InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Trex1

Summary

InnateDB Protein

IDBP-256819.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Trex1

Protein Name

three prime repair exonuclease 1

Synonyms

1661; AU041952;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000107684

InnateDB Gene

IDBG-201128 (Trex1)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10391904, ECO:0000269PubMed:11279105, ECO:0000269PubMed:15254239, ECO:0000269PubMed:17293595, ECO:0000269PubMed:17355961, ECO:0000269PubMed:18045533, ECO:0000269PubMed:18724932, ECO:0000269PubMed:18780819, ECO:0000269PubMed:23993650, ECO:0000269PubMed:24218451}.

Subcellular Localization

Nucleus. Cytoplasm, cytosol. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Retained in the cytoplasm through the C-terminal region. 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.

Disease Associations

Tissue Specificity

Widely expressed with high expression levels detected in spleen, thymus and uterus. {ECO:0000269PubMed:24218451}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 2 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	2 [view]
Protein-Protein	2 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003690	double-stranded DNA binding
GO:0003697	single-stranded DNA binding
GO:0004527	exonuclease activity
GO:0005515	protein binding
GO:0008296	3'-5'-exodeoxyribonuclease activity
GO:0008408	3'-5' exonuclease activity
GO:0008853	exodeoxyribonuclease III activity
GO:0032405	MutLalpha complex binding
GO:0032407	MutSalpha complex binding
GO:0032558	adenyl deoxyribonucleotide binding
GO:0042803	protein homodimerization activity
GO:0046872	metal ion binding

Biological Process

GO:0000738	DNA catabolic process, exonucleolytic
GO:0006259	DNA metabolic process
GO:0035458	cellular response to interferon-beta
GO:0090305	nucleic acid phosphodiester bond hydrolysis