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:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15064416, PubMed:15448695, PubMed:15456891, PubMed:15790808, PubMed:15916964, PubMed:17923702, PubMed:21757780, PubMed:24534091, PubMed:35076389, PubMed:9733514). Recognizes the substrate consensus sequence [ST]-Q (PubMed:10550055, PubMed:10839545, PubMed:10910365, PubMed:12556884, PubMed:14871926, PubMed:15448695, PubMed:15456891, PubMed:15916964, PubMed:17923702, PubMed:24534091, PubMed:9733514). Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism (By similarity).
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, FBXW7, FANCD2, NFKBIA, BRCA1, CREBBP/CBP, RBBP8/CTIP, FBXO46, MRE11, nibrin (NBN), RAD50, RAD17, PELI1, TERF1, UFL1, RAD9, UBQLN4 and DCLRE1C (PubMed:10550055, PubMed:10766245, PubMed:10802669, PubMed:10839545, PubMed:10910365, PubMed:10973490, PubMed:11375976, PubMed:12086603, PubMed:15456891, PubMed:19965871, PubMed:21757780, PubMed:24534091, PubMed:26240375, PubMed:26774286, PubMed:30171069, PubMed:30612738, PubMed:30886146, PubMed:30952868, PubMed:38128537, PubMed:9733515, PubMed:9843217).
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 (PubMed:19965871). Phosphorylates ATF2 which stimulates its function in DNA damage response (PubMed:15916964).
Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks (PubMed:29203878). Phosphorylates TTC5/STRAP at 'Ser-203' in the cytoplasm in response to DNA damage, which promotes TTC5/STRAP nuclear localization (PubMed:15448695). 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 (PubMed:26344566)
Homodimer (PubMed:12556884, PubMed:15790808, PubMed:28508083). Dimers or tetramers in inactive state (PubMed:12556884, PubMed:15790808, PubMed:28508083). On DNA damage, autophosphorylation dissociates ATM into monomers rendering them catalytically active (PubMed:12556884, PubMed:28508083).
Binds p53/TP53, ABL1, BRCA1 and TERF1 (PubMed:15790808, PubMed:9168117, PubMed:9843217). Interacts with NBN (via FxF/Y motif) (PubMed:35076389). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBN protein complex (PubMed:10783165).
This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165). Interacts with RAD17; DNA damage promotes the association (PubMed:11418864). Interacts with EEF1E1; the interaction, induced on DNA damage, up-regulates TP53 (PubMed:15680327).
Interacts with KAT8, NABP2, ATMIN and CEP164 (PubMed:15923642, PubMed:17525732, PubMed:18283122, PubMed:18449195). Interacts with AP2B1 and AP3B2; the interaction occurs in cytoplasmic vesicles (By similarity). Interacts with TELO2 and TTI1 (PubMed:20427287, PubMed:20801936, PubMed:20810650).
Interacts with DDX1 (PubMed:18710941). Interacts with BRAT1 (PubMed:22977523). Interacts with CYREN (via XLF motif) (By similarity).
Interacts (via microbody targeting signal) with PEX5; promoting translocation to peroxisomes in response to reactive oxygen species (ROS) (PubMed:26344566)
Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes
The FATC domain is required for interaction with KAT5
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.
Click a pathway to open the interactive Reactome viewer.
Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to GATM, aggregated across our SSL data sources. Click any partner node to view that gene’s page.
Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.
Total Trials Found: 1
| NCT ID | Condition | Brief Title | Phase | Status |
|---|---|---|---|---|
| NCT06177171 | BRCA1 Mutation, BRCA2 Mutation, BRCA Mutation, PALB2 Gene Mutation, Checkpoint Kinase 2 Gene Mutation, ATM Gene Mutation | Olaparib and ASTX727 in BRCA1/2- and Homologous Recombination Deficient (HRD)-Mutated Tumors | PHASE1 | RECRUITING |
| NCT06308263 | Solid Tumor | Tuvusertib (M1774) Human Mass Balance and Absolute Bioavailability Study (DDRIVER Solid Tumors 303) | PHASE1 | COMPLETED |
| NCT06462235 | Gram-negative Bacterial Infection | A Study to Learn About the Study Medicine Aztreonam-Avibactam (ATM-AVI) in Infants and Newborns Admitted in Hospitals With Bacterial Infection (CHERISH) | PHASE2 | RECRUITING |
| NCT05033756 | Malignant Neoplasm of Breast, Breast Cancer | Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO | PHASE2 | ACTIVE_NOT_RECRUITING |
| NCT00176774 | Colorectal Carcinoma | Irinotecan, 5-Fluorouracil, and Leucovorin in Colorectal Carcinoma | PHASE2 | COMPLETED |
| NCT00560495 | Lung Cancer | Radiation Therapy and Ammonium Tetrathiomolybdate in Treating Patients With Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer | PHASE1 | WITHDRAWN |
| NCT01689207 | Complicated Infection, Bacterial Infections | To Investigate the Safety and Tolerability of Aztreonam-Avibactam (ATM-AVI) | PHASE1 | COMPLETED |
| NCT03377556 | ATM Gene Mutation, ATR Gene Mutation, BARD1 Gene Mutation, BRCA1 Gene Mutation, BRCA2 Gene Mutation, BRIP1 Gene Mutation, CHEK1 Gene Mutation, CHEK2 Gene Mutation, FANCA Gene Mutation, FANCC Gene Mutation, FANCD2 Gene Mutation, FANCF Gene Mutation, FANCM Gene Mutation, NBN Gene Mutation, PALB2 Gene Mutation, RAD51 Gene Mutation, RAD51B Gene Mutation, RAD54L Gene Mutation, Recurrent Squamous Cell Lung Carcinoma, RPA1 Gene Mutation, Stage IV Squamous Cell Lung Carcinoma AJCC v7 | Lung-MAP: Talazoparib in Treating Patients With HRRD Positive Recurrent Stage IV Squamous Cell Lung Cancer | PHASE2 | COMPLETED |
| NCT01955668 | 11q-deleted Relapsed/Refractory Chronic Lymphocytic Leukaemia (CLL),, Prolymphocytic Leukaemia (PLL), B Cell Lymphomas | AZD6738 First Time in Patient Multiple Ascending Dose Study | PHASE1 | COMPLETED |
| NCT03423628 | Recurrent Glioblastoma Multiforme, Primary Glioblastoma Multiforme, Brain Neoplasms, Malignant, Leptomeningeal Disease (LMD) | A Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer | PHASE1 | RECRUITING |