InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Mtor

Summary

InnateDB Protein

IDBP-204405.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Mtor

Protein Name

mechanistic target of rapamycin (serine/threonine kinase)

Synonyms

2610315D21Rik; AI327068; flat; FRAP; Frap1; FRAP2; RAFT1; RAPT1;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000099510

InnateDB Gene

IDBG-204403 (Mtor)

Protein Structure

UniProt Annotation

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}.

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}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

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]
Protein-Protein	46 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	131 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001030	RNA polymerase III type 1 promoter DNA binding
GO:0001031	RNA polymerase III type 2 promoter DNA binding
GO:0001032	RNA polymerase III type 3 promoter DNA binding
GO:0001156	TFIIIC-class transcription factor binding
GO:0004674	protein serine/threonine kinase activity
GO:0005488	binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008144	drug binding
GO:0016301	kinase activity
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0019904	protein domain specific binding
GO:0043022	ribosome binding
GO:0051219	phosphoprotein binding

Biological Process

GO:0001934	positive regulation of protein phosphorylation
GO:0001938	positive regulation of endothelial cell proliferation
GO:0005979	regulation of glycogen biosynthetic process
GO:0006109	regulation of carbohydrate metabolic process
GO:0006468	protein phosphorylation
GO:0006950	response to stress
GO:0007281	germ cell development
GO:0010507	negative regulation of autophagy
GO:0010592	positive regulation of lamellipodium assembly
GO:0010628	positive regulation of gene expression
GO:0010831	positive regulation of myotube differentiation
GO:0016242	negative regulation of macroautophagy
GO:0016310	phosphorylation
GO:0018105	peptidyl-serine phosphorylation
GO:0018107	peptidyl-threonine phosphorylation
GO:0030030	cell projection organization
GO:0030838	positive regulation of actin filament polymerization
GO:0031529	ruffle organization
GO:0031669	cellular response to nutrient levels
GO:0031929	TOR signaling
GO:0031998	regulation of fatty acid beta-oxidation
GO:0032095	regulation of response to food
GO:0032314	regulation of Rac GTPase activity
GO:0032868	response to insulin
GO:0032956	regulation of actin cytoskeleton organization
GO:0043200	response to amino acid
GO:0043610	regulation of carbohydrate utilization
GO:0045087	innate immune response (InnateDB)
GO:0045727	positive regulation of translation
GO:0045792	negative regulation of cell size
GO:0045859	regulation of protein kinase activity
GO:0045945	positive regulation of transcription from RNA polymerase III promoter
GO:0046777	protein autophosphorylation
GO:0046889	positive regulation of lipid biosynthetic process
GO:0050731	positive regulation of peptidyl-tyrosine phosphorylation
GO:0051496	positive regulation of stress fiber assembly
GO:0051534	negative regulation of NFAT protein import into nucleus
GO:0051897	positive regulation of protein kinase B signaling
GO:0071456	cellular response to hypoxia

Cellular Component

GO:0000139	Golgi membrane
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005741	mitochondrial outer membrane
GO:0005764	lysosome
GO:0005765	lysosomal membrane
GO:0005789	endoplasmic reticulum membrane
GO:0005829	cytosol
GO:0012505	endomembrane system
GO:0016020	membrane
GO:0016605	PML body
GO:0030425	dendrite
GO:0031931	TORC1 complex
GO:0031932	TORC2 complex
GO:0043025	neuronal cell body
GO:0070438	mTOR-FKBP12-rapamycin complex

Protein Structure and Domains

PDB ID

MGI:1928394

InterPro

IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR009076 Rapamycin-binding domain
IPR011009 Protein kinase-like domain
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold
IPR024585 Domain of unknown function DUF3385, target of rapamycin protein

PFAM

PF00454
PF02259
PF02260
PF08771
PF11865

PRINTS

PIRSF

SMART

SM00146

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q9JLN9