This gene encodes the major 3'->5' DNA exonuclease in human cells. The protein is a non-processive exonuclease that may serve a proofreading function for a human DNA polymerase. It is also a component of the SET complex, and acts to rapidly degrade 3' ends of nicked DNA during granzyme A-mediated cell death. Mutations in this gene result in Aicardi-Goutieres syndrome, chilblain lupus, RVCL (Retinal Vasculopathy with Cerebral Leukodystrophy), and Cree encephalitis. Multiple transcript variants encoding different isoforms have been found for this gene.[8]
Clinical relevanceedit
Mutations within the TREX1 gene cause familial chilblain lupus. The TREX1 polymorphisms confer susceptibility to systemic lupus erythematosus. Missense mutations of the TREX1 gene significantly downregulate its exonucleolytic capacity and result in the accumulation of nucleic acids. The build-up of the nucleic acids within the cytoplasm stimulates type-I interferon responses that could trigger autoimmune responses.[9] The region containing the TREX1 gene (3p21.31) has been linked to COVID-19 severity in a recent genome-wide association study.[10] This might explain the occurrence of chilblain like lesions in patients infected with SARS-CoV-2.[11]
TREX1 helps HIV‑1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm[12]
^ abcGRCh38: Ensembl release 89: ENSG00000213689 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000049734 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Mazur DJ, Perrino FW (Aug 1999). "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases". J Biol Chem. 274 (28): 19655–60. doi:10.1074/jbc.274.28.19655. PMID 10391904.
^Hoss M, Robins P, Naven TJ, Pappin DJ, Sgouros J, Lindahl T (Aug 1999). "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein". EMBO J. 18 (13): 3868–75. doi:10.1093/emboj/18.13.3868. PMC1171463. PMID 10393201.
^Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, Corry PC, Cowan FM, Frints SG, Klepper J, Livingston JH, Lynch SA, Massey RF, Meritet JF, Michaud JL, Ponsot G, Voit T, Lebon P, Bonthron DT, Jackson AP, Barnes DE, Lindahl T (Jul 2006). "Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus". Nat Genet. 38 (8): 917–20. doi:10.1038/ng1845. PMID 16845398. S2CID 9069106.
^ ab"Entrez Gene: TREX1 three prime repair exonuclease 1".
^Jabalameli (2021). "Overlap between Genetic Susceptibility to COVID-19 and Skin Diseases". Immunological Investigations. 51 (4): 1087–1094. doi:10.1080/08820139.2021.1876086. PMID 33494631.
^Ellinghaus (2020). "Genomewide Association Study of Severe Covid-19 with Respiratory Failure". New England Journal of Medicine. 383 (16): 1522–1534. doi:10.1056/NEJMoa2020283. PMC7315890. PMID 32558485.
^Jabalameli, Navid (2021). "Overlap between Genetic Susceptibility to COVID-19 and Skin Diseases". Immunological Investigations. 51 (4): 1087–1094. doi:10.1080/08820139.2021.1876086. PMID 33494631.
^Doyle, Thomas (27 April 2015). "HIV-1 and interferons: who's interfering with whom?". Nature Reviews Microbiology. 13 (Nature Reviews Microbiology 13): 403–413. doi:10.1038/nrmicro3449. PMC7768976. PMID 25915633. S2CID 205499122.
^ abMcKinnon PJ. Genome integrity and disease prevention in the nervous system. Genes Dev. 2017 Jun 15;31(12):1180-1194. doi: 10.1101/gad.301325.117. PMID: 28765160; PMCID: PMC5558921
Further readingedit
Tolmie JL, Shillito P, Hughes-Benzie R, Stephenson JB (1996). "The Aicardi-Goutières syndrome (familial, early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis)". J. Med. Genet. 32 (11): 881–4. doi:10.1136/jmg.32.11.881. PMC1051740. PMID 8592332.
Black DN, Watters GV, Andermann E, et al. (1989). "Encephalitis among Cree children in northern Quebec". Ann. Neurol. 24 (4): 483–9. doi:10.1002/ana.410240402. PMID 3239950. S2CID 32112982.
Perrino FW, Miller H, Ealey KA (1994). "Identification of a 3'-->5'-exonuclease that removes cytosine arabinoside monophosphate from 3' termini of DNA". J. Biol. Chem. 269 (23): 16357–63. doi:10.1016/S0021-9258(17)34015-2. PMID 8206943.
Goutières F, Aicardi J, Barth PG, Lebon P (1999). "Aicardi-Goutières syndrome: an update and results of interferon-alpha studies". Ann. Neurol. 44 (6): 900–7. doi:10.1002/ana.410440608. PMID 9851434. S2CID 58224378.
Crow YJ, Jackson AP, Roberts E, et al. (2000). "Aicardi-Goutières Syndrome Displays Genetic Heterogeneity with One Locus (AGS1) on Chromosome 3p21". Am. J. Hum. Genet. 67 (1): 213–21. doi:10.1086/302955. PMC1287108. PMID 10827106.
Mazur DJ, Perrino FW (2001). "Structure and expression of the TREX1 and TREX2 3' --> 5' exonuclease genes". J. Biol. Chem. 276 (18): 14718–27. doi:10.1074/jbc.M010051200. PMID 11278605.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Crow YJ, Black DN, Ali M, et al. (2003). "Cree encephalitis is allelic with Aicardi-Goutiéres syndrome: implications for the pathogenesis of disorders of interferon alpha metabolism". J. Med. Genet. 40 (3): 183–7. doi:10.1136/jmg.40.3.183. PMC1735395. PMID 12624136.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC528928. PMID 15489334.
Unsal-Kaçmaz K, Mullen TE, Kaufmann WK, Sancar A (2005). "Coupling of Human Circadian and Cell Cycles by the Timeless Protein". Mol. Cell. Biol. 25 (8): 3109–16. doi:10.1128/MCB.25.8.3109-3116.2005. PMC1069621. PMID 15798197.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC1356129. PMID 16344560.
Yoshioka K, Yoshioka Y, Hsieh P (2006). "ATR Kinase Activation Mediated by MutSα and MutLα in Response to Cytotoxic O6-Methylguanine Adducts". Mol. Cell. 22 (4): 501–10. doi:10.1016/j.molcel.2006.04.023. PMC2423943. PMID 16713580.
Chowdhury D, Beresford PJ, Zhu P, et al. (2006). "The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death". Mol. Cell. 23 (1): 133–42. doi:10.1016/j.molcel.2006.06.005. PMID 16818237.
Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Aicardi-Goutières Syndrome
OMIM entries on Aicardi-Goutieres syndrome
This article on a gene on human chromosome 3 is a stub. You can help Wikipedia by expanding it.
trex1, three, prime, repair, exonuclease, enzyme, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes2ioc, 2o4g, 2o4i, 2oa8, 3b6o, 3b6p, 3mxi, 3mxj, 3mxm, 3u3y, 3u6f, 4ynqidentifiersaliases, ags1, drn3, herns, three, pr. Three prime repair exonuclease 1 is an enzyme that in humans is encoded by the TREX1 gene 5 6 7 8 TREX1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes2IOC 2O4G 2O4I 2OA8 3B6O 3B6P 3MXI 3MXJ 3MXM 3U3Y 3U6F 4YNQIdentifiersAliasesTREX1 AGS1 CRV DRN3 HERNS three prime repair exonuclease 1 RVCLSExternal IDsOMIM 606609 MGI 1328317 HomoloGene 7982 GeneCards TREX1Gene location Human Chr Chromosome 3 human 1 Band3p21 31Start48 465 811 bp 1 End48 467 645 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 9 F2Start108 887 001 bp 2 End108 888 802 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytespleenskin of abdomenanterior pituitarybloodsalivary glandminor salivary glandlymph noderight uterine tuberight adrenal glandTop expressed inlensspleenurinary bladderquadriceps femoris muscleadrenal glandbone marrowmuscle tissuewhite adipose tissueskeletal muscle tissuethymusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein homodimerization activity metal ion binding single stranded DNA binding exodeoxyribonuclease III activity MutSalpha complex binding protein binding 3 5 exodeoxyribonuclease activity MutLalpha complex binding nucleic acid binding nuclease activity exonuclease activity hydrolase activity 3 5 exonuclease activity double stranded DNA binding adenyl deoxyribonucleotide binding magnesium ion binding DNA binding DNA binding bending WW domain bindingCellular componentcytoplasm nuclear envelope endoplasmic reticulum membrane membrane endoplasmic reticulum nucleus cytosol oligosaccharyltransferase complex protein DNA complex nuclear replication forkBiological processDNA recombination regulation of type I interferon production DNA replication DNA mismatch repair nucleic acid phosphodiester bond hydrolysis DNA metabolic process DNA repair cellular response to interferon beta blood vessel development kidney development adaptive immune response organ or tissue specific immune response activation of immune response macrophage activation involved in immune response lymphoid progenitor cell differentiation immune response in brain or nervous system inflammatory response to antigenic stimulus T cell antigen processing and presentation regulation of immunoglobulin production heart morphogenesis heart process atrial cardiac muscle tissue development generation of precursor metabolites and energy regulation of glycolytic process DNA modification DNA catabolic process inflammatory response immune response cellular response to DNA damage stimulus determination of adult lifespan response to UV regulation of gene expression regulation of fatty acid metabolic process regulation of cellular metabolic process transposition RNA mediated DNA duplex unwinding interferon alpha production regulation of tumor necrosis factor production cellular response to oxidative stress cellular response to reactive oxygen species cellular response to UV CD86 biosynthetic process apoptotic cell clearance regulation of cellular respiration innate immune response regulation of innate immune response establishment of protein localization regulation of lipid biosynthetic process regulation of inflammatory response regulation of catalytic activity protein stabilization regulation of T cell activation defense response to virus type I interferon signaling pathway negative regulation of type I interferon mediated signaling pathway regulation of protein complex stability cellular response to organic substance cellular response to type I interferon cellular response to gamma radiation cellular response to hydroxyurea immune complex formation DNA synthesis involved in UV damage excision repair regulation of lysosome organizationSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez1127722040EnsemblENSG00000213689ENSMUSG00000049734UniProtQ9NSU2Q91XB0RefSeq mRNA NM 033629NM 007248NM 016381NM 033627NM 033628NM 001012236NM 011637RefSeq protein NP 009179NP 338599NP 001012236NP 035767Location UCSC Chr 3 48 47 48 47 MbChr 9 108 89 108 89 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Function 2 Clinical relevance 3 References 4 Further reading 5 External linksFunction editThis gene encodes the major 3 gt 5 DNA exonuclease in human cells The protein is a non processive exonuclease that may serve a proofreading function for a human DNA polymerase It is also a component of the SET complex and acts to rapidly degrade 3 ends of nicked DNA during granzyme A mediated cell death Mutations in this gene result in Aicardi Goutieres syndrome chilblain lupus RVCL Retinal Vasculopathy with Cerebral Leukodystrophy and Cree encephalitis Multiple transcript variants encoding different isoforms have been found for this gene 8 Clinical relevance editMutations within the TREX1 gene cause familial chilblain lupus The TREX1 polymorphisms confer susceptibility to systemic lupus erythematosus Missense mutations of the TREX1 gene significantly downregulate its exonucleolytic capacity and result in the accumulation of nucleic acids The build up of the nucleic acids within the cytoplasm stimulates type I interferon responses that could trigger autoimmune responses 9 The region containing the TREX1 gene 3p21 31 has been linked to COVID 19 severity in a recent genome wide association study 10 This might explain the occurrence of chilblain like lesions in patients infected with SARS CoV 2 11 TREX1 helps HIV 1 to evade cytosolic sensing by degrading viral cDNA in the cytoplasm 12 Mutations in TREX1 can give cause failure to appropriately remove ribonucleotides misincorporated into DNA 13 The removal process is ordinary performed by ribonucleotide excision repair In humans a defect in this process can give rise to Aicardi Goutieres syndrome involving microcephaly and neuroinflammation 13 References edit a b c GRCh38 Ensembl release 89 ENSG00000213689 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000049734 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mazur DJ Perrino FW Aug 1999 Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3 gt 5 exonucleases J Biol Chem 274 28 19655 60 doi 10 1074 jbc 274 28 19655 PMID 10391904 Hoss M Robins P Naven TJ Pappin DJ Sgouros J Lindahl T Aug 1999 A human DNA editing enzyme homologous to the Escherichia coli DnaQ MutD protein EMBO J 18 13 3868 75 doi 10 1093 emboj 18 13 3868 PMC 1171463 PMID 10393201 Crow YJ Hayward BE Parmar R Robins P Leitch A Ali M Black DN van Bokhoven H Brunner HG Hamel BC Corry PC Cowan FM Frints SG Klepper J Livingston JH Lynch SA Massey RF Meritet JF Michaud JL Ponsot G Voit T Lebon P Bonthron DT Jackson AP Barnes DE Lindahl T Jul 2006 Mutations in the gene encoding the 3 5 DNA exonuclease TREX1 cause Aicardi Goutieres syndrome at the AGS1 locus Nat Genet 38 8 917 20 doi 10 1038 ng1845 PMID 16845398 S2CID 9069106 a b Entrez Gene TREX1 three prime repair exonuclease 1 Jabalameli 2021 Overlap between Genetic Susceptibility to COVID 19 and Skin Diseases Immunological Investigations 51 4 1087 1094 doi 10 1080 08820139 2021 1876086 PMID 33494631 Ellinghaus 2020 Genomewide Association Study of Severe Covid 19 with Respiratory Failure New England Journal of Medicine 383 16 1522 1534 doi 10 1056 NEJMoa2020283 PMC 7315890 PMID 32558485 Jabalameli Navid 2021 Overlap between Genetic Susceptibility to COVID 19 and Skin Diseases Immunological Investigations 51 4 1087 1094 doi 10 1080 08820139 2021 1876086 PMID 33494631 Doyle Thomas 27 April 2015 HIV 1 and interferons who s interfering with whom Nature Reviews Microbiology 13 Nature Reviews Microbiology 13 403 413 doi 10 1038 nrmicro3449 PMC 7768976 PMID 25915633 S2CID 205499122 a b McKinnon PJ Genome integrity and disease prevention in the nervous system Genes Dev 2017 Jun 15 31 12 1180 1194 doi 10 1101 gad 301325 117 PMID 28765160 PMCID PMC5558921Further reading editTolmie JL Shillito P Hughes Benzie R Stephenson JB 1996 The Aicardi Goutieres syndrome familial early onset encephalopathy with calcifications of the basal ganglia and chronic cerebrospinal fluid lymphocytosis J Med Genet 32 11 881 4 doi 10 1136 jmg 32 11 881 PMC 1051740 PMID 8592332 Black DN Watters GV Andermann E et al 1989 Encephalitis among Cree children in northern Quebec Ann Neurol 24 4 483 9 doi 10 1002 ana 410240402 PMID 3239950 S2CID 32112982 Perrino FW Miller H Ealey KA 1994 Identification of a 3 gt 5 exonuclease that removes cytosine arabinoside monophosphate from 3 termini of DNA J Biol Chem 269 23 16357 63 doi 10 1016 S0021 9258 17 34015 2 PMID 8206943 Goutieres F Aicardi J Barth PG Lebon P 1999 Aicardi Goutieres syndrome an update and results of interferon alpha studies Ann Neurol 44 6 900 7 doi 10 1002 ana 410440608 PMID 9851434 S2CID 58224378 Crow YJ Jackson AP Roberts E et al 2000 Aicardi Goutieres Syndrome Displays Genetic Heterogeneity with One Locus AGS1 on Chromosome 3p21 Am J Hum Genet 67 1 213 21 doi 10 1086 302955 PMC 1287108 PMID 10827106 Mazur DJ Perrino FW 2001 Structure and expression of the TREX1 and TREX2 3 gt 5 exonuclease genes J Biol Chem 276 18 14718 27 doi 10 1074 jbc M010051200 PMID 11278605 Strausberg RL Feingold EA Grouse LH et al 2003 Generation and initial analysis of more than 15 000 full length human and mouse cDNA sequences Proc Natl Acad Sci U S A 99 26 16899 903 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Crow YJ Black DN Ali M et al 2003 Cree encephalitis is allelic with Aicardi Goutieres syndrome implications for the pathogenesis of disorders of interferon alpha metabolism J Med Genet 40 3 183 7 doi 10 1136 jmg 40 3 183 PMC 1735395 PMID 12624136 Ota T Suzuki Y Nishikawa T et al 2004 Complete sequencing and characterization of 21 243 full length human cDNAs Nat Genet 36 1 40 5 doi 10 1038 ng1285 PMID 14702039 Gerhard DS Wagner L Feingold EA et al 2004 The Status Quality and Expansion of the NIH Full Length cDNA Project The Mammalian Gene Collection MGC Genome Res 14 10B 2121 7 doi 10 1101 gr 2596504 PMC 528928 PMID 15489334 Unsal Kacmaz K Mullen TE Kaufmann WK Sancar A 2005 Coupling of Human Circadian and Cell Cycles by the Timeless Protein Mol Cell Biol 25 8 3109 16 doi 10 1128 MCB 25 8 3109 3116 2005 PMC 1069621 PMID 15798197 Rual JF Venkatesan K Hao T et al 2005 Towards a proteome scale map of the human protein protein interaction network Nature 437 7062 1173 8 Bibcode 2005Natur 437 1173R doi 10 1038 nature04209 PMID 16189514 S2CID 4427026 Kimura K Wakamatsu A Suzuki Y et al 2006 Diversification of transcriptional modulation Large scale identification and characterization of putative alternative promoters of human genes Genome Res 16 1 55 65 doi 10 1101 gr 4039406 PMC 1356129 PMID 16344560 Yoshioka K Yoshioka Y Hsieh P 2006 ATR Kinase Activation Mediated by MutSa and MutLa in Response to Cytotoxic O6 Methylguanine Adducts Mol Cell 22 4 501 10 doi 10 1016 j molcel 2006 04 023 PMC 2423943 PMID 16713580 Chowdhury D Beresford PJ Zhu P et al 2006 The exonuclease TREX1 is in the SET complex and acts in concert with NM23 H1 to degrade DNA during granzyme A mediated cell death Mol Cell 23 1 133 42 doi 10 1016 j molcel 2006 06 005 PMID 16818237 Olsen JV Blagoev B Gnad F et al 2006 Global in vivo and site specific phosphorylation dynamics in signaling networks Cell 127 3 635 48 doi 10 1016 j cell 2006 09 026 PMID 17081983 S2CID 7827573 External links editGeneReviews NCBI NIH UW entry on Aicardi Goutieres Syndrome OMIM entries on Aicardi Goutieres syndrome nbsp This article on a gene on human chromosome 3 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title TREX1 amp oldid 1142699468, wikipedia, wiki, book, books, library,
