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

    Gene ID: 545, updated on 19-Jul-2016
    Official Symbol
    ATRprovided by HGNC
    Official Full Name
    ATR serine/threonine kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:882
    See related
    Ensembl:ENSG00000175054 HPRD:08369; MIM:601215; Vega:OTTHUMG00000159234
    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 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. [provided by RefSeq, Jul 2008]
    Orthologs
    Location:
    3q23
    Exon count:
    49
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 3 NC_000003.12 (142449235..142578826, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (142168077..142297668, 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 eukaryotic translation initiation factor 2 alpha kinase 1 pseudogene Neighboring gene succinate-CoA ligase GDP-forming beta subunit pseudogene 1 Neighboring gene RNA, 5S ribosomal pseudogene 143 Neighboring gene ribosomal protein L6 pseudogene 9

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

    • Activation of ATR in response to replication stress, organism-specific biosystem (from REACTOME)
      Activation of ATR in response to replication stress, organism-specific biosystemGenotoxic stress caused by DNA damage or stalled replication forks can lead to genomic instability. To guard against such instability, genotoxically-stressed cells activate checkpoint factors that ha...
    • BARD1 signaling events, organism-specific biosystem (from Pathway Interaction Database)
      BARD1 signaling events, organism-specific biosystem
      BARD1 signaling events
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
      Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
    • Cell cycle, organism-specific biosystem (from WikiPathways)
      Cell cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cellular response to heat stress, organism-specific biosystem (from REACTOME)
      Cellular response to heat stress, organism-specific biosystemIn response to exposure to elevated temperature and certain other proteotoxic stimuli (e.g., hypoxia, free radicals) cells activate a number of cytoprotective mechanisms known collectively as "heat s...
    • Cellular responses to stress, organism-specific biosystem (from REACTOME)
      Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
    • Circadian rhythm pathway, organism-specific biosystem (from Pathway Interaction Database)
      Circadian rhythm pathway, organism-specific biosystem
      Circadian rhythm pathway
    • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
      DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
    • DNA Repair, organism-specific biosystem (from REACTOME)
      DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
    • DNA damage response, organism-specific biosystem (from WikiPathways)
      DNA damage response, organism-specific biosystemThis is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two ...
    • DNA damage-induced cell cycle checkpoints, organism-specific biosystem (from KEGG)
      DNA damage-induced cell cycle checkpoints, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
    • DNA damage-induced cell cycle checkpoints, conserved biosystem (from KEGG)
      DNA damage-induced cell cycle checkpoints, conserved biosystemFunctional set; Cellular processes; Cell signaling
    • Fanconi Anemia Pathway, organism-specific biosystem (from REACTOME)
      Fanconi Anemia Pathway, organism-specific biosystemFanconi anemia (FA) is a genetic disease of genome instability characterized by congenital skeletal defects, aplastic anemia, susceptibility to leukemias, and cellular sensitivity to DNA damaging age...
    • Fanconi anemia pathway, organism-specific biosystem (from KEGG)
      Fanconi anemia pathway, organism-specific biosystemThe Fanconi anemia pathway is required for the efficient repair of damaged DNA, especially interstrand cross-links (ICLs). DNA ICL is directly recognized by FANCM and associated proteins, that recrui...
    • Fanconi anemia pathway, conserved biosystem (from KEGG)
      Fanconi anemia pathway, conserved biosystemThe Fanconi anemia pathway is required for the efficient repair of damaged DNA, especially interstrand cross-links (ICLs). DNA ICL is directly recognized by FANCM and associated proteins, that recrui...
    • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
      G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
    • G2/M DNA damage checkpoint, organism-specific biosystem (from REACTOME)
      G2/M DNA damage checkpoint, organism-specific biosystemThroughout the cell cycle, the genome is constantly monitored for damage, resulting either from errors of replication, by-products of metabolism or through extrinsic sources such as ultra-violet or i...
    • Gene Expression, organism-specific biosystem (from REACTOME)
      Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
      Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
    • HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
      HDR through Homologous Recombination (HR) or Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) of replication-independent DNA double strand breaks (DSBs) via homologous recombination repair (HRR) or single strand annealing (SSA) requires the activation of ATM fol...
    • HDR through Homologous Recombination (HRR), organism-specific biosystem (from REACTOME)
      HDR through Homologous Recombination (HRR), organism-specific biosystemHomology directed repair (HDR) through homologous recombination is known as homologous recombination repair (HRR). HRR occurs after extensive resection of DNA double strand break (DSB) ends, which cr...
    • HDR through Single Strand Annealing (SSA), organism-specific biosystem (from REACTOME)
      HDR through Single Strand Annealing (SSA), organism-specific biosystemHomology directed repair (HDR) through single strand annealing (SSA), similar to HDR through homologous recombination repair (HRR), involves extensive resection of DNA double strand break ends (DSBs)...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • Homologous DNA Pairing and Strand Exchange, organism-specific biosystem (from REACTOME)
      Homologous DNA Pairing and Strand Exchange, organism-specific biosystemThe presynaptic phase of homologous DNA pairing and strand exchange begins with the displacement of RPA from 3'-ssDNA overhangs created by extensive resection of DNA double strand break (DSB) ends. R...
    • Homology Directed Repair, organism-specific biosystem (from REACTOME)
      Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
    • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
      Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
    • Integrated Cancer pathway, organism-specific biosystem (from WikiPathways)
      Integrated Cancer pathway, organism-specific biosystem
      Integrated Cancer pathway
    • Meiosis, organism-specific biosystem (from REACTOME)
      Meiosis, organism-specific biosystemDuring meiosis the replicated chromosomes of a single diploid cell are segregated into 4 haploid daughter cells by two successive divisions, meiosis I and meiosis II. In meiosis I, the distinguishing...
    • Meiotic synapsis, organism-specific biosystem (from REACTOME)
      Meiotic synapsis, organism-specific biosystemMeiotic synapsis is the stable physical pairing of homologous chromosomes that begins in leptonema of prophase I and lasts until anaphase of prophase I. First, short segments of axial elements form a...
    • Presynaptic phase of homologous DNA pairing and strand exchange, organism-specific biosystem (from REACTOME)
      Presynaptic phase of homologous DNA pairing and strand exchange, organism-specific biosystemThe presynaptic phase of homologous DNA pairing and strand exchange during homologous recombination repair (HRR) begins with the displacement of RPA from ssDNA (Thompson and Limoli 2003) by the joint...
    • Processing of DNA double-strand break ends, organism-specific biosystem (from REACTOME)
      Processing of DNA double-strand break ends, organism-specific biosystemHomology directed repair (HDR) through homologous recombination (HRR) or single strand annealing (SSA) requires extensive resection of DNA double strand break (DSB) ends (Thompson and Limoli 2003, Ci...
    • Prostate Cancer, organism-specific biosystem (from WikiPathways)
      Prostate Cancer, organism-specific biosystem
      Prostate Cancer
    • Regulation of HSF1-mediated heat shock response, organism-specific biosystem (from REACTOME)
      Regulation of HSF1-mediated heat shock response, organism-specific biosystemThe ability of HSF1 to respond to cellular stresses is under negative regulation by chaperones, modulation of nucleocytoplasmic shuttling, post-translational modifications and transition from monomer...
    • Regulation of TP53 Activity, organism-specific biosystem (from REACTOME)
      Regulation of TP53 Activity, organism-specific biosystemProtein stability and transcriptional activity of TP53 (p53) tumor suppressor are regulated by post-translational modifications that include ubiquitination, phosphorylation, acetylation, methylation,...
    • Regulation of TP53 Activity through Phosphorylation, organism-specific biosystem (from REACTOME)
      Regulation of TP53 Activity through Phosphorylation, organism-specific biosystemPhosphorylation of TP53 (p53) at the N-terminal serine residues S15 and S20 plays a critical role in protein stabilization as phosphorylation at these sites interferes with binding of the ubiquitin l...
    • Signaling events mediated by TCPTP, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by TCPTP, organism-specific biosystem
      Signaling events mediated by TCPTP
    • TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystem (from REACTOME)
      TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystemSeveral DNA repair genes contain p53 response elements and their transcription is positively regulated by TP53 (p53). TP53-mediated regulation probably ensures increased protein level of DNA repair g...
    • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
      Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...
    • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
      p53 pathway, organism-specific biosystem
      p53 pathway
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    MutLalpha complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MutSalpha complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    Process Evidence Code Pubs
    DNA damage checkpoint IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA repair TAS
    Traceable Author Statement
    more info
    PubMed 
    DNA replication TAS
    Traceable Author Statement
    more info
     
    cell cycle TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to DNA damage stimulus TAS
    Traceable Author Statement
    more info
    PubMed 
    cellular response to UV IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cellular response to gamma radiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    establishment of RNA localization to telomere IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    establishment of macromolecular complex localization to telomere IC
    Inferred by Curator
    more info
    PubMed 
    interstrand cross-link repair TAS
    Traceable Author Statement
    more info
     
    multicellular organism development TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of DNA damage response, signal transduction by p53 class mediator IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of telomerase catalytic core complex assembly IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of telomere maintenance via telomerase ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein localization to chromosome, telomeric region IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of cellular response to heat TAS
    Traceable Author Statement
    more info
     
    regulation of signal transduction by p53 class mediator TAS
    Traceable Author Statement
    more info
     
    replicative senescence IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    response to drug IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
     
    PML body IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromosome ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    colocalizes_with nuclear chromosome, telomeric region IC
    Inferred by Curator
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    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

    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
      5001..134592
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001184.3NP_001175.2  serine/threonine-protein kinase ATR

      See identical proteins and their annotated locations for NP_001175.2

      Status: REVIEWED

      Source sequence(s)
      BE859077, DC346860, U49844, U76308
      Consensus CDS
      CCDS3124.1
      UniProtKB/Swiss-Prot
      Q13535
      Related
      ENSP00000343741, OTTHUMP00000214450, ENST00000350721, OTTHUMT00000353995
      Conserved Domains (5) 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
      pfam02260
      Location:26132644
      FATC; FATC domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p7 Primary Assembly

      Range
      142449235..142578826 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017006643.1XP_016862132.1  

    2. XM_011512925.1XP_011511227.1  

      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]
      pfam02259
      Location:17092030
      FAT; FAT domain
      pfam02260
      Location:25502582
      FATC; FATC domain
      cd00892
      Location:22312505
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
    3. XM_011512924.1XP_011511226.1  

      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]
      pfam02259
      Location:17732094
      FAT; FAT domain
      pfam02260
      Location:26142646
      FATC; FATC domain
      cd00892
      Location:22952569
      PIKKc_ATR; Catalytic domain of Ataxia telangiectasia and Rad3-related proteins
    4. XM_011512926.2XP_011511228.1  

      Conserved Domains (2) summary
      smart00802
      Location:11191224
      UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
      pfam02259
      Location:17732076
      FAT; FAT domain

    RNA

    1. XR_924148.1 RNA Sequence

    2. XR_001740179.1 RNA Sequence

    3. XR_001740181.1 RNA Sequence

    4. XR_001740180.1 RNA Sequence

    5. XR_001740182.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018914.2 Alternate CHM1_1.1

      Range
      142131099..142260691 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)