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 (By similarity). Positively regulates the restart of stalled replication forks following activation by the KHDC3-OOEP scaffold complex (PubMed:29125140). Essential for preventing the occurrence of DNA damage during early embryogenesis. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Serine/threonine-protein kinase activity is directly stimulated by TOPBP1. ATR kinase activity is also directly activated by ETAA1, independently of TOPBP1. Activated by DNA and inhibited by BCR-ABL oncogene. Slightly activated by ATRIP. Inhibited by caffeine, wortmannin and LY294002. Forms a heterodimer with ATRIP (PubMed:20801936). Binds to DNA, and to UV-damaged DNA with higher affinity. Interacts with RAD17, MSH2 and HDAC2. Present in a complex containing ATRIP and RPA-coated single-stranded DNA. Present in a complex containing CHD4 and HDAC2. Interacts with EEF1E1, the interaction is enhanced by UV irradiation. Interacts with CLSPN and CEP164 (By similarity). Interacts with TELO2 AND TTI1 (By similarity). Interacts with UHRF2; this interaction promotes ATR activation (By similarity). Ubiquitous. Expression is highest in testis, where it is restricted to primary spermatocytes. Expression decreases as spermiogenesis proceeds (at protein level). Phosphorylated; autophosphorylates in vitro. Belongs to the PI3/PI4-kinase family. ATM subfamily.