TREX1_BOVIN
ID TREX1_BOVIN Reviewed; 315 AA.
AC Q9BG99;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Three-prime repair exonuclease 1 {ECO:0000305};
DE EC=3.1.11.2 {ECO:0000250|UniProtKB:Q9NSU2};
DE AltName: Full=3'-5' exonuclease TREX1 {ECO:0000303|PubMed:10391904};
GN Name=TREX1 {ECO:0000303|PubMed:10391904};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 42-60; 99-109 AND 161-184,
RP FUNCTION, AND HOMODIMERIZATION.
RC TISSUE=Thymus;
RX PubMed=10391904; DOI=10.1074/jbc.274.28.19655;
RA Mazur D.J., Perrino F.W.;
RT "Identification and expression of the TREX1 and TREX2 cDNA sequences
RT encoding mammalian 3'-->5' exonucleases.";
RL J. Biol. Chem. 274:19655-19660(1999).
CC -!- FUNCTION: Major cellular 3'-to-5' DNA exonuclease which digests single-
CC stranded DNA (ssDNA) and double-stranded DNA (dsDNA) with mismatched 3'
CC termini (PubMed:10391904). Prevents cell-intrinsic initiation of
CC autoimmunity (By similarity). Acts by metabolizing DNA fragments from
CC endogenous retroelements, including L1, LTR and SINE elements (By
CC similarity). Plays a key role in degradation of DNA fragments at
CC cytosolic micronuclei arising from genome instability: its association
CC with the endoplasmic reticulum membrane directs TREX1 to ruptured
CC micronuclei, leading to micronuclear DNA degradation (By similarity).
CC Micronuclear DNA degradation is required to limit CGAS activation and
CC subsequent inflammation (By similarity). Unless degraded, these DNA
CC fragments accumulate in the cytosol and activate the cGAS-STING innate
CC immune signaling, leading to the production of type I interferon (By
CC similarity). Prevents chronic ATM-dependent checkpoint activation, by
CC processing ssDNA polynucleotide species arising from the processing of
CC aberrant DNA replication intermediates (By similarity). Inefficiently
CC degrades oxidized DNA, such as that generated upon antimicrobial
CC reactive oxygen production or upon absorption of UV light (By
CC similarity). During GZMA-mediated cell death, contributes to DNA damage
CC in concert with NME1 (By similarity). NME1 nicks one strand of DNA and
CC TREX1 removes bases from the free 3' end to enhance DNA damage and
CC prevent DNA end reannealing and rapid repair (By similarity).
CC {ECO:0000250|UniProtKB:Q9NSU2, ECO:0000269|PubMed:10391904}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.2;
CC Evidence={ECO:0000250|UniProtKB:Q9NSU2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q91XB0};
CC Note=Binds 2 Mg(2+) per subunit. The second magnesium ion interacts
CC with only one residue. Substitution with Mn(2+) results in partial
CC activity. {ECO:0000250|UniProtKB:Q91XB0};
CC -!- SUBUNIT: Homodimer (PubMed:10391904). Interacts (via proline-rich
CC region) with TCERG1/CA150 (via the second WW domain) (By similarity).
CC Component of the SET complex, composed of at least ANP32A, APEX1,
CC HMGB2, NME1, SET and TREX1 (By similarity). Within this complex,
CC directly interacts with SET; this interaction does not result in TREX1
CC inhibition (By similarity). Also interacts with NME1, but only
CC following translocation to the nucleus (By similarity). Directly
CC interacts with UBQLN1 (via ubiquitin-like domain); the interaction may
CC control TREX1 subcellular location (By similarity).
CC {ECO:0000250|UniProtKB:Q91XB0, ECO:0000250|UniProtKB:Q9NSU2,
CC ECO:0000269|PubMed:10391904}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NSU2}.
CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9NSU2}. Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q9NSU2}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9NSU2}. Note=Retained in the cytoplasm
CC through the C-terminal region (By similarity). Localization to the
CC endoplasmic reticulum membrane is required to direct TREX1 to ruptured
CC micronuclei. In response to DNA damage, translocates to the nucleus
CC where it is specifically recruited to replication foci. Translocation
CC to the nucleus also occurs during GZMA-mediated cell death (By
CC similarity). {ECO:0000250|UniProtKB:Q91XB0,
CC ECO:0000250|UniProtKB:Q9NSU2}.
CC -!- PTM: Ubiquitinated, but not targeted to proteasomal degradation.
CC Ubiquitination may be important for interaction with UBQLN1.
CC {ECO:0000250|UniProtKB:Q9NSU2}.
CC -!- SIMILARITY: Belongs to the exonuclease superfamily. TREX family.
CC {ECO:0000305}.
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DR EMBL; AF319575; AAK07622.1; -; mRNA.
DR AlphaFoldDB; Q9BG99; -.
DR SMR; Q9BG99; -.
DR STRING; 9913.ENSBTAP00000011063; -.
DR PaxDb; Q9BG99; -.
DR PRIDE; Q9BG99; -.
DR eggNOG; KOG4793; Eukaryota.
DR InParanoid; Q9BG99; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0008408; F:3'-5' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0008853; F:exodeoxyribonuclease III activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006259; P:DNA metabolic process; ISS:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; ISS:UniProtKB.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR040393; TREX1/2.
DR PANTHER; PTHR13058; PTHR13058; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cytoplasm; Direct protein sequencing; Endoplasmic reticulum;
KW Exonuclease; Hydrolase; Magnesium; Membrane; Metal-binding; Nuclease;
KW Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..315
FT /note="Three-prime repair exonuclease 1"
FT /id="PRO_0000109867"
FT REGION 236..315
FT /note="Necessary for endoplasmic reticulum localization"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT REGION 243..315
FT /note="Interaction with UBQLN1"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT REGION 256..282
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 282..315
FT /note="Necessary for cytoplasmic retention"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT ACT_SITE 195
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 18
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 18
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 20..21
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 20
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q91XB0"
FT MOD_RES 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
FT MOD_RES 167
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NSU2"
SQ SEQUENCE 315 AA; 33132 MW; 90AD66D1513DFDE6 CRC64;
MGSRALPPGP VQTLIFLDLE ATGLPFSQPK ITELCLLAVH RYALEGLSAP QGPSPTAPVP
PRVLDKLSLC VAPGKVCSPA ASEITGLSTA VLAAHGRRAF DADLVNLIRT FLQRQPQPWC
LVAHNGDRYD FPLLRAELAL LGLASALDDA FCVDSIAALK ALEPTGSSSE HGPRKSYSLG
SVYTRLYGQA PPDSHTAEGD VLALLSVCQW RPRALLRWVD AHAKPFSTVK PMYVITTSTG
TNPRPSAVTA TVPLARASDT GPNLRGDRSP KPAPSPKMCP GAPPGEGLLA PLGLLAFLTL
AVAMLYGLSL AMPGQ
