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Protein

Three-prime repair exonuclease 1

Gene

Trex1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Major cellular 3'-to-5' DNA exonuclease which digests single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3' termini. Prevents cell-intrinsic initiation of autoimmunity. Acts by metabolizing DNA fragments from endogenous retroelements, including L1, LTR and SINE elements. Unless degraded, these DNA fragments accumulate in the cytosol and activate the IFN-stimulatory DNA (ISD) response and innate immune signaling. Prevents chronic ATM-dependent checkpoint activation, by processing ssDNA polynucleotide species arising from the processing of aberrant DNA replication intermediates. Inefficiently degrades oxidized DNA, such as that generated upon antimicrobial reactive oxygen production or upon absorption of UV light. During GZMA-mediated cell death, contributes to DNA damage in concert with NME1. 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.10 Publications

Catalytic activityi

Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.3 Publications

Cofactori

Mg2+4 PublicationsNote: Binds 2 Mg2+ per subunit. The second magnesium ion interacts with only one residue. Substitution with Mn2+ results in partial activity.4 Publications

Enzyme regulationi

Calcium, lithium and sodium inhibit the exonuclease activity but not the DNA binding.1 Publication

pH dependencei

Optimum pH is 7.5-8.0.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi18Magnesium 11
Metal bindingi18Magnesium 21
Metal bindingi20Magnesium 11
Binding sitei129Substrate1
Active sitei195Proton donor/acceptor1 Publication1
Metal bindingi200Magnesium 11
Binding sitei200Substrate1

GO - Molecular functioni

  • 3'-5'-exodeoxyribonuclease activity Source: UniProtKB
  • 3'-5' exonuclease activity Source: UniProtKB
  • adenyl deoxyribonucleotide binding Source: MGI
  • double-stranded DNA binding Source: MGI
  • exodeoxyribonuclease III activity Source: UniProtKB-EC
  • metal ion binding Source: UniProtKB-KW
  • MutLalpha complex binding Source: MGI
  • MutSalpha complex binding Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • single-stranded DNA binding Source: MGI

GO - Biological processi

  • cellular response to interferon-beta Source: MGI
  • DNA metabolic process Source: UniProtKB

Keywordsi

Molecular functionExonuclease, Hydrolase, Nuclease
LigandMagnesium, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Three-prime repair exonuclease 1By similarity (EC:3.1.11.2)
Alternative name(s):
3'-5' exonuclease TREX11 Publication
Gene namesi
Name:Trex1Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 9

Organism-specific databases

MGIiMGI:1328317 Trex1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant animals exhibit a dramatically reduced survival after weaning, with 50% of survival at 9 weeks (PubMed:18724932) or 17 weeks (PubMed:15254239). In 6-8 week old animals, multiple organs show extensive inflammation. The most severe diffuse lymphocytic infiltration occurs in the heart, followed by the lung, the liver, the smooth muscle of the uterus and the salivary gland with periductal infiltration. Other tissues exhibit only minimal to mild lymphocytic infiltration (PubMed:24218451). The heart phenotype includes inflammatory myocarditis leading to progressive, often dilated, cardiomyopathy and circulatory failure. Enlargement of the spleen and lymph nodes is observed in less than 10% of old mice (over 1 year of age) (PubMed:15254239). Mutant animals have a reduced 3'-exonuclease activity. They accumulate ssDNA from endogenous retroelements and produce high levels of autoantibodies. Do not show an increase in spontaneous mutation frequency or cancer incidence. Double knockout of TREX1 and either IRF3, IFNAR1 or RAG2 fully rescues the TREX1 single knockout phenotype (PubMed:18724932).3 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi114R → H: Reduces activity. Loss of endogenous retroelement metabolization. 2 Publications1
Mutagenesisi124H → A: Strongly reduces activity. 1 Publication1
Mutagenesisi195H → A: Loss of activity. Loss of endogenous retroelement metabolization. 3 Publications1
Mutagenesisi200D → N: Reduces activity. Loss of endogenous retroelement metabolization. 1 Publication1
Mutagenesisi201V → D: Reduces activity. Loss of endogenous retroelement metabolization. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001098691 – 314Three-prime repair exonuclease 1Add BLAST314

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei78PhosphoserineBy similarity1
Modified residuei167PhosphoserineBy similarity1
Modified residuei261PhosphoserineBy similarity1

Post-translational modificationi

Ubiquitinated, but not targeted to proteasomal degradation. Ubiquitination may be important for interaction with UBQLN1 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ91XB0
MaxQBiQ91XB0
PaxDbiQ91XB0
PeptideAtlasiQ91XB0
PRIDEiQ91XB0

PTM databases

iPTMnetiQ91XB0
PhosphoSitePlusiQ91XB0
SwissPalmiQ91XB0

Expressioni

Tissue specificityi

Widely expressed with high expression levels detected in spleen, thymus and uterus.1 Publication

Inductioni

Induced by cytosolic DNA. Induced by inflammatory stimuli in a cell-specific fashion. Up-regulated by IFN-alpha and IFN-gamma in B-cells and by LPS and viral and bacterial DNA (via Toll-like receptor signaling) in dendritic cells and macrophages.2 Publications

Gene expression databases

BgeeiENSMUSG00000049734
CleanExiMM_TREX1
GenevisibleiQ91XB0 MM

Interactioni

Subunit structurei

Homodimer. Interacts (via proline-rich region) with TCERG1/CA150 (via the second WW domain). Component of the SET complex, composed of at least ANP32A, APEX1, HMGB2, NME1, SET and TREX1. Within this complex, directly interacts with SET; this interaction does not result in TREX1 inhibition. Also interacts with NME1, but only following translocation to the nucleus. Directly interacts with UBQLN1 (via ubiquitin-like domain); the interaction may control TREX1 subcellular location.3 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi204312, 1 interactor
STRINGi10090.ENSMUSP00000050971

Structurei

Secondary structure

1314
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi12 – 23Combined sources12
Helixi25 – 27Combined sources3
Beta strandi31 – 40Combined sources10
Helixi41 – 45Combined sources5
Beta strandi52 – 54Combined sources3
Beta strandi65 – 70Combined sources6
Helixi79 – 85Combined sources7
Helixi89 – 94Combined sources6
Helixi102 – 113Combined sources12
Beta strandi117 – 123Combined sources7
Turni124 – 129Combined sources6
Helixi130 – 139Combined sources10
Beta strandi141 – 143Combined sources3
Turni146 – 149Combined sources4
Beta strandi151 – 154Combined sources4
Helixi155 – 166Combined sources12
Helixi179 – 187Combined sources9
Beta strandi194 – 196Combined sources3
Helixi197 – 208Combined sources12
Helixi212 – 222Combined sources11
Helixi226 – 228Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2IOCX-ray2.10A/B1-242[»]
2O4GX-ray2.35A/B/C/D9-245[»]
2O4IX-ray3.50A/B9-245[»]
2OA8X-ray2.10A/B5-234[»]
3B6OX-ray2.10A/B/C/D9-245[»]
3B6PX-ray2.30A/B/C/D9-245[»]
3MXIX-ray2.55A/B1-242[»]
3MXJX-ray1.95A/B1-242[»]
3MXMX-ray1.75A/B1-242[»]
3U3YX-ray2.28A/B1-314[»]
3U6FX-ray2.30A/B1-314[»]
4YNQX-ray2.80A/B/C/D1-235[»]
ProteinModelPortaliQ91XB0
SMRiQ91XB0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ91XB0

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni20 – 21Substrate binding2
Regioni54 – 63Proline-rich region10
Regioni236 – 314Necessary for endoplasmic reticulum localizationAdd BLAST79
Regioni244 – 314Interaction with UBQLN1By similarityAdd BLAST71
Regioni281 – 314Necessary for cytoplasmic retentionAdd BLAST34

Sequence similaritiesi

Belongs to the exonuclease superfamily. TREX family.Curated

Phylogenomic databases

eggNOGiKOG4793 Eukaryota
ENOG4111YSP LUCA
GeneTreeiENSGT00390000012715
HOGENOMiHOG000118119
HOVERGENiHBG079278
InParanoidiQ91XB0
KOiK10790
OMAiLLSICQW
OrthoDBiEOG091G0LSM
PhylomeDBiQ91XB0
TreeFamiTF323333

Family and domain databases

Gene3Di3.30.420.10, 1 hit
InterProiView protein in InterPro
IPR013520 Exonuclease_RNaseT/DNA_pol3
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
SMARTiView protein in SMART
SM00479 EXOIII, 1 hit
SUPFAMiSSF53098 SSF53098, 1 hit

Sequencei

Sequence statusi: Complete.

Q91XB0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSQTLPHGH MQTLIFLDLE ATGLPSSRPE VTELCLLAVH RRALENTSIS
60 70 80 90 100
QGHPPPVPRP PRVVDKLSLC IAPGKACSPG ASEITGLSKA ELEVQGRQRF
110 120 130 140 150
DDNLAILLRA FLQRQPQPCC LVAHNGDRYD FPLLQTELAR LSTPSPLDGT
160 170 180 190 200
FCVDSIAALK ALEQASSPSG NGSRKSYSLG SIYTRLYWQA PTDSHTAEGD
210 220 230 240 250
VLTLLSICQW KPQALLQWVD EHARPFSTVK PMYGTPATTG TTNLRPHAAT
260 270 280 290 300
ATTPLATANG SPSNGRSRRP KSPPPEKVPE APSQEGLLAP LSLLTLLTLA
310
IATLYGLFLA SPGQ
Length:314
Mass (Da):33,675
Last modified:May 24, 2004 - v2
Checksum:i52C4F63A23214A7F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti53H → L in AAH11133 (PubMed:15489334).Curated1
Sequence conflicti269R → G in AAH11133 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF151106 mRNA Translation: AAD48775.2
AF319574 mRNA Translation: AAK07621.1
AK009899 mRNA Translation: BAB26571.2
AK087832 mRNA Translation: BAC40020.1
AK171916 mRNA Translation: BAE42731.1
BC011133 mRNA Translation: AAH11133.1
CCDSiCCDS23544.1
RefSeqiNP_001012236.1, NM_001012236.1
NP_035767.4, NM_011637.6
UniGeneiMm.439964

Genome annotation databases

EnsembliENSMUST00000061973; ENSMUSP00000050971; ENSMUSG00000049734
ENSMUST00000112053; ENSMUSP00000107684; ENSMUSG00000049734
GeneIDi22040
KEGGimmu:22040
UCSCiuc009rrr.1 mouse

Similar proteinsi

Entry informationi

Entry nameiTREX1_MOUSE
AccessioniPrimary (citable) accession number: Q91XB0
Secondary accession number(s): Q3TAD7, Q9D6W2, Q9R1B0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 24, 2004
Last modified: May 23, 2018
This is version 133 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

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