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UniProtKB - P42345 (MTOR_HUMAN)

Protein

Serine/threonine-protein kinase mTOR

Gene

MTOR

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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' (PubMed:12087098, PubMed:12150925, PubMed:12150926, PubMed:12231510, PubMed:12718876, PubMed:14651849, PubMed:15268862, PubMed:15467718, PubMed:15545625, PubMed:15718470, PubMed:18497260, PubMed:18762023, PubMed:18925875, PubMed:20516213, PubMed:20537536, PubMed:21659604, PubMed:23429703, PubMed:23429704, PubMed:25799227, PubMed:26018084). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity).By similarity20 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity 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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

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
R-HSA-8943724 Regulation of PTEN gene transcription
SABIO-RKiP42345
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000198793.12
HGNCiHGNC:3942 MTOR
MIMi601231 gene
neXtProtiNX_P42345

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)3 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_0788321490W → R in SKS. 1 Publication1
Natural variantiVAR_0788331595M → I in SKS. 1 PublicationCorresponds to variant dbSNP:rs869312671EnsemblClinVar.1
Natural variantiVAR_0750721799E → K in SKS; results in increased mTOR signaling. 2 PublicationsCorresponds to variant dbSNP:rs863225264EnsemblClinVar.1
Natural variantiVAR_0788351832A → T in SKS. 1 PublicationCorresponds to variant dbSNP:rs369088781EnsemblClinVar.1
Natural variantiVAR_0788361888F → C in SKS. 1 PublicationCorresponds to variant dbSNP:rs869312666EnsemblClinVar.1
Natural variantiVAR_0788402327M → I in SKS. 1 PublicationCorresponds to variant dbSNP:rs878855328EnsemblClinVar.1
Focal cortical dysplasia 2 (FCORD2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of focal cortical dysplasia, a malformation of cortical development that results in medically refractory epilepsy in the pediatric population and in adults. FCORD2 is a severe form, with onset usually in childhood, characterized by disrupted cortical lamination and specific cytological abnormalities. It is classified in 2 subtypes: type IIA characterized by dysmorphic neurons and lack of balloon cells; type IIB with dysmorphic neurons and balloon cells.
See also OMIM:607341
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078824624R → H in FCORD2; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs913197212Ensembl.1
Natural variantiVAR_0788261450Y → D in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788271456W → G in FCORD2; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1085307114Ensembl.1
Natural variantiVAR_0788281459A → D in FCORD2; somatic mutation; increased TOR signaling. 1 Publication1
Natural variantiVAR_0788291459A → S in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788301460L → P in FCORD2; somatic mutation; increased TOR signaling. 2 PublicationsCorresponds to variant dbSNP:rs1057519779Ensembl.1
Natural variantiVAR_0788311483C → R in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1057519914Ensembl.1
Natural variantiVAR_0788341709R → H in FCORD2; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777895EnsemblClinVar.1
Natural variantiVAR_0788371977T → K in FCORD2; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587777893EnsemblClinVar.1
Natural variantiVAR_0788382193R → C in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788392215S → F in FCORD2; somatic mutation; increased TOR signaling. 3 PublicationsCorresponds to variant dbSNP:rs587777894EnsemblClinVar.1
Natural variantiVAR_0415432215S → Y in FCORD2; also found in a colorectal adenocarcinoma sample; somatic mutation; increased TOR signaling. 3 Publications1
Natural variantiVAR_0788412427L → P in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 Publication1
Natural variantiVAR_0788422427L → Q in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1085307113Ensembl.1

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
MalaCardsiMTOR
MIMi607341 phenotype
616638 phenotype
OpenTargetsiENSG00000198793
PharmGKBiPA28360

Chemistry databases

ChEMBLiCHEMBL2842
DrugBankiDB04974 AP1903
DB01590 Everolimus
DB00337 Pimecrolimus
DB05210 SF1126
DB00877 Sirolimus
DB06287 Temsirolimus
DB05241 XL765
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
ProteomicsDBi55511

PTM databases

iPTMnetiP42345
PhosphoSitePlusiP42345

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000198793 Expressed in 167 organ(s), highest expression level in testis
CleanExiHS_FRAP1
ExpressionAtlasiP42345 baseline and differential
GenevisibleiP42345 HS

Organism-specific databases

HPAiCAB069425
HPA071227

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 subunit 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 WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). 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 BRAT1.23 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108757, 197 interactors
CORUMiP42345
DIPiDIP-790N
IntActiP42345, 78 interactors
MINTiP42345
STRINGi9606.ENSP00000354558

Chemistry databases

BindingDBiP42345

Structurei

Secondary structure

12549
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG0891 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00920000149065
HOGENOMiHOG000163215
HOVERGENiHBG005744
InParanoidiP42345
KOiK07203
OMAiSSHQGLM
OrthoDBiEOG091G0046
PhylomeDBiP42345
TreeFamiTF105134

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
1.20.120.150, 1 hit
1.25.10.10, 4 hits
1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR024585 DUF3385_TOR
IPR003152 FATC_dom
IPR009076 FRB_dom
IPR036738 FRB_sf
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
IPR026683 TOR
IPR011990 TPR-like_helical_dom_sf
PANTHERiPTHR11139:SF9 PTHR11139:SF9, 1 hit
PfamiView protein in Pfam
PF11865 DUF3385, 1 hit
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF08771 FRB_dom, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
SMARTiView protein in SMART
SM01346 DUF3385, 1 hit
SM01343 FATC, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF47212 SSF47212, 1 hit
SSF48371 SSF48371, 5 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS51189 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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B1AKP8B1AKP8_HUMAN
Serine/threonine-protein kinase mTO...
MTOR
754Annotation score:
B1AKQ2B1AKQ2_HUMAN
Serine/threonine-protein kinase mTO...
MTOR
161Annotation score:

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_078824624R → H in FCORD2; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs913197212Ensembl.1
Natural variantiVAR_0415391083M → V1 PublicationCorresponds to variant dbSNP:rs56164650Ensembl.1
Natural variantiVAR_0415401134A → V1 PublicationCorresponds to variant dbSNP:rs28730685Ensembl.1
Natural variantiVAR_0415411178S → F1 PublicationCorresponds to variant dbSNP:rs55975118Ensembl.1
Natural variantiVAR_0788251376D → E Found in a patient with focal epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs975577894Ensembl.1
Natural variantiVAR_0788261450Y → D in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788271456W → G in FCORD2; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1085307114Ensembl.1
Natural variantiVAR_0788281459A → D in FCORD2; somatic mutation; increased TOR signaling. 1 Publication1
Natural variantiVAR_0788291459A → S in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788301460L → P in FCORD2; somatic mutation; increased TOR signaling. 2 PublicationsCorresponds to variant dbSNP:rs1057519779Ensembl.1
Natural variantiVAR_0788311483C → R in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1057519914Ensembl.1
Natural variantiVAR_0788321490W → R in SKS. 1 Publication1
Natural variantiVAR_0788331595M → I in SKS. 1 PublicationCorresponds to variant dbSNP:rs869312671EnsemblClinVar.1
Natural variantiVAR_0788341709R → H in FCORD2; somatic mutation; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs587777895EnsemblClinVar.1
Natural variantiVAR_0750721799E → K in SKS; results in increased mTOR signaling. 2 PublicationsCorresponds to variant dbSNP:rs863225264EnsemblClinVar.1
Natural variantiVAR_0788351832A → T in SKS. 1 PublicationCorresponds to variant dbSNP:rs369088781EnsemblClinVar.1
Natural variantiVAR_0788361888F → C in SKS. 1 PublicationCorresponds to variant dbSNP:rs869312666EnsemblClinVar.1
Natural variantiVAR_0788371977T → K in FCORD2; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587777893EnsemblClinVar.1
Natural variantiVAR_0415422011M → V in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0788382193R → C in FCORD2; somatic mutation. 1 Publication1
Natural variantiVAR_0788392215S → F in FCORD2; somatic mutation; increased TOR signaling. 3 PublicationsCorresponds to variant dbSNP:rs587777894EnsemblClinVar.1
Natural variantiVAR_0415432215S → Y in FCORD2; also found in a colorectal adenocarcinoma sample; somatic mutation; increased TOR signaling. 3 Publications1
Natural variantiVAR_0647332220L → F Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0788402327M → I in SKS. 1 PublicationCorresponds to variant dbSNP:rs878855328EnsemblClinVar.1
Natural variantiVAR_0647342406V → A Found in a renal cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_0788412427L → P in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 Publication1
Natural variantiVAR_0788422427L → Q in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity. 1 PublicationCorresponds to variant dbSNP:rs1085307113Ensembl.1
Natural variantiVAR_0415442476P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_0788432501I → V Found in a patient with non-lesional nocturnal frontal epilepsy; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs968817513Ensembl.1

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 Genomic DNA No translation available.
AL391561 Genomic DNA No translation available.
AL049653 Genomic DNA No translation available.
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

Similar proteinsi

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 Genomic DNA No translation available.
AL391561 Genomic DNA No translation available.
AL049653 Genomic DNA No translation available.
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[»]
3JBZelectron microscopy28.00A1385-2549[»]
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[»]
5H64electron microscopy4.40A/a1-2549[»]
5WBHX-ray1.75A/B/C/D/E2018-2114[»]
5WBUX-ray3.42A/B1376-2549[»]
5WBYX-ray3.10A/B1376-2549[»]
5ZCSelectron microscopy4.90A/B1-2549[»]
6BCUelectron microscopy3.43A/B1-2549[»]
6BCXelectron microscopy3.00A/B1-2549[»]
ProteinModelPortaliP42345
SMRiP42345
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108757, 197 interactors
CORUMiP42345
DIPiDIP-790N
IntActiP42345, 78 interactors
MINTiP42345
STRINGi9606.ENSP00000354558

Chemistry databases

BindingDBiP42345
ChEMBLiCHEMBL2842
DrugBankiDB04974 AP1903
DB01590 Everolimus
DB00337 Pimecrolimus
DB05210 SF1126
DB00877 Sirolimus
DB06287 Temsirolimus
DB05241 XL765
GuidetoPHARMACOLOGYi2109

PTM databases

iPTMnetiP42345
PhosphoSitePlusiP42345

Polymorphism and mutation databases

BioMutaiMTOR
DMDMi1169735

Proteomic databases

EPDiP42345
MaxQBiP42345
PaxDbiP42345
PeptideAtlasiP42345
PRIDEiP42345
ProteomicsDBi55511

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi2475
DisGeNETi2475
EuPathDBiHostDB:ENSG00000198793.12
GeneCardsiMTOR
HGNCiHGNC:3942 MTOR
HPAiCAB069425
HPA071227
MalaCardsiMTOR
MIMi601231 gene
607341 phenotype
616638 phenotype
neXtProtiNX_P42345
OpenTargetsiENSG00000198793
PharmGKBiPA28360
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0891 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00920000149065
HOGENOMiHOG000163215
HOVERGENiHBG005744
InParanoidiP42345
KOiK07203
OMAiSSHQGLM
OrthoDBiEOG091G0046
PhylomeDBiP42345
TreeFamiTF105134

Enzyme and pathway databases

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
R-HSA-8943724 Regulation of PTEN gene transcription
SABIO-RKiP42345
SignaLinkiP42345
SIGNORiP42345

Miscellaneous databases

ChiTaRSiMTOR human
EvolutionaryTraceiP42345
GeneWikiiMammalian_target_of_rapamycin
GenomeRNAii2475
PROiPR:P42345
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000198793 Expressed in 167 organ(s), highest expression level in testis
CleanExiHS_FRAP1
ExpressionAtlasiP42345 baseline and differential
GenevisibleiP42345 HS

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
1.20.120.150, 1 hit
1.25.10.10, 4 hits
1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR011989 ARM-like
IPR016024 ARM-type_fold
IPR024585 DUF3385_TOR
IPR003152 FATC_dom
IPR009076 FRB_dom
IPR036738 FRB_sf
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR003151 PIK-rel_kinase_FAT
IPR014009 PIK_FAT
IPR026683 TOR
IPR011990 TPR-like_helical_dom_sf
PANTHERiPTHR11139:SF9 PTHR11139:SF9, 1 hit
PfamiView protein in Pfam
PF11865 DUF3385, 1 hit
PF02259 FAT, 1 hit
PF02260 FATC, 1 hit
PF08771 FRB_dom, 1 hit
PF00454 PI3_PI4_kinase, 1 hit
SMARTiView protein in SMART
SM01346 DUF3385, 1 hit
SM01343 FATC, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF47212 SSF47212, 1 hit
SSF48371 SSF48371, 5 hits
SSF56112 SSF56112, 2 hits
PROSITEiView protein in PROSITE
PS51189 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
ProtoNetiSearch...

Entry informationi

Entry nameiMTOR_HUMAN
AccessioniPrimary (citable) accession number: P42345
Secondary accession number(s): Q4LE76
, Q5TER1, Q6LE87, Q96QG3, Q9Y4I3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: October 10, 2018
This is version 200 of the entry and version 1 of the sequence. See 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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