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Symbol ATR contributors: mct/ - updated : 04-07-2016
HGNC name ataxia telangiectasia and Rad3 related
HGNC id 882
Corresponding disease
OPCS oropharyngeal cancer and skin telangiectases
SCKL1 Seckel syndrome
Location 3q23      Physical location : 142.168.077 - 142.297.668
Synonym name
  • FRAP related protein 1
  • protein kinase ATR
  • phosphoinositol 3-kinase like kinase
  • MEC1, mitosis entry checkpoint 1, homolog (S. cerevisiae)
  • Rad3 related protein
  • serine/threonine-protein kinase ATR
  • Synonym symbol(s) FRP1, TEMB, MEC1, PIKK, FCTCS, SCKL, SCKL1
    TYPE functioning gene
    STRUCTURE 129.59 kb     47 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    47 - 8258 301 2644 - 1996 8610130
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  highly
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tractlarynx  highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    SystemCellPubmedSpeciesStageRna symbol
    Visualcone photoreceptor Mus musculus
    Visualrod photoreceptor Mus musculus
    cell lineage
    cell lines tumor endothelial cell lines
    at STAGE
  • FATC domain
  • VWFA domain
  • a domain critical for its activation by TOPBP1
  • a PRD (PIKK [phosphoinositide 3-kinase related kinase] Regulatory Domain
    interspecies homolog to cell cycle G2 checkpoint genes Drosophila Mei-41
    homolog to yeast S.cerevisiae Mec1p
    homolog to yeast S.pombe RAD3
    intraspecies homolog to ataxia telangiectasia and RAD3
  • PI3/PI4-kinase family
  • ATM subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
    intracellular,nucleus,nucleoplasm,nuclear bodies
  • localizes to unsynapsed chromosomes
  • localizes to the photoreceptor connecting cilium
  • basic FUNCTION
  • phosphatidylinositol kinase, catalytic domain, related (PIK related family) cell cycle protein
  • required for the G2/M checkpoint in response to DNA damage and inhibition of replication
  • required for meiosis prophase I (associated with synaptomenal complex in RAD51 and RPA sites)
  • regulating fragile site stability and playing a role in the maintenance of stability at common fragile sites
  • playing a role in regulating centrosome stability
  • playing a critical role in cellular responses to DNA structural abnormalities in conjunction with its interacting protein, TREX1
  • with ATM are required for recovery from replication-dependent DSBs and to regulate RAD51 foci formation
  • exhibiting selective substrate specificity in response to different genotoxic agents
  • regulates a DNA damage-response pathway
  • playing a role in the regulation of global-genomic nucleotide excision repair (GG-NER), uniquely during S phase of the cell cycle
  • with ATRIP (ATR-interacting protein) coordinate checkpoint responses to DNA damage and replication stress
  • with ATM control mitotic events in vertebrate cells by targeting CEP63 and centrosome dependent spindle assembly
  • required with ATM for accurate response to replication arrest crucial to preserve genome stability
  • phosphorylates many FA proteins including FANCI, and this phosphorylation acts as a molecular switch in the FA pathway
  • functions to monitor genomic integrity in a selective spatiotemporal manner during neurogenesis
  • essential regulator of genome integrity
  • controls and coordinates DNA-replication origin firing, replication-fork stability, cell-cycle checkpoints, and DNA repair
  • ATR, activated after DNA damage, phosphorylates DTL and promotes the rapid degradation of CDT1 after UV irradiation in the G1 phase of the cell cycle
  • new function for ATR in cellular adaptation to hypoxia through regulation of HIF1A translation
  • is an essential regulator of the nucleotide excision repair (NER) mechanism
  • coordinates much of the cellular response to replication stress
  • ATR signals the accumulation of replication protein A (RPA1)-covered single-stranded DNA (ssDNA), which is caused by replication obstacles.
  • activated by replication stress, protects replication forks locally and suppresses origin firing globally
  • in the absence of PIAS3, ATR fails to display normal kinase activity after DNA damage, which accompanies with reduced phosphorylation of ATR substrates
    a component
  • component of a DNA damage response signaling pathway
  • RAD17/ATR/RAD1, is the 9-1-1 complex
  • ATR and its partner ATRIP exist as a complex and function together in the DNA damage response
    small molecule metal binding,
  • Mn2+
  • protein
  • partner of TREX1 in DNA damage checkpoint pathway
  • inhibition PLK1 activity and regulating cyclin B1 phosphorylation
  • phosphorylation of CHEK1
  • associates with CLSPN
  • interacting with H2AFX (ATR and H2AX provide cooperative safeguards to ensure genome stability during DNA replication)
  • interacting with CDC5L
  • TIMELESS-TIPIN complex stabilizes replication forks both by preventing the accumulation of ssDNA upstream of ATR-CHEK1 function and by facilitating phosphorylation of CHEK1 by ATR
  • interaction with FANCM (FANCM is required for efficient activation of ATR by promoting TOPBP1 loading on chromatin)
  • nucleotide excision repair (NER) is regulated by the ATR/TP53 checkpoint via modulation of XPA nuclear import and this regulation occurs in a cell cycle-dependent manner
  • ATR can have a central role in inhibiting the initiation of DNA replication by the regulation of CDC6 by CDH1
  • HORMAD2-dependent recruitment of ATR to unsynapsed chromosome axes constitutes a mechanism for the surveillance of asynapsis
  • CCAR2 phosphorylation by ATM/ATR inhibits SIRT1 deacetylase in response to DNA damage
  • HORMAD2-dependent quality control mechanism that recognizes unsynapsis and recruits ATR activity during mammalian meiosis
  • novel control mechanism in the NER pathway by regulating the steady-state level of XPA1 through posttranslational modifications by which ATR-mediated phosphorylation induces XPA1 stabilization by antagonizing HERC2-catalyzed XPA1 ubiquitination
  • NEK1, is critical for initiating the ATR response
  • ATR functions in a complex with its regulatory partner ATRIP
  • NBN and TOPBP1 have the potential to activate ATR independently, although both are required for functional activation of ATR
  • DDB2 and XPC, two early UV damage recognition factors, are required for the damage-specific ATR and ATM recruitment and phosphorylation
  • ATR-ATRIP protein kinase complex plays a crucial role in the cellular response to replication stress and DNA damage
  • NBN-mediated mode of ATR activation is important for the repair of replication-associated DSBs
  • TICRR stimulates ATR phosphorylation of CHEK1 in a TOPBP1-dependent manner
  • ATR-FANCM feedback loop is present in the FA and replication stress response pathways and that it is required for both efficient ATR/CHEK1 checkpoint activation and FANCM function
  • phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity
  • catalyzes histone H2AFX phosphorylation, the epigenetic event leading to gene inactivation
  • role for ATR in the epigenetic regulation of gene expression and presents a new technique for ablating gene function in the germline
  • phosphorylation of SMARCAL1 is one mechanism by which ATR prevents fork collapse, promotes the completion of DNA replication, and maintains genome integrity
  • ATR signaling promoted the transient association of endogenous FANCD2 with the MCM2-MCM7 replicative helicase independently of FANCD2 monoubiquitination
  • HELQ is associated with the RAD51 paralogs RAD51B/C/D and XRCC2, and with the DNA damage-responsive kinase ATR
  • ATR-mediated suppression of dormant origins shields active forks against irreversible breakage via preventing exhaustion of nuclear RPA1
  • USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization
  • single-stranded DNA-binding protein complex, NABP1/NABP2-INTS3 can recruit the checkpoint complex to initiate ATR signaling
  • PIAS3 is the only member of the PIAS family that is indispensable for ATR activation
  • TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair
  • cell & other
    activated by TOPBP1 (TOPBP1-mediated ATR activation is required for checkpoint signaling and cellular viability)
    mild hypothermia in mammalian cells and subsequently activates TP53
    Phosphorylated by PRKACA (PRKACA directly phosphorylates ATR at Ser435, which actively recruits the key NER protein xeroderma pigmentosum complementation group A (XPA))
    corresponding disease(s) SCKL1 , OPCS
    Variant & Polymorphism
    Candidate gene
    Therapy target
  • mouse model of Seckel syndrome characterized by a severe deficiency in ATR
  • ATR(+/S) mouse retinas displayed a specific, severe and early degeneration of rod and cone cells resembling some characteristics of human retinal degenerations