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Serine-protein kinase ATM phospho S1987

Developmental stage

Highest expression in embryonic central nervous system, from 13.5 dpc day and during the whole cerebellar development. Decreased expression when maturation occurs.

Domain

The FATC domain is required for interaction with KAT5.

Function

Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor (PubMed:19047460). Recognizes the substrate consensus sequence [ST]-Q (PubMed:19047460). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (PubMed:11571274). Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes (By similarity). After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele (PubMed:19448632). Also involved in signal transduction and cell cycle control (By similarity). May function as a tumor suppressor (By similarity). Necessary for activation of ABL1 and SAPK (By similarity). Phosphorylates DYRK2, CHEK2, p53/TP53, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (By similarity). May play a role in vesicle and/or protein transport (By similarity). Could play a role in T-cell development, gonad and neurological function (By similarity). Binds DNA ends (By similarity). Plays a role in replication-dependent histone mRNA degradation (By similarity). Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation (By similarity). Phosphorylates ATF2 which stimulates its function in DNA damage response (By similarity). Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (By similarity). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (By similarity). Also involved in pexophagy by mediating phosphorylation of PEX5: translocated to peroxisomes in response to reactive oxygen species (ROS), and catalyzes phosphorylation of PEX5, promoting PEX5 ubiquitination and induction of pexophagy (By similarity).

Post-translational modifications

Phosphorylated by NUAK1/ARK5 (By similarity). Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase.

Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-1899, Ser-1987 correlates with DNA damage-mediated activation of the kinase. During the late stages of DNA damage response, dephosphorylated following deacetylation by SIRT7, leading to ATM deactivation.

Acetylation, on DNA damage, is required for activation of the kinase activity, dimer-monomer transition, and subsequent autophosphorylation on Ser-1987. Acetylated in vitro by KAT5/TIP60. Deacetylated by SIRT7 during the late stages of DNA damage response, promoting ATM dephosphorylation and subsequent deactivation.

Sequence Similarities

Belongs to the PI3/PI4-kinase family. ATM subfamily.

Tissue Specificity

Expressed in brain, skeletal muscle, testis, followed by spleen, lung, kidney, heart, liver and thymus. Ubiquitously expressed in embryonal tissues.

Cellular localization

Alternative names

Serine-protein kinase ATM, Ataxia telangiectasia mutated homolog, A-T mutated homolog, Atm

swissprot:Q62388