P42345 · MTOR_HUMAN
- ProteinSerine/threonine-protein kinase mTOR
- GeneMTOR
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids2549 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals (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, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:31601708, PubMed:32561715, PubMed:34519269, PubMed:37751742).
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29236692, PubMed:37751742).
Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704).
In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide 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, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269).
This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692).
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:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692).
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:23429703, PubMed:23429704).
Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213).
Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768).
In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360).
To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity).
In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715).
Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715).
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).
Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055).
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).
The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197).
The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823).
Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670).
The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345).
MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity).
As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton (PubMed:15268862, PubMed:15467718).
mTORC2 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).
MTOR directly or indirectly regulates the phosphorylation of at least 800 proteins (PubMed:15268862, PubMed:15467718, PubMed:17517883, PubMed:18372248, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704, PubMed:29236692, PubMed:37751742).
Functions as part of 2 structurally and functionally distinct signaling complexes mTORC1 and mTORC2 (mTOR complex 1 and 2) (PubMed:15268862, PubMed:15467718, PubMed:18497260, PubMed:18925875, PubMed:20516213, PubMed:21576368, PubMed:21659604, PubMed:23429704).
In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide 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, PubMed:29150432, PubMed:29236692, PubMed:31112131, PubMed:34519269).
This includes phosphorylation of EIF4EBP1 and release of its inhibition toward the elongation initiation factor 4E (eiF4E) (PubMed:24403073, PubMed:29236692).
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:12087098, PubMed:12150925, PubMed:18925875, PubMed:29150432, PubMed:29236692).
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:23429703, PubMed:23429704).
Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 an RNA polymerase III-repressor (PubMed:20516213).
Activates dormant ribosomes by mediating phosphorylation of SERBP1, leading to SERBP1 inactivation and reactivation of translation (PubMed:36691768).
In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1 (PubMed:23426360).
To maintain energy homeostasis mTORC1 may also regulate mitochondrial biogenesis through regulation of PPARGC1A (By similarity).
In the same time, mTORC1 inhibits catabolic pathways: negatively regulates autophagy through phosphorylation of ULK1 (PubMed:32561715).
Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-758', disrupting the interaction with AMPK and preventing activation of ULK1 (PubMed:32561715).
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).
Prevents autophagy by mediating phosphorylation of AMBRA1, thereby inhibiting AMBRA1 ability to mediate ubiquitination of ULK1 and interaction between AMBRA1 and PPP2CA (PubMed:23524951, PubMed:25438055).
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).
The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:24403073, PubMed:31695197).
The non-canonical mTORC1 complex, which acts independently of RHEB, specifically mediates phosphorylation of MiT/TFE factors MITF, TFEB and TFE3 in the presence of nutrients, promoting their cytosolic retention and inactivation (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670, PubMed:36697823).
Upon starvation or lysosomal stress, inhibition of mTORC1 induces dephosphorylation and nuclear translocation of TFEB and TFE3, promoting their transcription factor activity (PubMed:22343943, PubMed:22576015, PubMed:22692423, PubMed:24448649, PubMed:32612235, PubMed:36608670).
The mTORC1 complex regulates pyroptosis in macrophages by promoting GSDMD oligomerization (PubMed:34289345).
MTOR phosphorylates RPTOR which in turn inhibits mTORC1 (By similarity).
As part of the mTORC2 complex MTOR may regulate other cellular processes including survival and organization of the cytoskeleton (PubMed:15268862, PubMed:15467718).
mTORC2 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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
The mTORC1 complex is activated in response to nutrients, growth factors or amino acids: activation requires relocalization of the mTORC1 complex to lysosomes that is mediated by the Ragulator complex, SLC38A9, and the Rag GTPases RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and RagD/RRAGD (PubMed:18497260, PubMed:20381137, PubMed:25561175, PubMed:25567906).
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 (PubMed:14651849, PubMed:15545625, PubMed:29236692).
Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1 (PubMed:19487463).
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 (PubMed:14651849, PubMed:15545625).
The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 (PubMed:12718876).
The kinase activity of MTOR is inhibited by DEPTOR and AKT1S1 (PubMed:17386266, PubMed:19446321, PubMed:29236692, PubMed:34519268, PubMed:34519269).
The non-canonical mTORC1 complex is independent of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 but not other mTORC1 substrates: it is activated by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD (PubMed:32612235, PubMed:36697823).
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 (PubMed:10089303, PubMed:8662507).
mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (PubMed:15467718).
mTORC2 may also be regulated by RHEB but in an indirect manner through the PI3K signaling pathway (PubMed:15467718).
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 (PubMed:14651849, PubMed:15545625, PubMed:29236692).
Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1 (PubMed:19487463).
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 (PubMed:14651849, PubMed:15545625).
The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 (PubMed:12718876).
The kinase activity of MTOR is inhibited by DEPTOR and AKT1S1 (PubMed:17386266, PubMed:19446321, PubMed:29236692, PubMed:34519268, PubMed:34519269).
The non-canonical mTORC1 complex is independent of the RHEB GTPase and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3 but not other mTORC1 substrates: it is activated by FLCN, which activates Rag GTPases RagC/RRAGC and RagD/RRAGD (PubMed:32612235, PubMed:36697823).
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 (PubMed:10089303, PubMed:8662507).
mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive (PubMed:15467718).
mTORC2 may also be regulated by RHEB but in an indirect manner through the PI3K signaling pathway (PubMed:15467718).
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 2165 | ATP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 2167 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 2185 | ATP (UniProtKB | ChEBI) | ||||
Sequence: L | ||||||
Binding site | 2187 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 2190 | ATP (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 2225 | ATP (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 2238 | ATP (UniProtKB | ChEBI) | ||||
Sequence: G | ||||||
Binding site | 2239 | ATP (UniProtKB | ChEBI) | ||||
Sequence: W | ||||||
Binding site | 2240 | ATP (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 2245 | ATP (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 2343 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 2345 | ATP (UniProtKB | ChEBI) | ||||
Sequence: M | ||||||
Binding site | 2356 | ATP (UniProtKB | ChEBI) | ||||
Sequence: I | ||||||
Binding site | 2357 | Mg2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Activated mTORC1 regulates inflammatory immune responses in various innate immune cells.
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase mTOR
- EC number
- Alternative names
Gene names
- Community suggested namesmTOR
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP42345
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Lysosome membrane ; Peripheral membrane protein
Endoplasmic reticulum membrane ; Peripheral membrane protein
Golgi apparatus membrane ; Peripheral membrane protein
Mitochondrion outer membrane ; Peripheral membrane protein
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 (PubMed:18497260, PubMed:20381137).
Lysosome targeting also depends on interaction with MEAK7. Translocates to the lysosome membrane in the presence of TM4SF5 (PubMed:30956113).
Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB (PubMed:18497260, PubMed:20381137).
Lysosome targeting also depends on interaction with MEAK7. Translocates to the lysosome membrane in the presence of TM4SF5 (PubMed:30956113).
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Smith-Kingsmore syndrome (SKS)
- Note
- DescriptionAn autosomal dominant syndrome characterized by intellectual disability, macrocephaly, seizures, umbilical hernia, and facial dysmorphic features.
- See alsoMIM:616638
Natural variants in SKS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_078832 | 1490 | W>R | in SKS; dbSNP:rs2100566800 | |
VAR_078833 | 1595 | M>I | in SKS; dbSNP:rs869312671 | |
VAR_075072 | 1799 | E>K | in SKS; results in increased mTOR signaling; dbSNP:rs863225264 | |
VAR_078835 | 1832 | A>T | in SKS; dbSNP:rs369088781 | |
VAR_078836 | 1888 | F>C | in SKS; dbSNP:rs869312666 | |
VAR_078840 | 2327 | M>I | in SKS; dbSNP:rs878855328 |
Focal cortical dysplasia 2 (FCORD2)
- Note
- 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 alsoMIM:607341
Natural variants in FCORD2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_078824 | 624 | R>H | in FCORD2; uncertain significance; somatic mutation; dbSNP:rs913197212 | |
VAR_078826 | 1450 | Y>D | in FCORD2; somatic mutation | |
VAR_078827 | 1456 | W>G | in FCORD2; somatic mutation; dbSNP:rs1085307114 | |
VAR_078828 | 1459 | A>D | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs1644347782 | |
VAR_078829 | 1459 | A>S | in FCORD2; somatic mutation; dbSNP:rs1644347846 | |
VAR_078830 | 1460 | L>P | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs1057519779 | |
VAR_078831 | 1483 | C>R | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1057519914 | |
VAR_078834 | 1709 | R>H | in FCORD2; uncertain significance; somatic mutation; dbSNP:rs587777895 | |
VAR_078837 | 1977 | T>K | in FCORD2; somatic mutation; dbSNP:rs587777893 | |
VAR_078838 | 2193 | R>C | in FCORD2; somatic mutation; dbSNP:rs1642723200 | |
VAR_078839 | 2215 | S>F | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs587777894 | |
VAR_041543 | 2215 | S>Y | in FCORD2; also found in a colorectal adenocarcinoma sample; somatic mutation; increased TOR signaling; dbSNP:rs587777894 | |
VAR_078841 | 2427 | L>P | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1085307113 | |
VAR_078842 | 2427 | L>Q | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1085307113 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041537 | 8 | in a lung large cell carcinoma sample; somatic mutation; dbSNP:rs748801456 | |||
Sequence: A → S | ||||||
Natural variant | VAR_041538 | 135 | in a metastatic melanoma sample; somatic mutation | |||
Sequence: M → T | ||||||
Natural variant | VAR_078824 | 624 | in FCORD2; uncertain significance; somatic mutation; dbSNP:rs913197212 | |||
Sequence: R → H | ||||||
Natural variant | VAR_041539 | 1083 | in dbSNP:rs56164650 | |||
Sequence: M → V | ||||||
Natural variant | VAR_041540 | 1134 | in dbSNP:rs28730685 | |||
Sequence: A → V | ||||||
Natural variant | VAR_041541 | 1178 | in dbSNP:rs55975118 | |||
Sequence: S → F | ||||||
Natural variant | VAR_078825 | 1376 | found in a patient with focal epilepsy; uncertain significance; dbSNP:rs975577894 | |||
Sequence: D → E | ||||||
Natural variant | VAR_078826 | 1450 | in FCORD2; somatic mutation | |||
Sequence: Y → D | ||||||
Natural variant | VAR_078827 | 1456 | in FCORD2; somatic mutation; dbSNP:rs1085307114 | |||
Sequence: W → G | ||||||
Natural variant | VAR_078828 | 1459 | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs1644347782 | |||
Sequence: A → D | ||||||
Natural variant | VAR_078829 | 1459 | in FCORD2; somatic mutation; dbSNP:rs1644347846 | |||
Sequence: A → S | ||||||
Natural variant | VAR_078830 | 1460 | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs1057519779 | |||
Sequence: L → P | ||||||
Natural variant | VAR_078831 | 1483 | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1057519914 | |||
Sequence: C → R | ||||||
Natural variant | VAR_078832 | 1490 | in SKS; dbSNP:rs2100566800 | |||
Sequence: W → R | ||||||
Natural variant | VAR_078833 | 1595 | in SKS; dbSNP:rs869312671 | |||
Sequence: M → I | ||||||
Natural variant | VAR_078834 | 1709 | in FCORD2; uncertain significance; somatic mutation; dbSNP:rs587777895 | |||
Sequence: R → H | ||||||
Natural variant | VAR_075072 | 1799 | in SKS; results in increased mTOR signaling; dbSNP:rs863225264 | |||
Sequence: E → K | ||||||
Natural variant | VAR_078835 | 1832 | in SKS; dbSNP:rs369088781 | |||
Sequence: A → T | ||||||
Natural variant | VAR_078836 | 1888 | in SKS; dbSNP:rs869312666 | |||
Sequence: F → C | ||||||
Natural variant | VAR_078837 | 1977 | in FCORD2; somatic mutation; dbSNP:rs587777893 | |||
Sequence: T → K | ||||||
Natural variant | VAR_041542 | 2011 | in an ovarian mucinous carcinoma sample; somatic mutation; dbSNP:rs2100412651 | |||
Sequence: M → V | ||||||
Mutagenesis | 2159 | Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2164. Reduced activity of the mTORC1 complex. | ||||
Sequence: S → A | ||||||
Mutagenesis | 2159 | Mimics phosphorylation; leading to stronger phosphorylation of RPS6KB1; when associated with E-2164. Increased activity of the mTORC1 complex. | ||||
Sequence: S → D | ||||||
Mutagenesis | 2164 | Reduces mTORC1-associated S-2481 autophosphorylation; when associated with A-2159. | ||||
Sequence: T → A | ||||||
Mutagenesis | 2164 | Stronger phosphorylation of RPS6KB1; when associated with D-2159. | ||||
Sequence: T → E | ||||||
Mutagenesis | 2173 | Increased mTOR kinase activity. | ||||
Sequence: T → A | ||||||
Natural variant | VAR_078838 | 2193 | in FCORD2; somatic mutation; dbSNP:rs1642723200 | |||
Sequence: R → C | ||||||
Natural variant | VAR_078839 | 2215 | in FCORD2; somatic mutation; increased TOR signaling; dbSNP:rs587777894 | |||
Sequence: S → F | ||||||
Natural variant | VAR_041543 | 2215 | in FCORD2; also found in a colorectal adenocarcinoma sample; somatic mutation; increased TOR signaling; dbSNP:rs587777894 | |||
Sequence: S → Y | ||||||
Natural variant | VAR_064733 | 2220 | found in a renal cell carcinoma sample; somatic mutation; dbSNP:rs2100381099 | |||
Sequence: L → F | ||||||
Natural variant | VAR_078840 | 2327 | in SKS; dbSNP:rs878855328 | |||
Sequence: M → I | ||||||
Mutagenesis | 2340 | Barely detectable kinase activity. | ||||
Sequence: H → A | ||||||
Mutagenesis | 2357 | Kinase-dead mutant, loss of interaction with TM4SF5 and loss of lysosome membrane localization; when associated with I-2364. | ||||
Sequence: D → E | ||||||
Mutagenesis | 2364 | Kinase-dead mutant, loss of interaction with TM4SF5 and loss of lysosome membrane localization; when associated with E-2357. | ||||
Sequence: V → I | ||||||
Natural variant | VAR_064734 | 2406 | found in a renal cell carcinoma sample; somatic mutation; dbSNP:rs2100316251 | |||
Sequence: V → A | ||||||
Natural variant | VAR_078841 | 2427 | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1085307113 | |||
Sequence: L → P | ||||||
Natural variant | VAR_078842 | 2427 | in FCORD2; somatic mutation; increased TOR signaling; increased kinase activity; dbSNP:rs1085307113 | |||
Sequence: L → Q | ||||||
Natural variant | VAR_041544 | 2476 | in a glioblastoma multiforme sample; somatic mutation | |||
Sequence: P → L | ||||||
Natural variant | VAR_078843 | 2501 | found in a patient with non-lesional nocturnal frontal epilepsy; uncertain significance; dbSNP:rs968817513 | |||
Sequence: I → V |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 5,464 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000088808 | 1-2549 | UniProt | Serine/threonine-protein kinase mTOR | |||
Sequence: MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERFDAHLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPAFVMPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPRLIRPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGLEMRKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGYVVEPYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGALDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLPLDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQFLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHIRPYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFKLYLPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGANLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTESLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKYQIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADEEEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAARRVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYNPMARDLFNAAFVSCWSELNEDQQDELIRSIELALTSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVLLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKSTTTARHNAANKILKNMCEHSNTLVQQAMMVSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTYDPNQPIIRIQSIAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHKKTGTTVPESIHSFIGDGLVKPEALNKKAIQIINRVRDKLTGRDFSHDDTLDVPTQVELLIKQATSHENLCQCYIGWCPFW | |||||||
Modified residue | 567 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 567 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 916 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 920 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1162 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1162 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1166 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1218 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 1232 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 1261 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1261 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1262 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 1418 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 2159 | UniProt | Phosphoserine; by TBK1 | ||||
Sequence: S | |||||||
Modified residue | 2164 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 2173 | UniProt | Phosphothreonine; by PKB/AKT1 | ||||
Sequence: T | |||||||
Modified residue | 2446 | UniProt | Phosphothreonine; by RPS6KB1 | ||||
Sequence: T | |||||||
Modified residue | 2448 | UniProt | Phosphoserine; by RPS6KB1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2448 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2450 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2454 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2471 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 2473 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 2474 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 2478 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2478 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 2481 | UniProt | Phosphoserine; by autocatalysis | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 2481 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylates when part of mTORC1 or mTORC2 (PubMed:15467718, PubMed:9434772).
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation (PubMed:19487463).
Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40 and leads to increased intrinsic mTORC1 kinase activity (PubMed:15905173, PubMed:19145465, PubMed:21576368).
Phosphorylation at Ser-2159 by TBK1 in response to growth factors and pathogen recognition receptors promotes mTORC1 activity (PubMed:29150432).
Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity (PubMed:24247430).
Phosphorylation at Ser-1261, Ser-2159 and Thr-2164 promotes autophosphorylation (PubMed:19487463).
Phosphorylation in the kinase domain modulates the interactions of MTOR with RPTOR and AKT1S1/PRAS40 and leads to increased intrinsic mTORC1 kinase activity (PubMed:15905173, PubMed:19145465, PubMed:21576368).
Phosphorylation at Ser-2159 by TBK1 in response to growth factors and pathogen recognition receptors promotes mTORC1 activity (PubMed:29150432).
Phosphorylation at Thr-2173 in the ATP-binding region by AKT1 strongly reduces kinase activity (PubMed:24247430).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in numerous tissues, with highest levels in testis.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:12150925, PubMed:12150926, PubMed:12408816, PubMed:12718876, PubMed:18925875, PubMed:20542007, PubMed:23636326, PubMed:24403073, PubMed:26678875, PubMed:27909983, PubMed:29236692, PubMed:31601764, PubMed:34519268, PubMed:34519269, PubMed:36697823).
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 (PubMed:20542007, PubMed:23636326).
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 (PubMed:20542007, PubMed:23636326, PubMed:27909983).
The MLST8 subunit forms distal foot-like protuberances, and contacts only one MTOR within the complex, while the small AKT1S1/PRAS40 localizes to the midsection of the central core, in close proximity to RPTOR (PubMed:20542007, PubMed:23636326, PubMed:27909983, PubMed:29236692).
mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity by blocking MTOR substrate-recruitment site (PubMed:17386266, PubMed:29236692).
Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15268862, PubMed:15467718, PubMed:17599906, PubMed:18925875).
Interacts with PLPP7 and PML (By similarity).
Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex and interaction with RICTOR is enhanced by deubiquitination of RICTOR by USP9X (PubMed:17599906, PubMed:33378666, PubMed:34519268).
mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity (PubMed:19446321, PubMed:34519268, PubMed:34519269).
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 (PubMed:11853878).
Interacts with TTI1 and TELO2 (PubMed:20427287, PubMed:20801936, PubMed:20810650).
Interacts with CLIP1; phosphorylates and regulates CLIP1 (PubMed:12231510).
Interacts with NBN (PubMed:23762398).
Interacts with HTR6 (PubMed:23027611).
Interacts with BRAT1 (PubMed:25657994).
Interacts with MEAK7 (via C-terminal domain); the interaction increases upon nutrient stimulation (PubMed:29750193).
Interacts with TM4SF5; the interaction is positively regulated by arginine and is negatively regulated by leucine (PubMed:30956113).
Interacts with GPR137B (PubMed:31036939).
Interacts with NCKAP1L (PubMed:32647003).
Interacts with TPCN1 and TPCN2; the interaction is required for TPCN1 and TPCN2 sensitivity to ATP (PubMed:23394946).
Interacts with ATP6V1A and with CRYAB, forming a ternary complex (By similarity).
Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation (PubMed:35561222).
Interacts with TSPAN8 (PubMed:35904232).
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 (PubMed:20542007, PubMed:23636326).
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 (PubMed:20542007, PubMed:23636326, PubMed:27909983).
The MLST8 subunit forms distal foot-like protuberances, and contacts only one MTOR within the complex, while the small AKT1S1/PRAS40 localizes to the midsection of the central core, in close proximity to RPTOR (PubMed:20542007, PubMed:23636326, PubMed:27909983, PubMed:29236692).
mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity by blocking MTOR substrate-recruitment site (PubMed:17386266, PubMed:29236692).
Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15268862, PubMed:15467718, PubMed:17599906, PubMed:18925875).
Interacts with PLPP7 and PML (By similarity).
Interacts with PRR5 and RICTOR; the interaction is direct within the mTORC2 complex and interaction with RICTOR is enhanced by deubiquitination of RICTOR by USP9X (PubMed:17599906, PubMed:33378666, PubMed:34519268).
mTORC1 and mTORC2 associate with DEPTOR, which regulates its activity (PubMed:19446321, PubMed:34519268, PubMed:34519269).
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 (PubMed:11853878).
Interacts with TTI1 and TELO2 (PubMed:20427287, PubMed:20801936, PubMed:20810650).
Interacts with CLIP1; phosphorylates and regulates CLIP1 (PubMed:12231510).
Interacts with NBN (PubMed:23762398).
Interacts with HTR6 (PubMed:23027611).
Interacts with BRAT1 (PubMed:25657994).
Interacts with MEAK7 (via C-terminal domain); the interaction increases upon nutrient stimulation (PubMed:29750193).
Interacts with TM4SF5; the interaction is positively regulated by arginine and is negatively regulated by leucine (PubMed:30956113).
Interacts with GPR137B (PubMed:31036939).
Interacts with NCKAP1L (PubMed:32647003).
Interacts with TPCN1 and TPCN2; the interaction is required for TPCN1 and TPCN2 sensitivity to ATP (PubMed:23394946).
Interacts with ATP6V1A and with CRYAB, forming a ternary complex (By similarity).
Interacts with SLC38A7; this interaction mediates the recruitment of mTORC1 to the lysosome and its subsequent activation (PubMed:35561222).
Interacts with TSPAN8 (PubMed:35904232).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, repeat, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-651 | Interaction with NBN | ||||
Sequence: MLGTGPAAATTAATTSSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELREMSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGGNATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAGDTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISVPTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILTTQREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISSMEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHITPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRDLMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTDTQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVRSEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMGPGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIPQLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAHQLASPGLTTLPEASDVGSITLALRTLGSFEFEGHSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHLISGHAHVVSQTAVQV | ||||||
Repeat | 16-53 | HEAT 1 | ||||
Sequence: SSNVSVLQQFASGLKSRNEETRAKAAKELQHYVTMELR | ||||||
Repeat | 55-99 | HEAT 2 | ||||
Sequence: MSQEESTRFYDQLNHHIFELVSSSDANERKGGILAIASLIGVEGG | ||||||
Repeat | 100-137 | HEAT 3 | ||||
Sequence: NATRIGRFANYLRNLLPSNDPVVMEMASKAIGRLAMAG | ||||||
Repeat | 138-179 | HEAT 4 | ||||
Sequence: DTFTAEYVEFEVKRALEWLGADRNEGRRHAAVLVLRELAISV | ||||||
Repeat | 180-220 | HEAT 5 | ||||
Sequence: PTFFFQQVQPFFDNIFVAVWDPKQAIREGAVAALRACLILT | ||||||
Repeat | 222-276 | HEAT 6 | ||||
Sequence: QREPKEMQKPQWYRHTFEEAEKGFDETLAKEKGMNRDDRIHGALLILNELVRISS | ||||||
Repeat | 277-313 | HEAT 7 | ||||
Sequence: MEGERLREEMEEITQQQLVHDKYCKDLMGFGTKPRHI | ||||||
Repeat | 314-364 | HEAT 8 | ||||
Sequence: TPFTSFQAVQPQQSNALVGLLGYSSHQGLMGFGTSPSPAKSTLVESRCCRD | ||||||
Repeat | 365-409 | HEAT 9 | ||||
Sequence: LMEEKFDQVCQWVLKCRNSKNSLIQMTILNLLPRLAAFRPSAFTD | ||||||
Repeat | 410-445 | HEAT 10 | ||||
Sequence: TQYLQDTMNHVLSCVKKEKERTAAFQALGLLSVAVR | ||||||
Repeat | 446-494 | HEAT 11 | ||||
Sequence: SEFKVYLPRVLDIIRAALPPKDFAHKRQKAMQVDATVFTCISMLARAMG | ||||||
Repeat | 495-529 | HEAT 12 | ||||
Sequence: PGIQQDIKELLEPMLAVGLSPALTAVLYDLSRQIP | ||||||
Repeat | 530-563 | HEAT 13 | ||||
Sequence: QLKKDIQDGLLKMLSLVLMHKPLRHPGMPKGLAH | ||||||
Repeat | 564-596 | HEAT 14 | ||||
Sequence: QLASPGLTTLPEASDVGSITLALRTLGSFEFEG | ||||||
Repeat | 597-636 | HEAT 15 | ||||
Sequence: HSLTQFVRHCADHFLNSEHKEIRMEAARTCSRLLTPSIHL | ||||||
Repeat | 637-683 | HEAT 16 | ||||
Sequence: ISGHAHVVSQTAVQVVADVLSKLLVVGITDPDPDIRYCVLASLDERF | ||||||
Repeat | 686-724 | HEAT 17 | ||||
Sequence: HLAQAENLQALFVALNDQVFEIRELAICTVGRLSSMNPA | ||||||
Repeat | 727-766 | HEAT 18 | ||||
Sequence: MPFLRKMLIQILTELEHSGIGRIKEQSARMLGHLVSNAPR | ||||||
Repeat | 769-811 | HEAT 19 | ||||
Sequence: RPYMEPILKALILKLKDPDPDPNPGVINNVLATIGELAQVSGL | ||||||
Repeat | 814-853 | HEAT 20 | ||||
Sequence: RKWVDELFIIIMDMLQDSSLLAKRQVALWTLGQLVASTGY | ||||||
Repeat | 857-893 | HEAT 21 | ||||
Sequence: PYRKYPTLLEVLLNFLKTEQNQGTRREAIRVLGLLGA | ||||||
Repeat | 894-942 | HEAT 22 | ||||
Sequence: LDPYKHKVNIGMIDQSRDASAVSLSESKSSQDSSDYSTSEMLVNMGNLP | ||||||
Repeat | 943-988 | HEAT 23 | ||||
Sequence: LDEFYPAVSMVALMRIFRDQSLSHHHTMVVQAITFIFKSLGLKCVQ | ||||||
Repeat | 989-1027 | HEAT 24 | ||||
Sequence: FLPQVMPTFLNVIRVCDGAIREFLFQQLGMLVSFVKSHI | ||||||
Repeat | 1029-1068 | HEAT 25 | ||||
Sequence: PYMDEIVTLMREFWVMNTSIQSTIILLIEQIVVALGGEFK | ||||||
Repeat | 1069-1105 | HEAT 26 | ||||
Sequence: LYLPQLIPHMLRVFMHDNSPGRIVSIKLLAAIQLFGA | ||||||
Repeat | 1106-1144 | HEAT 27 | ||||
Sequence: NLDDYLHLLLPPIVKLFDAPEAPLPSRKAALETVDRLTE | ||||||
Repeat | 1145-1188 | HEAT 28 | ||||
Sequence: SLDFTDYASRIIHPIVRTLDQSPELRSTAMDTLSSLVFQLGKKY | ||||||
Repeat | 1189-1225 | HEAT 29 | ||||
Sequence: QIFIPMVNKVLVRHRINHQRYDVLICRIVKGYTLADE | ||||||
Repeat | 1226-1273 | HEAT 30 | ||||
Sequence: EEDPLIYQHRMLRSGQGDALASGPVETGPMKKLHVSTINLQKAWGAAR | ||||||
Repeat | 1274-1311 | HEAT 31 | ||||
Sequence: RVSKDDWLEWLRRLSLELLKDSSSPSLRSCWALAQAYN | ||||||
Repeat | 1312-1345 | HEAT 32 | ||||
Sequence: PMARDLFNAAFVSCWSELNEDQQDELIRSIELAL | ||||||
Repeat | 1346-1382 | TPR 1 | ||||
Sequence: TSQDIAEVTQTLLNLAEFMEHSDKGPLPLRDDNGIVL | ||||||
Domain | 1382-1982 | FAT | ||||
Sequence: LLGERAAKCRAYAKALHYKELEFQKGPTPAILESLISINNKLQQPEAAAGVLEYAMKHFGELEIQATWYEKLHEWEDALVAYDKKMDTNKDDPELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDETQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTHDGAFYRAVLALHQDLFSLAQQCIDKARDLLDAELTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREIIRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHEDMRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVHPQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHAIATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSWYKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQKKVTEDLSKTLLMYTVPAVQGFFRSISLSRGNNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAIQIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQALIYPLTVASKS | ||||||
Repeat | 1383-1408 | TPR 2 | ||||
Sequence: LGERAAKCRAYAKALHYKELEFQKGP | ||||||
Repeat | 1409-1442 | TPR 3 | ||||
Sequence: TPAILESLISINNKLQQPEAAAGVLEYAMKHFGE | ||||||
Repeat | 1443-1473 | TPR 4 | ||||
Sequence: LEIQATWYEKLHEWEDALVAYDKKMDTNKDD | ||||||
Repeat | 1474-1507 | TPR 5 | ||||
Sequence: PELMLGRMRCLEALGEWGQLHQQCCEKWTLVNDE | ||||||
Repeat | 1508-1541 | TPR 6 | ||||
Sequence: TQAKMARMAAAAAWGLGQWDSMEEYTCMIPRDTH | ||||||
Repeat | 1542-1574 | TPR 7 | ||||
Sequence: DGAFYRAVLALHQDLFSLAQQCIDKARDLLDAE | ||||||
Repeat | 1575-1614 | TPR 8 | ||||
Sequence: LTAMAGESYSRAYGAMVSCHMLSELEEVIQYKLVPERREI | ||||||
Repeat | 1615-1649 | TPR 9 | ||||
Sequence: IRQIWWERLQGCQRIVEDWQKILMVRSLVVSPHED | ||||||
Repeat | 1650-1693 | TPR 10 | ||||
Sequence: MRTWLKYASLCGKSGRLALAHKTLVLLLGVDPSRQLDHPLPTVH | ||||||
Repeat | 1694-1731 | TPR 11 | ||||
Sequence: PQVTYAYMKNMWKSARKIDAFQHMQHFVQTMQQQAQHA | ||||||
Repeat | 1732-1786 | TPR 12 | ||||
Sequence: IATEDQQHKQELHKLMARCFLKLGEWQLNLQGINESTIPKVLQYYSAATEHDRSW | ||||||
Repeat | 1787-1846 | TPR 13 | ||||
Sequence: YKAWHAWAVMNFEAVLHYKHQNQARDEKKKLRHASGANITNATTAATTAATATTTASTEG | ||||||
Region | 1812-1867 | Disordered | ||||
Sequence: DEKKKLRHASGANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQK | ||||||
Compositional bias | 1822-1867 | Polar residues | ||||
Sequence: GANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQK | ||||||
Repeat | 1898-1930 | TPR 14 | ||||
Sequence: NNLQDTLRVLTLWFDYGHWPDVNEALVEGVKAI | ||||||
Repeat | 1931-1970 | TPR 15 | ||||
Sequence: QIDTWLQVIPQLIARIDTPRPLVGRLIHQLLTDIGRYHPQ | ||||||
Repeat | 1971-2005 | TPR 16 | ||||
Sequence: ALIYPLTVASKSTTTARHNAANKILKNMCEHSNTL | ||||||
Region | 2012-2144 | Sufficient for interaction with the FKBP1A/rapamycin complex | ||||
Sequence: VSEELIRVAILWHEMWHEGLEEASRLYFGERNVKGMFEVLEPLHAMMERGPQTLKETSFNQAYGRDLMEAQEWCRKYMKSGNVKDLTQAWDLYYHVFRRISKQLPQLTSLELQYVSPKLLMCRDLELAVPGTY | ||||||
Domain | 2156-2469 | PI3K/PI4K catalytic | ||||
Sequence: IAPSLQVITSKQRPRKLTLMGSNGHEFVFLLKGHEDLRQDERVMQLFGLVNTLLANDPTSLRKNLSIQRYAVIPLSTNSGLIGWVPHCDTLHALIRDYREKKKILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAGDDLAKLLWLKSPSSEVWFDRRTNYTRSLAVMSMVGYILGLGDRHPSNLMLDRLSGKILHIDFGDCFEVAMTREKFPEKIPFRLTRMLTNAMEVTGLDGNYRITCHTVMEVLREHKDSVMAVLEAFVYDPLLNWRLMDTNTKGNKRSRTRTDSYSAGQSVEILDGVELGEPAHK | ||||||
Region | 2162-2168 | G-loop | ||||
Sequence: VITSKQR | ||||||
Region | 2258-2296 | Interaction with MLST8 | ||||
Sequence: KILLNIEHRIMLRMAPDYDHLTLMQKVEVFEHAVNNTAG | ||||||
Region | 2335-2343 | Catalytic loop | ||||
Sequence: GLGDRHPSN | ||||||
Region | 2355-2380 | Activation loop | ||||
Sequence: HIDFGDCFEVAMTREKFPEKIPFRLT | ||||||
Domain | 2517-2549 | FATC | ||||
Sequence: DTLDVPTQVELLIKQATSHENLCQCYIGWCPFW |
Domain
The kinase domain (PI3K/PI4K) is intrinsically active but has a highly restricted catalytic center.
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).
Sequence similarities
Belongs to the PI3/PI4-kinase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length2,549
- Mass (Da)288,892
- Last updated1995-11-01 v1
- Checksum7D9AD6E784882AB4
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8V8TRG9 | A0A8V8TRG9_HUMAN | MTOR | 2478 | ||
A0A8V8TQM6 | A0A8V8TQM6_HUMAN | MTOR | 1507 | ||
A0A8V8TQN3 | A0A8V8TQN3_HUMAN | MTOR | 2364 | ||
A0A8V8TQP2 | A0A8V8TQP2_HUMAN | MTOR | 985 | ||
A0A8V8TR74 | A0A8V8TR74_HUMAN | MTOR | 513 | ||
A0A8V8TQ52 | A0A8V8TQ52_HUMAN | MTOR | 1590 |
Sequence caution
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 353 | in Ref. 2; AAC39933 | ||||
Sequence: K → N | ||||||
Sequence conflict | 359 | in Ref. 2; AAC39933 | ||||
Sequence: S → N | ||||||
Sequence conflict | 364 | in Ref. 2; AAC39933 | ||||
Sequence: D → N | ||||||
Sequence conflict | 390 | in Ref. 2; AAC39933 | ||||
Sequence: M → L | ||||||
Sequence conflict | 430 | in Ref. 2; AAC39933 | ||||
Sequence: R → L | ||||||
Sequence conflict | 455-457 | in Ref. 2; AAC39933 | ||||
Sequence: VLD → GVE | ||||||
Sequence conflict | 461 | in Ref. 2; AAC39933 | ||||
Sequence: A → G | ||||||
Sequence conflict | 482-484 | in Ref. 2; AAC39933 | ||||
Sequence: VFT → FFN | ||||||
Sequence conflict | 489 | in Ref. 2; AAC39933 | ||||
Sequence: L → V | ||||||
Sequence conflict | 513 | in Ref. 2; AAC39933 | ||||
Sequence: L → I | ||||||
Sequence conflict | 539 | in Ref. 2; AAC39933 | ||||
Sequence: L → V | ||||||
Sequence conflict | 553 | in Ref. 2; AAC39933 | ||||
Sequence: R → C | ||||||
Sequence conflict | 857 | in Ref. 3; BAE06077 | ||||
Sequence: P → L | ||||||
Sequence conflict | 1075 | in Ref. 2; AAC39933 | ||||
Sequence: I → S | ||||||
Compositional bias | 1822-1867 | Polar residues | ||||
Sequence: GANITNATTAATTAATATTTASTEGSNSESEAESTENSPTPSPLQK |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L34075 EMBL· GenBank· DDBJ | AAA58486.1 EMBL· GenBank· DDBJ | mRNA | ||
U88966 EMBL· GenBank· DDBJ | AAC39933.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
AB209995 EMBL· GenBank· DDBJ | BAE06077.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AL109811 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL391561 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL049653 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC117166 EMBL· GenBank· DDBJ | AAI17167.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ300188 EMBL· GenBank· DDBJ | CAC15570.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
L35478 EMBL· GenBank· DDBJ | AAC41713.1 EMBL· GenBank· DDBJ | mRNA |