Three Prime Repair Exonuclease 1 (TREX1)

AGS1; ATRIP; DRN3; Aicardi-Goutieres Syndrome 1; 3'-5' exonuclease TREX1; DNase III

SPN	U047
HGNC	12269
MGI	1925349
PubMed	20871604
UniProt	Q9NSU2
Wiki	TREX1

Three prime repair exonuclease 1 is 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 Cerebral Dystrophy), and Cree encephalitis.TREX1 bound to cytosolic HIV DNA and digested excess HIV DNA that would otherwise activate interferon expression via a pathway dependent on the kinase TBK1, the adaptor STING and the transcription factor IRF3. HIV-stimulated interferon production in cells deficient in TREX1 did not involve known nucleic acid sensors.

Reference

"A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein."
EMBO J. 18:3868-3875(1999) [PubMed] [Europe PMC] [Abstract]

"Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases."
J. Biol. Chem. 274:19655-19660(1999) [PubMed] [Europe PMC] [Abstract]

"Structure and expression of the TREX1 and TREX2 3'-->5' exonuclease genes."
J. Biol. Chem. 276:14718-14727(2001) [PubMed] [Europe PMC] [Abstract]

"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"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 23:133-142(2006) [PubMed] [Europe PMC] [Abstract]

"Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease."
Cell 131:873-886(2007) [PubMed] [Europe PMC] [Abstract]

"The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering."
J. Biol. Chem. 282:10537-10543(2007) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
Immunity 39:482-495(2013) [PubMed] [Europe PMC] [Abstract]

"The TREX1 C-terminal region controls cellular localization through ubiquitination."
J. Biol. Chem. 288:28881-28892(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus."
Nat. Genet. 38:917-920(2006) [PubMed] [Europe PMC] [Abstract]

"Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome."
Am. J. Hum. Genet. 80:811-815(2007) [PubMed] [Europe PMC] [Abstract]

"Clinical and molecular phenotype of Aicardi-Goutieres syndrome."
Am. J. Hum. Genet. 81:713-725(2007) [PubMed] [Europe PMC] [Abstract]

"A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus."
J. Mol. Med. 85:531-537(2007) [PubMed] [Europe PMC] [Abstract]

"Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus."
Nat. Genet. 39:1065-1067(2007) [PubMed] [Europe PMC] [Abstract]

"C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy."
Nat. Genet. 39:1068-1070(2007) [PubMed] [Europe PMC] [Abstract]

"A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutieres syndrome."
Am. J. Med. Genet. A 152:2612-2617(2010) [PubMed] [Europe PMC] [Abstract]

"Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome."
Arthritis Rheum. 62:1469-1477(2010) [PubMed] [Europe PMC] [Abstract]