM01346. DUF3385. 1 hit.
SM01343. FATC. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMiSSF47212. SSF47212. 1 hit.
SSF48371. SSF48371. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS51189. 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]

Sequencei

Sequence statusi: Complete.

P42345-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM
60 70 80 90 100
ELREMSQEES TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN
110 120 130 140 150
ATRIGRFANY LRNLLPSNDP VVMEMASKAI GRLAMAGDTF TAEYVEFEVK
160 170 180 190 200
RALEWLGADR NEGRRHAAVL VLRELAISVP TFFFQQVQPF FDNIFVAVWD
210 220 230 240 250
PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE AEKGFDETLA
260 270 280 290 300
KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC
310 320 330 340 350
KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS
360 370 380 390 400
PAKSTLVESR CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA
410 420 430 440 450
AFRPSAFTDT QYLQDTMNHV LSCVKKEKER TAAFQALGLL SVAVRSEFKV
460 470 480 490 500
YLPRVLDIIR AALPPKDFAH KRQKAMQVDA TVFTCISMLA RAMGPGIQQD
510 520 530 540 550
IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL KMLSLVLMHK
560 570 580 590 600
PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT
610 620 630 640 650
QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ
660 670 680 690 700
VVADVLSKLL VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL
710 720 730 740 750
NDQVFEIREL AICTVGRLSS MNPAFVMPFL RKMLIQILTE LEHSGIGRIK
760 770 780 790 800
EQSARMLGHL VSNAPRLIRP YMEPILKALI LKLKDPDPDP NPGVINNVLA
810 820 830 840 850
TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA LWTLGQLVAS
860 870 880 890 900
TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK
910 920 930 940 950
VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV
960 970 980 990 1000
SMVALMRIFR DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV
1010 1020 1030 1040 1050
IRVCDGAIRE FLFQQLGMLV SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS
1060 1070 1080 1090 1100
TIILLIEQIV VALGGEFKLY LPQLIPHMLR VFMHDNSPGR IVSIKLLAAI
1110 1120 1130 1140 1150
QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD RLTESLDFTD
1160 1170 1180 1190 1200
YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV
1210 1220 1230 1240 1250
RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV
1260 1270 1280 1290 1300
ETGPMKKLHV STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL
1310 1320 1330 1340 1350
RSCWALAQAY NPMARDLFNA AFVSCWSELN EDQQDELIRS IELALTSQDI
1360 1370 1380 1390 1400
AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI VLLGERAAKC RAYAKALHYK
1410 1420 1430 1440 1450
ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF GELEIQATWY
1460 1470 1480 1490 1500
EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK
1510 1520 1530 1540 1550
WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL
1560 1570 1580 1590 1600
ALHQDLFSLA QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE
1610 1620 1630 1640 1650
EVIQYKLVPE RREIIRQIWW ERLQGCQRIV EDWQKILMVR SLVVSPHEDM
1660 1670 1680 1690 1700
RTWLKYASLC GKSGRLALAH KTLVLLLGVD PSRQLDHPLP TVHPQVTYAY
1710 1720 1730 1740 1750
MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK QELHKLMARC
1760 1770 1780 1790 1800
FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA
1810 1820 1830 1840 1850
VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE
1860 1870 1880 1890 1900
SEAESTENSP TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL
1910 1920 1930 1940 1950
QDTLRVLTLW FDYGHWPDVN EALVEGVKAI QIDTWLQVIP QLIARIDTPR
1960 1970 1980 1990 2000
PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS KSTTTARHNA ANKILKNMCE
2010 2020 2030 2040 2050
HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG ERNVKGMFEV
2060 2070 2080 2090 2100
LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA
2110 2120 2130 2140 2150
WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI
2160 2170 2180 2190 2200
IRIQSIAPSL QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ
2210 2220 2230 2240 2250
LFGLVNTLLA NDPTSLRKNL SIQRYAVIPL STNSGLIGWV PHCDTLHALI
2260 2270 2280 2290 2300
RDYREKKKIL LNIEHRIMLR MAPDYDHLTL MQKVEVFEHA VNNTAGDDLA
2310 2320 2330 2340 2350
KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH PSNLMLDRLS
2360 2370 2380 2390 2400
GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC
2410 2420 2430 2440 2450
HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS
2460 2470 2480 2490 2500
AGQSVEILDG VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI
2510 2520 2530 2540
INRVRDKLTG RDFSHDDTLD VPTQVELLIK QATSHENLCQ CYIGWCPFW
Length:2,549
Mass (Da):288,892
Last modified:November 1, 1995 - v1
Checksum:i7D9AD6E784882AB4
GO

Sequence cautioni

The sequence AAC39933 differs from that shown. Reason: Frameshift at positions 956 and 999.Curated
The sequence BAE06077 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti353K → N in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti359S → N in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti364D → N in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti390M → L in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti430R → L in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti455 – 457VLD → GVE in AAC39933 (PubMed:9653645).Curated3
Sequence conflicti461A → G in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti482 – 484VFT → FFN in AAC39933 (PubMed:9653645).Curated3
Sequence conflicti489L → V in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti513L → I in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti539L → V in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti553R → C in AAC39933 (PubMed:9653645).Curated1
Sequence conflicti857P → L in BAE06077 (Ref. 3) Curated1
Sequence conflicti1075I → S in AAC39933 (PubMed:9653645).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0415378A → S in a lung large cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041538135M → T in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0415391083M → V.1 PublicationCorresponds to variant rs56164650dbSNPEnsembl.1
Natural variantiVAR_0415401134A → V.1 PublicationCorresponds to variant rs28730685dbSNPEnsembl.1
Natural variantiVAR_0415411178S → F.1 PublicationCorresponds to variant rs55975118dbSNPEnsembl.1
Natural variantiVAR_0750721799E → K in SKS; results in increased mTOR signaling. 2 Publications1
Natural variantiVAR_0415422011M → V in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0415432215S → Y in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0647332220L → F Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0647342406V → A Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0415442476P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS127.1.
PIRiS45340.
RefSeqiNP_004949.1. NM_004958.3.
XP_005263495.1. XM_005263438.2.
UniGeneiHs.338207.

Genome annotation databases

EnsembliENST00000361445; ENSP00000354558; ENSG00000198793.
GeneIDi2475.
KEGGihsa:2475.
UCSCiuc001asd.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
Wikipedia

Mammalian target of rapamycin entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS127.1.
PIRiS45340.
RefSeqiNP_004949.1. NM_004958.3.
XP_005263495.1. XM_005263438.2.
UniGeneiHs.338207.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5FLCelectron microscopy5.90B/F1382-2549[»]
5GPGX-ray1.67B2021-2112[»]
ProteinModelPortaliP42345.
SMRiP42345.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108757. 161 interactors.
DIPiDIP-790N.
IntActiP42345. 70 interactors.
MINTiMINT-121301.
STRINGi9606.ENSP00000354558.

Chemistry databases

BindingDBiP42345.
ChEMBLiCHEMBL2842.
DrugBankiDB01590. Everolimus.
DB00337. Pimecrolimus.
DB00877. Sirolimus.
DB06287. Temsirolimus.
GuidetoPHARMACOLOGYi2109.

PTM databases

iPTMnetiP42345.
PhosphoSitePlusiP42345.

Polymorphism and mutation databases

BioMutaiMTOR.
DMDMi1169735.

Proteomic databases

EPDiP42345.
MaxQBiP42345.
PaxDbiP42345.
PeptideAtlasiP42345.
PRIDEiP42345.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361445; ENSP00000354558; ENSG00000198793.
GeneIDi2475.
KEGGihsa:2475.
UCSCiuc001asd.4. human.

Organism-specific databases

CTDi2475.
DisGeNETi2475.
GeneCardsiMTOR.
HGNCiHGNC:3942. MTOR.
HPAiCAB005057.
MIMi601231. gene.
616638. phenotype.
neXtProtiNX_P42345.
OpenTargetsiENSG00000198793.
PharmGKBiPA28360.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0891. Eukaryota.
COG5032. LUCA.
GeneTreeiENSGT00860000133856.
HOGENOMiHOG000163215.
HOVERGENiHBG005744.
InParanoidiP42345.
KOiK07203.
OMAiCCKLVAH.
OrthoDBiEOG091G0046.
PhylomeDBiP42345.
TreeFamiTF105134.

Enzyme and pathway databases

BioCyciZFISH:HS01439-MONOMER.
ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1632852. Macroautophagy.
R-HSA-165159. mTOR signalling.
R-HSA-166208. mTORC1-mediated signalling.
R-HSA-3371571. HSF1-dependent transactivation.
R-HSA-380972. Energy dependent regulation of mTOR by LKB1-AMPK.
R-HSA-389357. CD28 dependent PI3K/Akt signaling.
R-HSA-5218920. VEGFR2 mediated vascular permeability.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-5674400. Constitutive Signaling by AKT1 E17K in Cancer.
R-HSA-6804757. Regulation of TP53 Degradation.
SignaLinkiP42345.
SIGNORiP42345.

Miscellaneous databases

ChiTaRSiMTOR. human.
EvolutionaryTraceiP42345.
GeneWikiiMammalian_target_of_rapamycin.
GenomeRNAii2475.
PROiP42345.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198793.
CleanExiHS_FRAP1.
ExpressionAtlasiP42345. baseline and differential.
GenevisibleiP42345. HS.

Family and domain databases

Gene3Di1.10.1070.11. 3 hits.
1.20.120.150. 1 hit.
1.25.10.10. 4 hits.
1.25.40.10. 2 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR024585. DUF3385_TOR.
IPR003152. FATC_dom.
IPR009076. FRB_dom.
IPR011009. Kinase-like_dom.
IPR000403. PI3/4_kinase_cat_dom.
IPR018936. PI3/4_kinase_CS.
IPR003151. PIK-rel_kinase_FAT.
IPR014009. PIK_FAT.
IPR026683. TOR.
IPR011990. TPR-like_helical_dom.
[Graphical view]
PANTHERiPTHR11139:SF9. PTHR11139:SF9. 2 hits.
PfamiPF11865. DUF3385. 1 hit.
PF02259. FAT. 1 hit.
PF02260. FATC. 1 hit.
PF08771. FRB_dom. 1 hit.
PF00454. PI3_PI4_kinase. 1 hit.
[Graphical view]
SMARTiSM01346. DUF3385. 1 hit.
SM01343. FATC. 1 hit.
SM00146. PI3Kc. 1 hit.
[Graphical view]
SUPFAMiSSF47212. SSF47212. 1 hit.
SSF48371. SSF48371. 5 hits.
SSF56112. SSF56112. 2 hits.
PROSITEiPS51189. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiMTOR_HUMAN
AccessioniPrimary (citable) accession number: P42345
Secondary accession number(s): Q4LE76
, Q5TER1, Q6LE87, Q96QG3, Q9Y4I3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 30, 2016
This is version 179 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.