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Symbol TREX1 contributors: npt/mct/shn - updated : 07-04-2014
HGNC name three prime repair exonuclease 1
HGNC id 12269
Corresponding disease
AGS1 Aicardi-Goutieres syndrome 1
CHBL chilblain lupus
HERNS hereditary endotheliopathy with retinopathy, nephropathy and stroke
Location 3p21.31      Physical location : 48.507.228 - 48.509.043
Synonym name
  • deoxyribonuclease III
  • 3'-5' exonuclease TREX1
  • DNase III
  • Aicardi-Goutieres syndrome 1
  • 3' repair exonuclease 1
  • Synonym symbol(s) DRN3, CRV, DKFZp434J0310, AGS1, HERNS
    TYPE functioning gene
    text TREX1 as a single gene with two non-overlapping coding regions, represents only the downstream coding region encoding three prime repair exonuclease 1, the upstream coding region is represented by ATRIP
    STRUCTURE 2.13 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    alternative promoter
    MAPPING cloned Y linked N status provisional
    Map pter - D3S3729 - D3S3560 - TREX1 - D3S1581 - D3S2384 - cen
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 splicing 2145 - 369 - -
    2 splicing 1825 - 314 - -
    2 splicing 1647 32 304 - - 10391904
    Type widely
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   moderately Homo sapiensNM_016381
    Digestiveintestinesmall intestine  highly Homo sapiensNM_016381
     intestinelarge intestinecolon highly Homo sapiensNM_016381
     stomach   highly Homo sapiensNM_016381
    Lymphoid/Immunespleen   highly Homo sapiensNM_016381
     thymus   highly Homo sapiensNM_016381
    Reproductivefemale systembreast  highly Homo sapiensNM_016381
     female systemuterus  moderately Homo sapiensNM_016381
     male systemtestis  moderately Homo sapiensNM_016381
     male systemprostate  highly Homo sapiensNM_016381
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  moderately Homo sapiensNM_016381
    Muscularstriatum  moderately Homo sapiensNM_016381
    cell lineage
    cell lines
    at STAGE
  • N-terminal 242 AAs containing the catalytically robust 3'/5' exonuclease
  • three exonuclease domains
  • a coiled-coil domain near the N terminus, domain contributing to the cell cycle checkpoint by regulating the intranuclear localization of ATR
  • a conserved proline-rich region on the surface
  • three LRR motifs, involved in protein-protein or protein-membrane interactions
  • a C-terminal transmembrane doamin, with leucine-rich repeat 3 (possible role in nucleus-cytoplasmic localization), playing a role in the anchorage in the endoplasmic reticulum membrane, and localizes TREX1 to the cytosolic compartment
  • mono polymer homomer , dimer
    interspecies ortholog to Trex1, Mus musculus
    homolog to E.coli Dnel/MutD
    ortholog to Trex1, Rattus norvegicus
    ortholog to TREX1, Pan troglodytes
    intraspecies homolog to TREX2
  • exonuclease superfamily
  • TREX family
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,nuclear envelope
  • ORF forming focal nuclei after DNA-damage
  • each TREX1 monomer is anchored in the endoplasmic reticulum membrane via the C-terminal transmembrane domain
  • resides in the perinuclear space of cells where it is anchored to the endoplasmic reticulum by the C-terminal hydrophobic region with the catalytic core protruding into cytosol
  • in normal S-phase and also in response to genotoxic stress, TREX1 at least partly redistributes to the cell nucleus
  • located in the cytosol, TREX1 prevents the initiation of a cell-intrinsic autoimmune pathway by degrading ssDNA derived from endogenous retroelements
  • basic FUNCTION
  • DNA damage checkpoint (upstream ORF) 3'exonuclease activity (downstream ORF)
  • participates in a cell death process implicating this major 3' 5' exonuclease in genomic DNA degradation to minimize potential immune activation by persistent self DNA
  • playing a critical role in cellular responses to DNA structural abnormalities in conjunction with its interacting protein, ATR
  • may be involved in caspase-independent apoptosis, in degradation of apoptotic DNA together with the SET complex
  • having a dual role as DNA-degrading enzyme in granzyme A-mediated apoptosis and potentially as cytosolic DNA sensor and this function could induce an environment in which autoimmunity is perpetually stimulated and sustained
  • acting in concert with NME1 to degrade DNA during granzyme A-mediated cell death
  • playing a direct role in the degradation of double-stranded DNA to prevent autoimmune disease
  • degrades single-stranded DNA more efficiently than double-stranded DNA, and its catalytic properties are similar to those of Escherichia coli exonuclease X
  • play a role in DNA repair and drug resistance
  • may act in degrading DNA in all cell types undergoing a dying process before phagocytosis occurs
  • inhibits the innate immune response to human immunodeficiency virus type 1
  • TREX1 residues in one protomer contributing to DNA degradation catalyzed in the opposing protomer
  • SAMHD1, TREX1, and RNase H2 participate in a cellular nucleic acid metabolic pathway that overlaps the interferon-mediated innate antiviral and inflammatory responses
  • is a regulator of lysosomal biogenesis and interferon-independent activation of antiviral genes
  • autonomous 3prime-exonuclease that degrades DNA to prevent inappropriate immune activation
  • most abundant exonuclease in mammalian cells
  • function of TREX1 as a negative regulator of macrophage inflammatory activation
  • CELLULAR PROCESS nucleotide, repair
    protein, editing
  • 3'-5' exonuclease
    a component
  • member of the SET complex, dimerizing with TREX2, that normally resides in the cytoplasm but translocates to the nucleus in response to oxidative DNA damage
    small molecule
  • SET complex
  • CDK2 (Chung 2010)
  • ubiquilin 1 is a TREX1 C-terminal region (CTR)-interacting protein
  • TREX1 C terminus suppressed immune activation by interacting with the ER oligosaccharyltransferase (DDOST) complex and stabilizing its catalytic integrity
  • cell & other
    corresponding disease(s) AGS1 , CHBL , HERNS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --other  
    TREX1 post-translational modification indicates an additional mechanism by which mutations disrupt TREX1 biology, leading to human autoimmune disease
    Susceptibility to systemic lupus erythematosus
    Variant & Polymorphism other monoallelic frameshift or missense mutations and 3' UTR variant increasing the risk of systemic lupus erythematosus
    Candidate gene
    Therapy target
  • Trex1(-/-) mice are viable but exhibit a dramatically reduced survival and develop inflammatory myocarditis leading to cardiomyopathy and circulatory failure
  • Trex1(-/-) mice present inflammatory signatures in many different organs, including the brain
  • homodimer TREX1(R114H/R114H) exhibits a 23-fold reduced single-stranded DNA (ssDNA) exonuclease activity, TREX1(D201ins/D201ins) and TREX1(A124ins/A124ins) more than 10,000-fold reduced, relative to TREX1(WT)