ATR ATR checkpoint kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ATRprovided by HGNC
Official Full Name: ATR checkpoint kinaseprovided by HGNC
Primary source: HGNC:HGNC:882
See related: Ensembl:ENSG00000175054 MIM:601215; AllianceGenome:HGNC:882
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: FRP1; MEC1; SCKL; FCTCS; SCKL1
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]
Expression: Ubiquitous expression in testis (RPKM 5.4), adrenal (RPKM 5.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q23

Exon count:: 49

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (142449235..142578733, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (145196519..145326002, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (142168077..142297575, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.
Title: Telomeric DNA breaks in human induced pluripotent stem cells trigger ATR-mediated arrest and telomerase-independent telomere damage repair.
New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B.
Title: New insights into ATR inhibition in muscle invasive bladder cancer: The role of apolipoprotein B mRNA editing catalytic subunit 3B.
EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.
Title: EXO1 and DNA2-mediated ssDNA gap expansion is essential for ATR activation and to maintain viability in BRCA1-deficient cells.
SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.
Title: SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.
TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways.
Title: TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways.
ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress.
Title: ATR phosphorylates DHX9 at serine 321 to suppress R-loop accumulation upon genotoxic stress.
ADAR1 links R-loop homeostasis to ATR activation in replication stress response.
Title: ADAR1 links R-loop homeostasis to ATR activation in replication stress response.
Abrogation of ATR function preferentially augments cisplatin-induced cytotoxicity in PTEN-deficient breast cancer cells.
Title: Abrogation of ATR function preferentially augments cisplatin-induced cytotoxicity in PTEN-deficient breast cancer cells.
Expression variations of DNA damage response genes ATM and ATR in blood cancer patients.
Title: Expression variations of DNA damage response genes ATM and ATR in blood cancer patients.
Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.
Title: Exome sequencing identifies breast cancer susceptibility genes and defines the contribution of coding variants to breast cancer risk.

Submit: New GeneRIF Correction See all GeneRIFs (399)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Familial cutaneous telangiectasia and oropharyngeal predisposition cancer syndrome MedGen: C3281203 OMIM: 614564 GeneReviews: Not available	Compare labs
Seckel syndrome 1 MedGen: C4551474 OMIM: 210600 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2020-06-05) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2020-06-05) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Protein	Gene	Interaction	Pubs
Vpr	vpr	Upregulation of NKG2D ligands is dependent on HIV-1 Vpr-mediated activation of the ATR DNA damage/stress pathway, which requires the recruitment of the Cul4/DDB1/DCAF1 E3 ubiquitin ligase complex	PubMed
	vpr	HIV-1 Vpr activates ATR, resulting in phosphorylation of Chk1 and activation of the ATR-mediated DNA damage response	PubMed
	vpr	Depletion of A-alpha and C-beta subunits of PP2A reduces Vpr-induced G2 arrest to the same extent as depletion of ATM and Rad3-related (ATR)	PubMed
	vpr	HIV-1 Vpr-mediated upregulation of PVR (CD155) requires the interaction of Vpr with the DDB1-Cul4A E3 ligase and induction of ATR-mediated DNA damage repair and G2 arrest	PubMed
	vpr	ATR-induced phosphorylation of Chk1-Ser(345) requires PP2A only when Vpr activates ATR	PubMed
	vpr	HIV-1 Vpr induces phosphorylation of replication protein A (RPA32) at serine 4 and 8 in an ATR-dependent manner	PubMed
	vpr	HIV-1 Vpr-induced apoptosis is mediated via Bax, downstream of ATR activation	PubMed
	vpr	HIV-1 Vpr induces phosphorylation of BRCA1 at serine 1423 in an ATR-dependent manner	PubMed
integrase	gag-pol	ATR kinase is hypothesized to be required for successful completion of the HIV-1 viral DNA integration process, suggesting a functional interaction with HIV-1 Integrase	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

A008V33 (e-PCR)
- UniSTS:47401

GDB:4585095 (e-PCR)
- UniSTS:43824

STS-U76308 (e-PCR)
- UniSTS:71733

D3S1316 (e-PCR), detects polymorphism
- UniSTS:62280

SHGC-154915 (e-PCR)
- UniSTS:183720

D3S3710 (e-PCR)
- UniSTS:9418

SHGC-33010 (e-PCR)
- UniSTS:24535

G65709 (e-PCR)
- UniSTS:225505

D3S3694 (e-PCR), detects polymorphism
- UniSTS:16617

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables MutLalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
enables MutSalpha complex binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H2AXS139 kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase activity	IEA Inferred from Electronic Annotation more info
enables protein kinase activity	TAS Traceable Author Statement more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in DNA damage checkpoint signaling	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA damage checkpoint signaling	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA damage checkpoint signaling	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA damage response	IEA Inferred from Electronic Annotation more info
involved_in DNA damage response	TAS Traceable Author Statement more info	PubMed
involved_in DNA repair	IBA Inferred from Biological aspect of Ancestor more info
involved_in DNA repair	IEA Inferred from Electronic Annotation more info
involved_in DNA repair	TAS Traceable Author Statement more info	PubMed
involved_in DNA replication	IEA Inferred from Electronic Annotation more info
involved_in DNA replication	TAS Traceable Author Statement more info
acts_upstream_of_or_within DNA strand resection involved in replication fork processing	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within G2/M transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to UV	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to gamma radiation	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in double-strand break repair	IDA Inferred from Direct Assay more info	PubMed
involved_in establishment of RNA localization to telomere	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in establishment of protein-containing complex localization to telomere	IC Inferred by Curator more info	PubMed
involved_in interstrand cross-link repair	TAS Traceable Author Statement more info
involved_in mitotic G2/M transition checkpoint	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of DNA replication	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within nuclear envelope organization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of nuclear membrane disassembly	IDA Inferred from Direct Assay more info	PubMed
involved_in nucleobase-containing compound metabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of DNA damage response, signal transduction by p53 class mediator	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA damage response, signal transduction by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomerase catalytic core complex assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomere maintenance via telomerase	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to chromosome, telomeric region	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within protein localization to site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cellular response to heat	TAS Traceable Author Statement more info
involved_in regulation of cellular response to stress	IEA Inferred from Electronic Annotation more info
involved_in regulation of double-strand break repair	NAS Non-traceable Author Statement more info	PubMed
involved_in replication fork processing	ISS Inferred from Sequence or Structural Similarity more info
involved_in replicative senescence	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to arsenic-containing substance	IEA Inferred from Electronic Annotation more info
involved_in response to mechanical stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in telomere maintenance	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
part_of ATR-ATRIP complex	IEA Inferred from Electronic Annotation more info
part_of ATR-ATRIP complex	IPI Inferred from Physical Interaction more info	PubMed
located_in Golgi apparatus	IDA Inferred from Direct Assay more info
located_in PML body	IDA Inferred from Direct Assay more info	PubMed
is_active_in chromosome	IBA Inferred from Biological aspect of Ancestor more info
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in chromosome	ISS Inferred from Sequence or Structural Similarity more info
colocalizes_with chromosome, telomeric region	IC Inferred by Curator more info	PubMed
is_active_in nuclear envelope	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear envelope	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in nucleus	NAS Non-traceable Author Statement more info	PubMed
is_active_in site of DNA damage	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase ATR

Names: ATR serine/threonine kinase; FRAP-related protein-1; MEC1, mitosis entry checkpoint 1, homolog; ataxia telangiectasia and Rad3-related protein

NP_001175.2

EC 2.7.11.1

NP_001341508.1

EC 2.7.11.1

XP_011511226.1

EC 2.7.11.1

XP_011511227.1

EC 2.7.11.1

XP_047304316.1

EC 2.7.11.1

XP_047304317.1

EC 2.7.11.1

XP_047304318.1

EC 2.7.11.1

XP_047304319.1

EC 2.7.11.1

XP_047304320.1

EC 2.7.11.1

XP_054202913.1

EC 2.7.11.1

XP_054202914.1

EC 2.7.11.1

XP_054202915.1

EC 2.7.11.1

XP_054202916.1

EC 2.7.11.1

XP_054202917.1

EC 2.7.11.1

XP_054202918.1

EC 2.7.11.1

XP_054202919.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008951.1 RefSeqGene

Range

5094..134592

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1403

mRNA and Protein(s)

NM_001184.4 → NP_001175.2 serine/threonine-protein kinase ATR isoform 1

See identical proteins and their annotated locations for NP_001175.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

BE859077, U49844, U76308

Consensus CDS

CCDS3124.1

UniProtKB/Swiss-Prot

Q13535, Q59HB2, Q7KYL3, Q93051, Q9BXK4

UniProtKB/TrEMBL

A0A590UJ01

Related

ENSP00000343741.4, ENST00000350721.9

Conserved Domains (4) summary

smart00802
Location:1119 → 1224

UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1

COG5032
Location:2133 → 2644

TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]

cd00892
Location:2293 → 2567

PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins

pfam02259
Location:1771 → 2092

FAT; FAT domain
NM_001354579.2 → NP_001341508.1 serine/threonine-protein kinase ATR isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.

Source sequence(s)

AC109992, AC134509

Consensus CDS

CCDS93402.1

UniProtKB/TrEMBL

A0A590UJ01

Related

ENSP00000499589.1, ENST00000661310.1

Conserved Domains (4) summary

smart00802
Location:1055 → 1160

UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1

COG5032
Location:2069 → 2580

TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]

cd00892
Location:2229 → 2503

PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins

pfam02259
Location:1707 → 2028

FAT; FAT domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

142449235..142578733 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011512925.2 → XP_011511227.1 serine/threonine-protein kinase ATR isoform X4

UniProtKB/TrEMBL

A0A590UJ01

Conserved Domains (5) summary

smart00802
Location:1055 → 1160

UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1

COG5032
Location:2071 → 2582

TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]

cd00892
Location:2231 → 2505

PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins

pfam02259
Location:1709 → 2030

FAT; FAT domain

pfam02260
Location:2551 → 2582

FATC; FATC domain
XM_011512924.2 → XP_011511226.1 serine/threonine-protein kinase ATR isoform X1

UniProtKB/TrEMBL

A0A590UJ01

Conserved Domains (5) summary

smart00802
Location:1119 → 1224

UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1

COG5032
Location:2135 → 2646

TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]

cd00892
Location:2295 → 2569

PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins

pfam02259
Location:1773 → 2094

FAT; FAT domain

pfam02260
Location:2615 → 2646

FATC; FATC domain
XM_047448361.1 → XP_047304317.1 serine/threonine-protein kinase ATR isoform X3

UniProtKB/TrEMBL

A0A590UJ01
XM_047448360.1 → XP_047304316.1 serine/threonine-protein kinase ATR isoform X2

UniProtKB/TrEMBL

A0A590UJ01
XM_047448363.1 → XP_047304319.1 serine/threonine-protein kinase ATR isoform X6
XM_047448362.1 → XP_047304318.1 serine/threonine-protein kinase ATR isoform X5
XM_047448364.1 → XP_047304320.1 serine/threonine-protein kinase ATR isoform X7

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

145196519..145326002 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054346941.1 → XP_054202916.1 serine/threonine-protein kinase ATR isoform X4

UniProtKB/TrEMBL

A0A590UJ01
XM_054346938.1 → XP_054202913.1 serine/threonine-protein kinase ATR isoform X1

UniProtKB/TrEMBL

A0A590UJ01
XM_054346940.1 → XP_054202915.1 serine/threonine-protein kinase ATR isoform X3

UniProtKB/TrEMBL

A0A590UJ01
XM_054346939.1 → XP_054202914.1 serine/threonine-protein kinase ATR isoform X2

UniProtKB/TrEMBL

A0A590UJ01
XM_054346943.1 → XP_054202918.1 serine/threonine-protein kinase ATR isoform X6
XM_054346942.1 → XP_054202917.1 serine/threonine-protein kinase ATR isoform X5
XM_054346944.1 → XP_054202919.1 serine/threonine-protein kinase ATR isoform X7