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

Gene ID: 545, updated on 21-Oct-2014
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]
Location:
3q23
Exon count:
47
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 glycerol kinase 5 (putative) Neighboring gene 5'-3' exoribonuclease 1 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 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 HIV-1 Vpr activates ATR, resulting in phosphorylation of Chk1 and activation of the ATR-mediated DNA damage response PubMed
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 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 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 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. These cellular mechanisms that must cope with the plethora of DNA base pair ad...
  • 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 ...
  • 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...
  • 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...
  • 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...
  • 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 the Fanconi anemia pathway, organism-specific biosystem (from REACTOME)
    Regulation of the Fanconi anemia pathway, organism-specific biosystemThe Fanconi anemia DNA repair pathway is negatively regulated by the deubiquitination of FANCD2 an postively regulated by phosphorylation of the FANCD2 and FANCI. The USP1 deubiquitinating enzyme is...
  • 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
  • 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 
Process Evidence Code Pubs
DNA damage checkpoint IDA
Inferred from Direct Assay
more info
PubMed 
DNA repair TAS
Traceable Author Statement
more info
 
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 
multicellular organismal 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 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of protein binding IEA
Inferred from Electronic Annotation
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
PML body IDA
Inferred from Direct Assay
more info
PubMed 
XY body IEA
Inferred from Electronic Annotation
more info
 
chromosome ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
Preferred Names
serine/threonine-protein kinase ATR
Names
serine/threonine-protein kinase ATR
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 

    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 proteins identical to 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
    cd00892
    Location:22932567
    PIKKc_ATR; ATR (Ataxia telangiectasia and Rad3-related), catalytic domain; The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), ...
    smart00802
    Location:11191224
    UME; Domain in UVSB PI-3 kinase, MEI-41 and ESR-1
    COG5032
    Location:21332644
    TEL1; Phosphatidylinositol kinase and protein kinases of the PI-3 kinase family [Signal transduction mechanisms / Cell division and chromosome partitioning / Chromatin structure and dynamics / DNA replication, recombination, and repair / Intracellular ...
    pfam02259
    Location:17712092
    FAT; FAT domain
    pfam02260
    Location:26122644
    FATC; FATC domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000003.12 

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

RNA

  1. XR_241498.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000135.1 

    Range
    139541210..139670336
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018914.2 

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