Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q9NSU2

- TREX1_HUMAN

UniProt

Q9NSU2 - TREX1_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 1 (01 Oct 2000)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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

    Binds 2 Mg2+ per subunit. The second magnesium ion interacts with only one residue. Substitution with Mn2+ results in partial activity By similarity.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

    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. cytosol Source: UniProtKB-SubCell
    2. endoplasmic reticulum membrane Source: Reactome
    3. nuclear envelope Source: UniProtKB
    4. nucleolus Source: HPA
    5. nucleus Source: HPA

    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.
    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.
    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

    MGPGARRQGR IVQGRPEMCF CPPPTPLPPL RILTLGTHTP TPCSSPGSAA    50
    GTYPTMGSQA LPPGPMQTLI FFDMEATGLP FSQPKVTELC LLAVHRCALE 100
    SPPTSQGPPP TVPPPPRVVD KLSLCVAPGK ACSPAASEIT GLSTAVLAAH 150
    GRQCFDDNLA NLLLAFLRRQ PQPWCLVAHN GDRYDFPLLQ AELAMLGLTS 200
    ALDGAFCVDS ITALKALERA SSPSEHGPRK SYSLGSIYTR LYGQSPPDSH 250
    TAEGDVLALL SICQWRPQAL LRWVDAHARP FGTIRPMYGV TASARTKPRP 300
    SAVTTTAHLA TTRNTSPSLG ESRGTKDLPP VKDPGALSRE GLLAPLGLLA 350
    ILTLAVATLY GLSLATPGE 369
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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]
    CCDS43086.1. [Q9NSU2-1]
    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:
    EMBL
    GenBank
    DDBJ
    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 ]
    CCDS43086.1. [Q9NSU2-1 ]
    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.
    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

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

    Gene expression databases

    Bgeei Q9NSU2.
    CleanExi HS_TREX1.
    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

    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: October 1, 2014
    This is version 131 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