EXO1_HUMAN
ID EXO1_HUMAN Reviewed; 846 AA.
AC Q9UQ84; O60545; O75214; O75466; Q5T396; Q96IJ1; Q9UG38; Q9UNW0;
DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 24-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Exonuclease 1;
DE Short=hExo1;
DE EC=3.1.-.-;
DE AltName: Full=Exonuclease I;
DE Short=hExoI;
GN Name=EXO1; Synonyms=EXOI, HEX1;
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] (ISOFORM 1), INTERACTION WITH MSH2, TISSUE
RP SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670; CYS-723 AND LEU-757.
RX PubMed=9788596;
RA Schmutte C., Marinescu R.C., Sadoff M.M., Guerrette S., Overhauser J.,
RA Fishel R.;
RT "Human exonuclease I interacts with the mismatch repair protein hMSH2.";
RL Cancer Res. 58:4537-4542(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, TISSUE
RP SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
RX PubMed=9823303;
RA Tishkoff D.X., Amin N.S., Viars C.S., Arden K.C., Kolodner R.D.;
RT "Identification of a human gene encoding a homologue of Saccharomyces
RT cerevisiae EXO1, an exonuclease implicated in mismatch repair and
RT recombination.";
RL Cancer Res. 58:5027-5031(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], ALTERNATIVE SPLICING, FUNCTION,
RP TISSUE SPECIFICITY, AND VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
RC TISSUE=Sperm;
RX PubMed=9685493; DOI=10.1093/nar/26.16.3762;
RA Wilson D.M. III, Carney J.P., Coleman M.A., Adamson A.W., Christensen M.,
RA Lamerdin J.E.;
RT "Hex1: a new human Rad2 nuclease family member with homology to yeast
RT exonuclease 1.";
RL Nucleic Acids Res. 26:3762-3768(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PROTEIN SEQUENCE OF 1-7 (ISOFORMS
RP 1/2), FUNCTION, AND VARIANTS ARG-354; LYS-589; GLY-670 AND CYS-723.
RX PubMed=10364235; DOI=10.1074/jbc.274.25.17893;
RA Qiu J., Qian Y., Chen V., Guan M.-X., Shen B.;
RT "Human exonuclease 1 functionally complements its yeast homologues in DNA
RT recombination, RNA primer removal, and mutation avoidance.";
RL J. Biol. Chem. 274:17893-17900(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-76; GLY-93; SER-279;
RP SER-299; ARG-354; ASN-428; MET-439; TYR-456; MET-458; LEU-460; THR-503;
RP LYS-589; GLN-634; GLY-670; CYS-723; LEU-757 AND GLU-759.
RG NIEHS SNPs program;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS GLY-670
RP AND CYS-723.
RC TISSUE=Skin;
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 175-846 (ISOFORM 1), AND VARIANTS
RP LYS-589; GLY-670 AND CYS-723.
RC TISSUE=Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [9]
RP FUNCTION.
RX PubMed=10608837; DOI=10.1074/jbc.274.53.37763;
RA Lee B.-I., Wilson D.M. III;
RT "The RAD2 domain of human exonuclease 1 exhibits 5' to 3' exonuclease and
RT flap structure-specific endonuclease activities.";
RL J. Biol. Chem. 274:37763-37769(1999).
RN [10]
RP INTERACTION WITH MSH2, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10856833; DOI=10.1016/s0921-8777(00)00012-4;
RA Rasmussen L.J., Rasmussen M., Lee B.-I., Rasmussen A.K., Wilson D.M. III,
RA Nielsen F.C., Bisgaard H.C.;
RT "Identification of factors interacting with hMSH2 in the fetal liver
RT utilizing the yeast two-hybrid system. In vivo interaction through the C-
RT terminal domains of hEXO1 and hMSH2 and comparative expression analysis.";
RL Mutat. Res. 460:41-52(2000).
RN [11]
RP INTERACTION WITH MLH1; MSH2 AND MSH3.
RX PubMed=11427529; DOI=10.1074/jbc.m102670200;
RA Schmutte C., Sadoff M.M., Shim K.-S., Acharya S., Fishel R.;
RT "The interaction of DNA mismatch repair proteins with human exonuclease
RT I.";
RL J. Biol. Chem. 276:33011-33018(2001).
RN [12]
RP INTERACTION WITH MLH1 AND MSH2, AND SUBCELLULAR LOCATION.
RX PubMed=11429708; DOI=10.1038/sj.onc.1204467;
RA Jaeger A.C., Rasmussen M., Bisgaard H.C., Singh K.K., Nielsen F.C.,
RA Rasmussen L.J.;
RT "HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence
RT assembly of hMutLalpha and hMLH1-hEXO1 complexes.";
RL Oncogene 20:3590-3595(2001).
RN [13]
RP FUNCTION, INTERACTION WITH MLH1 AND MSH2, AND CHARACTERIZATION OF VARIANTS
RP LYS-109; ARG-410; SER-640; GLU-759 AND LEU-770.
RX PubMed=12414623;
RA Sun X., Zheng L., Shen B.;
RT "Functional alterations of human exonuclease 1 mutants identified in
RT atypical hereditary nonpolyposis colorectal cancer syndrome.";
RL Cancer Res. 62:6026-6030(2002).
RN [14]
RP FUNCTION.
RX PubMed=11809771; DOI=10.1074/jbc.m111854200;
RA Genschel J., Bazemore L.R., Modrich P.;
RT "Human exonuclease I is required for 5' and 3' mismatch repair.";
RL J. Biol. Chem. 277:13302-13311(2002).
RN [15]
RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF ASP-78; ASP-173 AND ASP-225.
RX PubMed=11842105; DOI=10.1093/nar/30.4.942;
RA Lee B.-I., Nguyen L.H., Barsky D., Fernandes M., Wilson D.M. III;
RT "Molecular interactions of human Exo1 with DNA.";
RL Nucleic Acids Res. 30:942-949(2002).
RN [16]
RP INVOLVEMENT IN COLORECTAL CANCER.
RX PubMed=14623461; DOI=10.1016/s0165-4608(03)00196-1;
RA Alam N.A., Gorman P., Jaeger E.E.M., Kelsell D., Leigh I.M., Ratnavel R.,
RA Murdoch M.E., Houlston R.S., Aaltonen L.A., Roylance R.R.,
RA Tomlinson I.P.M.;
RT "Germline deletions of EXO1 do not cause colorectal tumors and lesions
RT which are null for EXO1 do not have microsatellite instability.";
RL Cancer Genet. Cytogenet. 147:121-127(2003).
RN [17]
RP FUNCTION, AND INTERACTION WITH WRN.
RX PubMed=12704184; DOI=10.1074/jbc.m212798200;
RA Sharma S., Sommers J.A., Driscoll H.C., Uzdilla L.A., Wilson T.M.,
RA Brosh R.M. Jr.;
RT "The exonucleolytic and endonucleolytic cleavage activities of human
RT exonuclease 1 are stimulated by an interaction with the carboxyl-terminal
RT region of the Werner syndrome protein.";
RL J. Biol. Chem. 278:23487-23496(2003).
RN [18]
RP FUNCTION.
RX PubMed=14636568; DOI=10.1016/s1097-2765(03)00428-3;
RA Genschel J., Modrich P.;
RT "Mechanism of 5'-directed excision in human mismatch repair.";
RL Mol. Cell 12:1077-1086(2003).
RN [19]
RP FUNCTION, INTERACTION WITH PCNA, AND MUTAGENESIS OF ASP-173.
RX PubMed=15225546; DOI=10.1016/j.molcel.2004.06.016;
RA Dzantiev L., Constantin N., Genschel J., Iyer R.R., Burgers P.M.,
RA Modrich P.;
RT "A defined human system that supports bidirectional mismatch-provoked
RT excision.";
RL Mol. Cell 15:31-41(2004).
RN [20]
RP FUNCTION, INTERACTION WITH MLH1 AND MSH2, AND SUBCELLULAR LOCATION.
RX PubMed=14676842; DOI=10.1038/sj.onc.1207265;
RA Nielsen F.C., Jaeger A.C., Luetzen A., Bundgaard J.R., Rasmussen L.J.;
RT "Characterization of human exonuclease 1 in complex with mismatch repair
RT proteins, subcellular localization and association with PCNA.";
RL Oncogene 23:1457-1468(2004).
RN [21]
RP FUNCTION.
RX PubMed=16143102; DOI=10.1016/j.cell.2005.06.027;
RA Zhang Y., Yuan F., Presnell S.R., Tian K., Gao Y., Tomkinson A.E., Gu L.,
RA Li G.-M.;
RT "Reconstitution of 5'-directed human mismatch repair in a purified
RT system.";
RL Cell 122:693-705(2005).
RN [22]
RP FUNCTION, AND INTERACTION WITH RECQL.
RX PubMed=15886194; DOI=10.1074/jbc.m500265200;
RA Doherty K.M., Sharma S., Uzdilla L.A., Wilson T.M., Cui S., Vindigni A.,
RA Brosh R.M. Jr.;
RT "RECQ1 helicase interacts with human mismatch repair factors that regulate
RT genetic recombination.";
RL J. Biol. Chem. 280:28085-28094(2005).
RN [23]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-418 AND ARG-419.
RX PubMed=17426132; DOI=10.1093/nar/gkl1166;
RA Knudsen N.O., Nielsen F.C., Vinther L., Bertelsen R., Holten-Andersen S.,
RA Liberti S.E., Hofstra R., Kooi K., Rasmussen L.J.;
RT "Nuclear localization of human DNA mismatch repair protein exonuclease 1
RT (hEXO1).";
RL Nucleic Acids Res. 35:2609-2619(2007).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [25]
RP PHOSPHORYLATION AT SER-376; SER-422; SER-454; THR-581; SER-598; THR-621;
RP SER-623; SER-639; SER-660; SER-674; SER-714 AND SER-746, ACETYLATION AT
RP LYS-482, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-454;
RP THR-621 AND SER-714.
RX PubMed=18048416; DOI=10.1093/nar/gkm1052;
RA El-Shemerly M., Hess D., Pyakurel A.K., Moselhy S., Ferrari S.;
RT "ATR-dependent pathways control hEXO1 stability in response to stalled
RT forks.";
RL Nucleic Acids Res. 36:511-519(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-422, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [27]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-598; SER-610 AND SER-623, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [29]
RP VARIANTS ALA-27; LYS-109; ARG-410; GLY-610; ALA-640; SER-640; GLU-759 AND
RP LEU-770.
RX PubMed=11375940; DOI=10.1053/gast.2001.25117;
RA Wu Y., Berends M.J.W., Post J.G., Mensink R.G.J., Verlind E.,
RA van der Sluis T., Kempinga C., Sijmons R.H., van der Zee A.G.J.,
RA Hollema H., Kleibeuker J.H., Buys C.H.C.M., Hofstra R.M.W.;
RT "Germline mutations of EXO1 gene in patients with hereditary nonpolyposis
RT colorectal cancer (HNPCC) and atypical HNPCC forms.";
RL Gastroenterology 120:1580-1587(2001).
RN [30]
RP VARIANTS SER-137; ARG-410; CYS-438; GLY-610; ALA-640; SER-640; GLU-759 AND
RP VAL-827.
RX PubMed=12517792;
RA Jagmohan-Changur S., Poikonen T., Vilkki S., Launonen V., Wikman F.,
RA Orntoft T.F., Moeller P., Vasen H., Tops C., Kolodner R.D., Mecklin J.-P.,
RA Jaervinen H., Bevan S., Houlston R.S., Aaltonen L.A., Fodde R., Wijnen J.,
RA Karhu A.;
RT "EXO1 variants occur commonly in normal population: evidence against a role
RT in hereditary nonpolyposis colorectal cancer.";
RL Cancer Res. 63:154-158(2003).
RN [31]
RP VARIANTS MET-439; GLY-670; PRO-726 AND LEU-757.
RX PubMed=14756672; DOI=10.1111/j.1399-0004.2004.00214.x;
RA Thompson E., Meldrum C.J., Crooks R., McPhillips M., Thomas L.,
RA Spigelman A.D., Scott R.J.;
RT "Hereditary non-polyposis colorectal cancer and the role of hPMS2 and hEXO1
RT mutations.";
RL Clin. Genet. 65:215-225(2004).
RN [32]
RP VARIANTS MET-439 AND LEU-757.
RX PubMed=15550454; DOI=10.1093/carcin/bgh335;
RA Yamamoto H., Hanafusa H., Ouchida M., Yano M., Suzuki H., Murakami M.,
RA Aoe M., Shimizu N., Nakachi K., Shimizu K.;
RT "Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal
RT cancer in a Japanese population.";
RL Carcinogenesis 26:411-416(2005).
RN [33]
RP VARIANT VAL-153.
RX PubMed=25860647; DOI=10.1007/s10689-015-9803-2;
RA Hansen M.F., Johansen J., Bjoernevoll I., Sylvander A.E., Steinsbekk K.S.,
RA Saetrom P., Sandvik A.K., Drabloes F., Sjursen W.;
RT "A novel POLE mutation associated with cancers of colon, pancreas, ovaries
RT and small intestine.";
RL Fam. Cancer 14:437-448(2015).
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:10364235, ECO:0000269|PubMed:10608837,
CC ECO:0000269|PubMed:11809771, ECO:0000269|PubMed:11842105,
CC ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12704184,
CC ECO:0000269|PubMed:14636568, ECO:0000269|PubMed:14676842,
CC ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15886194,
CC ECO:0000269|PubMed:16143102, ECO:0000269|PubMed:9685493}.
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.
CC {ECO:0000269|PubMed:10856833, ECO:0000269|PubMed:11427529,
CC ECO:0000269|PubMed:11429708, ECO:0000269|PubMed:12414623,
CC ECO:0000269|PubMed:12704184, ECO:0000269|PubMed:14676842,
CC ECO:0000269|PubMed:15225546, ECO:0000269|PubMed:15886194,
CC ECO:0000269|PubMed:9788596}.
CC -!- INTERACTION:
CC Q9UQ84; Q99708: RBBP8; NbExp=4; IntAct=EBI-944667, EBI-745715;
CC Q9UQ84-1; P43246: MSH2; NbExp=3; IntAct=EBI-944694, EBI-355888;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11429708,
CC ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:17426132}.
CC Note=Colocalizes with PCNA to discrete nuclear foci in S-phase.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=B;
CC IsoId=Q9UQ84-1; Sequence=Displayed;
CC Name=2; Synonyms=A;
CC IsoId=Q9UQ84-4; Sequence=VSP_017029, VSP_017030;
CC -!- TISSUE SPECIFICITY: Highly expressed in bone marrow, testis and thymus.
CC Expressed at lower levels in colon, lymph nodes, ovary, placenta,
CC prostate, small intestine, spleen and stomach.
CC {ECO:0000269|PubMed:10856833, ECO:0000269|PubMed:9685493,
CC ECO:0000269|PubMed:9788596, ECO:0000269|PubMed:9823303}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed in fetal liver and at lower
CC levels in fetal brain, heart, kidney, spleen and thymus.
CC {ECO:0000269|PubMed:10856833}.
CC -!- PTM: Phosphorylated upon DNA damage and in response to agents stalling
CC DNA replication, probably by ATM or ATR. Phosphorylation at Ser-454,
CC Thr-621 and Ser-714 is induced upon DNA-damage caused by treatment with
CC hydroxyurea (HU) but not upon IR treatment. The HU-induced EXO1 triple
CC phosphorylation facilitates destabilization/degradation of the protein.
CC {ECO:0000269|PubMed:18048416}.
CC -!- POLYMORPHISM: Most naturally occurring variants in this protein are not
CC associated with familial disposition to hereditary non-polyposis
CC colorectal cancer (HNPCC) (PubMed:12517792). Furthermore, germline
CC deletions involving this locus are not associated with clinically
CC manifested colorectal tumors (PubMed:14623461).
CC {ECO:0000269|PubMed:12517792, ECO:0000269|PubMed:14623461}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. EXO1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC33874.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/exo1/";
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DR EMBL; AF084974; AAD13754.1; -; mRNA.
DR EMBL; AF091740; AAC63043.1; -; mRNA.
DR EMBL; AF091754; AAC69879.1; -; Genomic_DNA.
DR EMBL; AF091742; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091743; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091744; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091745; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091746; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091747; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091748; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091749; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091750; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091751; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091752; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091753; AAC69879.1; JOINED; Genomic_DNA.
DR EMBL; AF091754; AAC69880.1; -; Genomic_DNA.
DR EMBL; AF091742; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091743; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091744; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091745; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091746; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091747; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091748; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091749; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091750; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091751; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091752; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF091753; AAC69880.1; JOINED; Genomic_DNA.
DR EMBL; AF042282; AAC32259.1; -; mRNA.
DR EMBL; AC004783; AAC32424.1; -; Genomic_DNA.
DR EMBL; AF060479; AAC33874.1; ALT_FRAME; mRNA.
DR EMBL; AF549168; AAN39382.1; -; Genomic_DNA.
DR EMBL; AL365366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007491; AAH07491.1; -; mRNA.
DR EMBL; AL080139; CAB45733.1; -; mRNA.
DR CCDS; CCDS1620.1; -. [Q9UQ84-1]
DR CCDS; CCDS44336.1; -. [Q9UQ84-4]
DR PIR; T12524; T12524.
DR RefSeq; NP_003677.4; NM_003686.4. [Q9UQ84-4]
DR RefSeq; NP_006018.4; NM_006027.4. [Q9UQ84-1]
DR RefSeq; NP_569082.2; NM_130398.3. [Q9UQ84-1]
DR RefSeq; XP_006711903.1; XM_006711840.2. [Q9UQ84-1]
DR RefSeq; XP_011542623.1; XM_011544321.1. [Q9UQ84-1]
DR RefSeq; XP_011542624.1; XM_011544322.1. [Q9UQ84-1]
DR PDB; 3QE9; X-ray; 2.51 A; Y/Z=1-352.
DR PDB; 3QEA; X-ray; 3.10 A; Z=1-352.
DR PDB; 3QEB; X-ray; 3.00 A; Z=1-352.
DR PDB; 5UZV; X-ray; 2.45 A; Z=1-352.
DR PDB; 5V04; X-ray; 2.65 A; Z=1-352.
DR PDB; 5V05; X-ray; 2.90 A; Z=1-352.
DR PDB; 5V06; X-ray; 2.75 A; Z=1-352.
DR PDB; 5V07; X-ray; 2.15 A; Z=1-352.
DR PDB; 5V08; X-ray; 2.81 A; Z=1-352.
DR PDB; 5V09; X-ray; 2.75 A; Z=1-352.
DR PDB; 5V0A; X-ray; 2.38 A; Z=1-352.
DR PDB; 5V0B; X-ray; 2.63 A; Z=1-352.
DR PDB; 5V0C; X-ray; 2.58 A; Z=1-352.
DR PDB; 5V0D; X-ray; 2.63 A; Z=1-352.
DR PDB; 5V0E; X-ray; 2.74 A; Z=1-352.
DR PDBsum; 3QE9; -.
DR PDBsum; 3QEA; -.
DR PDBsum; 3QEB; -.
DR PDBsum; 5UZV; -.
DR PDBsum; 5V04; -.
DR PDBsum; 5V05; -.
DR PDBsum; 5V06; -.
DR PDBsum; 5V07; -.
DR PDBsum; 5V08; -.
DR PDBsum; 5V09; -.
DR PDBsum; 5V0A; -.
DR PDBsum; 5V0B; -.
DR PDBsum; 5V0C; -.
DR PDBsum; 5V0D; -.
DR PDBsum; 5V0E; -.
DR AlphaFoldDB; Q9UQ84; -.
DR SMR; Q9UQ84; -.
DR BioGRID; 114602; 47.
DR CORUM; Q9UQ84; -.
DR DIP; DIP-36701N; -.
DR IntAct; Q9UQ84; 19.
DR MINT; Q9UQ84; -.
DR STRING; 9606.ENSP00000355506; -.
DR ChEMBL; CHEMBL4523496; -.
DR iPTMnet; Q9UQ84; -.
DR PhosphoSitePlus; Q9UQ84; -.
DR BioMuta; EXO1; -.
DR DMDM; 85700954; -.
DR EPD; Q9UQ84; -.
DR jPOST; Q9UQ84; -.
DR MassIVE; Q9UQ84; -.
DR MaxQB; Q9UQ84; -.
DR PaxDb; Q9UQ84; -.
DR PeptideAtlas; Q9UQ84; -.
DR PRIDE; Q9UQ84; -.
DR ProteomicsDB; 85518; -. [Q9UQ84-1]
DR ProteomicsDB; 85519; -. [Q9UQ84-4]
DR Antibodypedia; 34705; 390 antibodies from 34 providers.
DR DNASU; 9156; -.
DR Ensembl; ENST00000348581.9; ENSP00000311873.5; ENSG00000174371.17. [Q9UQ84-1]
DR Ensembl; ENST00000366548.8; ENSP00000355506.3; ENSG00000174371.17. [Q9UQ84-1]
DR Ensembl; ENST00000518483.5; ENSP00000430251.1; ENSG00000174371.17. [Q9UQ84-4]
DR GeneID; 9156; -.
DR KEGG; hsa:9156; -.
DR MANE-Select; ENST00000366548.8; ENSP00000355506.3; NM_130398.4; NP_569082.2.
DR UCSC; uc001hzh.4; human. [Q9UQ84-1]
DR CTD; 9156; -.
DR DisGeNET; 9156; -.
DR GeneCards; EXO1; -.
DR HGNC; HGNC:3511; EXO1.
DR HPA; ENSG00000174371; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 606063; gene.
DR neXtProt; NX_Q9UQ84; -.
DR OpenTargets; ENSG00000174371; -.
DR PharmGKB; PA27923; -.
DR VEuPathDB; HostDB:ENSG00000174371; -.
DR eggNOG; KOG2518; Eukaryota.
DR GeneTree; ENSGT00510000047676; -.
DR HOGENOM; CLU_009851_0_0_1; -.
DR InParanoid; Q9UQ84; -.
DR OMA; VNSIWHR; -.
DR OrthoDB; 796591at2759; -.
DR PhylomeDB; Q9UQ84; -.
DR TreeFam; TF314997; -.
DR BRENDA; 3.1.11.1; 2681.
DR PathwayCommons; Q9UQ84; -.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; Q9UQ84; -.
DR SIGNOR; Q9UQ84; -.
DR BioGRID-ORCS; 9156; 31 hits in 1088 CRISPR screens.
DR ChiTaRS; EXO1; human.
DR EvolutionaryTrace; Q9UQ84; -.
DR GeneWiki; Exonuclease_1; -.
DR GenomeRNAi; 9156; -.
DR Pharos; Q9UQ84; Tbio.
DR PRO; PR:Q9UQ84; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9UQ84; protein.
DR Bgee; ENSG00000174371; Expressed in ventricular zone and 130 other tissues.
DR ExpressionAtlas; Q9UQ84; baseline and differential.
DR Genevisible; Q9UQ84; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0035312; F:5'-3' exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISS:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0051908; F:double-stranded DNA 5'-3' exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0004527; F:exonuclease activity; TAS:ProtInc.
DR GO; GO:0048256; F:flap endonuclease activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; TAS:ProtInc.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0006310; P:DNA recombination; IGI:UniProtKB.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; IEA:Ensembl.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IEA:Ensembl.
DR GO; GO:0090656; P:t-circle formation; TAS:BHF-UCL.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Direct protein sequencing;
KW DNA damage; DNA excision; DNA repair; DNA-binding; Endonuclease;
KW Excision nuclease; Exonuclease; Hydrolase; Immunity; Magnesium; Meiosis;
KW Metal-binding; Nuclease; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..846
FT /note="Exonuclease 1"
FT /id="PRO_0000154039"
FT REGION 1..99
FT /note="N-domain"
FT REGION 129..387
FT /note="Interaction with MSH3"
FT /evidence="ECO:0000269|PubMed:11427529"
FT REGION 138..229
FT /note="I-domain"
FT REGION 372..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 388..490
FT /note="Interaction with MLH1"
FT REGION 600..846
FT /note="Interaction with MSH2"
FT REGION 618..781
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 787..846
FT /note="Interaction with MLH1"
FT MOTIF 418..421
FT /note="Nuclear localization signal"
FT COMPBIAS 618..654
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..669
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..696
FT /note="Polar 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|UniProtKB:P39748"
FT BINDING 78
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT BINDING 150
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q17RS7"
FT BINDING 152
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:3QEB, ECO:0007744|PDB:5V05,
FT ECO:0007744|PDB:5V06, ECO:0007744|PDB:5V07,
FT ECO:0007744|PDB:5V08, ECO:0007744|PDB:5V09,
FT ECO:0007744|PDB:5V0A, ECO:0007744|PDB:5V0B,
FT ECO:0007744|PDB:5V0D"
FT BINDING 171
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:3QEB, ECO:0007744|PDB:5V05,
FT ECO:0007744|PDB:5V06, ECO:0007744|PDB:5V07,
FT ECO:0007744|PDB:5V08, ECO:0007744|PDB:5V09,
FT ECO:0007744|PDB:5V0A, ECO:0007744|PDB:5V0B,
FT ECO:0007744|PDB:5V0D"
FT BINDING 173
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:3QEB, ECO:0007744|PDB:5V05,
FT ECO:0007744|PDB:5V06, ECO:0007744|PDB:5V09,
FT ECO:0007744|PDB:5V0A, ECO:0007744|PDB:5V0B,
FT ECO:0007744|PDB:5V0D"
FT BINDING 225
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 270
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q58839"
FT MOD_RES 376
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 422
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 454
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 482
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 581
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 598
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 610
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 639
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 674
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 714
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:18048416"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18048416"
FT VAR_SEQ 803
FT /note="D -> F (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10364235"
FT /id="VSP_017029"
FT VAR_SEQ 804..846
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10364235"
FT /id="VSP_017030"
FT VARIANT 27
FT /note="V -> A (in dbSNP:rs1472620416)"
FT /evidence="ECO:0000269|PubMed:11375940"
FT /id="VAR_024966"
FT VARIANT 76
FT /note="V -> I (in dbSNP:rs4149864)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024967"
FT VARIANT 93
FT /note="R -> G (in dbSNP:rs4149865)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024968"
FT VARIANT 109
FT /note="E -> K (abrogates exonuclease activity;
FT dbSNP:rs143546023)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12414623"
FT /id="VAR_024969"
FT VARIANT 137
FT /note="A -> S (in dbSNP:rs147663824)"
FT /evidence="ECO:0000269|PubMed:12517792"
FT /id="VAR_024970"
FT VARIANT 153
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:25860647"
FT /id="VAR_077352"
FT VARIANT 279
FT /note="N -> S (in dbSNP:rs4149909)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024971"
FT VARIANT 299
FT /note="N -> S (in dbSNP:rs4149910)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024972"
FT VARIANT 354
FT /note="H -> R (in dbSNP:rs735943)"
FT /evidence="ECO:0000269|PubMed:10364235,
FT ECO:0000269|PubMed:9685493, ECO:0000269|PubMed:9788596,
FT ECO:0000269|PubMed:9823303, ECO:0000269|Ref.5"
FT /id="VAR_024973"
FT VARIANT 410
FT /note="L -> R (abrogates exonuclease activity;
FT dbSNP:rs571928768)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12517792"
FT /id="VAR_024974"
FT VARIANT 428
FT /note="D -> N (in dbSNP:rs4149962)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024975"
FT VARIANT 438
FT /note="F -> C"
FT /evidence="ECO:0000269|PubMed:12517792"
FT /id="VAR_024976"
FT VARIANT 439
FT /note="T -> M (may be associated with an increased risk of
FT colorectal cancer; dbSNP:rs4149963)"
FT /evidence="ECO:0000269|PubMed:14756672,
FT ECO:0000269|PubMed:15550454, ECO:0000269|Ref.5"
FT /id="VAR_024977"
FT VARIANT 456
FT /note="S -> Y (in dbSNP:rs4149964)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024978"
FT VARIANT 458
FT /note="V -> M (in dbSNP:rs4149965)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024979"
FT VARIANT 460
FT /note="V -> L (in dbSNP:rs4149966)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024980"
FT VARIANT 503
FT /note="R -> T (in dbSNP:rs4149967)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024981"
FT VARIANT 589
FT /note="E -> K (in dbSNP:rs1047840)"
FT /evidence="ECO:0000269|PubMed:10364235,
FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:9685493,
FT ECO:0000269|PubMed:9788596, ECO:0000269|PubMed:9823303,
FT ECO:0000269|Ref.5"
FT /id="VAR_024982"
FT VARIANT 610
FT /note="S -> G (in dbSNP:rs12122770)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12517792"
FT /id="VAR_024983"
FT VARIANT 634
FT /note="R -> Q (in dbSNP:rs4149978)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_024984"
FT VARIANT 640
FT /note="P -> A (in dbSNP:rs61736331)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12517792"
FT /id="VAR_024985"
FT VARIANT 640
FT /note="P -> S (reduces interaction with MSH2; abrogates
FT interaction with MSH2; when associated with L-770;
FT dbSNP:rs61736331)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12517792"
FT /id="VAR_024986"
FT VARIANT 670
FT /note="E -> G (in dbSNP:rs1776148)"
FT /evidence="ECO:0000269|PubMed:10364235,
FT ECO:0000269|PubMed:14756672, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17974005, ECO:0000269|PubMed:9685493,
FT ECO:0000269|PubMed:9788596, ECO:0000269|PubMed:9823303,
FT ECO:0000269|Ref.5"
FT /id="VAR_024987"
FT VARIANT 723
FT /note="R -> C (in dbSNP:rs1635498)"
FT /evidence="ECO:0000269|PubMed:10364235,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:9685493, ECO:0000269|PubMed:9788596,
FT ECO:0000269|PubMed:9823303, ECO:0000269|Ref.5"
FT /id="VAR_024988"
FT VARIANT 726
FT /note="H -> P"
FT /evidence="ECO:0000269|PubMed:14756672"
FT /id="VAR_024989"
FT VARIANT 757
FT /note="P -> L (may be associated with a reduced risk of
FT colorectal cancer; dbSNP:rs9350)"
FT /evidence="ECO:0000269|PubMed:14756672,
FT ECO:0000269|PubMed:15550454, ECO:0000269|PubMed:9788596,
FT ECO:0000269|Ref.5"
FT /id="VAR_024990"
FT VARIANT 759
FT /note="G -> E (reduces interaction with MSH2; abrogates
FT interaction with MSH2; when associated with L-770;
FT dbSNP:rs4150001)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:12517792,
FT ECO:0000269|Ref.5"
FT /id="VAR_024991"
FT VARIANT 770
FT /note="P -> L (reduces interaction with MSH2; abrogates
FT interaction with MSH2; when associated with S-640 or E-759;
FT dbSNP:rs200622305)"
FT /evidence="ECO:0000269|PubMed:11375940,
FT ECO:0000269|PubMed:12414623"
FT /id="VAR_024992"
FT VARIANT 827
FT /note="A -> V (in dbSNP:rs145975455)"
FT /evidence="ECO:0000269|PubMed:12517792"
FT /id="VAR_024993"
FT MUTAGEN 78
FT /note="D->A: Abrogates double-stranded DNA exonuclease
FT activity and endonuclease activity against 5'-overhanging
FT flap structures. Also reduces DNA-binding to 5'-overhanging
FT flap structures."
FT /evidence="ECO:0000269|PubMed:11842105"
FT MUTAGEN 173
FT /note="D->A: Abrogates double-stranded DNA exonuclease
FT activity and endonuclease activity against 5'-overhanging
FT flap structures. No effect on DNA-binding to 5'-overhanging
FT flap structures."
FT /evidence="ECO:0000269|PubMed:11842105,
FT ECO:0000269|PubMed:15225546"
FT MUTAGEN 225
FT /note="D->A: Abrogates double-stranded DNA exonuclease
FT activity and endonuclease activity against 5'-overhanging
FT flap structures. Also enhances DNA-binding to 5'-
FT overhanging flap structures."
FT /evidence="ECO:0000269|PubMed:11842105"
FT MUTAGEN 418
FT /note="K->A,T: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:17426132"
FT MUTAGEN 419
FT /note="R->A: Complete loss of nuclear localization."
FT /evidence="ECO:0000269|PubMed:17426132"
FT MUTAGEN 454
FT /note="S->A: No rescue of HU-induced degradation. No rescue
FT of HU-induced degradation; when associated with A-714. Loss
FT of HU-sensitivity and resistance to HU-induced degradation;
FT when associated with A-621 and A-714."
FT /evidence="ECO:0000269|PubMed:18048416"
FT MUTAGEN 621
FT /note="T->A: No rescue of HU-induced degradation. No rescue
FT of HU-induced degradation; when associated with A-714. Loss
FT of HU-sensitivity and resistance to HU-induced degradation;
FT when associated with A-454 and A-714."
FT /evidence="ECO:0000269|PubMed:18048416"
FT MUTAGEN 714
FT /note="S->A: No rescue of HU-induced degradation and loss
FT of HU-induced increase of phosphorylation. No rescue of HU-
FT induced degradation; when associated with A-621. No rescue
FT of HU-induced degradation; when associated with A-454. Loss
FT of HU-sensitivity and resistance to HU-induced degradation;
FT when associated with A-454 and A-621."
FT /evidence="ECO:0000269|PubMed:18048416"
FT HELIX 6..9
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 11..13
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 14..18
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 25..30
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 31..40
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 43..48
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 54..68
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 72..77
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 86..107
FT /evidence="ECO:0007829|PDB:5V07"
FT TURN 108..110
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 112..120
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 127..139
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 143..146
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 151..160
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 172..177
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 180..185
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 197..202
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:5V07"
FT TURN 207..210
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 212..221
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:5UZV"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 250..255
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 257..261
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 269..284
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:5V07"
FT TURN 290..293
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 294..299
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 303..305
FT /evidence="ECO:0007829|PDB:5V05"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:5V07"
FT HELIX 319..326
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 332..334
FT /evidence="ECO:0007829|PDB:5V07"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:5V07"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:5V0D"
SQ SEQUENCE 846 AA; 94103 MW; 850BC21CA9790D08 CRC64;
MGIQGLLQFI KEASEPIHVR KYKGQVVAVD TYCWLHKGAI ACAEKLAKGE PTDRYVGFCM
KFVNMLLSHG IKPILVFDGC TLPSKKEVER SRRERRQANL LKGKQLLREG KVSEARECFT
RSINITHAMA HKVIKAARSQ GVDCLVAPYE ADAQLAYLNK AGIVQAIITE DSDLLAFGCK
KVILKMDQFG NGLEIDQARL GMCRQLGDVF TEEKFRYMCI LSGCDYLSSL RGIGLAKACK
VLRLANNPDI VKVIKKIGHY LKMNITVPED YINGFIRANN TFLYQLVFDP IKRKLIPLNA
YEDDVDPETL SYAGQYVDDS IALQIALGNK DINTFEQIDD YNPDTAMPAH SRSHSWDDKT
CQKSANVSSI WHRNYSPRPE SGTVSDAPQL KENPSTVGVE RVISTKGLNL PRKSSIVKRP
RSAELSEDDL LSQYSLSFTK KTKKNSSEGN KSLSFSEVFV PDLVNGPTNK KSVSTPPRTR
NKFATFLQRK NEESGAVVVP GTRSRFFCSS DSTDCVSNKV SIQPLDETAV TDKENNLHES
EYGDQEGKRL VDTDVARNSS DDIPNNHIPG DHIPDKATVF TDEESYSFES SKFTRTISPP
TLGTLRSCFS WSGGLGDFSR TPSPSPSTAL QQFRRKSDSP TSLPENNMSD VSQLKSEESS
DDESHPLREE ACSSQSQESG EFSLQSSNAS KLSQCSSKDS DSEESDCNIK LLDSQSDQTS
KLRLSHFSKK DTPLRNKVPG LYKSSSADSL STTKIKPLGP ARASGLSKKP ASIQKRKHHN
AENKPGLQIK LNELWKNFGF KKDSEKLPPC KKPLSPVRDN IQLTPEAEED IFNKPECGRV
QRAIFQ
