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P42345

- MTOR_HUMAN

UniProt

P42345 - MTOR_HUMAN

Protein

Serine/threonine-protein kinase mTOR

Gene

MTOR

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    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'.18 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 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.5 Publications

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. drug binding Source: InterPro
    3. kinase activity Source: UniProtKB
    4. phosphoprotein binding Source: UniProtKB
    5. protein binding Source: UniProtKB
    6. protein serine/threonine kinase activity Source: UniProtKB
    7. ribosome binding Source: Ensembl
    8. RNA polymerase III type 1 promoter DNA binding Source: UniProtKB
    9. RNA polymerase III type 2 promoter DNA binding Source: UniProtKB
    10. RNA polymerase III type 3 promoter DNA binding Source: UniProtKB
    11. TFIIIC-class transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. cell growth Source: UniProtKB
    2. cellular response to hypoxia Source: UniProtKB
    3. cellular response to nutrient levels Source: UniProtKB
    4. epidermal growth factor receptor signaling pathway Source: Reactome
    5. Fc-epsilon receptor signaling pathway Source: Reactome
    6. fibroblast growth factor receptor signaling pathway Source: Reactome
    7. germ cell development Source: Ensembl
    8. growth Source: UniProtKB
    9. innate immune response Source: Reactome
    10. insulin receptor signaling pathway Source: Reactome
    11. negative regulation of autophagy Source: UniProtKB
    12. negative regulation of cell size Source: Ensembl
    13. negative regulation of macroautophagy Source: Ensembl
    14. negative regulation of NFAT protein import into nucleus Source: Ensembl
    15. neurotrophin TRK receptor signaling pathway Source: Reactome
    16. peptidyl-serine phosphorylation Source: UniProtKB
    17. peptidyl-threonine phosphorylation Source: Ensembl
    18. phosphatidylinositol-mediated signaling Source: Reactome
    19. phosphorylation Source: UniProtKB
    20. positive regulation of actin filament polymerization Source: Ensembl
    21. positive regulation of endothelial cell proliferation Source: Ensembl
    22. positive regulation of gene expression Source: UniProtKB
    23. positive regulation of lamellipodium assembly Source: Ensembl
    24. positive regulation of lipid biosynthetic process Source: UniProtKB
    25. positive regulation of myotube differentiation Source: Ensembl
    26. positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
    27. positive regulation of protein kinase B signaling Source: Ensembl
    28. positive regulation of protein phosphorylation Source: UniProtKB
    29. positive regulation of stress fiber assembly Source: Ensembl
    30. positive regulation of transcription from RNA polymerase III promoter Source: UniProtKB
    31. positive regulation of translation Source: UniProtKB
    32. protein autophosphorylation Source: MGI
    33. protein catabolic process Source: UniProtKB
    34. protein phosphorylation Source: UniProtKB
    35. regulation of actin cytoskeleton organization Source: UniProtKB
    36. regulation of carbohydrate utilization Source: Ensembl
    37. regulation of fatty acid beta-oxidation Source: Ensembl
    38. regulation of glycogen biosynthetic process Source: Ensembl
    39. regulation of protein kinase activity Source: Ensembl
    40. regulation of Rac GTPase activity Source: Ensembl
    41. regulation of response to food Source: Ensembl
    42. response to amino acid Source: UniProtKB
    43. response to nutrient Source: UniProtKB
    44. response to stress Source: UniProtKB
    45. ruffle organization Source: Ensembl
    46. signal transduction Source: UniProtKB
    47. T cell costimulation Source: Reactome
    48. TOR signaling Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiREACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_200775. HSF1-dependent transactivation.
    REACT_6754. S6K1-mediated signalling.
    REACT_6836. Release of eIF4E.
    REACT_6838. mTOR signalling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinkiP42345.

    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
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:3942. MTOR.

    Subcellular locationi

    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. endomembrane system Source: UniProtKB
    4. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    5. Golgi membrane Source: UniProtKB-SubCell
    6. lysosomal membrane Source: UniProtKB
    7. lysosome Source: UniProtKB
    8. membrane Source: UniProtKB
    9. mitochondrial outer membrane Source: UniProtKB-SubCell
    10. phosphatidylinositol 3-kinase complex Source: UniProtKB
    11. PML body Source: UniProtKB-SubCell
    12. TORC1 complex Source: UniProtKB
    13. TORC2 complex Source: UniProtKB

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2159 – 21591S → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2164. 1 Publication
    Mutagenesisi2159 – 21591S → D: Stronger phosphorylation of RPS6KB1; when associated with E-2164. 1 Publication
    Mutagenesisi2164 – 21641T → A: Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2159. 1 Publication
    Mutagenesisi2164 – 21641T → E: Stronger phosphorylation of RPS6KB1; when associated with D-2159. 1 Publication
    Mutagenesisi2173 – 21731T → A: Increased mTOR kinase activity. 1 Publication
    Mutagenesisi2340 – 23401H → A: Barely detectable kinase activity. 1 Publication

    Organism-specific databases

    PharmGKBiPA28360.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 25492549Serine/threonine-protein kinase mTORPRO_0000088808Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei567 – 5671Phosphoserine3 Publications
    Modified residuei1162 – 11621Phosphothreonine1 Publication
    Modified residuei1218 – 12181N6-acetyllysine1 Publication
    Modified residuei1261 – 12611Phosphoserine1 Publication
    Modified residuei2159 – 21591Phosphoserine1 Publication
    Modified residuei2164 – 21641Phosphothreonine1 Publication
    Modified residuei2173 – 21731Phosphothreonine; by PKB/AKT11 Publication
    Modified residuei2446 – 24461Phosphothreonine; by RPS6KB11 Publication
    Modified residuei2448 – 24481Phosphoserine; by RPS6KB12 Publications
    Modified residuei2478 – 24781Phosphoserine1 Publication
    Modified residuei2481 – 24811Phosphoserine; by autocatalysis2 Publications

    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.11 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP42345.
    PaxDbiP42345.
    PRIDEiP42345.

    PTM databases

    PhosphoSiteiP42345.

    Expressioni

    Tissue specificityi

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

    Gene expression databases

    ArrayExpressiP42345.
    BgeeiP42345.
    CleanExiHS_FRAP1.
    GenevestigatoriP42345.

    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 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.20 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
    PREX1Q8TCU611EBI-359260,EBI-1046542
    RICTORQ6R32727EBI-359260,EBI-1387196
    RPTORQ8N12230EBI-359260,EBI-1567928
    SIRT1Q96EB62EBI-359260,EBI-1802965
    TPCN2Q8NHX92EBI-359260,EBI-5239949

    Protein-protein interaction databases

    BioGridi108757. 84 interactions.
    DIPiDIP-790N.
    IntActiP42345. 50 interactions.
    MINTiMINT-121301.
    STRINGi9606.ENSP00000354558.

    Structurei

    Secondary structure

    1
    2549
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi1387 – 140620
    Helixi1410 – 142213
    Helixi1426 – 143914
    Helixi1446 – 14527
    Helixi1456 – 146914
    Helixi1474 – 148613
    Helixi1490 – 14989
    Beta strandi1501 – 15033
    Helixi1506 – 152116
    Turni1522 – 15243
    Helixi1526 – 15338
    Helixi1541 – 155313
    Helixi1557 – 157216
    Turni1573 – 15775
    Turni1584 – 15863
    Helixi1587 – 160519
    Beta strandi1606 – 16083
    Helixi1609 – 16113
    Helixi1612 – 162413
    Helixi1630 – 164011
    Turni1641 – 16433
    Turni1646 – 16483
    Helixi1650 – 166314
    Helixi1666 – 167712
    Beta strandi1681 – 16844
    Helixi1694 – 170613
    Helixi1710 – 172920
    Helixi1737 – 176226
    Turni1766 – 17683
    Helixi1769 – 178214
    Turni1783 – 17853
    Helixi1787 – 181327
    Helixi1868 – 189326
    Beta strandi1896 – 18983
    Helixi1900 – 191314
    Helixi1917 – 192913
    Helixi1933 – 19386
    Helixi1939 – 19435
    Turni1944 – 19474
    Helixi1951 – 196616
    Helixi1970 – 198011
    Helixi1985 – 202036
    Helixi2025 – 203915
    Helixi2044 – 205815
    Helixi2065 – 209127
    Helixi2094 – 211118
    Helixi2115 – 21173
    Beta strandi2119 – 21224
    Helixi2123 – 21264
    Helixi2128 – 21325
    Beta strandi2137 – 21393
    Beta strandi2152 – 21565
    Beta strandi2158 – 21625
    Beta strandi2165 – 21673
    Beta strandi2170 – 21767
    Beta strandi2181 – 21899
    Helixi2193 – 221119
    Helixi2213 – 22175
    Beta strandi2227 – 22293
    Beta strandi2231 – 22333
    Beta strandi2235 – 22384
    Beta strandi2243 – 22453
    Helixi2246 – 225611
    Helixi2263 – 22719
    Helixi2275 – 22773
    Helixi2280 – 229112
    Helixi2298 – 23069
    Helixi2310 – 233425
    Turni2341 – 23433
    Beta strandi2344 – 23474
    Turni2348 – 23503
    Beta strandi2353 – 23553
    Helixi2364 – 23674
    Beta strandi2369 – 23713
    Helixi2381 – 23866
    Turni2389 – 23946
    Helixi2395 – 240915
    Helixi2411 – 242212
    Turni2425 – 24273
    Helixi2428 – 24358
    Helixi2493 – 250715
    Turni2508 – 25103
    Beta strandi2512 – 25165
    Helixi2521 – 253313
    Helixi2535 – 25384
    Helixi2543 – 25453

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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[»]
    ProteinModelPortaliP42345.
    SMRiP42345. Positions 149-175, 1447-1496, 2025-2114, 2140-2422, 2517-2549.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP42345.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati16 – 5338HEAT 1Add
    BLAST
    Repeati55 – 9945HEAT 2Add
    BLAST
    Repeati100 – 13738HEAT 3Add
    BLAST
    Repeati138 – 17942HEAT 4Add
    BLAST
    Repeati180 – 22041HEAT 5Add
    BLAST
    Repeati222 – 27655HEAT 6Add
    BLAST
    Repeati277 – 31337HEAT 7Add
    BLAST
    Repeati314 – 36451HEAT 8Add
    BLAST
    Repeati365 – 40945HEAT 9Add
    BLAST
    Repeati410 – 44536HEAT 10Add
    BLAST
    Repeati446 – 49449HEAT 11Add
    BLAST
    Repeati495 – 52935HEAT 12Add
    BLAST
    Repeati530 – 56334HEAT 13Add
    BLAST
    Repeati564 – 59633HEAT 14Add
    BLAST
    Repeati597 – 63640HEAT 15Add
    BLAST
    Repeati637 – 68347HEAT 16Add
    BLAST
    Repeati686 – 72439HEAT 17Add
    BLAST
    Repeati727 – 76640HEAT 18Add
    BLAST
    Repeati769 – 81143HEAT 19Add
    BLAST
    Repeati814 – 85340HEAT 20Add
    BLAST
    Repeati857 – 89337HEAT 21Add
    BLAST
    Repeati894 – 94249HEAT 22Add
    BLAST
    Repeati943 – 98846HEAT 23Add
    BLAST
    Repeati989 – 102739HEAT 24Add
    BLAST
    Repeati1029 – 106840HEAT 25Add
    BLAST
    Repeati1069 – 110537HEAT 26Add
    BLAST
    Repeati1106 – 114439HEAT 27Add
    BLAST
    Repeati1145 – 118844HEAT 28Add
    BLAST
    Repeati1189 – 122537HEAT 29Add
    BLAST
    Repeati1226 – 127348HEAT 30Add
    BLAST
    Repeati1274 – 131138HEAT 31Add
    BLAST
    Repeati1312 – 134534HEAT 32Add
    BLAST
    Repeati1346 – 138237TPR 1Add
    BLAST
    Domaini1382 – 1982601FATPROSITE-ProRule annotationAdd
    BLAST
    Repeati1383 – 140826TPR 2Add
    BLAST
    Repeati1409 – 144234TPR 3Add
    BLAST
    Repeati1443 – 147331TPR 4Add
    BLAST
    Repeati1474 – 150734TPR 5Add
    BLAST
    Repeati1508 – 154134TPR 6Add
    BLAST
    Repeati1542 – 157433TPR 7Add
    BLAST
    Repeati1575 – 161440TPR 8Add
    BLAST
    Repeati1615 – 164935TPR 9Add
    BLAST
    Repeati1650 – 169344TPR 10Add
    BLAST
    Repeati1694 – 173138TPR 11Add
    BLAST
    Repeati1732 – 178655TPR 12Add
    BLAST
    Repeati1787 – 184660TPR 13Add
    BLAST
    Repeati1898 – 193033TPR 14Add
    BLAST
    Repeati1931 – 197040TPR 15Add
    BLAST
    Repeati1971 – 200535TPR 16Add
    BLAST
    Domaini2182 – 2516335PI3K/PI4KPROSITE-ProRule annotationAdd
    BLAST
    Domaini2517 – 254933FATCPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 651651Interaction with NBNAdd
    BLAST
    Regioni2012 – 2144133Sufficient for interaction with the FKBP1A/rapamycin complexBy similarityAdd
    BLAST
    Regioni2258 – 229639Interaction with MLST8Add
    BLAST

    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

    eggNOGiCOG5032.
    HOGENOMiHOG000163215.
    HOVERGENiHBG005744.
    InParanoidiP42345.
    KOiK07203.
    OMAiTYKQNIG.
    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.
    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.
    IPR011990. TPR-like_helical.
    [Graphical view]
    PfamiPF11865. DUF3385. 1 hit.
    PF02259. FAT. 1 hit.
    PF02260. FATC. 1 hit.
    PF00454. PI3_PI4_kinase. 1 hit.
    PF08771. Rapamycin_bind. 1 hit.
    [Graphical view]
    SMARTiSM00146. 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

    MLGTGPAAAT TAATTSSNVS VLQQFASGLK SRNEETRAKA AKELQHYVTM     50
    ELREMSQEES TRFYDQLNHH IFELVSSSDA NERKGGILAI ASLIGVEGGN 100
    ATRIGRFANY LRNLLPSNDP VVMEMASKAI GRLAMAGDTF TAEYVEFEVK 150
    RALEWLGADR NEGRRHAAVL VLRELAISVP TFFFQQVQPF FDNIFVAVWD 200
    PKQAIREGAV AALRACLILT TQREPKEMQK PQWYRHTFEE AEKGFDETLA 250
    KEKGMNRDDR IHGALLILNE LVRISSMEGE RLREEMEEIT QQQLVHDKYC 300
    KDLMGFGTKP RHITPFTSFQ AVQPQQSNAL VGLLGYSSHQ GLMGFGTSPS 350
    PAKSTLVESR CCRDLMEEKF DQVCQWVLKC RNSKNSLIQM TILNLLPRLA 400
    AFRPSAFTDT QYLQDTMNHV LSCVKKEKER TAAFQALGLL SVAVRSEFKV 450
    YLPRVLDIIR AALPPKDFAH KRQKAMQVDA TVFTCISMLA RAMGPGIQQD 500
    IKELLEPMLA VGLSPALTAV LYDLSRQIPQ LKKDIQDGLL KMLSLVLMHK 550
    PLRHPGMPKG LAHQLASPGL TTLPEASDVG SITLALRTLG SFEFEGHSLT 600
    QFVRHCADHF LNSEHKEIRM EAARTCSRLL TPSIHLISGH AHVVSQTAVQ 650
    VVADVLSKLL VVGITDPDPD IRYCVLASLD ERFDAHLAQA ENLQALFVAL 700
    NDQVFEIREL AICTVGRLSS MNPAFVMPFL RKMLIQILTE LEHSGIGRIK 750
    EQSARMLGHL VSNAPRLIRP YMEPILKALI LKLKDPDPDP NPGVINNVLA 800
    TIGELAQVSG LEMRKWVDEL FIIIMDMLQD SSLLAKRQVA LWTLGQLVAS 850
    TGYVVEPYRK YPTLLEVLLN FLKTEQNQGT RREAIRVLGL LGALDPYKHK 900
    VNIGMIDQSR DASAVSLSES KSSQDSSDYS TSEMLVNMGN LPLDEFYPAV 950
    SMVALMRIFR DQSLSHHHTM VVQAITFIFK SLGLKCVQFL PQVMPTFLNV 1000
    IRVCDGAIRE FLFQQLGMLV SFVKSHIRPY MDEIVTLMRE FWVMNTSIQS 1050
    TIILLIEQIV VALGGEFKLY LPQLIPHMLR VFMHDNSPGR IVSIKLLAAI 1100
    QLFGANLDDY LHLLLPPIVK LFDAPEAPLP SRKAALETVD RLTESLDFTD 1150
    YASRIIHPIV RTLDQSPELR STAMDTLSSL VFQLGKKYQI FIPMVNKVLV 1200
    RHRINHQRYD VLICRIVKGY TLADEEEDPL IYQHRMLRSG QGDALASGPV 1250
    ETGPMKKLHV STINLQKAWG AARRVSKDDW LEWLRRLSLE LLKDSSSPSL 1300
    RSCWALAQAY NPMARDLFNA AFVSCWSELN EDQQDELIRS IELALTSQDI 1350
    AEVTQTLLNL AEFMEHSDKG PLPLRDDNGI VLLGERAAKC RAYAKALHYK 1400
    ELEFQKGPTP AILESLISIN NKLQQPEAAA GVLEYAMKHF GELEIQATWY 1450
    EKLHEWEDAL VAYDKKMDTN KDDPELMLGR MRCLEALGEW GQLHQQCCEK 1500
    WTLVNDETQA KMARMAAAAA WGLGQWDSME EYTCMIPRDT HDGAFYRAVL 1550
    ALHQDLFSLA QQCIDKARDL LDAELTAMAG ESYSRAYGAM VSCHMLSELE 1600
    EVIQYKLVPE RREIIRQIWW ERLQGCQRIV EDWQKILMVR SLVVSPHEDM 1650
    RTWLKYASLC GKSGRLALAH KTLVLLLGVD PSRQLDHPLP TVHPQVTYAY 1700
    MKNMWKSARK IDAFQHMQHF VQTMQQQAQH AIATEDQQHK QELHKLMARC 1750
    FLKLGEWQLN LQGINESTIP KVLQYYSAAT EHDRSWYKAW HAWAVMNFEA 1800
    VLHYKHQNQA RDEKKKLRHA SGANITNATT AATTAATATT TASTEGSNSE 1850
    SEAESTENSP TPSPLQKKVT EDLSKTLLMY TVPAVQGFFR SISLSRGNNL 1900
    QDTLRVLTLW FDYGHWPDVN EALVEGVKAI QIDTWLQVIP QLIARIDTPR 1950
    PLVGRLIHQL LTDIGRYHPQ ALIYPLTVAS KSTTTARHNA ANKILKNMCE 2000
    HSNTLVQQAM MVSEELIRVA ILWHEMWHEG LEEASRLYFG ERNVKGMFEV 2050
    LEPLHAMMER GPQTLKETSF NQAYGRDLME AQEWCRKYMK SGNVKDLTQA 2100
    WDLYYHVFRR ISKQLPQLTS LELQYVSPKL LMCRDLELAV PGTYDPNQPI 2150
    IRIQSIAPSL QVITSKQRPR KLTLMGSNGH EFVFLLKGHE DLRQDERVMQ 2200
    LFGLVNTLLA NDPTSLRKNL SIQRYAVIPL STNSGLIGWV PHCDTLHALI 2250
    RDYREKKKIL LNIEHRIMLR MAPDYDHLTL MQKVEVFEHA VNNTAGDDLA 2300
    KLLWLKSPSS EVWFDRRTNY TRSLAVMSMV GYILGLGDRH PSNLMLDRLS 2350
    GKILHIDFGD CFEVAMTREK FPEKIPFRLT RMLTNAMEVT GLDGNYRITC 2400
    HTVMEVLREH KDSVMAVLEA FVYDPLLNWR LMDTNTKGNK RSRTRTDSYS 2450
    AGQSVEILDG VELGEPAHKK TGTTVPESIH SFIGDGLVKP EALNKKAIQI 2500
    INRVRDKLTG RDFSHDDTLD VPTQVELLIK QATSHENLCQ CYIGWCPFW 2549
    Length:2,549
    Mass (Da):288,892
    Last modified:November 1, 1995 - v1
    Checksum:i7D9AD6E784882AB4
    GO

    Sequence cautioni

    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti353 – 3531K → N in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti359 – 3591S → N in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti364 – 3641D → N in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti390 – 3901M → L in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti430 – 4301R → L in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti455 – 4573VLD → GVE in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti461 – 4611A → G in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti482 – 4843VFT → FFN in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti489 – 4891L → V in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti513 – 5131L → I in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti539 – 5391L → V in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti553 – 5531R → C in AAC39933. (PubMed:9653645)Curated
    Sequence conflicti857 – 8571P → L in BAE06077. 1 PublicationCurated
    Sequence conflicti1075 – 10751I → S in AAC39933. (PubMed:9653645)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti8 – 81A → S in a lung large cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041537
    Natural varianti135 – 1351M → T in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041538
    Natural varianti1083 – 10831M → V.1 Publication
    Corresponds to variant rs56164650 [ dbSNP | Ensembl ].
    VAR_041539
    Natural varianti1134 – 11341A → V.1 Publication
    Corresponds to variant rs28730685 [ dbSNP | Ensembl ].
    VAR_041540
    Natural varianti1178 – 11781S → F.1 Publication
    Corresponds to variant rs55975118 [ dbSNP | Ensembl ].
    VAR_041541
    Natural varianti2011 – 20111M → V in an ovarian mucinous carcinoma sample; somatic mutation. 1 Publication
    VAR_041542
    Natural varianti2215 – 22151S → Y in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041543
    Natural varianti2220 – 22201L → F Found in a renal cell carcinoma sample; somatic mutation. 1 Publication
    VAR_064733
    Natural varianti2406 – 24061V → A Found in a renal cell carcinoma sample; somatic mutation. 1 Publication
    VAR_064734
    Natural varianti2476 – 24761P → L in a glioblastoma multiforme sample; somatic mutation. 1 Publication
    VAR_041544

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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_005263438.1.
    UniGeneiHs.338207.

    Genome annotation databases

    EnsembliENST00000361445; ENSP00000354558; ENSG00000198793.
    GeneIDi2475.
    KEGGihsa:2475.
    UCSCiuc001asd.3. human.

    Polymorphism databases

    DMDMi1169735.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    Wikipedia

    Mammalian target of rapamycin entry

    Target mTOR

    mTOR signaling pathway and mTOR inhibition resource

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS127.1.
    PIRi S45340.
    RefSeqi NP_004949.1. NM_004958.3.
    XP_005263495.1. XM_005263438.1.
    UniGenei Hs.338207.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AUE X-ray 2.33 A/B 2015-2114 [» ]
    1FAP X-ray 2.70 B 2018-2112 [» ]
    1NSG X-ray 2.20 B 2019-2112 [» ]
    2FAP X-ray 2.20 B 2019-2112 [» ]
    2GAQ NMR - A 2015-2114 [» ]
    2NPU NMR - A 2015-2114 [» ]
    2RSE NMR - B 2019-2112 [» ]
    3FAP X-ray 1.85 B 2019-2112 [» ]
    4DRH X-ray 2.30 B/E 2025-2114 [» ]
    4DRI X-ray 1.45 B 2025-2114 [» ]
    4DRJ X-ray 1.80 B 2025-2114 [» ]
    4FAP X-ray 2.80 B 2019-2112 [» ]
    4JSN X-ray 3.20 A/B 1376-2549 [» ]
    4JSP X-ray 3.30 A/B 1376-2549 [» ]
    4JSV X-ray 3.50 A/B 1376-2549 [» ]
    4JSX X-ray 3.50 A/B 1376-2549 [» ]
    4JT5 X-ray 3.45 A/B 1376-2549 [» ]
    4JT6 X-ray 3.60 A/B 1376-2549 [» ]
    ProteinModelPortali P42345.
    SMRi P42345. Positions 149-175, 1447-1496, 2025-2114, 2140-2422, 2517-2549.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108757. 84 interactions.
    DIPi DIP-790N.
    IntActi P42345. 50 interactions.
    MINTi MINT-121301.
    STRINGi 9606.ENSP00000354558.

    Chemistry

    BindingDBi P42345.
    ChEMBLi CHEMBL2221341.
    GuidetoPHARMACOLOGYi 2109.

    PTM databases

    PhosphoSitei P42345.

    Polymorphism databases

    DMDMi 1169735.

    Proteomic databases

    MaxQBi P42345.
    PaxDbi P42345.
    PRIDEi P42345.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000361445 ; ENSP00000354558 ; ENSG00000198793 .
    GeneIDi 2475.
    KEGGi hsa:2475.
    UCSCi uc001asd.3. human.

    Organism-specific databases

    CTDi 2475.
    GeneCardsi GC01M011166.
    HGNCi HGNC:3942. MTOR.
    HPAi CAB005057.
    MIMi 601231. gene.
    neXtProti NX_P42345.
    PharmGKBi PA28360.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5032.
    HOGENOMi HOG000163215.
    HOVERGENi HBG005744.
    InParanoidi P42345.
    KOi K07203.
    OMAi TYKQNIG.
    PhylomeDBi P42345.
    TreeFami TF105134.

    Enzyme and pathway databases

    Reactomei REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_19358. CD28 dependent PI3K/Akt signaling.
    REACT_200775. HSF1-dependent transactivation.
    REACT_6754. S6K1-mediated signalling.
    REACT_6836. Release of eIF4E.
    REACT_6838. mTOR signalling.
    REACT_75829. PIP3 activates AKT signaling.
    SignaLinki P42345.

    Miscellaneous databases

    ChiTaRSi MTOR. human.
    EvolutionaryTracei P42345.
    GeneWikii Mammalian_target_of_rapamycin.
    GenomeRNAii 2475.
    NextBioi 9805.
    PROi P42345.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42345.
    Bgeei P42345.
    CleanExi HS_FRAP1.
    Genevestigatori P42345.

    Family and domain databases

    Gene3Di 1.10.1070.11. 3 hits.
    1.20.120.150. 1 hit.
    1.25.10.10. 4 hits.
    1.25.40.10. 2 hits.
    InterProi IPR011989. ARM-like.
    IPR016024. ARM-type_fold.
    IPR024585. DUF3385_TOR.
    IPR003152. FATC.
    IPR011009. Kinase-like_dom.
    IPR000403. PI3/4_kinase_cat_dom.
    IPR018936. PI3/4_kinase_CS.
    IPR003151. PIK-rel_kinase_FAT.
    IPR014009. PIK_FAT.
    IPR009076. Rapamycin-bd_dom.
    IPR011990. TPR-like_helical.
    [Graphical view ]
    Pfami PF11865. DUF3385. 1 hit.
    PF02259. FAT. 1 hit.
    PF02260. FATC. 1 hit.
    PF00454. PI3_PI4_kinase. 1 hit.
    PF08771. Rapamycin_bind. 1 hit.
    [Graphical view ]
    SMARTi SM00146. PI3Kc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47212. SSF47212. 1 hit.
    SSF48371. SSF48371. 5 hits.
    SSF56112. SSF56112. 2 hits.
    PROSITEi 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.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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. 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. 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. 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. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    48. "Phosphorylation of the TOR ATP binding domain by AGC kinase constitutes a novel mode of TOR inhibition."
      Halova L., Du W., Kirkham S., Smith D.L., Petersen J.
      J. Cell Biol. 203:595-604(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-2173, MUTAGENESIS OF THR-2173.
    49. "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.
    50. "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.
    51. "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.
    52. "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.
    53. "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.
    54. "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.
    55. "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.
    56. Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 1376-2549 IN COMPLEX WITH MLST8, SUBUNIT, TPR-REPEATS, DOMAINS, MUTAGENESIS OF HIS-2340.
    57. "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.
      , 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.
    58. Cited for: VARIANTS PHE-2220 AND ALA-2406.

    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: October 1, 2014
    This is version 154 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

    External Data

    Dasty 3