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 mTOR 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 due to a mutation in POU1F1, GHR knockout mice and PAPPA knock-out mice. Lowering mTOR enhances MGMT and NDRG1 levels, two proteins involved in DNA repair [4356].

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
And 82 more GO terms
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
And 7 more GO terms
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
And 3 more GO terms
Show all 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
Protein-Protein network diagram for MTOR

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

Selected references

External links

EPD
ORF Accession
NM_004958
CDS Accession
NP_004949
OMIM
601231
HPRD
03134
Ensembl
MTOR
UniProt/Swiss-Prot
FRAP_HUMAN
GeneCards
MTOR
Entrez Gene
2475
UniGene
338207
GenAtlas
MTOR
Internet
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