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IID00598
UniprotP42345
ProteinSerine/threonine-protein kinase mTOR
GeneMTOR
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
2549
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 1376-2549 Hetero trimer : IID00599Complex,Q96B36
 Evidence X-RAY 5wbu A Reference
       Region 5wbu A 1376-1384 disorder
       Region 5wbu A 1385-1605 order
       Region 5wbu A 1606-1611 disorder
       Region 5wbu A 1612-1814 order
       Region 5wbu A 1815-1866 disorder
       Region 5wbu A 1867-2436 order
       Region 5wbu A 2437-2491 disorder
       Region 5wbu A 2492-2549 order
 Evidence X-RAY 5wbu B Reference
       Region 5wbu B 1376-1384 disorder
       Region 5wbu B 1385-1814 order
       Region 5wbu B 1815-1866 disorder
       Region 5wbu B 1867-2436 order
       Region 5wbu B 2437-2491 disorder
       Region 5wbu B 2492-2549 order
Seq 1376-2549 Hetero trimer : IID00599Complex
 Evidence X-RAY 5wby A Reference
       Region 5wby A 1376-1384 disorder
       Region 5wby A 1385-1605 order
       Region 5wby A 1606-1611 disorder
       Region 5wby A 1612-1814 order
       Region 5wby A 1815-1866 disorder
       Region 5wby A 1867-2436 order
       Region 5wby A 2437-2491 disorder
       Region 5wby A 2492-2549 order
 Evidence X-RAY 5wby B Reference
       Region 5wby B 1376-1384 disorder
       Region 5wby B 1385-1814 order
       Region 5wby B 1815-1866 disorder
       Region 5wby B 1867-2436 order
       Region 5wby B 2437-2491 disorder
       Region 5wby B 2492-2549 order
Seq 1376-2549 Hetero dimer : IID00599Complex
 Evidence X-RAY 4jt6 A Reference
       Region 4jt6 A 1376-1384 disorder
       Region 4jt6 A 1385-1606 order
       Region 4jt6 A 1607-1610 disorder
       Region 4jt6 A 1611-1814 order
       Region 4jt6 A 1815-1866 disorder
       Region 4jt6 A 1867-2436 order
       Region 4jt6 A 2437-2491 disorder
       Region 4jt6 A 2492-2549 order
 Evidence X-RAY 4jt6 B Reference
       Region 4jt6 B 1376-1384 disorder
       Region 4jt6 B 1385-1814 order
       Region 4jt6 B 1815-1866 disorder
       Region 4jt6 B 1867-2436 order
       Region 4jt6 B 2437-2491 disorder
       Region 4jt6 B 2492-2549 order
 Evidence X-RAY 4jt5 A Reference
       Region 4jt5 A 1376-1384 disorder
       Region 4jt5 A 1385-1606 order
       Region 4jt5 A 1607-1610 disorder
       Region 4jt5 A 1611-1814 order
       Region 4jt5 A 1815-1866 disorder
       Region 4jt5 A 1867-2436 order
       Region 4jt5 A 2437-2491 disorder
       Region 4jt5 A 2492-2549 order
 Evidence X-RAY 4jt5 B Reference
       Region 4jt5 B 1376-1384 disorder
       Region 4jt5 B 1385-1814 order
       Region 4jt5 B 1815-1866 disorder
       Region 4jt5 B 1867-2436 order
       Region 4jt5 B 2437-2491 disorder
       Region 4jt5 B 2492-2549 order
 Evidence X-RAY 4jsx A Reference
       Region 4jsx A 1376-1384 disorder
       Region 4jsx A 1385-1606 order
       Region 4jsx A 1607-1610 disorder
       Region 4jsx A 1611-1814 order
       Region 4jsx A 1815-1866 disorder
       Region 4jsx A 1867-2436 order
       Region 4jsx A 2437-2491 disorder
       Region 4jsx A 2492-2549 order
 Evidence X-RAY 4jsx B Reference
       Region 4jsx B 1376-1384 disorder
       Region 4jsx B 1385-1814 order
       Region 4jsx B 1815-1866 disorder
       Region 4jsx B 1867-2436 order
       Region 4jsx B 2437-2491 disorder
       Region 4jsx B 2492-2549 order
 Evidence X-RAY 4jsv A Reference
       Region 4jsv A 1376-1384 disorder
       Region 4jsv A 1385-1814 order
       Region 4jsv A 1815-1866 disorder
       Region 4jsv A 1867-2436 order
       Region 4jsv A 2437-2491 disorder
       Region 4jsv A 2492-2549 order
 Evidence X-RAY 4jsv B Reference
       Region 4jsv B 1376-1384 disorder
       Region 4jsv B 1385-1814 order
       Region 4jsv B 1815-1866 disorder
       Region 4jsv B 1867-2436 order
       Region 4jsv B 2437-2491 disorder
       Region 4jsv B 2492-2549 order
 Evidence X-RAY 4jsp A Reference
       Region 4jsp A 1376-1384 disorder
       Region 4jsp A 1385-1814 order
       Region 4jsp A 1815-1866 disorder
       Region 4jsp A 1867-2436 order
       Region 4jsp A 2437-2491 disorder
       Region 4jsp A 2492-2549 order
 Evidence X-RAY 4jsp B Reference
       Region 4jsp B 1376-1384 disorder
       Region 4jsp B 1385-1814 order
       Region 4jsp B 1815-1866 disorder
       Region 4jsp B 1867-2436 order
       Region 4jsp B 2437-2491 disorder
       Region 4jsp B 2492-2549 order
 Evidence X-RAY 4jsn A Reference
       Region 4jsn A 1376-1384 disorder
       Region 4jsn A 1385-1606 order
       Region 4jsn A 1607-1610 disorder
       Region 4jsn A 1611-1814 order
       Region 4jsn A 1815-1866 disorder
       Region 4jsn A 1867-2436 order
       Region 4jsn A 2437-2491 disorder
       Region 4jsn A 2492-2549 order
 Evidence X-RAY 4jsn B Reference
       Region 4jsn B 1376-1384 disorder
       Region 4jsn B 1385-1814 order
       Region 4jsn B 1815-1866 disorder
       Region 4jsn B 1867-2436 order
       Region 4jsn B 2437-2491 disorder
       Region 4jsn B 2492-2549 order
Seq 2015-2114 Monomer :
 Evidence NMR 2npu A Reference
       Region 2npu A 2015-2114 order
       Region 2npu A 2015-2018 high_rmsd
 Evidence NMR 2gaq A Reference
       Region 2gaq A 2015-2114 order
       Region 2gaq A 2015-2019 high_rmsd
 Evidence X-RAY 1aue B Reference
       Region 1aue B 2015-2020 disorder
       Region 1aue B 2021-2114 order
 Evidence X-RAY 1aue A Reference
       Region 1aue A 2015-2021 disorder
       Region 1aue A 2022-2113 order
       Region 1aue A 2114-2114 disorder
Seq 2018-2112 Hetero dimer : P62942
 Evidence NMR 2rse B Reference
       Region 2rse B 2019-2112 order
 Evidence X-RAY 1nsg B Reference
       Region 1nsg B 2019-2112 order
 Evidence X-RAY 4fap B Reference
       Region 4fap B 2019-2112 order
 Evidence X-RAY 3fap B Reference
       Region 3fap B 2019-2112 order
 Evidence X-RAY 2fap B Reference
       Region 2fap B 2019-2112 order
 Evidence X-RAY 1fap B Reference
       Region 1fap B 2018-2112 order
Seq 2018-2114 Hetero hexamer : P23443
 Evidence X-RAY 5wbh A Reference
       Region 5wbh A 2018-2021 disorder
       Region 5wbh A 2022-2113 order
       Region 5wbh A 2114-2114 disorder
 Evidence X-RAY 5wbh B Reference
       Region 5wbh B 2018-2021 disorder
       Region 5wbh B 2022-2113 order
       Region 5wbh B 2114-2114 disorder
 Evidence X-RAY 5wbh C Reference
       Region 5wbh C 2018-2113 order
       Region 5wbh C 2114-2114 disorder
 Evidence X-RAY 5wbh D Reference
       Region 5wbh D 2018-2021 disorder
       Region 5wbh D 2022-2113 order
       Region 5wbh D 2114-2114 disorder
 Evidence X-RAY 5wbh E Reference
       Region 5wbh E 2018-2021 disorder
       Region 5wbh E 2022-2114 order
Seq 2021-2112 Hetero dimer : IID00063Complex
 Evidence X-RAY 5gpg B Reference
       Region 5gpg B 2021-2112 order
Seq 2025-2114 Hetero dimer : IID00073Complex
 Evidence X-RAY 4dri B Reference
       Region 4dri B 2025-2112 order
       Region 4dri B 2113-2114 disorder
 Evidence X-RAY 4drh E Reference
       Region 4drh E 2025-2059 order
       Region 4drh E 2060-2064 disorder
       Region 4drh E 2065-2112 order
       Region 4drh E 2113-2114 disorder
 Evidence X-RAY 4drh B Reference
       Region 4drh B 2025-2112 order
       Region 4drh B 2113-2114 disorder
Seq 2025-2114 Hetero dimer : IID00068Complex
 Evidence X-RAY 4drj B Reference
       Region 4drj B 2025-2114 order
Seqphosphorylation
    2478-2478 Phosphoserine
    2481-2481 Phosphoserine; by autocatalysis
    2448-2448 Phosphoserine; by RPS6KB1
    2446-2446 Phosphothreonine; by RPS6KB1
    2173-2173 Phosphothreonine; by PKB/AKT1
    2164-2164 Phosphothreonine
    2159-2159 Phosphoserine; by TBK1
    1261-1261 Phosphoserine
    1162-1162 Phosphothreonine
    567-567 Phosphoserine
Seqacetylation
    1218-1218 N6-acetyllysine
    1-1 N-acetylmethionine
 
Prediction
NeProc
Disorder 1-18,554-576,640-644,906-929,1233-1256,1733-1740,1847-1864,2435-2488
Order 19-248,254-337,342-348,355-464,476-553,577-639,645-905,930-1232,1257-1727,1741-1833,1839-1846,1865-2434,2489-2549
ProS 640-644,906-915,926-929,1233-1245,2442-2446,2454-2461,2472-2488
AlphaFold
Disorder 1-20,49-60,95-101,118-118,136-139,159-160,226-231,247-256,285-358,410-410,464-479,515-516,548-578,595-599,632-645,648-648,786-791,830-835,904-940,961-964,1219-1261,1271-1273,1349-1349,1442-1445,1580-1581,1731-1733,1735-1735,1811-1870,1896-1897,2420-2420,2424-2493
Order 21-48,61-94,102-117,119-135,140-158,161-225,232-246,257-284,359-409,411-463,480-514,517-547,579-594,600-631,646-647,649-785,792-829,836-903,941-960,965-1218,1262-1270,1274-1348,1350-1441,1446-1579,1582-1730,1734-1734,1736-1810,1871-1895,1898-2419,2421-2423,2494-2549
Pfam Hmmer
PF02259 1513-1910 1.1e-164
PF00454 2181-2431 8e-113
PF02260 2517-2549 2e-19
SEG 7-15 ,179-191 ,277-288 ,774-790 ,913-932 ,1279-1300 ,1510-1520 ,1610-1622 ,1666-1677 ,1820-1863
Function
Function in SwissProt
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 (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). 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) (PubMed:15268862, PubMed:15467718, PubMed:18925875, PubMed:18497260, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704). Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis (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). This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (By similarity). 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 (PubMed:12150925, PubMed:12087098, PubMed:18925875). This also includes mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3: in the presence of nutrients, mediates phosphorylation of TFEB and TFE3, promoting their cytosolic retention and inactivation (PubMed:22576015, PubMed:22343943, PubMed:22692423). Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22576015, PubMed:22343943, PubMed:22692423). 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 (PubMed:23429704, PubMed:23429703). Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213). In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (By similarity). To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity). mTORC1 also negatively regulates autophagy through phosphorylation of ULK1 (By similarity). Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (By similarity). Also prevents autophagy through phosphorylation of the autophagy inhibitor DAP (PubMed:20537536). Also prevents autophagy by phosphorylating RUBCNL/Pacer under nutrient-rich conditions (PubMed:30704899). mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor (PubMed:21659604). Among other potential targets mTORC1 may phosphorylate CLIP1 and regulate microtubules (PubMed:12231510). As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton (PubMed:15268862, PubMed:15467718). 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 (PubMed:15718470). 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 (PubMed:15268862). mTORC2 also regulates the phosphorylation of SGK1 at 'Ser-422' (PubMed:18925875). Regulates osteoclastogenesis by adjusting the expression of CEBPB isoforms (By similarity). Plays an important regulatory role in the circadian clock function; regulates period length and rhythm amplitude of the suprachiasmatic nucleus (SCN) and liver clocks (By similarity). Phosphorylates SQSTM1, promoting interaction between SQSTM1 and KEAP1 and subsequent inactivation of the BCR(KEAP1) complex (By similarity).
Biological Process
Diagram with PDB data
MTOR/MLST8/AKT1S1Crystal structure of mTOR(deltaN)-mLST8-PRAS40(alpha-helix & beta-strand) complex