GenAge entry for ATR (Homo sapiens)

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

Gene name (HAGRID: 231)

HGNC symbol: ATR
Aliases: FRP1; SCKL; SCKL1; MEC1
Common name: ATR 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

ATR is involved in DNA repair by activating checkpoint signalling during genotoxic stresses including the phosphorylation of ageing-related proteins such as BRCA1 and TP53. Together with ATM, ATR has been suggested to regulate TP53 and WRN [1681].

ATR disruption in mice results in embryonic lethality in homozygous animals while heterozygous mice develop normally but have increased tumour incidence [1679]. Deletion of ATR in young adult mice eliminates 80-90% of proliferating cells and results in several age-related phenotypes accompanied by a depletion of stem and progenitor cells and exhaustion of tissue renewal and homeostatic capacity [1864]. Patients with mutations affecting ATR develop Seckel syndrome, characterized by growth retardation, dwarfism, and mental retardation, clinical features often found in disorders involving impaired DNA-damage responses [1680]. A possible role in human ageing is plausible though further research is necessary to confirm this hypothesis.

Cytogenetic information

Cytogenetic band: 3q23
Location: 142,449,235 bp to 142,578,826 bp
Orientation: Minus strand

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

Protein information

Gene Ontology

Process:

GO:0000077; DNA damage checkpoint
GO:0006260; DNA replication
GO:0006281; DNA repair
GO:0006974; cellular response to DNA damage stimulus
GO:0007049; cell cycle
GO:0007275; multicellular organism development
GO:0008156; negative regulation of DNA replication
GO:0018105; peptidyl-serine phosphorylation
GO:0032212; positive regulation of telomere maintenance via telomerase
GO:0034644; cellular response to UV
GO:0036297; interstrand cross-link repair

And 12 more GO terms

Cellular component:

GO:0000784; nuclear chromosome, telomeric region
GO:0005654; nucleoplasm
GO:0005694; chromosome
GO:0005794; Golgi apparatus
GO:0016605; PML body

Function:

GO:0003677; DNA binding
GO:0004672; protein kinase activity
GO:0004674; protein serine/threonine kinase activity
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0032405; MutLalpha complex binding
GO:0032407; MutSalpha complex binding

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, TERT, ATM, WRN, E2F1, EGFR, NBN, BRCA1, RPA1, BLM, HSP90AA1, ABL1, BRCA2, EP300, XRCC5, POLD1, XPA, HDAC1, CREB1, HDAC2, H2AFX, CDKN2A, ATR, CHEK2, PIK3CA
STRING interaction network

Retrieve sequences for ATR

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: atr
Drosophila melanogaster: mei-41
Mus musculus: Atr
Rattus norvegicus: Atr
Saccharomyces cerevisiae: MEC1
Schizosaccharomyces pombe: rad3

In other databases

GenAge model organism genes

A homolog of this gene for Saccharomyces cerevisiae is present as MEC1

LongevityMap

This gene is present as ATR

CellAge

This gene is present as ATR