GenAge entry for MTOR (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 221)

HGNC symbol: MTOR
Aliases: RAFT1; RAPT1; FLJ44809; FRAP; FRAP2; FRAP1
Common name: mechanistic target of rapamycin (serine/threonine kinase)

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Description

The MTOR kinase belongs to the target of rapamycin group of enzymes which regulate cellular growth and proliferation [1318]. TOR enzymes, homologues of MTOR, have been linked to ageing in lower organisms. In yeast, deletions in the nutrient-responsive TOR pathway increased lifespan, and caloric restriction failed to further increase lifespan [1570]. Similarly, in roundworms, TOR deficiency more than doubled the lifespan [1319], and TOR disruption in fruit flies also extended lifespan [1317].

In invertebrates, a functional link between MTOR and insulin (INS)/IGF1 signalling has been proposed [1322], which further hints of a role for MTOR in ageing. Mice hypomorphic for mTOR have reduced mTORC1 expression, are smaller and live 20% longer [3258]. Female mice heterozygous for both mTOR and mLST8 also exhibit decreased mTORC1 activity and extended life span but have normal glucose tolerance and insulin sensitivity. While rapamycin also disrupts the mTORC2 complex, the lifespan extension is mediated through the mTORC1 complex [3628]. MTORC1 activity is reduced in the tissues of three long lived mice mutants: Snell dwarf mice (POU1F1 mutants), GHR knockout mice and PAPPA knock-out mice [4356]. In GHR knockout mice mTORC2 signalling is upregulated. Treating GHR knockout mice with rapamycin causes no further downregulation of mTORC1 but does interfere with mTORC2 and disrupts whole body homoeostasis [4493]. There, mTORC1 and mTORC2 play different roles in the ageing process.

In human cell cultures MTOR inhibition supresses the senescence associated secretory phenotype (SASP), which can disrupt tissues and contribute to age-related pathologies, including cancer. MTOR normally acts to regulate the SASP by promoting IL1A translation, which in turn promotes NFKB1 transcriptional activity [4337]. More work is needed to determine whether MTOR is associated with human ageing but it is a promising target for further research.

Cytogenetic information

Cytogenetic band: 1p36.2
Location: 11,106,531 bp to 11,262,551 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0001933; negative regulation of protein phosphorylation
GO:0001934; positive regulation of protein phosphorylation
GO:0001938; positive regulation of endothelial cell proliferation
GO:0003007; heart morphogenesis
GO:0003179; heart valve morphogenesis
GO:0005979; regulation of glycogen biosynthetic process
GO:0006112; energy reserve metabolic process
GO:0006207; 'de novo' pyrimidine nucleobase biosynthetic process
GO:0006281; DNA repair
GO:0006468; protein phosphorylation
GO:0006914; autophagy
GO:0006950; response to stress
GO:0007050; cell cycle arrest
GO:0007165; signal transduction
GO:0007281; germ cell development
GO:0007420; brain development
GO:0007569; cell aging
GO:0007584; response to nutrient
GO:0007616; long-term memory
GO:0008542; visual learning
GO:0009791; post-embryonic 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:0014042; positive regulation of neuron maturation
GO:0014736; negative regulation of muscle atrophy
GO:0016049; cell growth
GO:0016236; macroautophagy
GO:0016242; negative regulation of macroautophagy
GO:0016310; phosphorylation
GO:0018105; peptidyl-serine phosphorylation
GO:0018107; peptidyl-threonine phosphorylation
GO:0021510; spinal cord development
GO:0030163; protein catabolic process
GO:0030838; positive regulation of actin filament polymerization
GO:0031295; T cell costimulation
GO:0031397; negative regulation of protein ubiquitination
GO:0031529; ruffle organization
GO:0031641; regulation of myelination
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:0032868; response to insulin
GO:0032956; regulation of actin cytoskeleton organization
GO:0035176; social behavior
GO:0035264; multicellular organism growth
GO:0038202; TORC1 signaling
GO:0040007; growth
GO:0042060; wound healing
GO:0042220; response to cocaine
GO:0043087; regulation of GTPase activity
GO:0043200; response to amino acid
GO:0043278; response to morphine
GO:0043610; regulation of carbohydrate utilization
GO:0045429; positive regulation of nitric oxide biosynthetic process
GO:0045670; regulation of osteoclast differentiation
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:0048015; phosphatidylinositol-mediated signaling
GO:0048255; mRNA stabilization
GO:0048661; positive regulation of smooth muscle cell proliferation
GO:0048714; positive regulation of oligodendrocyte differentiation
GO:0050731; positive regulation of peptidyl-tyrosine phosphorylation
GO:0050882; voluntary musculoskeletal movement
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:0055013; cardiac muscle cell development
GO:0060048; cardiac muscle contraction
GO:0060135; maternal process involved in female pregnancy
GO:0060252; positive regulation of glial cell proliferation
GO:0060999; positive regulation of dendritic spine development
GO:0061051; positive regulation of cell growth involved in cardiac muscle cell development
GO:0071456; cellular response to hypoxia
GO:0090335; regulation of brown fat cell differentiation
GO:0090559; regulation of membrane permeability
GO:1900034; regulation of cellular response to heat
GO:1901216; positive regulation of neuron death
GO:1901838; positive regulation of transcription of nuclear large rRNA transcript from RNA polymerase I promoter
GO:1904000; positive regulation of eating behavior
GO:1904056; positive regulation of cholangiocyte proliferation
GO:1904058; positive regulation of sensory perception of pain
GO:1904193; negative regulation of cholangiocyte apoptotic process
GO:1904197; positive regulation of granulosa cell proliferation
GO:1904206; positive regulation of skeletal muscle hypertrophy
GO:1904213; negative regulation of iodide transmembrane transport

Cellular component:

GO:0000139; Golgi membrane
GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005737; cytoplasm
GO:0005741; mitochondrial outer membrane
GO:0005764; lysosome
GO:0005765; lysosomal membrane
GO:0005789; endoplasmic reticulum membrane
GO:0005829; cytosol
GO:0005942; phosphatidylinositol 3-kinase complex
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

Function:

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:0004672; protein kinase activity
GO:0004674; protein serine/threonine kinase activity
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0016301; kinase activity
GO:0019901; protein kinase binding
GO:0019904; protein domain specific binding
GO:0043022; ribosome binding
GO:0051219; phosphoprotein binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, TERT, STAT3, IRS1, AKT1, EGFR, NBN, PRKCD, BRCA1, VCP, ABL1, PML, GSK3B, PRKCA, TERF1, SIRT1, MAPK8, YWHAZ, SUMO1, NFKBIA, MTOR, SIRT7, IKBKB, SQSTM1, RICTOR
STRING interaction network

Retrieve sequences for MTOR

ORF: ORF
CDS: CDS

Homologs in model organisms

Caenorhabditis elegans: let-363
Danio rerio: mtor
Drosophila melanogaster: Tor
Mus musculus: Mtor
Rattus norvegicus: Mtor
Saccharomyces cerevisiae: TOR2
Schizosaccharomyces pombe: tor2

In other databases

GenAge model organism genes

A homolog of this gene for Caenorhabditis elegans is present as let-363
A homolog of this gene for Drosophila melanogaster is present as Tor
A homolog of this gene for Mus musculus is present as Mtor

GenDR gene manipulations

A homolog of this gene for Caenorhabditis elegans is present as let-363

LongevityMap

This gene is present as MTOR

CellAge

This gene is present as MTOR