ATR

The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017]

ataxia telangiectasia and Rad3 related

Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication. Positively regulates the restart of stalled replication forks following activation by the KHDC3L-OOEP scaffold complex (By similarity).

Cellular response to DNA damage stimulus Source: UniProtKB
Cellular response to gamma radiation Source: BHF-UCL
Cellular response to UV Source: BHF-UCL
DNA damage checkpoint Source: UniProtKB
DNA repair Source: ProtInc
DNA replication Source: Reactome
Establishment of protein-containing complex localization to telomere Source: BHF-UCL
Establishment of RNA localization to telomere Source: BHF-UCL
Interstrand cross-link repair Source: Reactome
Multicellular organism development Source: ProtInc
Negative regulation of DNA replication Source: UniProtKB
Peptidyl-serine phosphorylation Source: BHF-UCL
Positive regulation of DNA damage response, signal transduction by p53 class mediator Source: BHF-UCL
Positive regulation of telomerase catalytic core complex assembly Source: BHF-UCL
Positive regulation of telomere maintenance via telomerase Source: BHF-UCL
Protein autophosphorylation Source: BHF-UCL
Protein localization to chromosome, telomeric region Source: BHF-UCL
Regulation of cellular response to heat Source: Reactome
Regulation of signal transduction by p53 class mediator Source: Reactome
Replication fork processing Source: UniProtKB
Replicative senescence Source: BHF-UCL
Response to drug Source: Ensembl
Telomere maintenance Source: GO_Central

Nucleus; Chromosome. Depending on the cell type, it can also be found in PML nuclear bodies. Recruited to chromatin during S-phase. Redistributes to discrete nuclear foci upon DNA damage, hypoxia or replication fork stalling.

Seckel syndrome 1 (SCKL1): A rare autosomal recessive disorder characterized by proportionate dwarfism of prenatal onset associated with low birth weight, growth retardation, severe microcephaly with a bird-headed like appearance, and mental retardation.
Cutaneous telangiectasia and cancer syndrome, familial (FCTCS): A disease characterized by cutaneous telangiectases in infancy with patchy alopecia over areas of affected skin, thinning of the lateral eyebrows, and mild dental and nail anomalies. Affected individuals are at increased risk of developing oropharyngeal cancer, and other malignancies have been reported as well.

Phosphorylated; autophosphorylates in vitro.