InnateDB Protein
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IDBP-204407.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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Mtor
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Protein Name
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mechanistic target of rapamycin (serine/threonine kinase)
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Synonyms
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2610315D21Rik; AI327068; flat; FRAP; Frap1; FRAP2; RAFT1; RAPT1;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000054164
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InnateDB Gene
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IDBG-204403 (Mtor)
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Protein Structure
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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. 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'. {ECO:0000269PubMed:11792863, ECO:0000269PubMed:15467718, ECO:0000269PubMed:15545625, ECO:0000269PubMed:16221682, ECO:0000269PubMed:16915281, ECO:0000269PubMed:16962653, ECO:0000269PubMed:18046414, ECO:0000269PubMed:21258367, ECO:0000269PubMed:21659604}.
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Subcellular Localization |
Endoplasmic reticulum membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Golgi apparatus membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Mitochondrion outer membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome {ECO:0000250}. Cytoplasm. Nucleus, PML body. Note=Shuttles between cytoplasm and nucleus. Accumulates in the nucleus in response to hypoxia. Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB (By similarity). {ECO:0000250}.
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Disease Associations |
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Tissue Specificity |
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 47 experimentally validated interaction(s) in this database.
They are also associated with 131 interaction(s) predicted by orthology.
Experimentally validated |
Total |
47
[view]
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Protein-Protein |
46
[view]
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Protein-DNA |
1
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Predicted by orthology |
Total |
131 [view]
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Molecular Function |
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Biological Process |
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Cellular Component |
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PDB ID |
MGI:1928394
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InterPro |
IPR016024
Armadillo-type fold
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PFAM |
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PRINTS |
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
Q9JLN9
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PhosphoSite |
PhosphoSite-Q9JLN9
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TrEMBL |
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UniProt Splice Variant |
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Entrez Gene |
56717
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UniGene |
Mm.21158
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RefSeq |
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MGI ID |
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MGI Symbol |
Mtor
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OMIM |
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CCDS |
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HPRD |
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IMGT |
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EMBL |
AF152838
AK012031
AL713995
AL731654
BC043920
BC112904
CU210865
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GenPept |
AAF73196
AAH43920
AAI12905
BAB27985
CAM22525
CAM23943
CAQ51622
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