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Q9NSU2 (TREX1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Three-prime repair exonuclease 1

EC=3.1.11.2
Alternative name(s):
3'-5' exonuclease TREX1
DNase III
Gene names
Name:TREX1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length369 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1 Ref.2 Ref.8 Ref.9 Ref.10 Ref.12

Catalytic activity

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

Cofactor

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

Subunit structure

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. Ref.8 Ref.13

Subcellular location

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. Ref.1 Ref.8

Tissue specificity

Detected in thymus, spleen, liver, brain, heart, small intestine and colon. Ref.1 Ref.3

Induction

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.

Post-translational modification

Ubiquitinated, but not targeted to proteasomal degradation. Ubiquitination may be important for interaction with UBQLN1. Ref.13

Involvement in disease

Aicardi-Goutieres syndrome 1 (AGS1) [MIM:225750]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.20 Ref.21

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.
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 (Ref.12). Ref.12 Ref.13 Ref.18 Ref.21

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.17

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.19

Sequence similarities

Belongs to the exonuclease superfamily. TREX family.

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.

Sequence caution

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

Ontologies

Keywords
   Cellular componentCytoplasm
Endoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityAlternative splicing
   DiseaseAicardi-Goutieres syndrome
Disease mutation
Neurodegeneration
Systemic lupus erythematosus
   LigandMagnesium
Metal-binding
   Molecular functionExonuclease
Hydrolase
Nuclease
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA catabolic process, exonucleolytic

Inferred from sequence or structural similarity. Source: GOC

DNA metabolic process

Inferred from sequence or structural similarity. Source: UniProtKB

DNA recombination

Non-traceable author statement Ref.2Ref.3. Source: UniProtKB

DNA repair

Traceable author statement Ref.1. Source: ProtInc

DNA replication

Non-traceable author statement Ref.2Ref.3. Source: UniProtKB

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to interferon-beta

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

mismatch repair

Non-traceable author statement Ref.2Ref.3. Source: UniProtKB

nucleic acid phosphodiester bond hydrolysis

Inferred from direct assay Ref.2. Source: GOC

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

regulation of type I interferon production

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

nuclear envelope

Non-traceable author statement Ref.2. Source: UniProtKB

nucleolus

Inferred from direct assay. Source: HPA

nucleus

Inferred from direct assay. Source: HPA

   Molecular_function3'-5' exonuclease activity

Inferred from direct assay Ref.2. Source: UniProtKB

3'-5'-exodeoxyribonuclease activity

Inferred from sequence or structural similarity. Source: UniProtKB

MutLalpha complex binding

Inferred from direct assay PubMed 16713580. Source: MGI

MutSalpha complex binding

Inferred from direct assay PubMed 16713580. Source: MGI

adenyl deoxyribonucleotide binding

Inferred from electronic annotation. Source: Ensembl

double-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

exodeoxyribonuclease III activity

Inferred from electronic annotation. Source: UniProtKB-EC

metal ion binding

Non-traceable author statement Ref.2. Source: UniProtKB

protein homodimerization activity

Non-traceable author statement Ref.2. Source: UniProtKB

single-stranded DNA binding

Traceable author statement Ref.2. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9NSU2-1)

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.
Isoform 2 (identifier: Q9NSU2-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
Isoform 3 (identifier: Q9NSU2-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 369369Three-prime repair exonuclease 1
PRO_0000109868

Regions

Region75 – 762Substrate binding By similarity
Region109 – 11810Proline-rich region By similarity
Region291 – 36979Necessary for endoplasmic reticulum localization By similarity
Region298 – 36972Interaction with UBQLN1
Region336 – 36934Necessary for cytoplasmic retention By similarity

Sites

Active site2501Proton donor/acceptor By similarity
Metal binding731Magnesium 1 By similarity
Metal binding731Magnesium 2 By similarity
Metal binding751Magnesium 1 By similarity
Metal binding2551Magnesium 1 By similarity
Binding site1841Substrate By similarity
Binding site2551Substrate By similarity

Amino acid modifications

Modified residue1331Phosphoserine Ref.11
Modified residue3161Phosphoserine Ref.11

Natural variations

Alternative sequence1 – 6565Missing in isoform 2.
VSP_010445
Alternative sequence1 – 5555Missing in isoform 3.
VSP_010446
Natural variant731D → N in CHBL1 and AGS1; loss of function. Ref.17 Ref.20
VAR_037948
Natural variant1691R → H in AGS1 and SLE; strongly reduces activity; produces a defective G1/S transition and chronic G2/M DNA damage checkpoint activation. Ref.9 Ref.10 Ref.14 Ref.16 Ref.18 Ref.21
VAR_028319
Natural variant1771V → A in AGS1; increases ubiquitination levels; no effect on exonuclease activity. Ref.13 Ref.16
VAR_070899
Natural variant2131A → V in SLE. Ref.18
VAR_037949
Natural variant2531E → K in AGS1; increases ubiquitination levels; no effect on exonuclease activity. Ref.13 Ref.21
VAR_070900
Natural variant2551D → DD in AGS1; heterozygous compound with H-169; loss of activity. Ref.10 Ref.14
VAR_028320
Natural variant2551D → H in AGS1 and SLE. Ref.21
VAR_070901
Natural variant2551D → N in AGS1; autosomal dominant form; no effect on dsDNA exonuclease activity; abolishes ssDNA exonuclease activity. Ref.13 Ref.15 Ref.16
VAR_032940
Natural variant2561V → D in AGS1; reduces activity by 75%. Ref.10 Ref.14 Ref.16
VAR_028321
Natural variant2821G → S in SLE; associated in cis with P-302. Ref.18
Corresponds to variant rs113107733 [ dbSNP | Ensembl ].
VAR_037950
Natural variant2951R → S in SLE. Ref.18
Corresponds to variant rs72556555 [ dbSNP | Ensembl ].
VAR_037951
Natural variant3021A → P in SLE; associated in cis with S-282. Ref.18
Corresponds to variant rs112741962 [ dbSNP | Ensembl ].
VAR_037952
Natural variant3211E → G. Ref.18
Corresponds to variant rs55999987 [ dbSNP | Ensembl ].
VAR_037953
Natural variant3451P → L in SLE; increases ubiquitination levels; no effect on exonuclease activity. Ref.13 Ref.18
VAR_037954
Natural variant3581T → P in AGS1; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. Ref.13 Ref.16
VAR_070902
Natural variant3601Y → C in SLE; decreases ubiquitination levels; decreases colocalization with UBQLN1; no effect on exonuclease activity. Ref.13 Ref.18
VAR_037955
Natural variant3611G → A in SLE. Ref.18
VAR_037956

Experimental info

Mutagenesis851K → R: Reduces ubiquitination. Ref.13
Mutagenesis1211K → R: No effect on ubiquitination. Ref.13
Mutagenesis1301K → R: Reduces ubiquitination. Ref.13
Mutagenesis2151K → R: Reduces ubiquitination. Ref.13
Mutagenesis2301K → R: Reduces ubiquitination. Ref.13
Mutagenesis2971K → R: Reduces ubiquitination. Ref.13
Mutagenesis3261K → R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-332. Ref.13
Mutagenesis3321K → R: Reduces ubiquitination. Strongly reduces ubiquitination; when associated with R-326. Ref.13
Sequence conflict3201G → R in CAB50866. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 42B79047A9AD9837

FASTA36938,923
        10         20         30         40         50         60 
MGPGARRQGR IVQGRPEMCF CPPPTPLPPL RILTLGTHTP TPCSSPGSAA GTYPTMGSQA 

        70         80         90        100        110        120 
LPPGPMQTLI FFDMEATGLP FSQPKVTELC LLAVHRCALE SPPTSQGPPP TVPPPPRVVD 

       130        140        150        160        170        180 
KLSLCVAPGK ACSPAASEIT GLSTAVLAAH GRQCFDDNLA NLLLAFLRRQ PQPWCLVAHN 

       190        200        210        220        230        240 
GDRYDFPLLQ AELAMLGLTS ALDGAFCVDS ITALKALERA SSPSEHGPRK SYSLGSIYTR 

       250        260        270        280        290        300 
LYGQSPPDSH TAEGDVLALL SICQWRPQAL LRWVDAHARP FGTIRPMYGV TASARTKPRP 

       310        320        330        340        350        360 
SAVTTTAHLA TTRNTSPSLG ESRGTKDLPP VKDPGALSRE GLLAPLGLLA ILTLAVATLY 


GLSLATPGE 

« Hide

Isoform 2 [UniParc].

Checksum: 922048DCC4122124
Show »

FASTA30432,276
Isoform 3 [UniParc].

Checksum: EE8F63B6496D72F4
Show »

FASTA31433,212

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus."
Crow Y.J., Hayward B.E., Parmar R., Robins P., Leitch A., Ali M., Black D.N., van Bokhoven H., Brunner H.G., Hamel B.C.J., Corry P.C., Cowan F.M., Frints S.G., Klepper J., Livingston J.H., Lynch S.A., Massey R.F., Meritet J.F. expand/collapse author list , Michaud J.L., Ponsot G., Voit T., Lebon P., Bonthron D.T., Jackson A.P., Barnes D.E., Lindahl T.
Nat. Genet. 38:917-920(2006) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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]"Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus."
Lee-Kirsch M.A., Gong M., Chowdhury D., Senenko L., Engel K., Lee Y.A., de Silva U., Bailey S.L., Witte T., Vyse T.J., Kere J., Pfeiffer C., Harvey S., Wong A., Koskenmies S., Hummel O., Rohde K., Schmidt R.E. expand/collapse author list , Dominiczak A.F., Gahr M., Hollis T., Perrino F.W., Lieberman J., Huebner N.
Nat. Genet. 39:1065-1067(2007) [PubMed] [Europe PMC] [Abstract]
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]"C-terminal truncations in human 3'-5' DNA exonuclease TREX1 cause autosomal dominant retinal vasculopathy with cerebral leukodystrophy."
Richards A., van den Maagdenberg A.M.J.M., Jen J.C., Kavanagh D., Bertram P., Spitzer D., Liszewski M.K., Barilla-Labarca M.-L., Terwindt G.M., Kasai Y., McLellan M., Grand M.G., Vanmolkot K.R.J., de Vries B., Wan J., Kane M.J., Mamsa H., Schaefer R. expand/collapse author list , Stam A.H., Haan J., de Jong P.T.V.M., Storimans C.W., van Schooneveld M.J., Oosterhuis J.A., Gschwendter A., Dichgans M., Kotschet K.E., Hodgkinson S., Hardy T.A., Delatycki M.B., Hajj-Ali R.A., Kothari P.H., Nelson S.F., Frants R.R., Baloh R.W., Ferrari M.D., Atkinson J.P.
Nat. Genet. 39:1068-1070(2007) [PubMed] [Europe PMC] [Abstract]
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]"Expanding the phenotypic spectrum of lupus erythematosus in Aicardi-Goutieres syndrome."
Ramantani G., Kohlhase J., Hertzberg C., Innes A.M., Engel K., Hunger S., Borozdin W., Mah J.K., Ungerath K., Walkenhorst H., Richardt H.H., Buckard J., Bevot A., Siegel C., von Stuelpnagel C., Ikonomidou C., Thomas K., Proud V. expand/collapse author list , Niemann F., Wieczorek D., Haeusler M., Niggemann P., Baltaci V., Conrad K., Lebon P., Lee-Kirsch M.A.
Arthritis Rheum. 62:1469-1477(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS AGS1 HIS-169; LYS-253 AND HIS-255, VARIANT SLE HIS-255.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS2769.1. [Q9NSU2-3]
CCDS43086.1. [Q9NSU2-1]
CCDS59451.1. [Q9NSU2-2]
PIRT46299.
RefSeqNP_009179.2. NM_007248.3. [Q9NSU2-2]
NP_057465.1. NM_016381.5. [Q9NSU2-1]
NP_338599.1. NM_033629.4. [Q9NSU2-3]
UniGeneHs.707026.
Hs.713742.
Hs.744646.

3D structure databases

ProteinModelPortalQ9NSU2.
SMRQ9NSU2. Positions 61-289.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116433. 5 interactions.
MINTMINT-1466830.
STRING9606.ENSP00000379035.

PTM databases

PhosphoSiteQ9NSU2.

Polymorphism databases

DMDM47606216.

Proteomic databases

MaxQBQ9NSU2.
PaxDbQ9NSU2.
PRIDEQ9NSU2.

Protocols and materials databases

DNASU11277.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296443; ENSP00000296443; ENSG00000213689. [Q9NSU2-3]
ENST00000422277; ENSP00000390478; ENSG00000213689. [Q9NSU2-1]
ENST00000436480; ENSP00000392569; ENSG00000213689. [Q9NSU2-3]
ENST00000444177; ENSP00000415972; ENSG00000213689. [Q9NSU2-2]
GeneID11277.
KEGGhsa:11277.
UCSCuc003ctj.3. human. [Q9NSU2-1]

Organism-specific databases

CTD11277.
GeneCardsGC03P048506.
GeneReviewsTREX1.
HGNCHGNC:12269. TREX1.
HPAHPA035437.
MIM152700. phenotype.
192315. phenotype.
225750. phenotype.
606609. gene.
610448. phenotype.
neXtProtNX_Q9NSU2.
Orphanet51. Aicardi-Goutieres syndrome.
3421. Cerebroretinal vasculopathy.
90280. Chilblain lupus.
71291. Hereditary vascular retinopathy.
63261. HERNS syndrome.
536. Systemic lupus erythematosus.
PharmGKBPA36949.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG293314.
HOGENOMHOG000118119.
HOVERGENHBG079278.
InParanoidQ9NSU2.
KOK10790.
OMAHNGDRYD.
OrthoDBEOG7DC26B.
PhylomeDBQ9NSU2.
TreeFamTF323333.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeQ9NSU2.
CleanExHS_TREX1.
GenevestigatorQ9NSU2.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
InterProIPR012337. RNaseH-like_dom.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
ProtoNetSearch...

Other

GeneWikiTREX1.
GenomeRNAi11277.
NextBio42927.
PROQ9NSU2.
SOURCESearch...

Entry information

Entry nameTREX1_HUMAN
AccessionPrimary (citable) accession number: Q9NSU2
Secondary accession number(s): B2RCN9 expand/collapse secondary AC list , Q8TEU2, Q9BPW1, Q9Y4X2
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: October 1, 2000
Last modified: July 9, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM