InterPro domain: IPR044107

This entry represents the catalytic domain found in serine-protein kinase ATM.

ATM acts as a DNA damage sensor upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA) [ 1 , 2 ]. It regulate DNA damage response mechanism through recognising the substrate consensus sequence [ST]-Q and phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs) [ 3 ]. On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active [ 4 , 5 ]. It can phosphorylate DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C [ 6 , 7 , 8 , 9 , 10 ]. ATM is also required for telomere elongation [ 11 ]. ATM 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 [ 12 ]. It is also involved in signal transduction and cell cycle control and may function as a tumour suppressor [ 13 ].

1. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc. Natl. Acad. Sci. U.S.A. 97, 10389-94
2. Ataxia-telangiectasia: phenotype/genotype studies of ATM protein expression, mutations, and radiosensitivity. Mol. Genet. Metab. 70, 122-33
3. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem. 276, 42462-7
4. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421, 499-506
5. Involvement of novel autophosphorylation sites in ATM activation. EMBO J. 25, 3504-14
6. ATM gene product phosphorylates I kappa B-alpha. Cancer Res. 57, 24-7
7. ATM associates with and phosphorylates p53: mapping the region of interaction. Nat. Genet. 20, 398-400
8. ATM binds to beta-adaptin in cytoplasmic vesicles. Proc. Natl. Acad. Sci. U.S.A. 95, 10146-51
9. Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286, 1162-6
10. ATM phosphorylates p95/nbs1 in an S-phase checkpoint pathway. Nature 404, 613-7
11. ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells. Cell Rep 13, 1623-32
12. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nat. Immunol. 10, 655-64
13. The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR. Cell 120, 209-21