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    ATR ATR serine/threonine kinase [ Homo sapiens (human) ]

    Gene ID: 545, updated on 5-May-2024

    Summary

    Official Symbol
    ATRprovided by HGNC
    Official Full Name
    ATR serine/threonine 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
    NEW
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    Try the new Transcript table

    Genomic context

    Location:
    3q23
    Exon count:
    49
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (142449235..142578733, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (145196519..145326002, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (142168077..142297575, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene 5'-3' exoribonuclease 1 Neighboring gene RNA, U6 small nuclear 1294, pseudogene Neighboring gene RNA, U1 small nuclear 100, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr3:142162923-142163129 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20641 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20642 Neighboring gene EIF2AK1 pseudogene 1 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr3:142203676-142204875 Neighboring gene SUCLG2 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20643 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20644 Neighboring gene RNA, 5S ribosomal pseudogene 143 Neighboring gene ribosomal protein L6 pseudogene 9

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    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

    HIV-1 interactions

    Protein interactions

    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

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    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 protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity IDA
    Inferred from Direct Assay
    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 TAS
    Traceable Author Statement
    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 response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 replication TAS
    Traceable Author Statement
    more info
     
    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 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 peptidyl-serine phosphorylation 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 autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein localization to chromosome, telomeric region IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of cellular response to heat TAS
    Traceable Author Statement
    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 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 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 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 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

    Preferred Names
    serine/threonine-protein kinase ATR
    Names
    FRAP-related protein-1
    MEC1, mitosis entry checkpoint 1, homolog
    ataxia telangiectasia and Rad3-related protein
    NP_001175.2
    NP_001341508.1
    XP_011511226.1
    XP_011511227.1
    XP_047304316.1
    XP_047304317.1
    XP_047304318.1
    XP_047304319.1
    XP_047304320.1
    XP_054202913.1
    XP_054202914.1
    XP_054202915.1
    XP_054202916.1
    XP_054202917.1
    XP_054202918.1
    XP_054202919.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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

    1. NG_008951.1 RefSeqGene

      Range
      5094..134592
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1403

    mRNA and Protein(s)

    1. NM_001184.4NP_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:11191224
      UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
      COG5032
      Location:21332644
      TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]
      cd00892
      Location:22932567
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
      pfam02259
      Location:17712092
      FAT; FAT domain
    2. NM_001354579.2NP_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:10551160
      UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
      COG5032
      Location:20692580
      TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]
      cd00892
      Location:22292503
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
      pfam02259
      Location:17072028
      FAT; FAT domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      142449235..142578733 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

      UniProtKB/TrEMBL
      A0A590UJ01
      Conserved Domains (5) summary
      smart00802
      Location:10551160
      UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
      COG5032
      Location:20712582
      TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]
      cd00892
      Location:22312505
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
      pfam02259
      Location:17092030
      FAT; FAT domain
      pfam02260
      Location:25512582
      FATC; FATC domain
    2. XM_011512924.2XP_011511226.1  serine/threonine-protein kinase ATR isoform X1

      UniProtKB/TrEMBL
      A0A590UJ01
      Conserved Domains (5) summary
      smart00802
      Location:11191224
      UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
      COG5032
      Location:21352646
      TEL1; Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms]
      cd00892
      Location:22952569
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
      pfam02259
      Location:17732094
      FAT; FAT domain
      pfam02260
      Location:26152646
      FATC; FATC domain
    3. XM_047448361.1XP_047304317.1  serine/threonine-protein kinase ATR isoform X3

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

    5. XM_047448363.1XP_047304319.1  serine/threonine-protein kinase ATR isoform X6

    6. XM_047448362.1XP_047304318.1  serine/threonine-protein kinase ATR isoform X5

    7. XM_047448364.1XP_047304320.1  serine/threonine-protein kinase ATR isoform X7

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      145196519..145326002 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

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

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

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

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

    5. XM_054346943.1XP_054202918.1  serine/threonine-protein kinase ATR isoform X6

    6. XM_054346942.1XP_054202917.1  serine/threonine-protein kinase ATR isoform X5

    7. XM_054346944.1XP_054202919.1  serine/threonine-protein kinase ATR isoform X7