Homo sapiens Protein: ATM
InnateDB Protein IDBP-70195.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol ATM
Protein Name ataxia telangiectasia mutated
Synonyms AT1; ATA; ATC; ATD; ATDC; ATE; TEL1; TELO1;
Species Homo sapiens
Ensembl Protein ENSP00000278616
InnateDB Gene IDBG-70193 (ATM)
Protein Structure
UniProt Annotation
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. {ECO:0000269PubMed:10973490, ECO:0000269PubMed:12556884, ECO:0000269PubMed:14871926, ECO:0000269PubMed:15916964, ECO:0000269PubMed:16086026, ECO:0000269PubMed:16858402, ECO:0000269PubMed:17923702, ECO:0000269PubMed:19965871}.
Subcellular Localization Nucleus. Cytoplasmic vesicle. Note=Primarily nuclear. Found also in endocytic vesicles in association with beta-adaptin.
Disease Associations Ataxia telangiectasia (AT) [MIM:208900]: 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. {ECO:0000269PubMed:10234507, ECO:0000269PubMed:10425038, ECO:0000269PubMed:10817650, ECO:0000269PubMed:10873394, ECO:0000269PubMed:7792600, ECO:0000269PubMed:8698354, ECO:0000269PubMed:8755918, ECO:0000269PubMed:8789452, ECO:0000269PubMed:8797579, ECO:0000269PubMed:8808599, ECO:0000269PubMed:8845835, ECO:0000269PubMed:9043869, ECO:0000269PubMed:9150358, ECO:0000269PubMed:9443866, ECO:0000269PubMed:9450874, ECO:0000269PubMed:9463314, ECO:0000269PubMed:9497252, ECO:0000269PubMed:9521587, ECO:0000269PubMed:9711876, ECO:0000269PubMed:9792409, ECO:0000269PubMed:9792410, ECO:0000269PubMed:9872980, ECO:0000269PubMed:9887333}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in ATM contribute to T-cell acute lymphoblastic leukemia (TALL) and T-prolymphocytic leukemia (TPLL). TPLL is characterized by a high white blood cell count, with a predominance of prolymphocytes, marked splenomegaly, lymphadenopathy, skin lesions and serous effusion. The clinical course is highly aggressive, with poor response to chemotherapy and short survival time. TPLL occurs both in adults as a sporadic disease and in younger AT patients.Note=Defects in ATM contribute to B-cell non-Hodgkin lymphomas (BNHL), including mantle cell lymphoma (MCL).Note=Defects in ATM contribute to B-cell chronic lymphocytic leukemia (BCLL). BCLL is the commonest form of leukemia in the elderly. It is characterized by the accumulation of mature CD5+ B-lymphocytes, lymphadenopathy, immunodeficiency and bone marrow failure.
Tissue Specificity Found in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon and leukocytes.
Number of Interactions This gene and/or its encoded proteins are associated with 221 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
Experimentally validated
Total 221 [view]
Protein-Protein 210 [view]
Protein-DNA 8 [view]
Protein-RNA 1 [view]
DNA-DNA 2 [view]
Predicted by orthology
Total 7 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003677 DNA binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0004677 DNA-dependent protein kinase activity
GO:0005488 binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016303 1-phosphatidylinositol-3-kinase activity
GO:0016772 transferase activity, transferring phosphorus-containing groups
GO:0016773 phosphotransferase activity, alcohol group as acceptor
GO:0032403 protein complex binding
GO:0035174 histone serine kinase activity
GO:0046983 protein dimerization activity
GO:0047485 protein N-terminus binding
Biological Process
GO:0000077 DNA damage checkpoint
GO:0000723 telomere maintenance
GO:0000724 double-strand break repair via homologous recombination
GO:0001666 response to hypoxia
GO:0001756 somitogenesis
GO:0002331 pre-B cell allelic exclusion
GO:0006281 DNA repair
GO:0006302 double-strand break repair
GO:0006468 protein phosphorylation
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0006975 DNA damage induced protein phosphorylation
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007050 cell cycle arrest
GO:0007094 mitotic spindle assembly checkpoint
GO:0007131 reciprocal meiotic recombination
GO:0007165 signal transduction
GO:0007292 female gamete generation
GO:0007420 brain development
GO:0007507 heart development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010212 response to ionizing radiation
GO:0016572 histone phosphorylation
GO:0018105 peptidyl-serine phosphorylation
GO:0030889 negative regulation of B cell proliferation
GO:0035404 histone-serine phosphorylation
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0042159 lipoprotein catabolic process
GO:0043065 positive regulation of apoptotic process
GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator
GO:0043525 positive regulation of neuron apoptotic process
GO:0046777 protein autophosphorylation
GO:0048599 oocyte development
GO:0051402 neuron apoptotic process
GO:0051726 regulation of cell cycle
GO:0071044 histone mRNA catabolic process
GO:0071480 cellular response to gamma radiation
GO:0072434 signal transduction involved in mitotic G2 DNA damage checkpoint
GO:0090399 replicative senescence
Cellular Component
GO:0000781 chromosome, telomeric region
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005819 spindle
GO:0016023 cytoplasmic membrane-bounded vesicle
Protein Structure and Domains
InterPro IPR000403 Phosphatidylinositol 3-/4-kinase, catalytic domain
IPR003151 PIK-related kinase, FAT
IPR003152 PIK-related kinase, FATC
IPR011009 Protein kinase-like domain
IPR014009 PIK-related kinase
IPR016024 Armadillo-type fold
IPR021668 Telomere-length maintenance and DNA damage repair
PFAM PF00454
Post-translational Modifications
SwissProt Q13315
PhosphoSite PhosphoSite-Q13315
UniProt Splice Variant
Entrez Gene 472
UniGene Hs.710771
RefSeq NP_000042
OMIM 607585
HPRD 06347
EMBL AP001925 AP005718 AY220758 BC137169 CH471065 KF455499 U26455 U33841 U55704 U55705 U55707 U55708 U55709 U55710 U55711 U55712 U55713 U55714 U55715 U55716 U55717 U55718 U55719 U55720 U55721 U55722 U55723 U55724 U55725 U55726 U55727 U55728 U55729 U55730 U55731 U55732 U55733 U55734 U55735 U55736 U55737 U55738 U55739 U55740 U55741 U55742 U55743 U55744 U55745 U55746 U55747 U55748 U55749 U55750 U55751 U55752 U55753 U55754 U55755 U55756 U55757 U67092 U82828 X91196
GenPept AAA86520 AAB38309 AAB38310 AAB65827 AAC50289 AAC51298 AAI37170 AAO26044 CAA62603 EAW67108 EAW67111 EAW67113