GenAge entry for ATM (Homo sapiens)

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

Gene name (HAGRID: 9)

HGNC symbol
ATM 
Aliases
TEL1; TELO1; ATA; ATDC; ATC; ATD 
Common name
ATM 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

ATM is involved diverse aspects of cellular physiology including DNA repair and cell cycle control. It appears to activate DNA repair pathways in response to DNA damage [35]. Mutations in human ATM cause ataxia telangiectasia [190], an early-onset disease some argue is characterized by signs of premature ageing [238]. Patients display cerebellar atrophy and neurodegeneration.

In mouse and worm models that are ATM deficient replenishing intracellular NAD+ reduces the severity of neuropathy, normalizes neuromuscular function, delays memory loss, and extends lifespan [4365]. In mice, mutations in ATM in late-generation TERC mutants with short telomeres results in signs of premature ageing starting at about 6 months of age [12]. In mouse and human cells ATM is required for the recruitment of telomerase and inhibition of ATM leads to shortening of telomeres [4494][4495]. However, it has also been shown that inhibiting ATM attenuates senescence. Inhibiting ATM induces the functional recovery of the lysosome/autophagy system and accelerates the removal of dysfunctional mitochondria [4496]. Overall, it is possible ATM plays a role in human ageing and may link two major theories on ageing: DNA damage accumulation and mitochondrial dysfunction.

Cytogenetic information

Cytogenetic band
11q22-q23
Location
108,222,832 bp to 108,369,099 bp
Orientation
Plus strand
Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology
Process: GO:0000724; double-strand break repair via homologous recombination
GO:0000729; DNA double-strand break processing
GO:0000731; DNA synthesis involved in DNA repair
GO:0000732; strand displacement
GO:0001541; ovarian follicle development
GO:0001666; response to hypoxia
GO:0001756; somitogenesis
GO:0002331; pre-B cell allelic exclusion
GO:0002377; immunoglobulin production
GO:0006260; DNA replication
GO:0006281; DNA repair
GO:0006303; double-strand break repair via nonhomologous end joining
GO:0006468; protein phosphorylation
GO:0006974; cellular response to DNA damage stimulus
GO:0006975; DNA damage induced protein phosphorylation
GO:0006977; DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007004; telomere maintenance via telomerase
GO:0007050; cell cycle arrest
GO:0007094; mitotic spindle assembly checkpoint
GO:0007131; reciprocal meiotic recombination
GO:0007140; male meiosis
GO:0007143; female meiotic division
GO:0007165; signal transduction
GO:0007420; brain development
GO:0007507; heart development
GO:0008340; determination of adult lifespan
GO:0008630; intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009791; post-embryonic development
GO:0010212; response to ionizing radiation
GO:0010506; regulation of autophagy
GO:0016572; histone phosphorylation
GO:0018105; peptidyl-serine phosphorylation
GO:0030889; negative regulation of B cell proliferation
GO:0032212; positive regulation of telomere maintenance via telomerase
GO:0033129; positive regulation of histone phosphorylation
GO:0033151; V(D)J recombination
GO:0035264; multicellular organism growth
GO:0036092; phosphatidylinositol-3-phosphate biosynthetic process
GO:0036289; peptidyl-serine autophosphorylation
GO:0042159; lipoprotein catabolic process
GO:0042981; regulation of apoptotic process
GO:0043065; positive regulation of apoptotic process
GO:0043517; positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0043525; positive regulation of neuron apoptotic process
GO:0045141; meiotic telomere clustering
GO:0046777; protein autophosphorylation
GO:0048538; thymus development
GO:0048599; oocyte development
GO:0051402; neuron apoptotic process
GO:0051972; regulation of telomerase activity
GO:0071044; histone mRNA catabolic process
GO:0071480; cellular response to gamma radiation
GO:0071481; cellular response to X-ray
GO:0071500; cellular response to nitrosative stress
GO:0072434; signal transduction involved in mitotic G2 DNA damage checkpoint
GO:0090399; replicative senescence
GO:0097694; establishment of RNA localization to telomere
GO:0097695; establishment of macromolecular complex localization to telomere
GO:1900034; regulation of cellular response to heat
GO:1901796; regulation of signal transduction by p53 class mediator
GO:1904262; negative regulation of TORC1 signaling
GO:1904354; negative regulation of telomere capping
GO:1904358; positive regulation of telomere maintenance via telomere lengthening
GO:1904884; positive regulation of telomerase catalytic core complex assembly
Cellular component: GO:0000781; chromosome, telomeric region
GO:0000784; nuclear chromosome, telomeric region
GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005819; spindle
GO:0031410; cytoplasmic vesicle
GO:1990391; DNA repair complex
Function: GO:0003677; DNA binding
GO:0004674; protein serine/threonine kinase activity
GO:0004677; DNA-dependent protein kinase activity
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0016303; 1-phosphatidylinositol-3-kinase activity
GO:0032403; protein complex binding
GO:0046983; protein dimerization activity
GO:0047485; protein N-terminus binding
Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge
TP53, ATM, WRN, PEX5, PARP1, BRCA1, HIF1A, RPA1, BLM, ABL1, BRCA2, TOP1, RAD51, TERF1, PRKDC, XRCC5, TERF2, HSPA8, FOXO3, XPA, HDAC1, MAPK14, MED1, BMI1, CREB1, ATF2, E2F1, MDM2, TAF1, RELA, NBN, H2AFX, PPP1CA, ATR, MLH1, CHEK2, SIRT7, TP53BP1
STRING interaction network
Protein-Protein network diagram for ATM

Retrieve sequences for ATM

ORF
ORF
CDS
CDS

Homologs in model organisms

Danio rerio
atm
Drosophila melanogaster
tefu
Mus musculus
Atm
Rattus norvegicus
Atm

In other databases

GenAge model organism genes
  • A homolog of this gene for Mus musculus is present as Atm
LongevityMap
  • This gene is present as ATM
CellAge
  • This gene is present as ATM

Selected references

External links

EPD
ORF Accession
NM_000051
CDS Accession
NP_000042
OMIM
607585
HPRD
06347
Ensembl
ATM
UniProt/Swiss-Prot
ATM_HUMAN
GeneCards
ATM
Entrez Gene
472
UniGene
367437
GenAtlas
ATM
Internet
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