Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | ATM |
| Gene Name: | ATM |
| Protein Full Name: | Serine-protein kinase ATM |
| Alias: | A-T, mutated; ATA; Ataxia telangiectasia mutated; Ataxia telangiectasia mutated homolog; ATC; ATD; ATDC; Kinase ATM; TEL1; TEL1, telomere maintenance 1; TELO1 |
| Mass (Da): | 350687 |
| Number AA: | 3056 |
| UniProt ID: | Q13315 |
| Locus ID: | 472 |
| COSMIC ID: | ATM |
| Gene location on chromosome: | 11q22.3 |
| Cancer protein type: | TSP |
| Effect of cancer mutation on protein: | LOSS |
| Effect of active protein on cancer: | INHIBITS |
| Number of cancer specimens: | 25049 |
| Percent of cancer specimens with mutations: | 4.78 |
| General distribution of mutations: | Multi-site |
| Location of most mutations: | Broad distribution of mutation sites with point mutations, complex mutations, insertions and deletions over entire protein length. |
| Mutations observed as inherited: | Ataxia telangiectasia (AT). |
| Normal role description: | ATM is a protein-serine/threonine kinase and phosphorylates and activates p53, while also inhibiting the p53-inhibitor: MDM2. Mutation in ATM are responsible for taxia telangiectasia (AT), and is associate with lymphomas and leukimias in AT patients. ATM mutations are also associated with melanoma, breast, lymphoid tissue, lung, ovarian, stomach, and upper aerodigestive tract tumors. |
| Commentary on involvement of protein in cancer: | 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 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. |