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Q9NSU2

- TREX1_HUMAN

UniProt

Q9NSU2 - TREX1_HUMAN

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Protein

Three-prime repair exonuclease 1

Gene

TREX1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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.6 Publications

Catalytic activityi

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

Cofactori

Mg2+By similarityNote: Binds 2 Mg(2+) per subunit. The second magnesium ion interacts with only one residue. Substitution with Mn(2+) results in partial activity.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi73 – 731Magnesium 1By similarity
Metal bindingi73 – 731Magnesium 2By similarity
Metal bindingi75 – 751Magnesium 1By similarity
Binding sitei184 – 1841SubstrateBy similarity
Active sitei250 – 2501Proton donor/acceptorBy similarity
Metal bindingi255 – 2551Magnesium 1By similarity
Binding sitei255 – 2551SubstrateBy similarity

GO - Molecular functioni

  1. 3'-5'-exodeoxyribonuclease activity Source: UniProtKB
  2. 3'-5' exonuclease activity Source: UniProtKB
  3. adenyl deoxyribonucleotide binding Source: Ensembl
  4. double-stranded DNA binding Source: Ensembl
  5. exodeoxyribonuclease III activity Source: UniProtKB-EC
  6. metal ion binding Source: UniProtKB
  7. MutLalpha complex binding Source: MGI
  8. MutSalpha complex binding Source: MGI
  9. protein homodimerization activity Source: UniProtKB
  10. single-stranded DNA binding Source: UniProtKB

GO - Biological processi

  1. cell death Source: UniProtKB-KW
  2. cellular response to interferon-beta Source: Ensembl
  3. DNA catabolic process, exonucleolytic Source: GOC
  4. DNA metabolic process Source: UniProtKB
  5. DNA recombination Source: UniProtKB
  6. DNA repair Source: ProtInc
  7. DNA replication Source: UniProtKB
  8. innate immune response Source: Reactome
  9. mismatch repair Source: UniProtKB
  10. nucleic acid phosphodiester bond hydrolysis Source: GOC
  11. positive regulation of type I interferon production Source: Reactome
  12. regulation of type I interferon production Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_163652. Regulation by TREX1.
REACT_163993. IRF3-mediated induction of type I IFN.

Names & Taxonomyi

Protein namesi
Recommended name:
Three-prime repair exonuclease 1 (EC:3.1.11.2)
Alternative name(s):
3'-5' exonuclease TREX1
DNase III
Gene namesi
Name:TREX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:12269. TREX1.

Subcellular locationi

Nucleus. Cytoplasmcytosol. Endoplasmic reticulum membrane; Peripheral membrane protein
Note: Retained in the cytoplasm through the C-terminal region (By similarity). In response to DNA damage, translocates to the nucleus where it is specifically recruited to replication foci. Translocation to the nucleus also occurs during GZMA-mediated cell death.By similarity

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
  2. nuclear envelope Source: UniProtKB
  3. nucleolus Source: HPA
  4. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

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.5 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731D → N in CHBL1 and AGS1; loss of function. 2 Publications
VAR_037948
Natural varianti169 – 1691R → H in AGS1 and SLE; strongly reduces activity; produces a defective G1/S transition and chronic G2/M DNA damage checkpoint activation. 4 Publications
VAR_028319
Natural varianti177 – 1771V → A in AGS1; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_070899
Natural varianti253 – 2531E → K in AGS1; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_070900
Natural varianti255 – 2551D → DD in AGS1; heterozygous compound with H-169; loss of activity. 1 Publication
VAR_028320
Natural varianti255 – 2551D → H in AGS1 and SLE. 1 Publication
VAR_070901
Natural varianti255 – 2551D → N in AGS1; autosomal dominant form; no effect on dsDNA exonuclease activity; abolishes ssDNA exonuclease activity. 2 Publications
VAR_032940
Natural varianti256 – 2561V → D in AGS1; reduces activity by 75%. 2 Publications
VAR_028321
Natural varianti358 – 3581T → P in AGS1; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. 1 Publication
VAR_070902
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.2 Publications
Note: Disease susceptibility is associated with variations 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).1 Publication
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti169 – 1691R → H in AGS1 and SLE; strongly reduces activity; produces a defective G1/S transition and chronic G2/M DNA damage checkpoint activation. 4 Publications
VAR_028319
Natural varianti213 – 2131A → V in SLE. 1 Publication
VAR_037949
Natural varianti255 – 2551D → H in AGS1 and SLE. 1 Publication
VAR_070901
Natural varianti282 – 2821G → S in SLE; associated in cis with P-302. 1 Publication
Corresponds to variant rs113107733 [ dbSNP | Ensembl ].
VAR_037950
Natural varianti295 – 2951R → S in SLE. 1 Publication
Corresponds to variant rs72556555 [ dbSNP | Ensembl ].
VAR_037951
Natural varianti302 – 3021A → P in SLE; associated in cis with S-282. 1 Publication
Corresponds to variant rs112741962 [ dbSNP | Ensembl ].
VAR_037952
Natural varianti345 – 3451P → L in SLE; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_037954
Natural varianti360 – 3601Y → C in SLE; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. 1 Publication
VAR_037955
Natural varianti361 – 3611G → A in SLE. 1 Publication
VAR_037956
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 at temperatures less than 10 degrees centigrade.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731D → N in CHBL1 and AGS1; loss of function. 2 Publications
VAR_037948
Vasculopathy, retinal, with cerebral leukodystrophy (RVCL) [MIM:192315]: A microvascular endotheliopathy resulting 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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi85 – 851K → R: Reduces ubiquitination. 1 Publication
Mutagenesisi121 – 1211K → R: No effect on ubiquitination. 1 Publication
Mutagenesisi130 – 1301K → R: Reduces ubiquitination. 1 Publication
Mutagenesisi215 – 2151K → R: Reduces ubiquitination. 1 Publication
Mutagenesisi230 – 2301K → R: Reduces ubiquitination. 1 Publication
Mutagenesisi297 – 2971K → R: Reduces ubiquitination. 1 Publication
Mutagenesisi326 – 3261K → R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-332. 1 Publication
Mutagenesisi332 – 3321K → R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-326. 1 Publication

Keywords - Diseasei

Aicardi-Goutieres syndrome, Disease mutation, Neurodegeneration, Systemic lupus erythematosus

Organism-specific databases

MIMi152700. phenotype.
192315. phenotype.
225750. phenotype.
610448. phenotype.
Orphaneti51. Aicardi-Goutieres syndrome.
3421. Cerebroretinal vasculopathy.
90280. Chilblain lupus.
71291. Hereditary vascular retinopathy.
63261. HERNS syndrome.
536. Systemic lupus erythematosus.
PharmGKBiPA36949.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 369369Three-prime repair exonuclease 1PRO_0000109868Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei133 – 1331Phosphoserine1 Publication
Modified residuei316 – 3161Phosphoserine1 Publication

Post-translational modificationi

Ubiquitinated, but not targeted to proteasomal degradation. Ubiquitination may be important for interaction with UBQLN1.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9NSU2.
PaxDbiQ9NSU2.
PRIDEiQ9NSU2.

PTM databases

PhosphoSiteiQ9NSU2.

Expressioni

Tissue specificityi

Detected in thymus, spleen, liver, brain, heart, small intestine and colon.2 Publications

Inductioni

Induced by cytosolic DNA. Induced by inflammatory stimuli such as IFN-alpha and IFN-gamma in B cells and also by LPS and viral and bacterial DNA (via TLR9) in dendritic cells and macrophages (By similarity).By similarity

Gene expression databases

BgeeiQ9NSU2.
CleanExiHS_TREX1.
ExpressionAtlasiQ9NSU2. baseline.
GenevestigatoriQ9NSU2.

Organism-specific databases

HPAiHPA035437.

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.2 Publications

Protein-protein interaction databases

BioGridi116433. 5 interactions.
MINTiMINT-1466830.
STRINGi9606.ENSP00000379035.

Structurei

3D structure databases

ProteinModelPortaliQ9NSU2.
SMRiQ9NSU2. Positions 61-289.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni75 – 762Substrate bindingBy similarity
Regioni109 – 11810Proline-rich regionBy similarity
Regioni291 – 36979Necessary for endoplasmic reticulum localizationBy similarityAdd
BLAST
Regioni298 – 36972Interaction with UBQLN1Add
BLAST
Regioni336 – 36934Necessary for cytoplasmic retentionBy similarityAdd
BLAST

Sequence similaritiesi

Belongs to the exonuclease superfamily. TREX family.Curated

Phylogenomic databases

eggNOGiNOG293314.
GeneTreeiENSGT00390000012715.
ENSGT00390000012850.
HOGENOMiHOG000118119.
HOVERGENiHBG079278.
InParanoidiQ9NSU2.
KOiK10790.
OMAiHNGDRYD.
OrthoDBiEOG7DC26B.
PhylomeDBiQ9NSU2.
TreeFamiTF323333.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR012337. RNaseH-like_dom.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9NSU2-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGPGARRQGR IVQGRPEMCF CPPPTPLPPL RILTLGTHTP TPCSSPGSAA
60 70 80 90 100
GTYPTMGSQA LPPGPMQTLI FFDMEATGLP FSQPKVTELC LLAVHRCALE
110 120 130 140 150
SPPTSQGPPP TVPPPPRVVD KLSLCVAPGK ACSPAASEIT GLSTAVLAAH
160 170 180 190 200
GRQCFDDNLA NLLLAFLRRQ PQPWCLVAHN GDRYDFPLLQ AELAMLGLTS
210 220 230 240 250
ALDGAFCVDS ITALKALERA SSPSEHGPRK SYSLGSIYTR LYGQSPPDSH
260 270 280 290 300
TAEGDVLALL SICQWRPQAL LRWVDAHARP FGTIRPMYGV TASARTKPRP
310 320 330 340 350
SAVTTTAHLA TTRNTSPSLG ESRGTKDLPP VKDPGALSRE GLLAPLGLLA
360
ILTLAVATLY GLSLATPGE
Length:369
Mass (Da):38,923
Last modified:October 1, 2000 - v1
Checksum:i42B79047A9AD9837
GO
Isoform 2 (identifier: Q9NSU2-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.

Show »
Length:304
Mass (Da):32,276
Checksum:i922048DCC4122124
GO
Isoform 3 (identifier: Q9NSU2-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-55: Missing.

Show »
Length:314
Mass (Da):33,212
Checksum:iEE8F63B6496D72F4
GO

Sequence cautioni

The sequence AAD48774.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti320 – 3201G → R in CAB50866. (PubMed:10393201)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti73 – 731D → N in CHBL1 and AGS1; loss of function. 2 Publications
VAR_037948
Natural varianti169 – 1691R → H in AGS1 and SLE; strongly reduces activity; produces a defective G1/S transition and chronic G2/M DNA damage checkpoint activation. 4 Publications
VAR_028319
Natural varianti177 – 1771V → A in AGS1; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_070899
Natural varianti213 – 2131A → V in SLE. 1 Publication
VAR_037949
Natural varianti253 – 2531E → K in AGS1; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_070900
Natural varianti255 – 2551D → DD in AGS1; heterozygous compound with H-169; loss of activity. 1 Publication
VAR_028320
Natural varianti255 – 2551D → H in AGS1 and SLE. 1 Publication
VAR_070901
Natural varianti255 – 2551D → N in AGS1; autosomal dominant form; no effect on dsDNA exonuclease activity; abolishes ssDNA exonuclease activity. 2 Publications
VAR_032940
Natural varianti256 – 2561V → D in AGS1; reduces activity by 75%. 2 Publications
VAR_028321
Natural varianti282 – 2821G → S in SLE; associated in cis with P-302. 1 Publication
Corresponds to variant rs113107733 [ dbSNP | Ensembl ].
VAR_037950
Natural varianti295 – 2951R → S in SLE. 1 Publication
Corresponds to variant rs72556555 [ dbSNP | Ensembl ].
VAR_037951
Natural varianti302 – 3021A → P in SLE; associated in cis with S-282. 1 Publication
Corresponds to variant rs112741962 [ dbSNP | Ensembl ].
VAR_037952
Natural varianti321 – 3211E → G.1 Publication
Corresponds to variant rs55999987 [ dbSNP | Ensembl ].
VAR_037953
Natural varianti345 – 3451P → L in SLE; increases ubiquitination levels; no effect on exonuclease activity. 1 Publication
VAR_037954
Natural varianti358 – 3581T → P in AGS1; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. 1 Publication
VAR_070902
Natural varianti360 – 3601Y → C in SLE; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. 1 Publication
VAR_037955
Natural varianti361 – 3611G → A in SLE. 1 Publication
VAR_037956

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6565Missing in isoform 2. 1 PublicationVSP_010445Add
BLAST
Alternative sequencei1 – 5555Missing in isoform 3. 1 PublicationVSP_010446Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ243797 mRNA. Translation: CAB50866.1.
AF319566 mRNA. Translation: AAK07613.1.
AF319567 mRNA. Translation: AAK07614.1.
AF319568 mRNA. Translation: AAK07615.1.
AF319569 mRNA. Translation: AAK07616.1.
AF151105 mRNA. Translation: AAD48774.2. Different initiation.
AK315196 mRNA. Translation: BAG37636.1.
AL137745 mRNA. No translation available.
AF483777 Genomic DNA. Translation: AAL82504.1.
BC023630 mRNA. Translation: AAH23630.1.
CCDSiCCDS2769.1. [Q9NSU2-3]
CCDS59451.1. [Q9NSU2-2]
PIRiT46299.
RefSeqiNP_009179.2. NM_007248.3. [Q9NSU2-2]
NP_057465.1. NM_016381.5. [Q9NSU2-1]
NP_338599.1. NM_033629.4. [Q9NSU2-3]
UniGeneiHs.707026.
Hs.713742.
Hs.744646.

Genome annotation databases

EnsembliENST00000296443; ENSP00000296443; ENSG00000213689. [Q9NSU2-3]
ENST00000444177; ENSP00000415972; ENSG00000213689. [Q9NSU2-2]
GeneIDi11277.
KEGGihsa:11277.
UCSCiuc003ctj.3. human. [Q9NSU2-1]

Polymorphism databases

DMDMi47606216.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ243797 mRNA. Translation: CAB50866.1 .
AF319566 mRNA. Translation: AAK07613.1 .
AF319567 mRNA. Translation: AAK07614.1 .
AF319568 mRNA. Translation: AAK07615.1 .
AF319569 mRNA. Translation: AAK07616.1 .
AF151105 mRNA. Translation: AAD48774.2 . Different initiation.
AK315196 mRNA. Translation: BAG37636.1 .
AL137745 mRNA. No translation available.
AF483777 Genomic DNA. Translation: AAL82504.1 .
BC023630 mRNA. Translation: AAH23630.1 .
CCDSi CCDS2769.1. [Q9NSU2-3 ]
CCDS59451.1. [Q9NSU2-2 ]
PIRi T46299.
RefSeqi NP_009179.2. NM_007248.3. [Q9NSU2-2 ]
NP_057465.1. NM_016381.5. [Q9NSU2-1 ]
NP_338599.1. NM_033629.4. [Q9NSU2-3 ]
UniGenei Hs.707026.
Hs.713742.
Hs.744646.

3D structure databases

ProteinModelPortali Q9NSU2.
SMRi Q9NSU2. Positions 61-289.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 116433. 5 interactions.
MINTi MINT-1466830.
STRINGi 9606.ENSP00000379035.

PTM databases

PhosphoSitei Q9NSU2.

Polymorphism databases

DMDMi 47606216.

Proteomic databases

MaxQBi Q9NSU2.
PaxDbi Q9NSU2.
PRIDEi Q9NSU2.

Protocols and materials databases

DNASUi 11277.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296443 ; ENSP00000296443 ; ENSG00000213689 . [Q9NSU2-3 ]
ENST00000444177 ; ENSP00000415972 ; ENSG00000213689 . [Q9NSU2-2 ]
GeneIDi 11277.
KEGGi hsa:11277.
UCSCi uc003ctj.3. human. [Q9NSU2-1 ]

Organism-specific databases

CTDi 11277.
GeneCardsi GC03P048506.
GeneReviewsi TREX1.
HGNCi HGNC:12269. TREX1.
HPAi HPA035437.
MIMi 152700. phenotype.
192315. phenotype.
225750. phenotype.
606609. gene.
610448. phenotype.
neXtProti NX_Q9NSU2.
Orphaneti 51. Aicardi-Goutieres syndrome.
3421. Cerebroretinal vasculopathy.
90280. Chilblain lupus.
71291. Hereditary vascular retinopathy.
63261. HERNS syndrome.
536. Systemic lupus erythematosus.
PharmGKBi PA36949.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG293314.
GeneTreei ENSGT00390000012715.
ENSGT00390000012850.
HOGENOMi HOG000118119.
HOVERGENi HBG079278.
InParanoidi Q9NSU2.
KOi K10790.
OMAi HNGDRYD.
OrthoDBi EOG7DC26B.
PhylomeDBi Q9NSU2.
TreeFami TF323333.

Enzyme and pathway databases

Reactomei REACT_163652. Regulation by TREX1.
REACT_163993. IRF3-mediated induction of type I IFN.

Miscellaneous databases

ChiTaRSi TREX1. human.
GeneWikii TREX1.
GenomeRNAii 11277.
NextBioi 42927.
PROi Q9NSU2.
SOURCEi Search...

Gene expression databases

Bgeei Q9NSU2.
CleanExi HS_TREX1.
ExpressionAtlasi Q9NSU2. baseline.
Genevestigatori Q9NSU2.

Family and domain databases

Gene3Di 3.30.420.10. 1 hit.
InterProi IPR012337. RNaseH-like_dom.
[Graphical view ]
SUPFAMi SSF53098. SSF53098. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A human DNA editing enzyme homologous to the Escherichia coli DnaQ/MutD protein."
    Hoess M., Robins P., Naven T.J.P., Pappin D.J.C., Sgouros J., Lindahl T.
    EMBO J. 18:3868-3875(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  2. "Identification and expression of the TREX1 and TREX2 cDNA sequences encoding mammalian 3'-->5' exonucleases."
    Mazur D.J., Perrino F.W.
    J. Biol. Chem. 274:19655-19660(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), FUNCTION.
  3. "Structure and expression of the TREX1 and TREX2 3'-->5' exonuclease genes."
    Mazur D.J., Perrino F.W.
    J. Biol. Chem. 276:14718-14727(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Thymus.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Testis.
  6. NIEHS SNPs program
    Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Eye.
  8. "The exonuclease TREX1 is in the SET complex and acts in concert with NM23-H1 to degrade DNA during granzyme A-mediated cell death."
    Chowdhury D., Beresford P.J., Zhu P., Zhang D., Sung J.S., Demple B., Perrino F.W., Lieberman J.
    Mol. Cell 23:133-142(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL DEATH, IDENTIFICATION IN THE SET COMPLEX, INTERACTION WITH NME1 AND SET, SUBCELLULAR LOCATION.
  9. "Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease."
    Yang Y.G., Lindahl T., Barnes D.E.
    Cell 131:873-886(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL CYCLE REGULATION, CHARACTERIZATION OF VARIANT AGS1 HIS-169.
  10. "The crystal structure of TREX1 explains the 3' nucleotide specificity and reveals a polyproline II helix for protein partnering."
    de Silva U., Choudhury S., Bailey S.L., Harvey S., Perrino F.W., Hollis T.
    J. Biol. Chem. 282:10537-10543(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS AGS1 HIS-169; ASP-255 INS AND ASP-256.
  11. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-133 AND SER-316, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  12. "Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing."
    Gehrke N., Mertens C., Zillinger T., Wenzel J., Bald T., Zahn S., Tueting T., Hartmann G., Barchet W.
    Immunity 39:482-495(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN OXIDIZED DNA DEGRADATION, POTENTIAL ROLE IN SLE SKIN LESIONS.
  13. "The TREX1 C-terminal region controls cellular localization through ubiquitination."
    Orebaugh C.D., Fye J.M., Harvey S., Hollis T., Wilkinson J.C., Perrino F.W.
    J. Biol. Chem. 288:28881-28892(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UBQLN1, UBIQUITINATION, CHARACTERIZATION OF VARIANTS AGS1 ALA-177; LYS-253; ASN-255 AND PRO-358, CHARACTERIZATION OF VARIANTS SLE LEU-345 AND CYS-360, MUTAGENESIS OF LYS-85; LYS-121; LYS-130; LYS-215; LYS-230; LYS-297; LYS-326 AND LYS-332.
  14. Cited for: VARIANTS AGS1 HIS-169; ASP-255 INS AND ASP-256.
  15. "Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome."
    Rice G., Newman W.G., Dean J., Patrick T., Parmar R., Flintoff K., Robins P., Harvey S., Hollis T., O'Hara A., Herrick A.L., Bowden A.P., Perrino F.W., Lindahl T., Barnes D.E., Crow Y.J.
    Am. J. Hum. Genet. 80:811-815(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CHBL1, VARIANT AGS1 ASN-255, CHARACTERIZATION OF VARIANT AGS1 ASN-255.
  16. "Clinical and molecular phenotype of Aicardi-Goutieres syndrome."
    Rice G., Patrick T., Parmar R., Taylor C.F., Aeby A., Aicardi J., Artuch R., Montalto S.A., Bacino C.A., Barroso B., Baxter P., Benko W.S., Bergmann C., Bertini E., Biancheri R., Blair E.M., Blau N., Bonthron D.T.
    , Briggs T., Brueton L.A., Brunner H.G., Burke C.J., Carr I.M., Carvalho D.R., Chandler K.E., Christen H.J., Corry P.C., Cowan F.M., Cox H., D'Arrigo S., Dean J., De Laet C., De Praeter C., Dery C., Ferrie C.D., Flintoff K., Frints S.G., Garcia-Cazorla A., Gener B., Goizet C., Goutieres F., Green A.J., Guet A., Hamel B.C., Hayward B.E., Heiberg A., Hennekam R.C., Husson M., Jackson A.P., Jayatunga R., Jiang Y.H., Kant S.G., Kao A., King M.D., Kingston H.M., Klepper J., van der Knaap M.S., Kornberg A.J., Kotzot D., Kratzer W., Lacombe D., Lagae L., Landrieu P.G., Lanzi G., Leitch A., Lim M.J., Livingston J.H., Lourenco C.M., Lyall E.G., Lynch S.A., Lyons M.J., Marom D., McClure J.P., McWilliam R., Melancon S.B., Mewasingh L.D., Moutard M.L., Nischal K.K., Ostergaard J.R., Prendiville J., Rasmussen M., Rogers R.C., Roland D., Rosser E.M., Rostasy K., Roubertie A., Sanchis A., Schiffmann R., Scholl-Burgi S., Seal S., Shalev S.A., Corcoles C.S., Sinha G.P., Soler D., Spiegel R., Stephenson J.B., Tacke U., Tan T.Y., Till M., Tolmie J.L., Tomlin P., Vagnarelli F., Valente E.M., Van Coster R.N., Van der Aa N., Vanderver A., Vles J.S., Voit T., Wassmer E., Weschke B., Whiteford M.L., Willemsen M.A., Zankl A., Zuberi S.M., Orcesi S., Fazzi E., Lebon P., Crow Y.J.
    Am. J. Hum. Genet. 81:713-725(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS AGS1 HIS-169; ALA-177; ASN-255; ASP-256 AND PRO-358.
  17. "A mutation in TREX1 that impairs susceptibility to granzyme A-mediated cell death underlies familial chilblain lupus."
    Lee-Kirsch M.A., Chowdhury D., Harvey S., Gong M., Senenko L., Engel K., Pfeiffer C., Hollis T., Gahr M., Perrino F.W., Lieberman J., Hubner N.
    J. Mol. Med. 85:531-537(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CHBL1 ASN-73, CHARACTERIZATION OF VARIANT CHBL1 ASN-73.
  18. Cited for: VARIANTS SLE HIS-169; VAL-213; SER-282; SER-295; PRO-302; LEU-345; CYS-360 AND ALA-361, VARIANT GLY-321.
  19. Cited for: INVOLVEMENT IN RVCL.
  20. "A de novo p.Asp18Asn mutation in TREX1 in a patient with Aicardi-Goutieres syndrome."
    Haaxma C.A., Crow Y.J., van Steensel M.A., Lammens M.M., Rice G.I., Verbeek M.M., Willemsen M.A.
    Am. J. Med. Genet. A 152:2612-2617(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT AGS1 ASN-73.
  21. Cited for: VARIANTS AGS1 HIS-169; LYS-253 AND HIS-255, VARIANT SLE HIS-255.

Entry informationi

Entry nameiTREX1_HUMAN
AccessioniPrimary (citable) accession number: Q9NSU2
Secondary accession number(s): B2RCN9
, Q8TEU2, Q9BPW1, Q9Y4X2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: October 1, 2000
Last modified: November 26, 2014
This is version 133 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

The gene for this protein is either identical to or adjacent to that of ATRIP. Some of the mRNAs that encode ATRIP also encode TREX1 in another reading frame.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3