Anti-ATR antibody (ab10946)

Function

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/H2AFX 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.

Tissue specificity

Ubiquitous, with highest expression in testis. Isoform 2 is found in pancreas, placenta and liver but not in heart, testis and ovary.

Involvement in disease

Defects in ATR are a cause of Seckel syndrome type 1 (SCKL1) [MIM:210600]. SCKL1 is a rare autosomal recessive disorder characterized by growth retardation, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance.

Sequence similarities

Belongs to the PI3/PI4-kinase family. ATM subfamily.
Contains 1 FAT domain.
Contains 1 FATC domain.
Contains 2 HEAT repeats.
Contains 1 PI3K/PI4K domain.

Post-translational
modifications

Phosphorylated; autophosphorylates in vitro.

Cellular localization

Nucleus. Nucleus > PML body. 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.

Alternative names

Database links