EXD2_MOUSE
ID EXD2_MOUSE Reviewed; 650 AA.
AC Q8VEG4; F8WID1; Q3TPJ5; Q3TS84;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Exonuclease 3'-5' domain-containing protein 2 {ECO:0000305};
DE EC=3.1.11.1 {ECO:0000250|UniProtKB:Q9NVH0};
DE AltName: Full=3'-5' exoribonuclease EXD2 {ECO:0000305};
DE EC=3.1.13.- {ECO:0000250|UniProtKB:Q9NVH0};
DE AltName: Full=Exonuclease 3'-5' domain-like-containing protein 2 {ECO:0000305};
GN Name=Exd2 {ECO:0000312|MGI:MGI:1922485};
GN Synonyms=Exdl2 {ECO:0000312|MGI:MGI:1922485};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE36791.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Exonuclease that has both 3'-5' exoribonuclease and
CC exodeoxyribonuclease activities, depending on the divalent metal cation
CC used as cofactor. In presence of Mg(2+), only shows 3'-5'
CC exoribonuclease activity, while it shows both exoribonuclease and
CC exodeoxyribonuclease activities in presence of Mn(2+). Acts as an
CC exoribonuclease in mitochondrion, possibly by regulating ATP production
CC and mitochondrial translation. Also involved in the response to DNA
CC damage. Acts as 3'-5' exodeoxyribonuclease for double-strand breaks
CC resection and efficient homologous recombination. Plays a key role in
CC controlling the initial steps of chromosomal break repair, it is
CC recruited to chromatin in a damage-dependent manner and functionally
CC interacts with the MRN complex to accelerate resection through its 3'-
CC 5' exonuclease activity, which efficiently processes double-stranded
CC DNA substrates containing nicks. Also involved in response to
CC replicative stress: recruited to stalled forks and is required to
CC stabilize and restart stalled replication forks by restraining
CC excessive fork regression, thereby suppressing their degradation.
CC {ECO:0000250|UniProtKB:Q9NVH0}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.11.1;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH0};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH0};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q9NVH0};
CC Note=Divalent metal cations; Mg(2+) or Mn(2+). Acts as a 3'-5'
CC exoribonuclease in presence of Mg(2+), while it has no 3'-5'
CC exodeoxyribonuclease activity. Has both as a 3'-5' exoribonuclease and
CC exodeoxyribonuclease activities in presence of Mn(2+).
CC {ECO:0000250|UniProtKB:Q9NVH0};
CC -!- SUBUNIT: Homodimer. Interacts with RBBP8, MRE11 and BRCA1.
CC {ECO:0000250|UniProtKB:Q9NVH0}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q9NVH0}; Single-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NVH0, ECO:0000255}. Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q9NVH0}. Nucleus {ECO:0000250|UniProtKB:Q9NVH0}.
CC Chromosome {ECO:0000250|UniProtKB:Q9NVH0}. Note=Mainly localizes to the
CC mitochondrial outer membrane. May translocate to the nucleus in
CC response to DNA damage; however mechanism that explain nuclear
CC localization are unknown and require experimental evidences. Recruited
CC to replication forks following replication stress.
CC {ECO:0000250|UniProtKB:Q9NVH0}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VEG4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VEG4-2; Sequence=VSP_058326;
CC -!- SIMILARITY: Belongs to the EXD2 family. {ECO:0000305}.
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DR EMBL; BC018508; AAH18508.1; -; mRNA.
DR EMBL; AK158201; BAE34403.1; -; mRNA.
DR EMBL; AK167692; BAE39739.1; -; mRNA.
DR EMBL; AK162206; BAE36791.1; -; mRNA.
DR EMBL; AK164329; BAE37741.1; -; mRNA.
DR EMBL; AC163282; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS49098.1; -. [Q8VEG4-1]
DR RefSeq; NP_598559.2; NM_133798.3. [Q8VEG4-1]
DR RefSeq; XP_011242528.1; XM_011244226.2.
DR AlphaFoldDB; Q8VEG4; -.
DR SMR; Q8VEG4; -.
DR STRING; 10090.ENSMUSP00000043049; -.
DR iPTMnet; Q8VEG4; -.
DR PhosphoSitePlus; Q8VEG4; -.
DR EPD; Q8VEG4; -.
DR MaxQB; Q8VEG4; -.
DR PaxDb; Q8VEG4; -.
DR PRIDE; Q8VEG4; -.
DR ProteomicsDB; 275788; -. [Q8VEG4-1]
DR ProteomicsDB; 275789; -. [Q8VEG4-2]
DR Antibodypedia; 123; 121 antibodies from 19 providers.
DR DNASU; 97827; -.
DR Ensembl; ENSMUST00000038185; ENSMUSP00000043049; ENSMUSG00000032705. [Q8VEG4-1]
DR GeneID; 97827; -.
DR KEGG; mmu:97827; -.
DR UCSC; uc007oas.2; mouse.
DR CTD; 55218; -.
DR MGI; MGI:1922485; Exd2.
DR VEuPathDB; HostDB:ENSMUSG00000032705; -.
DR eggNOG; KOG4373; Eukaryota.
DR GeneTree; ENSGT00390000014318; -.
DR InParanoid; Q8VEG4; -.
DR OMA; RYYQTPK; -.
DR OrthoDB; 692844at2759; -.
DR PhylomeDB; Q8VEG4; -.
DR TreeFam; TF324246; -.
DR BioGRID-ORCS; 97827; 1 hit in 107 CRISPR screens.
DR ChiTaRS; Exd2; mouse.
DR PRO; PR:Q8VEG4; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8VEG4; protein.
DR Bgee; ENSMUSG00000032705; Expressed in spermatocyte and 247 other tissues.
DR ExpressionAtlas; Q8VEG4; baseline and differential.
DR Genevisible; F8WID1; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0090734; C:site of DNA damage; ISS:UniProtKB.
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:0000175; F:3'-5'-exoribonuclease activity; ISS:UniProtKB.
DR GO; GO:0008852; F:exodeoxyribonuclease I activity; IEA:UniProtKB-EC.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0000729; P:DNA double-strand break processing; ISO:MGI.
DR GO; GO:0006302; P:double-strand break repair; ISO:MGI.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISO:MGI.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:MGI.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF01612; DNA_pol_A_exo1; 1.
DR SMART; SM00474; 35EXOc; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW Alternative initiation; Chromosome; DNA damage; DNA repair; Exonuclease;
KW Hydrolase; Magnesium; Manganese; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion outer membrane; Nuclease; Nucleus; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..650
FT /note="Exonuclease 3'-5' domain-containing protein 2"
FT /id="PRO_0000089925"
FT TOPO_DOM 1..6
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000305"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..650
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT DOMAIN 184..276
FT /note="3'-5' exonuclease"
FT REGION 34..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 47..69
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 137
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 137
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 139
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT BINDING 275
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9NVH0"
FT VAR_SEQ 1..154
FT /note="Missing (in isoform 2)"
FT /id="VSP_058326"
FT CONFLICT 257
FT /note="S -> N (in Ref. 2; BAE37741)"
FT /evidence="ECO:0000305"
FT CONFLICT 390
FT /note="Q -> R (in Ref. 2; BAE37741)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 650 AA; 74332 MW; E4BDAE3FC4E44076 CRC64;
MSRQNLVALT VTTLLGVAMG GFVLWKGIQR RWSKTSRVMQ QQPQQPQQPQ QPQPQPQPQP
QPQPEHPQPQ QQVPGGREWP PPEDDQLPFG ALRAPRASWE ERILQAEVVT VSQEAEWNQI
QPFLKRELED FPVLGIDCEW VNLEGKASPL SLLQMASPSG FCALVRLPRL IYGGRTLPRT
LLDILADGAI LKVGVGCSED ANKLLQDYGL IVRGCLDLRY LAMKQGNNIL CNGLSLKSLA
ETILNFPLDK SLLLRCSNWD AENLTEDQVT YAARDAQISV ALFLHLLGYP FSRDSYEEES
TDQINWQKAL ERCRNMVDIP FRSKGLGRLV EEVNGEALES QLKPRNRKAK TDRMVPGNNQ
GRDPRKHKRK PLGVGYSARK SPLYDNCFLQ APDGQPLCTC DRRKAQWYLD KGIGELVSKE
PFVVRLQFEP AGRPESPGDY YLMVKENLCV VCGKTDTYIR KNIIPHEYRK HFPIEMKDHN
SHDVLLLCTS CHAISNYYDN HLKQQLAKEF QAPIGSEEGL RLLEDLERRQ VRSGARALLN
AESLPAHRKE ELLHALREFY NTDIITEEML HEAASLETRI YNESYIPHGL KVVQRHTEGG
LRSLMQLESR WRQHFLDSMQ PKHLPQQWSV DHNHQKLLRK YGDDLPIKLS
