Ataxia Telangiectasia And Rad3 Related Protein (ATR)

FRP1; SCKL; SCKL1; MEC1; FRAP-related protein 1; Serine/threonine-protein kinase ATR

SPN	N448
HGNC	882
MGI	108028
PubMed	15533933
UniProt	Q13535
Wiki	ATR

ATR belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1.

Mutations of this gene are associated with Seckel syndrome. An alternatively spliced transcript variant of this gene has been reported, however, its full length nature is not known. Transcript variants utilizing alternative polyA sites exist.

Reference

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Proc. Natl. Acad. Sci. U.S.A. 93:2850-2855(1996) [PubMed] [Europe PMC] [Abstract]

"Evidence for alternate splicing within the mRNA transcript encoding the DNA damage response kinase ATR."
Gene 272:35-43(2001) [PubMed] [Europe PMC] [Abstract]

"The Atr and Atm protein kinases associate with different sites along meiotically pairing chromosomes."
Genes Dev. 10:2423-2437(1996) [PubMed] [Europe PMC] [Abstract]

"Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin."
Cancer Res. 58:4375-4382(1998) [PubMed] [Europe PMC] [Abstract]

"Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints."
EMBO J. 17:159-169(1998) [PubMed] [Europe PMC] [Abstract]

"Protein kinase mutants of human ATR increase sensitivity to UV and ionizing radiation and abrogate cell cycle checkpoint control."
Proc. Natl. Acad. Sci. U.S.A. 95:7445-7450(1998) [PubMed] [Europe PMC] [Abstract]

"Molecular association between ATR and two components of the nucleosome remodeling and deacetylating complex, HDAC2 and CHD4."
Biochemistry 38:14711-14717(1999) [PubMed] [Europe PMC] [Abstract]

"A role for ATR in the DNA damage-induced phosphorylation of p53."
Genes Dev. 13:152-157(1999) [PubMed] [Europe PMC] [Abstract]

"Substrate specificities and identification of putative substrates of ATM kinase family members."
J. Biol. Chem. 274:37538-37543(1999) [PubMed] [Europe PMC] [Abstract]

"ATR is a caffeine-sensitive, DNA-activated protein kinase with a substrate specificity distinct from DNA-PK."
Oncogene 18:6707-6713(1999) [PubMed] [Europe PMC] [Abstract]

"Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint."
Genes Dev. 14:1448-1459(2000) [PubMed] [Europe PMC] [Abstract]

"Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress."
Genes Dev. 14:2989-3002(2000) [PubMed] [Europe PMC] [Abstract]

"Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress."
J. Biol. Chem. 276:47759-47762(2001) [PubMed] [Europe PMC] [Abstract]

"ATR/ATM-mediated phosphorylation of human Rad17 is required for genotoxic stress responses."
Nature 411:969-974(2001) [PubMed] [Europe PMC] [Abstract]

"ATR and ATRIP: partners in checkpoint signaling."
Science 294:1713-1716(2001) [PubMed] [Europe PMC] [Abstract]

"ATR regulates fragile site stability."
Cell 111:779-789(2002) [PubMed] [Europe PMC] [Abstract]

"Hypoxia links ATR and p53 through replication arrest."
Mol. Cell. Biol. 22:1834-1843(2002) [PubMed] [Europe PMC] [Abstract]

"Preferential binding of ATR protein to UV-damaged DNA."
Proc. Natl. Acad. Sci. U.S.A. 99:6673-6678(2002) [PubMed] [Europe PMC] [Abstract]

"ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation."
Curr. Biol. 13:1047-1051(2003) [PubMed] [Europe PMC] [Abstract]

"Human claspin is required for replication checkpoint control."
J. Biol. Chem. 278:30057-30062(2003) [PubMed] [Europe PMC] [Abstract]

"MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation."
Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003) [PubMed] [Europe PMC] [Abstract]

"Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes."
Science 300:1542-1548(2003) [PubMed] [Europe PMC] [Abstract]

"BCR/ABL translocates to the nucleus and disrupts an ATR-dependent intra-S phase checkpoint."
Cancer Cell 5:275-285(2004) [PubMed] [Europe PMC] [Abstract]

"UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress."
J. Biol. Chem. 279:9677-9680(2004) [PubMed] [Europe PMC] [Abstract]

"Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase."
J. Biol. Chem. 279:16433-16440(2004) [PubMed] [Europe PMC] [Abstract]

"ATR couples FANCD2 monoubiquitination to the DNA-damage response."
Genes Dev. 18:1958-1963(2004) [PubMed] [Europe PMC] [Abstract]

"Seckel syndrome exhibits cellular features demonstrating defects in the ATR-signalling pathway."
Hum. Mol. Genet. 13:3127-3138(2004) [PubMed] [Europe PMC] [Abstract]

"Quaternary structure of ATR and effects of ATRIP and replication protein A on its DNA binding and kinase activities."
Mol. Cell. Biol. 24:1292-1300(2004) [PubMed] [Europe PMC] [Abstract]

"Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases."
Proc. Natl. Acad. Sci. U.S.A. 101:10078-10083(2004) [PubMed] [Europe PMC] [Abstract]

"The haploinsufficient tumor suppressor p18 upregulates p53 via interactions with ATM/ATR."
Cell 120:209-221(2005) [PubMed] [Europe PMC] [Abstract]

"Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage."
Nature 434:605-611(2005) [PubMed] [Europe PMC] [Abstract]

"Cep164 is a mediator protein required for the maintenance of genomic stability through modulation of MDC1, RPA, and CHK1."
Genes Dev. 22:587-600(2008) [PubMed] [Europe PMC] [Abstract]

"A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome."
Nat. Genet. 33:497-501(2003) [PubMed] [Europe PMC] [Abstract]

"Protein phosphatase 5 is required for ATR-mediated checkpoint activation."
Mol. Cell. Biol. 25:9910-9919(2005) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability."
Genes Dev. 24:1939-1950(2010) [PubMed] [Europe PMC] [Abstract]

"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes."
Genes Dev. 24:2019-2030(2010) [PubMed] [Europe PMC] [Abstract]

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BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Protein phosphatase 5 is necessary for ATR-mediated DNA repair."
Biochem. Biophys. Res. Commun. 404:476-481(2011) [PubMed] [Europe PMC] [Abstract]

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Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"Patterns of somatic mutation in human cancer genomes."
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]

"Germline mutation in ATR in autosomal- dominant oropharyngeal cancer syndrome."
Am. J. Hum. Genet. 90:511-517(2012) [PubMed] [Europe PMC] [Abstract]