TREX1
entrez
11277
canonical
uniprot
Q9NSU2
canonical
ensembl
ENSG00000213689
resolver
ensp
ENSP00000415972
resolver
ensp
ENSP00000486676
resolver
genesymbol
TREX1
resolver
hgnc
HGNC:12269
resolver
uniprot
B2RCN9
resolver
uniprot
Q5TZT0
resolver
uniprot
Q8TEU2
resolver
uniprot
Q9BPW1
resolver
uniprot
Q9Y4X2
resolver
uniprot_entry
Q5TZT0_HUMAN
resolver
uniprot_entry
TREX1_HUMAN
resolver
uniprot_sec
B2RCN9
resolver
uniprot_sec
Q8TEU2
resolver
uniprot_sec
Q9BPW1
resolver
uniprot_sec
Q9Y4X2
resolver
amino_acid_sequence
MGSQALPPGPMQTLIFFDMEATGLPFSQPKVTELCLLAVHRCALESPPTSQGPPPTVPPPPRVVDKLSLCVAPGKACSPAASEITGLSTAVLAAHGRQCFDDNLANLLLAFLRRQPQPWCLVAHNGDRYDFPLLQAELAMLGLTSALDGAFCVDSITALKALERASSPSEHGPRKSYSLGSIYTRLYGQSPPDSHTAEGDVLALLSICQWRPQALLRWVDAHARPFGTIRPMYGVTASARTKPRPSAVTTTAHLATTRNTSPSLGESRGTKDLPPVKDPGALSREGLLAPLGLLAILTLAVATLYGLSLATPGE
uniprot
proteins
disease_involvement
DISEASE: Aicardi-Goutieres syndrome 1 (AGS1) [MIM:225750]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269|PubMed:16845398, ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17357087, ECO:0000269|PubMed:17846997, ECO:0000269|PubMed:18045533, ECO:0000269|PubMed:20131292, ECO:0000269|PubMed:20799324, ECO:0000269|PubMed:23979357, ECO:0000269|PubMed:33476576}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Systemic lupus erythematosus (SLE) [MIM:152700]: A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. {ECO:0000269|PubMed:17660818, ECO:0000269|PubMed:20131292, ECO:0000269|PubMed:23979357}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. Enhanced immune sensing of oxidized DNA may be involved in the phototoxicity experienced by SLE patients. Exposure to UV-light produces DNA oxidative damage. Oxidized DNA being a poor TREX1 substrate, it accumulates in skin, leading to enhanced auto-immune reactivity and eventually skin lesions (PubMed:23993650). {ECO:0000269|PubMed:23993650}.; DISEASE: Chilblain lupus 1 (CHBL1) [MIM:610448]: A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure. {ECO:0000269|PubMed:17357087, ECO:0000269|PubMed:17440703}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Vasculopathy, retinal, with cerebral leukoencephalopathy and systemic manifestations (RVCLS) [MIM:192315]: An adult-onset, autosomal dominant endotheliopathy affecting the microvessels of the brain. It results in central nervous system degeneration and retinopathy, with progressive loss of vision, stroke, motor impairment, and cognitive decline. The ocular manifestations are characterized by telangiectasias, microaneurysms and retinal capillary obliteration starting in the macula. Diseased cerebral white matter has prominent small infarcts that often coalesce to pseudotumors. A subset of patients have systemic vascular involvement that can manifest as Raynaud phenomenon, micronodular cirrhosis, and glomerular dysfunction. {ECO:0000269|PubMed:17660820}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.1.11.2
uniprot
proteins
function
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}.
uniprot
proteins
mass_dalton
33212
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="K->R: Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 66; /note="K->R: No effect on ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 75; /note="K->R: Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 160; /note="K->R: Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 175; /note="K->R: Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 242; /note="K->R: Reduces ubiquitination."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 271; /note="K->R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-277."; /evidence="ECO:0000269|PubMed:23979357"; MUTAGEN 277; /note="K->R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-271."; /evidence="ECO:0000269|PubMed:23979357
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated, but not targeted to proteasomal degradation. Ubiquitination may be important for interaction with UBQLN1. {ECO:0000269|PubMed:23979357}.
uniprot
proteins
protein_family
Exonuclease superfamily
uniprot
proteins
protein_family
TREX family
uniprot
proteins
pubmed
10391904
uniprot
proteins
pubmed
10393201
uniprot
proteins
pubmed
11278605
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
16818237
uniprot
proteins
pubmed
16845398
uniprot
proteins
pubmed
17293595
uniprot
proteins
pubmed
17357087
uniprot
proteins
pubmed
17440703
uniprot
proteins
pubmed
17660818
uniprot
proteins
pubmed
17660820
uniprot
proteins
pubmed
17846997
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18045533
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
20131292
uniprot
proteins
pubmed
20799324
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23979357
uniprot
proteins
pubmed
23993650
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
33476576
uniprot
proteins
sequence_length
314
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10393201}. Cytoplasm, cytosol {ECO:0000269|PubMed:16818237}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:33476576}; Peripheral membrane protein {ECO:0000269|PubMed:33476576}. Note=Retained in the cytoplasm through the C-terminal region (By similarity). Localization to the endoplasmic reticulum membrane is required to direct TREX1 to ruptured micronuclei (PubMed:33476576). In response to DNA damage, translocates to the nucleus where it is specifically recruited to replication foci (PubMed:16818237). Translocation to the nucleus also occurs during GZMA-mediated cell death (PubMed:16818237). {ECO:0000250|UniProtKB:Q91XB0, ECO:0000269|PubMed:16818237, ECO:0000269|PubMed:33476576}.
uniprot
proteins