TREX1
UniProt ID: Q9NSU2
Entrez ID: 11277
Protein name: Three-prime repair exonuclease 1 (EC 3.1.11.2) (3'-5' exonuclease TREX1) (Deoxyribonuclease III) (DNase III)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:172...
FUNCTION: Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini (PubMed:10391904, PubMed:10393201, PubMed:17293595). Prevents cell-intrinsic initiation of autoimmunity (PubMed:10391904, PubMed:10393201, PubMed:17293595). Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements (PubMed:10391904, PubMed:10393201, PubMed:17293595). Plays a key role in degradation of DNA fragments at cytosolic micronuclei arising from genome instability: its association with the endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei, leading to micronuclear DNA degradation (PubMed:33476576). Micronuclear DNA degradation is required to limit CGAS activation and subsequent inflammation (PubMed:33476576). Unless degraded, these DNA fragments accumulate in the cytosol and activate the cGAS-STING innate immune signaling, leading to the production of type I interferon (PubMed:33476576). Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates (PubMed:18045533). Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA damage in concert with NME1 (PubMed:16818237). NME1 nicks one strand of DNA and TREX1 removes bases from the free 3' end to enhance DNA damage and prevent DNA end reannealing and rapid repair (PubMed:16818237). {ECO:0000269|PubMed:10391904, ECO:0000269|PubMed:10393201, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:18045533, ECO:0000269|PubMed:23993650, ECO:0000269|PubMed:33476576}.
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GO - Biological processes (BP):
activation of immune response [GO:0002253]; apoptotic cell clearance [GO:0043277]; atrial cardiac muscle tissue development [GO:0003228]; blood vessel development [GO:0001568]; CD86 biosynthetic process [GO:0035781]; cellular response to gamma radiation [GO:0071480]; cellular response to hydroxyurea...
activation of immune response [GO:0002253]; apoptotic cell clearance [GO:0043277]; atrial cardiac muscle tissue development [GO:0003228]; blood vessel development [GO:0001568]; CD86 biosynthetic process [GO:0035781]; cellular response to gamma radiation [GO:0071480]; cellular response to hydroxyurea [GO:0072711]; cellular response to interferon-beta [GO:0035458]; cellular response to reactive oxygen species [GO:0034614]; defense response to virus [GO:0051607]; determination of adult lifespan [GO:0008340]; DNA catabolic process, exonucleolytic [GO:0000738]; DNA duplex unwinding [GO:0032508]; DNA metabolic process [GO:0006259]; DNA modification [GO:0006304]; DNA recombination [GO:0006310]; DNA repair [GO:0006281]; DNA replication [GO:0006260]; DNA synthesis involved in UV-damage excision repair [GO:1904161]; establishment of protein localization [GO:0045184]; generation of precursor metabolites and energy [GO:0006091]; heart morphogenesis [GO:0003007]; heart process [GO:0003015]; immune complex formation [GO:0097281]; immune response in brain or nervous system [GO:0002383]; inflammatory response to antigenic stimulus [GO:0002437]; kidney development [GO:0001822]; lymphoid progenitor cell differentiation [GO:0002320]; macrophage activation involved in immune response [GO:0002281]; mismatch repair [GO:0006298]; mitotic G1 DNA damage checkpoint signaling [GO:0031571]; negative regulation of innate immune response [GO:0045824]; negative regulation of type I interferon-mediated signaling pathway [GO:0060339]; protein stabilization [GO:0050821]; regulation of catalytic activity [GO:0050790]; regulation of cellular respiration [GO:0043457]; regulation of fatty acid metabolic process [GO:0019217]; regulation of glycolytic process [GO:0006110]; regulation of immunoglobulin production [GO:0002637]; regulation of inflammatory response [GO:0050727]; regulation of lipid biosynthetic process [GO:0046890]; regulation of lysosome organization [GO:1905671]; regulation of protein complex stability [GO:0061635]; regulation of T cell activation [GO:0050863]; regulation of tumor necrosis factor production [GO:0032680]; regulation of type I interferon production [GO:0032479]; T cell antigen processing and presentation [GO:0002457]; transposition, RNA-mediated [GO:0032197]; type I interferon signaling pathway [GO:0060337]
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GO - Molecular function (MF):
3'-5'-exodeoxyribonuclease activity [GO:0008296]; 3'-5' exonuclease activity [GO:0008408]; adenyl deoxyribonucleotide binding [GO:0032558]; DNA binding, bending [GO:0008301]; double-stranded DNA binding [GO:0003690]; exodeoxyribonuclease III activity [GO:0008853]; magnesium ion binding [GO:0000287];...
3'-5'-exodeoxyribonuclease activity [GO:0008296]; 3'-5' exonuclease activity [GO:0008408]; adenyl deoxyribonucleotide binding [GO:0032558]; DNA binding, bending [GO:0008301]; double-stranded DNA binding [GO:0003690]; exodeoxyribonuclease III activity [GO:0008853]; magnesium ion binding [GO:0000287]; metal ion binding [GO:0046872]; MutLalpha complex binding [GO:0032405]; MutSalpha complex binding [GO:0032407]; protein homodimerization activity [GO:0042803]; single-stranded DNA binding [GO:0003697]; WW domain binding [GO:0050699]
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GO - Cellular component (CC):
cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; nuclear envelope [GO:0005635]; nuclear replication fork [GO:0043596]; oligosaccharyltransferase complex [GO:0008250]; protein-DNA complex [GO:0032993]...
cytoplasm [GO:0005737]; cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; nuclear envelope [GO:0005635]; nuclear replication fork [GO:0043596]; oligosaccharyltransferase complex [GO:0008250]; protein-DNA complex [GO:0032993]
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TREX1
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*NOTE: the Kaplan plots were collected from OncoLnc