ATR

Gene Information

Official Symbol: ATR
Official Name: ATR serine/threonine kinase
Aliases and Previous Symbols: N/A
Entrez ID: 545
UniProt: Q13535
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: The protein encoded by this gene is a serine/threonine kinase and DNA damage sensor, activating cell cycle checkpoint signaling upon DNA stress. The encoded protein can phosphorylate and activate several proteins involved in the inhibition of DNA replication and mitosis, and can promote DNA repair, recombination, and apoptosis. This protein is also important for fragile site stability and centrosome duplication. Defects in this gene are a cause of Seckel syndrome 1. [provided by RefSeq, Aug 2017].
UniProt Summary: Serine/threonine protein kinase which activates checkpoint signaling upon genotoxic stresses such as ionizing radiation (IR), ultraviolet light (UV), or DNA replication stalling, thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates BRCA1, CHEK1, MCM2, RAD17, RPA2, SMC1 and p53/TP53, which collectively inhibit DNA replication and mitosis and promote DNA repair, recombination and apoptosis. Phosphorylates 'Ser-139' of histone variant H2AX/H2AFX at sites of DNA damage, thereby regulating DNA damage response mechanism. Required for FANCD2 ubiquitination. Critical for maintenance of fragile site stability and efficient regulation of centrosome duplication. {ECO:0000269|PubMed:10597277, ECO:0000269|PubMed:10608806, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11114888, ECO:0000269|PubMed:11418864, ECO:0000269|PubMed:11673449, ECO:0000269|PubMed:11721054, ECO:0000269|PubMed:11865061, ECO:0000269|PubMed:12526805, ECO:0000269|PubMed:12791985, ECO:0000269|PubMed:12814551, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14729973, ECO:0000269|PubMed:14742437, ECO:0000269|PubMed:15210935, ECO:0000269|PubMed:15314022, ECO:0000269|PubMed:15496423, ECO:0000269|PubMed:16260606, ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:27723717, ECO:0000269|PubMed:27723720, ECO:0000269|PubMed:9427750, ECO:0000269|PubMed:9636169, ECO:0000269|PubMed:9925639}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Diepoxybutane 3μM R07 exp354	-2.75
ABT-702 5μM plus Deferoxamine 11μM R07 exp321	-2.49
ABT-702 5μM plus CoCl2 18μM R07 exp320	-2.15
Olaparib 4μM R08 exp512	-1.91
Trimetrexate 0.03μM R08 exp535	-1.85
NMS-873 0.07μM R07 exp380	-1.82

Global Fraction of Cell Lines Where Essential: 278/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	1/1
909776.0	0/1
bile duct	15/28
blood	10/28
bone	13/26
breast	17/33
central nervous system	21/56
cervix	0/4
colorectal	2/17
esophagus	3/13
fibroblast	1/1
gastric	8/16
kidney	6/21
liver	9/20
lung	30/75
lymphocyte	3/16
ovary	8/26
pancreas	6/24
peripheral nervous system	7/16
plasma cell	3/15
prostate	0/1
skin	10/24
soft tissue	2/9
thyroid	0/2
upper aerodigestive	4/22
urinary tract	5/29
uterus	2/5

Essentiality in NALM6

Essentiality Rank: 677
Expression level (log2 read counts): 7.15

Expression Distribution

FAT
FATC
PI3 PI4 kinase
UME

establishment of RNA localization to telomere
establishment of protein-containing complex localization to telomere
positive regulation of telomerase catalytic core complex assembly
regulation of telomerase catalytic core complex assembly
MutSalpha complex binding
MutLalpha complex binding
establishment of protein localization to telomere
replicative senescence
establishment of protein localization to chromosome
protein localization to chromosome, telomeric region
positive regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of signal transduction by p53 class mediator
cellular response to gamma radiation
regulation of DNA damage response, signal transduction by p53 class mediator
positive regulation of telomere maintenance via telomerase
positive regulation of telomere maintenance via telomere lengthening
negative regulation of DNA replication
positive regulation of telomere maintenance
interstrand cross-link repair
regulation of telomere maintenance via telomerase
response to gamma radiation
regulation of telomere maintenance via telomere lengthening
protein localization to chromosome
cell aging
positive regulation of DNA biosynthetic process
cellular response to ionizing radiation
regulation of cellular response to heat
regulation of telomere maintenance
cellular response to UV
positive regulation of response to DNA damage stimulus
telomere maintenance
PML body
telomere organization
regulation of DNA replication
nuclear chromosome, telomeric region
regulation of DNA biosynthetic process
cellular response to light stimulus
chromosome
DNA damage checkpoint
response to UV