ATM
ATM (ATM serine/threonine kinase, also known as TEL1, TELO1, ATA, ATDC, ATC and ATD) is a checkpoint kinase that senses DNA damage and activates cell cycle checkpoint signalling. It belongs to the PI3/PI4-kinase family and is a master regulator of the cellular response to double strand breaks. Browse Assay Genie's current range of ATM research reagents below, or read on for the biology behind the target.
ATM is a serine/threonine protein kinase that activates checkpoint signalling in response to double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light, and so acts as a DNA damage sensor. It recognises the substrate consensus sequence [ST]-Q and binds DNA ends. At DSBs it phosphorylates Ser-139 of the histone variant H2AX, which regulates the DNA damage response. It is also necessary for activation of ABL1 and SAPK, and is involved in signal transduction and cell cycle control.
The ATM protein phosphorylates a wide range of downstream targets, including p53/TP53, BRCA1, CHEK2, RAD17, RAD9, nibrin (NBN), MRE11, RAD50, FANCD2, CTIP (RBBP8) and ATF2. Phosphorylation of DYRK2 in the nucleus after genotoxic stress prevents its MDM2-mediated ubiquitination and proteasomal degradation. ATM also phosphorylates TTC5/STRAP in the cytoplasm, promoting its nuclear localisation, and ERCC6, which is essential for its chromatin remodelling activity at DSBs. Beyond genome surveillance, ATM contributes to pre-B cell allelic exclusion by repositioning the second immunoglobulin allele to pericentromeric heterochromatin after RAG-induced breaks. It also functions in replication-dependent histone mRNA degradation, and may play roles in vesicle and protein transport, T-cell development, and gonad and neurological function. In response to reactive oxygen species, ATM translocates to peroxisomes and phosphorylates PEX5, promoting pexophagy.
The ATM gene encodes a member of the PI3/PI4-kinase family, ATM subfamily, which HGNC also places among the armadillo-like helical domain-containing proteins and the BRCA1-associated genome surveillance complex. Together with the related kinase ATR, it is thought to be a master controller of checkpoint pathways required for genome stability. The name derives from ataxia telangiectasia mutated: mutations in the gene are associated with ataxia telangiectasia, an autosomal recessive disorder, and ATM may function as a tumour suppressor. The mouse ortholog is Atm.
ATM senses double strand breaks and phosphorylates H2AX, CHEK2 and p53 to drive checkpoint signalling and repair.
As a checkpoint kinase, ATM regulates downstream proteins such as BRCA1, RAD17 and RAD9 that govern cell response to genotoxic stress.
ATM may function as a tumour suppressor and, with ATR, is considered a master controller of genome stability pathways.
Loss of ATM function causes ataxia telangiectasia, and the kinase contributes to B-cell allelic exclusion, T-cell development and neurological function.
ATM is a serine/threonine kinase that acts as a DNA damage sensor. It activates checkpoint signalling after double strand breaks, phosphorylating H2AX at Ser-139 and substrates such as p53, CHEK2 and BRCA1. It also contributes to cell cycle control and, in response to reactive oxygen species, to pexophagy.
ATM stands for ataxia telangiectasia mutated, and the protein is also called serine-protein kinase ATM. Aliases and previous symbols include TEL1, TELO1, ATA, ATDC, ATC and ATD. Earlier names referred to complementation groups A, C and D of ataxia telangiectasia.
Mutations in the ATM gene are associated with ataxia telangiectasia, an autosomal recessive disorder, and ATM may act as a tumour suppressor. The mouse ortholog is Atm; check the datasheet of any product for its validated reactivity.
Other DNA damage response kinases, checkpoint proteins and ATM substrates with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13315; product specifications from Assay Genie datasheets.