TREX2_HUMAN
ID TREX2_HUMAN Reviewed; 236 AA.
AC Q9BQ50; Q45F08; Q9UN77;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2019, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Three prime repair exonuclease 2;
DE EC=3.1.11.2;
DE AltName: Full=3'-5' exonuclease TREX2;
GN Name=TREX2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-137.
RG NIEHS SNPs program;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=11278605; DOI=10.1074/jbc.m010051200;
RA Mazur D.J., Perrino F.W.;
RT "Structure and expression of the TREX1 and TREX2 3'-->5' exonuclease
RT genes.";
RL J. Biol. Chem. 276:14718-14727(2001).
RN [4]
RP FUNCTION, CHARACTERIZATION, AND HOMODIMERIZATION.
RX PubMed=11279105; DOI=10.1074/jbc.m100623200;
RA Mazur D.J., Perrino F.W.;
RT "Excision of 3' termini by the Trex1 and TREX2 3'-->5' exonucleases.
RT Characterization of the recombinant proteins.";
RL J. Biol. Chem. 276:17022-17029(2001).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT, AND MUTAGENESIS OF ASP-14;
RP GLU-16; ASP-123; ARG-163; ARG-165; ARG-167; HIS-188 AND ASP-193.
RX PubMed=15661738; DOI=10.1074/jbc.m500108200;
RA Perrino F.W., Harvey S., McMillin S., Hollis T.;
RT "The human TREX2 3' ->5'-exonuclease structure suggests a mechanism for
RT efficient nonprocessive DNA catalysis.";
RL J. Biol. Chem. 280:15212-15218(2005).
CC -!- FUNCTION: Exonuclease with a preference for double-stranded DNA with
CC mismatched 3' termini. May play a role in DNA repair.
CC {ECO:0000269|PubMed:11279105}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
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};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.5-8.0.;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:15661738}.
CC -!- INTERACTION:
CC Q9BQ50; Q14696: MESD; NbExp=3; IntAct=EBI-22217464, EBI-6165891;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=2;
CC IsoId=Q9BQ50-2; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9BQ50-1; Sequence=VSP_060357;
CC -!- TISSUE SPECIFICITY: Detected in heart, breast, prostate, skeletal
CC muscle, testis, uterus, bone marrow, colon, small intestine, stomach
CC and thymus. {ECO:0000269|PubMed:11278605}.
CC -!- MISCELLANEOUS: [Isoform 1]: Only supported by readthrough transcripts
CC formed via the splicing of exons from UCHL5IP and TREX2 genes.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the exonuclease superfamily. TREX family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/trex2/";
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DR EMBL; AF151107; AAD48776.1; -; mRNA.
DR EMBL; AF319570; AAK07617.1; -; mRNA.
DR EMBL; AF319571; AAK07618.1; -; mRNA.
DR EMBL; AF319572; AAK07619.1; -; mRNA.
DR EMBL; AF319573; AAK07620.1; -; mRNA.
DR EMBL; DQ145722; AAZ38719.1; -; Genomic_DNA.
DR CCDS; CCDS35437.1; -. [Q9BQ50-2]
DR RefSeq; NP_542432.2; NM_080701.3. [Q9BQ50-2]
DR PDB; 1Y97; X-ray; 2.50 A; A/B=1-236.
DR PDBsum; 1Y97; -.
DR AlphaFoldDB; Q9BQ50; -.
DR SMR; Q9BQ50; -.
DR BioGRID; 116388; 74.
DR IntAct; Q9BQ50; 7.
DR STRING; 9606.ENSP00000333441; -.
DR PhosphoSitePlus; Q9BQ50; -.
DR BioMuta; TREX2; -.
DR DMDM; 47606206; -.
DR EPD; Q9BQ50; -.
DR MassIVE; Q9BQ50; -.
DR PaxDb; Q9BQ50; -.
DR PeptideAtlas; Q9BQ50; -.
DR PRIDE; Q9BQ50; -.
DR ProteomicsDB; 78622; -. [Q9BQ50-1]
DR ProteomicsDB; 78623; -. [Q9BQ50-2]
DR Antibodypedia; 30811; 138 antibodies from 28 providers.
DR DNASU; 11219; -.
DR Ensembl; ENST00000330912.7; ENSP00000333441.2; ENSG00000183479.13. [Q9BQ50-2]
DR Ensembl; ENST00000334497.7; ENSP00000334993.2; ENSG00000183479.13. [Q9BQ50-1]
DR Ensembl; ENST00000338525.7; ENSP00000345218.2; ENSG00000183479.13. [Q9BQ50-2]
DR Ensembl; ENST00000370212.5; ENSP00000359231.5; ENSG00000183479.13. [Q9BQ50-1]
DR Ensembl; ENST00000370231.3; ENSP00000359251.2; ENSG00000183479.13. [Q9BQ50-2]
DR Ensembl; ENST00000370232.4; ENSP00000359252.1; ENSG00000183479.13. [Q9BQ50-1]
DR Ensembl; ENST00000393862.7; ENSP00000377442.2; ENSG00000183479.13. [Q9BQ50-2]
DR GeneID; 11219; -.
DR KEGG; hsa:11219; -.
DR MANE-Select; ENST00000370231.3; ENSP00000359251.2; NM_080701.4; NP_542432.2.
DR UCSC; uc011myp.2; human. [Q9BQ50-2]
DR CTD; 11219; -.
DR DisGeNET; 11219; -.
DR GeneCards; TREX2; -.
DR HGNC; HGNC:12270; TREX2.
DR HPA; ENSG00000183479; Tissue enriched (skin).
DR MIM; 300370; gene.
DR neXtProt; NX_Q9BQ50; -.
DR OpenTargets; ENSG00000183479; -.
DR PharmGKB; PA36950; -.
DR VEuPathDB; HostDB:ENSG00000183479; -.
DR eggNOG; KOG4793; Eukaryota.
DR GeneTree; ENSGT00390000012715; -.
DR HOGENOM; CLU_067419_1_0_1; -.
DR InParanoid; Q9BQ50; -.
DR OrthoDB; 1365966at2759; -.
DR PhylomeDB; Q9BQ50; -.
DR TreeFam; TF323333; -.
DR PathwayCommons; Q9BQ50; -.
DR SignaLink; Q9BQ50; -.
DR BioGRID-ORCS; 11219; 10 hits in 690 CRISPR screens.
DR EvolutionaryTrace; Q9BQ50; -.
DR GeneWiki; TREX2; -.
DR GenomeRNAi; 11219; -.
DR Pharos; Q9BQ50; Tbio.
DR PRO; PR:Q9BQ50; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9BQ50; protein.
DR Bgee; ENSG00000183479; Expressed in skin of abdomen and 83 other tissues.
DR Genevisible; Q9BQ50; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0008296; F:3'-5'-exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0008853; F:exodeoxyribonuclease III activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IBA:GO_Central.
DR GO; GO:0006259; P:DNA metabolic process; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR DisProt; DP02710; -.
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 InterPro; IPR034926; TREX2.
DR PANTHER; PTHR13058; PTHR13058; 1.
DR PANTHER; PTHR13058:SF24; PTHR13058:SF24; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; DNA damage; DNA repair; Exonuclease;
KW Hydrolase; Magnesium; Metal-binding; Nuclease; Nucleus; Reference proteome.
FT CHAIN 1..236
FT /note="Three prime repair exonuclease 2"
FT /id="PRO_0000109870"
FT ACT_SITE 188
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000250"
FT BINDING 14
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 14
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 16..17
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 16
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 122
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 193
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 193
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1
FT /note="M -> MGRAGSPLPRSSWPRMDDCGSRSRCSPTLCSSLRTCYPRGNITM
FT (in isoform 1)"
FT /id="VSP_060357"
FT VARIANT 137
FT /note="R -> C (in dbSNP:rs35132777)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_025211"
FT MUTAGEN 14
FT /note="D->A: Loss of enzyme activity; when associated with
FT A-16. Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 16
FT /note="E->A: Loss of enzyme activity; when associated with
FT A-14. Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 123
FT /note="D->A: Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 163
FT /note="R->A: Strongly reduces DNA-binding; when associated
FT with A-165 and A-167."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 165
FT /note="R->A: Strongly reduces DNA-binding; when associated
FT with A-163 and A-167."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 167
FT /note="R->A: Strongly reduces DNA-binding; when associated
FT with A-165 and A-165."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 188
FT /note="H->A: Loss of enzyme activity; when associated with
FT A-193. Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15661738"
FT MUTAGEN 193
FT /note="D->A: Loss of enzyme activity; when associated with
FT A-188. Almost abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:15661738"
FT STRAND 8..19
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 21..23
FT /evidence="ECO:0007829|PDB:1Y97"
FT STRAND 27..36
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 37..40
FT /evidence="ECO:0007829|PDB:1Y97"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 72..78
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 82..87
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 95..105
FT /evidence="ECO:0007829|PDB:1Y97"
FT STRAND 110..116
FT /evidence="ECO:0007829|PDB:1Y97"
FT TURN 117..122
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 123..133
FT /evidence="ECO:0007829|PDB:1Y97"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 147..157
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 172..180
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 190..203
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 205..215
FT /evidence="ECO:0007829|PDB:1Y97"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:1Y97"
SQ SEQUENCE 236 AA; 25922 MW; 3363BE40CFCC2300 CRC64;
MSEAPRAETF VFLDLEATGL PSVEPEIAEL SLFAVHRSSL ENPEHDESGA LVLPRVLDKL
TLCMCPERPF TAKASEITGL SSEGLARCRK AGFDGAVVRT LQAFLSRQAG PICLVAHNGF
DYDFPLLCAE LRRLGARLPR DTVCLDTLPA LRGLDRAHSH GTRARGRQGY SLGSLFHRYF
RAEPSAAHSA EGDVHTLLLI FLHRAAELLA WADEQARGWA HIEPMYLPPD DPSLEA
