EXO1_MOUSE
ID EXO1_MOUSE Reviewed; 837 AA.
AC Q9QZ11; Q3TLM4; Q923A5;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Exonuclease 1;
DE Short=mExo1;
DE EC=3.1.-.-;
DE AltName: Full=Exonuclease I;
GN Name=Exo1;
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 [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10497278; DOI=10.1093/nar/27.20.4114;
RA Lee B.-I., Shannon M., Stubbs L., Wilson D.M. III;
RT "Expression specificity of the mouse exonuclease 1 (mExo1) gene.";
RL Nucleic Acids Res. 27:4114-4120(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland, and Skin;
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 MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP FUNCTION.
RX PubMed=12629043; DOI=10.1101/gad.1060603;
RA Wei K., Clark A.B., Wong E., Kane M.F., Mazur D.J., Parris T., Kolas N.K.,
RA Russell R., Hou H. Jr., Kneitz B., Yang G., Kunkel T.A., Kolodner R.D.,
RA Cohen P.E., Edelmann W.;
RT "Inactivation of exonuclease 1 in mice results in DNA mismatch repair
RT defects, increased cancer susceptibility, and male and female sterility.";
RL Genes Dev. 17:603-614(2003).
RN [5]
RP FUNCTION.
RX PubMed=14716311; DOI=10.1038/ni1031;
RA Bardwell P.D., Woo C.J., Wei K., Li Z., Martin A., Sack S.Z., Parris T.,
RA Edelmann W., Scharff M.D.;
RT "Altered somatic hypermutation and reduced class-switch recombination in
RT exonuclease 1-mutant mice.";
RL Nat. Immunol. 5:224-229(2004).
CC -!- FUNCTION: 5'->3' double-stranded DNA exonuclease which may also possess
CC a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in
CC DNA mismatch repair (MMR) to excise mismatch-containing DNA tracts
CC directed by strand breaks located either 5' or 3' to the mismatch. Also
CC exhibits endonuclease activity against 5'-overhanging flap structures
CC similar to those generated by displacement synthesis when DNA
CC polymerase encounters the 5'-end of a downstream Okazaki fragment.
CC Required for somatic hypermutation (SHM) and class switch recombination
CC (CSR) of immunoglobulin genes. Essential for male and female meiosis.
CC {ECO:0000269|PubMed:12629043, ECO:0000269|PubMed:14716311}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000250};
CC -!- SUBUNIT: Interacts with the MLH1-PMS2 heterodimer via MLH1. Interacts
CC with MSH3. Interacts with the MSH2-MSH6 heterodimer via MSH2, and this
CC interaction may increase the processivity of the 5'->3' exonuclease
CC activity. Interacts with PCNA, and this interaction may both stimulate
CC the cryptic 3'->5' exonuclease activity and suppress the 5'->3'
CC exonuclease activity. Interacts with WRN, and this interaction
CC stimulates both the 5'->3' exonuclease activity and cleavage of 5'-
CC overhanging flap structures. Interacts with RECQL/RECQ1, and this
CC interaction stimulates cleavage of 5'-overhanging flap structures (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Note=Colocalizes with PCNA
CC to discrete nuclear foci in S-phase. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in the spleen and testis. Also
CC expressed in the bone marrow, brain, lung, lymph node and thymus.
CC {ECO:0000269|PubMed:10497278}.
CC -!- DEVELOPMENTAL STAGE: Postnatal expression in the testis is elevated at
CC the onset of pachytene (day 14). {ECO:0000269|PubMed:10497278}.
CC -!- PTM: Phosphorylated upon DNA damage and in response to agents stalling
CC DNA replication, probably by ATM or ATR. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. EXO1
CC subfamily. {ECO:0000305}.
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DR EMBL; AJ238213; CAB51863.1; -; mRNA.
DR EMBL; AK028728; BAC26086.1; -; mRNA.
DR EMBL; AK166425; BAE38768.1; -; mRNA.
DR EMBL; BC006671; AAH06671.1; -; mRNA.
DR CCDS; CCDS15551.1; -.
DR RefSeq; NP_036142.2; NM_012012.4.
DR RefSeq; XP_006496925.1; XM_006496862.3.
DR RefSeq; XP_006496926.1; XM_006496863.3.
DR AlphaFoldDB; Q9QZ11; -.
DR SMR; Q9QZ11; -.
DR BioGRID; 205057; 1.
DR STRING; 10090.ENSMUSP00000039376; -.
DR iPTMnet; Q9QZ11; -.
DR PhosphoSitePlus; Q9QZ11; -.
DR EPD; Q9QZ11; -.
DR MaxQB; Q9QZ11; -.
DR PaxDb; Q9QZ11; -.
DR PeptideAtlas; Q9QZ11; -.
DR PRIDE; Q9QZ11; -.
DR ProteomicsDB; 275555; -.
DR Antibodypedia; 34705; 390 antibodies from 34 providers.
DR DNASU; 26909; -.
DR Ensembl; ENSMUST00000039725; ENSMUSP00000039376; ENSMUSG00000039748.
DR GeneID; 26909; -.
DR KEGG; mmu:26909; -.
DR UCSC; uc007dtu.2; mouse.
DR CTD; 9156; -.
DR MGI; MGI:1349427; Exo1.
DR VEuPathDB; HostDB:ENSMUSG00000039748; -.
DR eggNOG; KOG2518; Eukaryota.
DR GeneTree; ENSGT00510000047676; -.
DR HOGENOM; CLU_009851_0_0_1; -.
DR InParanoid; Q9QZ11; -.
DR OMA; VNSIWHR; -.
DR OrthoDB; 796591at2759; -.
DR PhylomeDB; Q9QZ11; -.
DR TreeFam; TF314997; -.
DR Reactome; R-MMU-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR BioGRID-ORCS; 26909; 14 hits in 112 CRISPR screens.
DR ChiTaRS; Exo1; mouse.
DR PRO; PR:Q9QZ11; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9QZ11; protein.
DR Bgee; ENSMUSG00000039748; Expressed in epiblast (generic) and 192 other tissues.
DR ExpressionAtlas; Q9QZ11; baseline and differential.
DR Genevisible; Q9QZ11; MM.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0035312; F:5'-3' exodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISO:MGI.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0051908; F:double-stranded DNA 5'-3' exodeoxyribonuclease activity; ISO:MGI.
DR GO; GO:0048256; F:flap endonuclease activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; ISS:UniProtKB.
DR GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; IMP:MGI.
DR GO; GO:0045190; P:isotype switching; IMP:MGI.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006298; P:mismatch repair; ISS:UniProtKB.
DR GO; GO:0006139; P:nucleobase-containing compound metabolic process; ISO:MGI.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:MGI.
DR CDD; cd09908; H3TH_EXO1; 1.
DR CDD; cd09857; PIN_EXO1; 1.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR032641; Exo1.
DR InterPro; IPR037315; EXO1_H3TH.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR044752; PIN-like_EXO1.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR019974; XPG_CS.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR PANTHER; PTHR11081; PTHR11081; 1.
DR PANTHER; PTHR11081:SF8; PTHR11081:SF8; 1.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; SSF47807; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
DR PROSITE; PS00841; XPG_1; 1.
DR PROSITE; PS00842; XPG_2; 1.
PE 2: Evidence at transcript level;
KW Acetylation; DNA damage; DNA excision; DNA repair; DNA-binding;
KW Endonuclease; Excision nuclease; Exonuclease; Hydrolase; Immunity;
KW Magnesium; Meiosis; Metal-binding; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..837
FT /note="Exonuclease 1"
FT /id="PRO_0000154040"
FT REGION 1..99
FT /note="N-domain"
FT REGION 129..386
FT /note="Interaction with MSH3"
FT /evidence="ECO:0000250"
FT REGION 138..229
FT /note="I-domain"
FT REGION 345..367
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 387..488
FT /note="Interaction with MLH1"
FT /evidence="ECO:0000250"
FT REGION 440..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 555..589
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 591..837
FT /note="Interaction with MSH2"
FT /evidence="ECO:0000250"
FT REGION 608..740
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 778..837
FT /note="Interaction with MLH1"
FT /evidence="ECO:0000250"
FT COMPBIAS 347..367
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 446..468
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..626
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 651..713
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 714..728
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 30
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 78
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 150
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT MOD_RES 480
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 589
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 601
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 612
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 666
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQ84"
FT CONFLICT 366
FT /note="T -> A (in Ref. 1; CAB51863 and 2; BAE38768)"
FT /evidence="ECO:0000305"
FT CONFLICT 523
FT /note="P -> T (in Ref. 2; BAE38768)"
FT /evidence="ECO:0000305"
FT CONFLICT 557
FT /note="T -> M (in Ref. 1; CAB51863)"
FT /evidence="ECO:0000305"
FT CONFLICT 560
FT /note="L -> P (in Ref. 2; BAE38768)"
FT /evidence="ECO:0000305"
FT CONFLICT 648
FT /note="K -> Q (in Ref. 1; CAB51863)"
FT /evidence="ECO:0000305"
FT CONFLICT 652
FT /note="L -> P (in Ref. 1; CAB51863 and 2; BAE38768)"
FT /evidence="ECO:0000305"
FT CONFLICT 666
FT /note="S -> L (in Ref. 1; CAB51863)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 837 AA; 92022 MW; 5AE4AC617535DEBC CRC64;
MGIQGLLQFI QEASEPVNVK KYKGQAVAVD TYCWLHKGAI ACAEKLAKGE PTDRYVGFCM
KFVNMLLSYG VKPILIFDGC TLPSKKEVER SRRERRQSNL LKGKQLLREG KVSEARDCFA
RSINITHAMA HKVIKAARAL GVDCLVAPYE ADAQLAYLNK AGIVQAVITE DSDLLAFGCK
KVILKMDQFG NGLEVDQARL GMCKQLGDVF TEEKFRYMCI LSGCDYLASL RGIGLAKACK
VLRLANNPDI VKVIKKIGHY LRMNITVPED YITGFIRANN TFLYQLVFDP IQRKLVPLNA
YGDDVNPETL TYAGQYVGDS VALQIALGNR DVNTFEQIDD YSPDTMPAHS RSHSWNEKAG
QKPPGTNSIW HKNYCPRLEV NSVSHAPQLK EKPSTLGLKQ VISTKGLNLP RKSCVLKRPR
NEALAEDDLL SQYSSVSKKI KENGCGDGTS PNSSKMSKSC PDSGTAHKTD AHTPSKMRNK
FATFLQRRNE ESGAVVVPGT RSRFFCSSQD FDNFIPKKES GQPLNETVAT GKATTSLLGA
LDCPDTEGHK PVDANGTHNL SSQIPGNAAV SPEDEAQSSE TSKLLGAMSP PSLGTLRSCF
SWSGTLREFS RTPSPSASTT LQQFRRKSDP PACLPEASAV VTDRCDSKSE MLGETSQPLH
ELGCSSRSQE SMDSSCGLNT SSLSQPSSRD SGSEESDCNN KSLDNQGEQN SKQHLPHFSK
KDGLRRNKVP GLCRSSSMDS FSTTKIKPLV PARVSGLSKK SGSMQTRKHH DVENKPGLQT
KISELWKNFG FKKDSEKLPS CKKPLSPVKD NIQLTPETED EIFNKPECVR AQRAIFH
