TREX1_MOUSE
ID TREX1_MOUSE Reviewed; 314 AA.
AC Q91XB0; Q3TAD7; Q9D6W2; Q9R1B0;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 2.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Three-prime repair exonuclease 1 {ECO:0000305};
DE EC=3.1.11.2 {ECO:0000269|PubMed:11279105, ECO:0000269|PubMed:15254239, ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819};
DE AltName: Full=3'-5' exonuclease TREX1 {ECO:0000303|PubMed:10391904};
GN Name=Trex1 {ECO:0000303|PubMed:10391904, ECO:0000312|MGI:MGI:1328317};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=10391904; DOI=10.1074/jbc.274.28.19655;
RA Mazur D.J., Perrino F.W.;
RT "Identification and expression of the TREX1 and TREX2 cDNA sequences
RT encoding mammalian 3'-->5' exonucleases.";
RL J. Biol. Chem. 274:19655-19660(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Spleen, and Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF N-TERMINUS, FUNCTION, CATALYTIC ACTIVITY,
RP HOMODIMERIZATION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11279105; DOI=10.1074/jbc.m100623200;
RA Mazur D.J., Perrino F.W.;
RT "Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases.
RT Characterization of the recombinant proteins.";
RL J. Biol. Chem. 276:17022-17029(2001).
RN [5]
RP FUNCTION IN INFLAMMATION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=15254239; DOI=10.1128/mcb.24.15.6719-6727.2004;
RA Morita M., Stamp G., Robins P., Dulic A., Rosewell I., Hrivnak G., Daly G.,
RA Lindahl T., Barnes D.E.;
RT "Gene-targeted mice lacking the Trex1 (DNase III) 3'-->5' DNA exonuclease
RT develop inflammatory myocarditis.";
RL Mol. Cell. Biol. 24:6719-6727(2004).
RN [6]
RP FUNCTION IN CELL CYCLE REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=18045533; DOI=10.1016/j.cell.2007.10.017;
RA Yang Y.G., Lindahl T., Barnes D.E.;
RT "Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation
RT and autoimmune disease.";
RL Cell 131:873-886(2007).
RN [7]
RP FUNCTION AS REGULATOR OF IFN RESPONSE, SUBCELLULAR LOCATION, INDUCTION BY
RP CYTOSOLIC DNA, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ARG-114; HIS-195;
RP ASP-200 AND VAL-201.
RX PubMed=18724932; DOI=10.1016/j.cell.2008.06.032;
RA Stetson D.B., Ko J.S., Heidmann T., Medzhitov R.;
RT "Trex1 prevents cell-intrinsic initiation of autoimmunity.";
RL Cell 134:587-598(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP FUNCTION IN OXIDIZED DNA DEGRADATION.
RX PubMed=23993650; DOI=10.1016/j.immuni.2013.08.004;
RA Gehrke N., Mertens C., Zillinger T., Wenzel J., Bald T., Zahn S.,
RA Tueting T., Hartmann G., Barchet W.;
RT "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1
RT degradation and potentiates STING-dependent immune sensing.";
RL Immunity 39:482-495(2013).
RN [11]
RP FUNCTION IN INNATE IMMUNE SYSTEM REGULATION, TISSUE SPECIFICITY, DISRUPTION
RP PHENOTYPE, AND INDUCTION BY INFLAMMATORY STIMULI.
RX PubMed=24218451; DOI=10.4049/jimmunol.1301603;
RA Pereira-Lopes S., Celhar T., Sans-Fons G., Serra M., Fairhurst A.M.,
RA Lloberas J., Celada A.;
RT "The exonuclease trex1 restrains macrophage proinflammatory activation.";
RL J. Immunol. 191:6128-6135(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-242 IN COMPLEXES WITH DNA; AMP;
RP CALCIUM AND MANGANESE IONS, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBUNIT, AND MUTAGENESIS OF ARG-114 AND VAL-201.
RX PubMed=17293595; DOI=10.1074/jbc.m700039200;
RA de Silva U., Choudhury S., Bailey S.L., Harvey S., Perrino F.W., Hollis T.;
RT "The crystal structure of TREX1 explains the 3' nucleotide specificity and
RT reveals a polyproline II helix for protein partnering.";
RL J. Biol. Chem. 282:10537-10543(2007).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 9-245 AND MUTANT ALA-195 IN
RP COMPLEXES WITH DNA AND MAGNESIUM IONS, FUNCTION, CATALYTIC ACTIVITY, ACTIVE
RP SITE, COFACTOR, DNA-BINDING, SUBUNIT, INTERACTION WITH TCERG1, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF HIS-195.
RX PubMed=17355961; DOI=10.1074/jbc.m700236200;
RA Brucet M., Querol-Audi J., Serra M., Ramirez-Espain X., Bertlik K.,
RA Ruiz L., Lloberas J., Macias M.J., Fita I., Celada A.;
RT "Structure of the dimeric exonuclease TREX1 in complex with DNA displays a
RT proline-rich binding site for WW Domains.";
RL J. Biol. Chem. 282:14547-14557(2007).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 9-245 IN COMPLEXES WITH TMP;
RP LITHIUM; SODIUM AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, DNA-BINDING,
RP COFACTOR, ACTIVITY REGULATION, AND MUTAGENESIS OF HIS-124 AND HIS-195.
RX PubMed=18780819; DOI=10.1110/ps.036426.108;
RA Brucet M., Querol-Audi J., Bertlik K., Lloberas J., Fita I., Celada A.;
RT "Structural and biochemical studies of TREX1 inhibition by metals.
RT Identification of a new active histidine conserved in DEDDh exonucleases.";
RL Protein Sci. 17:2059-2069(2008).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-142 AND MUTANTS ASN-18;
RP HIS-200; ASN-200 AND ASP-201 IN COMPLEXES WITH DNA; CALCIUM AND MAGNESIUM
RP IONS, COFACTOR, AND SUBUNIT.
RX PubMed=22071149; DOI=10.1016/j.dnarep.2011.10.007;
RA Bailey S.L., Harvey S., Perrino F.W., Hollis T.;
RT "Defects in DNA degradation revealed in crystal structures of TREX1
RT exonuclease mutations linked to autoimmune disease.";
RL DNA Repair 11:65-73(2012).
RN [16] {ECO:0007744|PDB:6W10}
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1-242 OF MUTANT LYS-198, AND
RP MUTAGENESIS OF GLU-198.
RX PubMed=33606975; DOI=10.1016/j.molcel.2021.01.024;
RA Zhou W., Mohr L., Maciejowski J., Kranzusch P.J.;
RT "cGAS phase separation inhibits TREX1-mediated DNA degradation and enhances
RT cytosolic DNA sensing.";
RL Mol. Cell 81:739-755(2021).
CC -!- FUNCTION: Major cellular 3'-to-5' DNA exonuclease which digests single-
CC stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3'
CC termini (PubMed:10391904, PubMed:11279105, PubMed:15254239,
CC PubMed:17293595, PubMed:17355961, PubMed:18780819). Prevents cell-
CC intrinsic initiation of autoimmunity (PubMed:18724932,
CC PubMed:24218451). Acts by metabolizing DNA fragments from endogenous
CC retroelements, including L1, LTR and SINE elements (PubMed:18724932).
CC Plays a key role in degradation of DNA fragments at cytosolic
CC micronuclei arising from genome instability: its association with the
CC endoplasmic reticulum membrane directs TREX1 to ruptured micronuclei,
CC leading to micronuclear DNA degradation (By similarity). Micronuclear
CC DNA degradation is required to limit CGAS activation and subsequent
CC inflammation (By similarity). Unless degraded, these DNA fragments
CC accumulate in the cytosol and activate the cGAS-STING innate immune
CC signaling, leading to the production of type I interferon
CC (PubMed:18724932). Prevents chronic ATM-dependent checkpoint
CC activation, by processing ssDNA polynucleotide species arising from the
CC processing of aberrant DNA replication intermediates (PubMed:18045533).
CC Inefficiently degrades oxidized DNA, such as that generated upon
CC antimicrobial reactive oxygen production or upon absorption of UV light
CC (PubMed:23993650). During GZMA-mediated cell death, contributes to DNA
CC damage in concert with NME1 (By similarity). NME1 nicks one strand of
CC DNA and TREX1 removes bases from the free 3' end to enhance DNA damage
CC and prevent DNA end reannealing and rapid repair (By similarity).
CC {ECO:0000250|UniProtKB:Q9NSU2, ECO:0000269|PubMed:10391904,
CC ECO:0000269|PubMed:11279105, ECO:0000269|PubMed:15254239,
CC ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17355961,
CC ECO:0000269|PubMed:18045533, ECO:0000269|PubMed:18724932,
CC ECO:0000269|PubMed:18780819, ECO:0000269|PubMed:23993650,
CC ECO:0000269|PubMed:24218451}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.2;
CC Evidence={ECO:0000269|PubMed:11279105, ECO:0000269|PubMed:15254239,
CC ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17355961,
CC ECO:0000269|PubMed:18780819};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17355961,
CC ECO:0000269|PubMed:18780819, ECO:0000269|PubMed:22071149};
CC Note=Binds 2 Mg(2+) per subunit. The second magnesium ion interacts
CC with only one residue. Substitution with Mn(2+) results in partial
CC activity. {ECO:0000269|PubMed:17293595, ECO:0000269|PubMed:17355961,
CC ECO:0000269|PubMed:18780819, ECO:0000269|PubMed:22071149};
CC -!- ACTIVITY REGULATION: Calcium, lithium and sodium inhibit the
CC exonuclease activity but not the DNA binding.
CC {ECO:0000269|PubMed:18780819}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.0. {ECO:0000269|PubMed:11279105};
CC -!- SUBUNIT: Homodimer (PubMed:17293595, PubMed:17355961, PubMed:22071149).
CC Interacts (via proline-rich region) with TCERG1/CA150 (via the second
CC WW domain) (PubMed:17355961). Component of the SET complex, composed of
CC at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1 (By similarity).
CC Within this complex, directly interacts with SET; this interaction does
CC not result in TREX1 inhibition (By similarity). Also interacts with
CC NME1, but only following translocation to the nucleus (By similarity).
CC Directly interacts with UBQLN1 (via ubiquitin-like domain); the
CC interaction may control TREX1 subcellular location (By similarity).
CC {ECO:0000250|UniProtKB:Q9NSU2, ECO:0000269|PubMed:17293595,
CC ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:22071149}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15254239,
CC ECO:0000269|PubMed:18045533}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18045533}. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:18724932}; Peripheral membrane
CC protein {ECO:0000269|PubMed:18724932}. Note=Retained in the cytoplasm
CC through the C-terminal region (PubMed:18045533). Localization to the
CC endoplasmic reticulum membrane is required to direct TREX1 to ruptured
CC micronuclei (By similarity). In response to DNA damage, translocates to
CC the nucleus where it is specifically recruited to replication foci
CC (PubMed:18045533). Translocation to the nucleus also occurs during
CC GZMA-mediated cell death (PubMed:18045533).
CC {ECO:0000250|UniProtKB:Q9NSU2, ECO:0000269|PubMed:18045533}.
CC -!- TISSUE SPECIFICITY: Widely expressed with high expression levels
CC detected in spleen, thymus and uterus. {ECO:0000269|PubMed:24218451}.
CC -!- INDUCTION: Induced by cytosolic DNA. Induced by inflammatory stimuli in
CC a cell-specific fashion. Up-regulated by IFN-alpha and IFN-gamma in B-
CC cells and by LPS and viral and bacterial DNA (via Toll-like receptor
CC signaling) in dendritic cells and macrophages.
CC {ECO:0000269|PubMed:18724932, ECO:0000269|PubMed:24218451}.
CC -!- PTM: Ubiquitinated, but not targeted to proteasomal degradation.
CC Ubiquitination may be important for interaction with UBQLN1 (By
CC similarity). {ECO:0000250|UniProtKB:Q9NSU2}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals exhibit a dramatically reduced
CC survival after weaning, with 50% of survival at 9 weeks
CC (PubMed:18724932) or 17 weeks (PubMed:15254239). In 6-8 week old
CC animals, multiple organs show extensive inflammation. The most severe
CC diffuse lymphocytic infiltration occurs in the heart, followed by the
CC lung, the liver, the smooth muscle of the uterus and the salivary gland
CC with periductal infiltration. Other tissues exhibit only minimal to
CC mild lymphocytic infiltration (PubMed:24218451). The heart phenotype
CC includes inflammatory myocarditis leading to progressive, often
CC dilated, cardiomyopathy and circulatory failure. Enlargement of the
CC spleen and lymph nodes is observed in less than 10% of old mice (over 1
CC year of age) (PubMed:15254239). Mutant animals have a reduced 3'-
CC exonuclease activity. They accumulate ssDNA from endogenous
CC retroelements and produce high levels of autoantibodies. Do not show an
CC increase in spontaneous mutation frequency or cancer incidence. Double
CC knockout of TREX1 and either IRF3, IFNAR1 or RAG2 fully rescues the
CC TREX1 single knockout phenotype (PubMed:18724932).
CC {ECO:0000269|PubMed:15254239, ECO:0000269|PubMed:18724932,
CC ECO:0000269|PubMed:24218451}.
CC -!- SIMILARITY: Belongs to the exonuclease superfamily. TREX family.
CC {ECO:0000305}.
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DR EMBL; AF151106; AAD48775.2; -; mRNA.
DR EMBL; AF319574; AAK07621.1; -; mRNA.
DR EMBL; AK009899; BAB26571.2; -; mRNA.
DR EMBL; AK087832; BAC40020.1; -; mRNA.
DR EMBL; AK171916; BAE42731.1; -; mRNA.
DR EMBL; BC011133; AAH11133.1; -; mRNA.
DR CCDS; CCDS23544.1; -.
DR RefSeq; NP_001012236.1; NM_001012236.1.
DR RefSeq; NP_035767.4; NM_011637.6.
DR PDB; 2IOC; X-ray; 2.10 A; A/B=1-242.
DR PDB; 2O4G; X-ray; 2.35 A; A/B/C/D=9-245.
DR PDB; 2O4I; X-ray; 3.50 A; A/B=9-245.
DR PDB; 2OA8; X-ray; 2.10 A; A/B=5-234.
DR PDB; 3B6O; X-ray; 2.10 A; A/B/C/D=9-245.
DR PDB; 3B6P; X-ray; 2.30 A; A/B/C/D=9-245.
DR PDB; 3MXI; X-ray; 2.55 A; A/B=1-242.
DR PDB; 3MXJ; X-ray; 1.95 A; A/B=1-242.
DR PDB; 3MXM; X-ray; 1.75 A; A/B=1-242.
DR PDB; 3U3Y; X-ray; 2.28 A; A/B=1-314.
DR PDB; 3U6F; X-ray; 2.30 A; A/B=1-314.
DR PDB; 4YNQ; X-ray; 2.80 A; A/B/C/D=1-235.
DR PDB; 5YWS; X-ray; 2.00 A; A/B=1-242.
DR PDB; 5YWT; X-ray; 1.70 A; A/B=1-242.
DR PDB; 5YWU; X-ray; 3.40 A; A/B=1-242.
DR PDB; 5YWV; X-ray; 2.30 A; A/B=1-242.
DR PDB; 6W10; X-ray; 1.80 A; A/B=1-242.
DR PDBsum; 2IOC; -.
DR PDBsum; 2O4G; -.
DR PDBsum; 2O4I; -.
DR PDBsum; 2OA8; -.
DR PDBsum; 3B6O; -.
DR PDBsum; 3B6P; -.
DR PDBsum; 3MXI; -.
DR PDBsum; 3MXJ; -.
DR PDBsum; 3MXM; -.
DR PDBsum; 3U3Y; -.
DR PDBsum; 3U6F; -.
DR PDBsum; 4YNQ; -.
DR PDBsum; 5YWS; -.
DR PDBsum; 5YWT; -.
DR PDBsum; 5YWU; -.
DR PDBsum; 5YWV; -.
DR PDBsum; 6W10; -.
DR AlphaFoldDB; Q91XB0; -.
DR SMR; Q91XB0; -.
DR BioGRID; 204312; 4.
DR STRING; 10090.ENSMUSP00000050971; -.
DR iPTMnet; Q91XB0; -.
DR PhosphoSitePlus; Q91XB0; -.
DR SwissPalm; Q91XB0; -.
DR EPD; Q91XB0; -.
DR MaxQB; Q91XB0; -.
DR PaxDb; Q91XB0; -.
DR PeptideAtlas; Q91XB0; -.
DR PRIDE; Q91XB0; -.
DR ProteomicsDB; 300118; -.
DR Antibodypedia; 30103; 296 antibodies from 35 providers.
DR DNASU; 22040; -.
DR Ensembl; ENSMUST00000061973; ENSMUSP00000050971; ENSMUSG00000049734.
DR Ensembl; ENSMUST00000112053; ENSMUSP00000107684; ENSMUSG00000049734.
DR GeneID; 22040; -.
DR KEGG; mmu:22040; -.
DR UCSC; uc009rrr.1; mouse.
DR CTD; 11277; -.
DR MGI; MGI:1328317; Trex1.
DR VEuPathDB; HostDB:ENSMUSG00000049734; -.
DR eggNOG; KOG4793; Eukaryota.
DR GeneTree; ENSGT00390000012715; -.
DR HOGENOM; CLU_067419_1_0_1; -.
DR InParanoid; Q91XB0; -.
DR OMA; ICQWRPR; -.
DR OrthoDB; 1365966at2759; -.
DR PhylomeDB; Q91XB0; -.
DR TreeFam; TF323333; -.
DR BioGRID-ORCS; 22040; 3 hits in 108 CRISPR screens.
DR ChiTaRS; Trex1; mouse.
DR EvolutionaryTrace; Q91XB0; -.
DR PRO; PR:Q91XB0; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q91XB0; protein.
DR Bgee; ENSMUSG00000049734; Expressed in lens of camera-type eye and 61 other tissues.
DR Genevisible; Q91XB0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0043596; C:nuclear replication fork; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0008250; C:oligosaccharyltransferase complex; IDA:MGI.
DR GO; GO:0032993; C:protein-DNA complex; IDA:MGI.
DR GO; GO:0008408; F:3'-5' exonuclease activity; IMP:MGI.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0032558; F:adenyl deoxyribonucleotide binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0008301; F:DNA binding, bending; IDA:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MGI.
DR GO; GO:0008853; F:exodeoxyribonuclease III activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MGI.
DR GO; GO:0032405; F:MutLalpha complex binding; ISO:MGI.
DR GO; GO:0032407; F:MutSalpha complex binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:MGI.
DR GO; GO:0050699; F:WW domain binding; IDA:MGI.
DR GO; GO:0002253; P:activation of immune response; IMP:MGI.
DR GO; GO:0002250; P:adaptive immune response; IMP:MGI.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:MGI.
DR GO; GO:0003228; P:atrial cardiac muscle tissue development; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0035781; P:CD86 biosynthetic process; IMP:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0071480; P:cellular response to gamma radiation; IMP:MGI.
DR GO; GO:0072711; P:cellular response to hydroxyurea; IMP:MGI.
DR GO; GO:0035458; P:cellular response to interferon-beta; IDA:MGI.
DR GO; GO:0071310; P:cellular response to organic substance; IMP:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MGI.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:MGI.
DR GO; GO:0071357; P:cellular response to type I interferon; IMP:MGI.
DR GO; GO:0034644; P:cellular response to UV; IDA:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR GO; GO:0006308; P:DNA catabolic process; IDA:MGI.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IBA:GO_Central.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0032508; P:DNA duplex unwinding; IDA:MGI.
DR GO; GO:0006259; P:DNA metabolic process; IDA:UniProtKB.
DR GO; GO:0006304; P:DNA modification; IMP:MGI.
DR GO; GO:0006260; P:DNA replication; IMP:MGI.
DR GO; GO:1904161; P:DNA synthesis involved in UV-damage excision repair; IMP:MGI.
DR GO; GO:0045184; P:establishment of protein localization; IMP:MGI.
DR GO; GO:0006091; P:generation of precursor metabolites and energy; IMP:MGI.
DR GO; GO:0003007; P:heart morphogenesis; IMP:MGI.
DR GO; GO:0003015; P:heart process; IMP:MGI.
DR GO; GO:0097281; P:immune complex formation; IMP:MGI.
DR GO; GO:0006955; P:immune response; IMP:MGI.
DR GO; GO:0002383; P:immune response in brain or nervous system; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0002437; P:inflammatory response to antigenic stimulus; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IMP:MGI.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:MGI.
DR GO; GO:0031571; P:mitotic G1 DNA damage checkpoint signaling; IMP:MGI.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IMP:MGI.
DR GO; GO:0002251; P:organ or tissue specific immune response; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; IDA:MGI.
DR GO; GO:0050790; P:regulation of catalytic activity; IMP:MGI.
DR GO; GO:0043457; P:regulation of cellular respiration; IMP:MGI.
DR GO; GO:0019217; P:regulation of fatty acid metabolic process; IMP:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:0006110; P:regulation of glycolytic process; IMP:MGI.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IMP:MGI.
DR GO; GO:0050727; P:regulation of inflammatory response; IGI:MGI.
DR GO; GO:0045088; P:regulation of innate immune response; IMP:MGI.
DR GO; GO:0046890; P:regulation of lipid biosynthetic process; IGI:MGI.
DR GO; GO:1905671; P:regulation of lysosome organization; IMP:MGI.
DR GO; GO:0061635; P:regulation of protein complex stability; IMP:MGI.
DR GO; GO:0050863; P:regulation of T cell activation; IGI:MGI.
DR GO; GO:0032680; P:regulation of tumor necrosis factor production; IMP:MGI.
DR GO; GO:0032479; P:regulation of type I interferon production; IMP:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0002457; P:T cell antigen processing and presentation; IMP:MGI.
DR GO; GO:0032197; P:transposition, RNA-mediated; IMP:MGI.
DR GO; GO:0060337; P:type I interferon signaling pathway; IMP:MGI.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR040393; TREX1/2.
DR PANTHER; PTHR13058; PTHR13058; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum;
KW Exonuclease; Hydrolase; Magnesium; Membrane; Metal-binding; Nuclease;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..314
FT /note="Three-prime repair exonuclease 1"
FT /id="PRO_0000109869"
FT REGION 236..314
FT /note="Necessary for endoplasmic reticulum localization"
FT /evidence="ECO:0000269|PubMed:18724932"
FT REGION 237..284
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..314
FT /note="Interaction with UBQLN1"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT REGION 281..314
FT /note="Necessary for cytoplasmic retention"
FT /evidence="ECO:0000269|PubMed:18724932"
FT COMPBIAS 237..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 195
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000269|PubMed:17355961"
FT BINDING 18
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 18
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 20..21
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:17355961, ECO:0000269|PubMed:18780819,
FT ECO:0000269|PubMed:22071149"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT MUTAGEN 114
FT /note="R->H: Reduces activity. Loss of endogenous
FT retroelement metabolization."
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:18724932"
FT MUTAGEN 124
FT /note="H->A: Strongly reduces activity."
FT /evidence="ECO:0000269|PubMed:18780819"
FT MUTAGEN 195
FT /note="H->A: Loss of activity. Loss of endogenous
FT retroelement metabolization."
FT /evidence="ECO:0000269|PubMed:17355961,
FT ECO:0000269|PubMed:18724932, ECO:0000269|PubMed:18780819"
FT MUTAGEN 198
FT /note="E->K: Impaired ability to associate with CGAS-DNA
FT droplets."
FT /evidence="ECO:0000269|PubMed:33606975"
FT MUTAGEN 200
FT /note="D->N: Reduces activity. Loss of endogenous
FT retroelement metabolization."
FT /evidence="ECO:0000269|PubMed:18724932"
FT MUTAGEN 201
FT /note="V->D: Reduces activity. Loss of endogenous
FT retroelement metabolization."
FT /evidence="ECO:0000269|PubMed:17293595,
FT ECO:0000269|PubMed:18724932"
FT CONFLICT 53
FT /note="H -> L (in Ref. 3; AAH11133)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="R -> G (in Ref. 3; AAH11133)"
FT /evidence="ECO:0000305"
FT STRAND 13..23
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 25..27
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 31..40
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 41..45
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 79..85
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 89..94
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 102..113
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:5YWT"
FT TURN 124..129
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 130..140
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:5YWT"
FT TURN 146..149
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 155..163
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 179..187
FT /evidence="ECO:0007829|PDB:5YWT"
FT TURN 192..195
FT /evidence="ECO:0007829|PDB:6W10"
FT HELIX 197..208
FT /evidence="ECO:0007829|PDB:5YWT"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:5YWU"
FT HELIX 212..222
FT /evidence="ECO:0007829|PDB:5YWT"
FT HELIX 226..228
FT /evidence="ECO:0007829|PDB:5YWT"
SQ SEQUENCE 314 AA; 33675 MW; 52C4F63A23214A7F CRC64;
MGSQTLPHGH MQTLIFLDLE ATGLPSSRPE VTELCLLAVH RRALENTSIS QGHPPPVPRP
PRVVDKLSLC IAPGKACSPG ASEITGLSKA ELEVQGRQRF DDNLAILLRA FLQRQPQPCC
LVAHNGDRYD FPLLQTELAR LSTPSPLDGT FCVDSIAALK ALEQASSPSG NGSRKSYSLG
SIYTRLYWQA PTDSHTAEGD VLTLLSICQW KPQALLQWVD EHARPFSTVK PMYGTPATTG
TTNLRPHAAT ATTPLATANG SPSNGRSRRP KSPPPEKVPE APSQEGLLAP LSLLTLLTLA
IATLYGLFLA SPGQ
