| 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. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. 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. 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. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Plays a role in replication-dependent histone mRNA degradation. Binds DNA ends. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. |
| Tissue Specificity: |
Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes. |
| Involvement in Disease: |
Ataxia telangiectasia: A rare recessive disorder characterized by progressive cerebellar ataxia, dilation of the blood vessels in the conjunctiva and eyeballs, immunodeficiency, growth retardation and sexual immaturity. Patients have a strong predisposition to cancer; about 30% of patients develop tumors, particularly lymphomas and leukemias. Cells from affected individuals are highly sensitive to damage by ionizing radiation and resistant to inhibition of DNA synthesis following irradiation. |
| Sequence Similarities: |
Belongs to the PI3/PI4-kinase family. ATM subfamily. |
| Post-Translational Modification: |
Phosphorylated by NUAK1/ARK5. Autophosphorylation on Ser-367, Ser-1893, Ser-1981 correlates with DNA damage-mediated activation of the kinase. |
| Cellular Location: |
Nucleus. Cytoplasmic vesicle.
Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin. |
| Database Links: |
Entrez Gene: 472?HumanOmim: 607585?HumanSwissProt: Q13315?HumanUnigene: 367437?Human |
| Synonyms: |
A-T mutated AntibodyA-T mutated homolog AntibodyAT mutated AntibodyAT1 AntibodyATA AntibodyAtaxia telangiectasia mutated AntibodyAtaxia telangiectasia mutated gene AntibodyAtaxia telangiectasia mutated homolog AntibodyAtaxia telangiectasia mutated homolog (human) AntibodyATC AntibodyATD AntibodyATDC AntibodyATE AntibodyATM AntibodyATM serine/threonine kinase AntibodyATM_HUMAN AntibodyDKFZp781A0353 AntibodyMGC74674 AntibodyOTTHUMP00000232981 AntibodySerine protein kinase ATM AntibodySerine-protein kinase ATM AntibodySerine/threonine-protein kinase ATM AntibodyTefu AntibodyTEL1 AntibodyTEL1, telomere maintenance 1, homolog AntibodyTELO1 AntibodyTelomere fusion protein Antibody |
| Information: |
Target information shown above is from the UniProt Consortium. |
