ATM protein (Ataxia Telangiectasia mutated)
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Introduction
Protein product of gene mutated in ataxia telangiectasia
Function
- serine/threonine protein kinas
- activates checkpoint signaling upon double strand breaks), apoptosis & genotoxic stresses, including ionizing ultraviolet light, thus acting as a DNA damage sensor
- role in cell-cycle control at G1->S & G2->M boundaries
- phosphorylates many proteins in response to DNA damage
- recognizes substrate consensus sequence [ST]-Q
- phosphorylates Ser-139 of histone variant H2AX/H2AFX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism
- role in signal transduction & cell cycle control
- may function as a tumor suppressor
- necessary for activation of ABL1 & SAPK
- phosphorylates p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin, TERF1, RAD9 & DCLRE1C
- phosphorylated by ARK5
- autophosphorylated on Ser-1981 upon DNA damage
- acetylated by HTATIP upon DNA damage, required for autophosphorylation & subsequent activation
- role in vesicle &/or protein transport
- role in T-cell development, gonad & neurological function
- binds DNA ends, p53/TP53, ABL1, BRCA1, NBN/nibrin & TERF1
- component of BRCA1-associated genome surveillance complex (BASC) - association could be a dynamic process changing throughout cell cycle & within subnuclear domains
- DNA damage promotes association with RAD17
- interaction with EEF1E1, independent of TP53, induced by DNA damage
- interacts with DCLRE1C
- interacts with MYST1
- HTATIP.
- unlike p53-deficient cells, ATM-deficient cells show no impairment of DNA damage-induced apoptosis
ATP + a protein = ADP + a phosphoprotein
Inhibited by wortmannin
Structure
- monomeric & tetrameric states
- belongs to the PI3/PI4-kinase family, ATM subfamily
- contains 1 FAT domain
- contains 1 FATC domain, required for interaction with HTATIP
- contains 1 PI3K/PI4K domain
- C-terminal region is homologous to PI-3-kinase p110 subunit, thus the assignment as a kinase
Compartment
- nucleus, cytoplasmic vesicle
- primarily nuclear
- found also in endocytic vesicles in association with beta-adaptin
Expression
- expressed in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain, heart, spleen, thymus, testis, ovary, small intestine, colon, leukocytes
- induced by ionizing radiation
Pathology
- defects in ATM are the cause of ataxia telangiectasia
- defects in ATM contribute to T-cell ALL & T cell prolymphocytic leukemia
- defects in ATM contribute to B-cell non-Hodgkin lymphomas including mantle cell lymphoma
- defects in ATM may contribute to B-cell CLL
More general terms
Additional terms
Component of
References
- ↑ Lavin MF, Khanna KK, Beamish H, Spring K, Watters D, Shiloh Y. Relationship of the ataxia-telangiectasia protein ATM to phosphoinositide 3-kinase. Trends Biochem Sci. 1995 Oct;20(10):382-3. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/8533147
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=472
- ↑ Uniprot :accession
- ↑ Ataxia talangiectasia mutation db http://benaroyaresearch.org/investigators/concannon_patrick/atm.htm
- ↑ Atlas of Genetics and Cytogenetics in Oncology and Haematology http://atlasgeneticsoncology.org/Genes/ATM123.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=ATM
- ↑ Wikipedia ataxia telangiectasia mutated entry http://en.wikipedia.org/wiki/Ataxia_telangiectasia_mutated
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=472
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:472
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- Kegg: http://www.genome.jp/dbget-bin/www_bget?
- OMIM: https://mirror.omim.org/entry/208900
- OMIM: https://mirror.omim.org/entry/607585
- UniProt: http://www.uniprot.org/uniprot/Q13315.html