ID MSH2_HUMAN Reviewed; 934 AA.
AC P43246; B4E2Z2; O75488;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 27-MAR-2024, entry version 247.
DE RecName: Full=DNA mismatch repair protein Msh2;
DE Short=hMSH2;
DE AltName: Full=MutS protein homolog 2;
GN Name=MSH2;
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).
RX PubMed=8252616; DOI=10.1016/0092-8674(93)90546-3;
RA Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J.,
RA Kane M.F., Kolodner R.D.;
RT "The human mutator gene homolog MSH2 and its association with hereditary
RT nonpolyposis colon cancer.";
RL Cell 75:1027-1038(1993).
RN [2]
RP ERRATUM OF PUBMED:8252616.
RX PubMed=8156592;
RA Fishel R., Lescoe M., Rao M., Copeland N.G., Jenkins N.A., Garber J.,
RA Kane M.F., Kolodner R.D.;
RL Cell 77:167-167(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS LYNCH1 LEU-622 AND
RP TYR-639.
RX PubMed=8261515; DOI=10.1016/0092-8674(93)90330-s;
RA Leach F.S., Nicolaides N.C., Papadopoulos N., Liu B., Jen J., Parsons R.,
RA Peltomaeki P., Sistonen P., Aaltonen L.A., Nystroem-Lahti M., Guan X.-Y.,
RA Zhang J., Meltzer P.S., Yu J.-W., Kao F.-T., Chen D.J., Cerosaletti K.M.,
RA Fournier R.E.K., Todd S., Lewis T., Leach R.J., Naylor S.L.,
RA Weissenbach J., Mecklin J.-P., Jaervinen H., Petersen G.M., Hamilton S.R.,
RA Green J., Jass J., Watson P., Lynch H.T., Trent J.M., de la Chapelle A.,
RA Kinzler K.W., Vogelstein B.;
RT "Mutations of a mutS homolog in hereditary nonpolyposis colorectal
RT cancer.";
RL Cell 75:1215-1225(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND INVOLVEMENT IN MRTES.
RX PubMed=7713503; DOI=10.1006/geno.1994.1661;
RA Kolodner R.D., Hall N.R., Lipford J., Kane M.F., Rao M.R.S., Morrison P.,
RA Wirth L., Finan P.J., Burn J., Chapman P., Earabino C., Merchant E.,
RA Bishop D.T.;
RT "Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds
RT for msh2 mutations.";
RL Genomics 24:516-526(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT HIS-96.
RX PubMed=7726159;
RA Wijnen J., Vasen H., Khan P.M., Menko F.H., van der Klift H.,
RA van Leeuwen C., van den Broek M., van Leeuwen-Cornelisse I., Nagengast F.,
RA Meijers-Heijboer A., Lindhout D., Griffioen G., Cats A., Kleibeuker J.,
RA Varesco L., Bertario L., Bisgaard M.-L., Mohr J., Fodde R.;
RT "Seven new mutations in hMSH2, an HNPCC gene, identified by denaturing
RT gradient-gel electrophoresis.";
RL Am. J. Hum. Genet. 56:1060-1066(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-8; CYS-43; SER-127;
RP ASP-322 AND PHE-390.
RG NIEHS SNPs program;
RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Muscle;
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 [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 375-425.
RC TISSUE=Blood;
RA Corvello C.M., Bevilacqua R.A.U., Rossi B.M., Simpson A.J.G.;
RT "A novel germline mutation at exon 7 of the hMSH2 gene (417 del G) in a
RT large HNPCC Brazilian kindred.";
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP DNA-BINDING.
RX PubMed=7923193;
RA Fishel R., Ewel A., Lescoe M.K.;
RT "Purified human MSH2 protein binds to DNA containing mismatched
RT nucleotides.";
RL Cancer Res. 54:5539-5542(1994).
RN [13]
RP DNA-BINDING.
RX PubMed=8769132; DOI=10.1006/bbrc.1996.1168;
RA Whitehouse A., Taylor G.R., Deeble J., Phillips S.E., Meredith D.M.,
RA Markham A.F.;
RT "A carboxy terminal domain of the hMSH-2 gene product is sufficient for
RT binding specific mismatched oligonucleotides.";
RL Biochem. Biophys. Res. Commun. 225:289-295(1996).
RN [14]
RP INTERACTION WITH MSH3 AND MSH6.
RX PubMed=8942985; DOI=10.1073/pnas.93.24.13629;
RA Acharya S., Wilson T., Gradia S., Kane M.F., Guerrette S., Marsischky G.T.,
RA Kolodner R.D., Fishel R.;
RT "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:13629-13634(1996).
RN [15]
RP INTERACTION WITH EXO1.
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 [16]
RP FUNCTION.
RX PubMed=9822680; DOI=10.1074/jbc.273.48.32055;
RA Blackwell L.J., Martik D., Bjornson K.P., Bjornson E.S., Modrich P.;
RT "Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is
RT consistent with an ATP-dependent translocation mechanism.";
RL J. Biol. Chem. 273:32055-32062(1998).
RN [17]
RP FUNCTION.
RX PubMed=9822679; DOI=10.1074/jbc.273.48.32049;
RA Blackwell L.J., Bjornson K.P., Modrich P.;
RT "DNA-dependent activation of the hMutSalpha ATPase.";
RL J. Biol. Chem. 273:32049-32054(1998).
RN [18]
RP FUNCTION, AND MUTAGENESIS OF LYS-675.
RX PubMed=9564049; DOI=10.1093/emboj/17.9.2677;
RA Iaccarino I., Marra G., Palombo F., Jiricny J.;
RT "hMSH2 and hMSH6 play distinct roles in mismatch binding and contribute
RT differently to the ATPase activity of hMutSalpha.";
RL EMBO J. 17:2677-2686(1998).
RN [19]
RP MISMATCH-BINDING, AND CHARACTERIZATION OF VARIANT LYNCH1 PRO-524.
RX PubMed=9889267; DOI=10.1093/nar/27.3.736;
RA Clark A.B., Cook M.E., Tran H.T., Gordenin D.A., Resnick M.A., Kunkel T.A.;
RT "Functional analysis of human MutSalpha and MutSbeta complexes in yeast.";
RL Nucleic Acids Res. 27:736-742(1999).
RN [20]
RP FUNCTION.
RX PubMed=10078208; DOI=10.1016/s1097-2765(00)80316-0;
RA Gradia S., Subramanian D., Wilson T., Acharya S., Makhov A., Griffith J.,
RA Fishel R.;
RT "hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched
RT DNA.";
RL Mol. Cell 3:255-261(1999).
RN [21]
RP IDENTIFICATION OF MSH2 AS MEMBER OF BASC.
RX PubMed=10783165;
RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.;
RT "BASC, a super complex of BRCA1-associated proteins involved in the
RT recognition and repair of aberrant DNA structures.";
RL Genes Dev. 14:927-939(2000).
RN [22]
RP INTERACTION WITH EXO1, AND TISSUE SPECIFICITY.
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 [23]
RP FUNCTION.
RX PubMed=10660545; DOI=10.1074/jbc.275.6.3922;
RA Gradia S., Acharya S., Fishel R.;
RT "The role of mismatched nucleotides in activating the hMSH2-hMSH6 molecular
RT switch.";
RL J. Biol. Chem. 275:3922-3930(2000).
RN [24]
RP POSSIBLE INVOLVEMENT IN ENDMC.
RX PubMed=11306449;
RA Schweizer P., Moisio A.L., Kuismanen S.A., Truninger K., Vierumaeki R.,
RA Salovaara R., Arola J., Butzow R., Jiricny J., Peltomaeki P.,
RA Nystroem-Lahti M.;
RT "Lack of MSH2 and MSH6 characterizes endometrial but not colon carcinomas
RT in hereditary nonpolyposis colorectal cancer.";
RL Cancer Res. 61:2813-2815(2001).
RN [25]
RP INTERACTION WITH EXO1.
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 [26]
RP INTERACTION WITH EXO1.
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 [27]
RP INTERACTION WITH EXO1.
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 [28]
RP INVOLVEMENT IN MMRCS2.
RX PubMed=12549480; DOI=10.1086/345297;
RA Bougeard G., Charbonnier F., Moerman A., Martin C., Ruchoux M.M.,
RA Drouot N., Frebourg T.;
RT "Early onset brain tumor and lymphoma in MSH2-deficient children.";
RL Am. J. Hum. Genet. 72:213-216(2003).
RN [29]
RP INTERACTION WITH ATR, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14657349; DOI=10.1073/pnas.2536810100;
RA Wang Y., Qin J.;
RT "MSH2 and ATR form a signaling module and regulate two branches of the
RT damage response to DNA methylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
RN [30]
RP INTERACTION WITH EXO1.
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 [31]
RP FUNCTION.
RX PubMed=15064730; DOI=10.1038/sj.onc.1207462;
RA Yang Q., Zhang R., Wang X.W., Linke S.P., Sengupta S., Hickson I.D.,
RA Pedrazzi G., Perrera C., Stagljar I., Littman S.J., Modrich P.,
RA Harris C.C.;
RT "The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM helicase.";
RL Oncogene 23:3749-3756(2004).
RN [32]
RP PHOSPHORYLATION BY PRKCZ.
RX PubMed=15808853; DOI=10.1016/j.jmb.2005.02.001;
RA Hernandez-Pigeon H., Quillet-Mary A., Louat T., Schambourg A., Humbert O.,
RA Selves J., Salles B., Laurent G., Lautier D.;
RT "hMutS alpha is protected from ubiquitin-proteasome-dependent degradation
RT by atypical protein kinase C zeta phosphorylation.";
RL J. Mol. Biol. 348:63-74(2005).
RN [33]
RP INVOLVEMENT IN MMRCS2.
RX PubMed=16372347; DOI=10.1002/ajmg.a.31070;
RA Mueller A., Schackert H.K., Lange B., Rueschoff J., Fuezesi L., Willert J.,
RA Burfeind P., Shah P., Becker H., Epplen J.T., Stemmler S.;
RT "A novel MSH2 germline mutation in homozygous state in two brothers with
RT colorectal cancers diagnosed at the age of 11 and 12 years.";
RL Am. J. Med. Genet. A 140:195-199(2006).
RN [34]
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 [35]
RP FUNCTION.
RX PubMed=17611581; DOI=10.1038/sj.jid.5700941;
RA Seifert M., Scherer S.J., Edelmann W., Bohm M., Meineke V., Lobrich M.,
RA Tilgen W., Reichrath J.;
RT "The DNA-mismatch repair enzyme hMSH2 modulates UV-B-induced cell cycle
RT arrest and apoptosis in melanoma cells.";
RL J. Invest. Dermatol. 128:203-213(2008).
RN [36]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-555, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [37]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [38]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-921, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [40]
RP FUNCTION, IDENTIFICATION IN THE MMR COMPLEX, INTERACTION WITH MCM9 AND
RP MCM8, AND SUBCELLULAR LOCATION.
RX PubMed=26300262; DOI=10.1016/j.molcel.2015.07.010;
RA Traver S., Coulombe P., Peiffer I., Hutchins J.R., Kitzmann M.,
RA Latreille D., Mechali M.;
RT "MCM9 Is Required for Mammalian DNA Mismatch Repair.";
RL Mol. Cell 59:831-839(2015).
RN [41]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-430, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [42]
RP CHARACTERIZATION OF VARIANTS LYNCH1 PRO-33; MET-44; VAL-45; SER-127;
RP MET-145; ASP-161; ARG-162; ARG-164; PRO-173; ARG-187; PRO-187; VAL-272;
RP TYR-333; LEU-519; ASN-603; PRO-636; ALA-674; VAL-688; PHE-697;
RP 745-ILE-ILE-746 DEL; LYS-749; THR-834; GLY-886 AND GLU-923,
RP CHARACTERIZATION OF VARIANTS ASP-322 AND ILE-722, AND FUNCTION.
RX PubMed=21120944; DOI=10.1002/humu.21409;
RA Kansikas M., Kariola R., Nystroem M.;
RT "Verification of the three-step model in assessing the pathogenicity of
RT mismatch repair gene variants.";
RL Hum. Mutat. 32:107-115(2011).
RN [43]
RP REVIEW.
RX PubMed=8036718; DOI=10.1016/0168-9525(94)90093-0;
RA Jiricny J.;
RT "Colon cancer and DNA repair: have mismatches met their match?";
RL Trends Genet. 10:164-168(1994).
RN [44]
RP REVIEW ON VARIANTS.
RX PubMed=9259192;
RX DOI=10.1002/(sici)1098-1004(1997)10:2<89::aid-humu1>3.0.co;2-h;
RA Papadopoulos N., Lindblom A.;
RT "Molecular basis of HNPCC: mutations of MMR genes.";
RL Hum. Mutat. 10:89-99(1997).
RN [45]
RP REVIEW.
RX PubMed=17080293; DOI=10.1007/s10735-006-9062-5;
RA Seifert M., Reichrath J.;
RT "The role of the human DNA mismatch repair gene hMSH2 in DNA repair, cell
RT cycle control and apoptosis: implications for pathogenesis, progression and
RT therapy of cancer.";
RL J. Mol. Histol. 37:301-307(2006).
RN [46]
RP INTERACTION WITH SMARCAD1.
RX PubMed=18675275; DOI=10.1016/j.jmb.2008.07.031;
RA Okazaki N., Ikeda S., Ohara R., Shimada K., Yanagawa T., Nagase T.,
RA Ohara O., Koga H.;
RT "The novel protein complex with SMARCAD1/KIAA1122 binds to the vicinity of
RT TSS.";
RL J. Mol. Biol. 382:257-265(2008).
RN [47]
RP INTERACTION WITH SLX4.
RX PubMed=19596235; DOI=10.1016/j.cell.2009.06.030;
RA Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P.,
RA Elledge S.J., Harper J.W.;
RT "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is
RT required for DNA repair.";
RL Cell 138:63-77(2009).
RN [48]
RP POSSIBLE INVOLVEMENT IN ENDMC.
RX PubMed=21642682; DOI=10.1001/jama.2011.743;
RG French Cancer Genetics Network;
RA Bonadona V., Bonaiti B., Olschwang S., Grandjouan S., Huiart L., Longy M.,
RA Guimbaud R., Buecher B., Bignon Y.J., Caron O., Colas C., Nogues C.,
RA Lejeune-Dumoulin S., Olivier-Faivre L., Polycarpe-Osaer F., Nguyen T.D.,
RA Desseigne F., Saurin J.C., Berthet P., Leroux D., Duffour J.,
RA Manouvrier S., Frebourg T., Sobol H., Lasset C., Bonaiti-Pellie C.;
RT "Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6
RT genes in Lynch syndrome.";
RL JAMA 305:2304-2310(2011).
RN [49]
RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS).
RX PubMed=17531815; DOI=10.1016/j.molcel.2007.04.018;
RA Warren J.J., Pohlhaus T.J., Changela A., Iyer R.R., Modrich P.L.,
RA Beese L.S.;
RT "Structure of the human MutSalpha DNA lesion recognition complex.";
RL Mol. Cell 26:579-592(2007).
RN [50]
RP VARIANT LYNCH1 ASN-596 DEL.
RX PubMed=7874129;
RA Mary J.-L., Bishop T., Kolodner R.D., Lipford J.R., Kane M.F., Weber W.,
RA Torhorst J., Mueller H., Spycher M., Scott R.J.;
RT "Mutational analysis of the hMSH2 gene reveals a three base pair deletion
RT in a family predisposed to colorectal cancer development.";
RL Hum. Mol. Genet. 3:2067-2069(1994).
RN [51]
RP VARIANTS PHE-390 AND LYS-419.
RX PubMed=8690195; DOI=10.1053/gast.1996.v111.pm8690195;
RA Konishi M., Kikuchi-Yanoshita R., Tanaka K., Muraoka M., Onda A.,
RA Okumura Y., Kishi N., Iwama T., Mori T., Koike M., Ushio K., Chiba M.,
RA Nomizu S., Konishi F., Utsunomiya J., Miyaki M.;
RT "Molecular nature of colon tumors in hereditary nonpolyposis colon cancer,
RT familial polyposis, and sporadic colon cancer.";
RL Gastroenterology 111:307-317(1996).
RN [52]
RP VARIANT ASP-322.
RX PubMed=8566964; DOI=10.1007/bf02265276;
RA Maliaka Y.K., Chudina A.P., Belev N.F., Alday P., Bochkov N.P.,
RA Buerstedde J.-M.;
RT "CpG dinucleotides in the hMSH2 and hMLH1 genes are hotspots for HNPCC
RT mutations.";
RL Hum. Genet. 97:251-255(1996).
RN [53]
RP VARIANT LYNCH1 ASN-596 DEL, AND VARIANT HIS-167.
RX PubMed=8872463; DOI=10.1093/hmg/5.9.1245;
RA Moslein G., Tester D.J., Lindor N.M., Honchel R., Cunningham J.M.,
RA French A.J., Halling K.C., Schwab M., Goretzki P., Thibodeau S.N.;
RT "Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in
RT patients with sporadic, familial and hereditary colorectal cancer.";
RL Hum. Mol. Genet. 5:1245-1252(1996).
RN [54]
RP VARIANT LYNCH1 TYR-506.
RX PubMed=8797773; DOI=10.1093/jnci/88.18.1317;
RA Han H.-J., Yuan Y., Ku J.-L., Oh J.-H., Won Y.-J., Kang K.J., Kim K.Y.,
RA Kim S., Kim C.Y., Kim J.-P., Oh N.-G., Lee K.H., Choe K.J., Nakamura Y.,
RA Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in Korean hereditary
RT nonpolyposis colorectal cancer.";
RL J. Natl. Cancer Inst. 88:1317-1319(1996).
RN [55]
RP VARIANT LYNCH1 GLN-46.
RX PubMed=8700523;
RA Bubb V.J., Curtis L.J., Cunningham C., Dunlop M.G., Carothers A.D.,
RA Morris R.G., White S., Bird C.C., Wyllie A.H.;
RT "Microsatellite instability and the role of hMSH2 in sporadic colorectal
RT cancer.";
RL Oncogene 12:2641-2649(1996).
RN [56]
RP VARIANTS LYNCH1 THR-305; ASN-596 DEL AND THR-834.
RX PubMed=9311737; DOI=10.1086/514847;
RA Wijnen J., Khan P.M., Vasen H., van der Klift H., Mulder A.,
RA van Leeuwen-Cornelisse I., Bakker B., Losekoot M., Moeller P., Fodde R.;
RT "Hereditary nonpolyposis colorectal cancer families not complying with the
RT Amsterdam criteria show extremely low frequency of mismatch-repair-gene
RT mutations.";
RL Am. J. Hum. Genet. 61:329-335(1997).
RN [57]
RP VARIANT LYNCH1 CYS-323.
RX PubMed=9240418; DOI=10.1006/bbrc.1997.6942;
RA Akiyama Y., Tsubouchi N., Yuasa Y.;
RT "Frequent somatic mutations of hMSH3 with reference to microsatellite
RT instability in hereditary nonpolyposis colorectal cancers.";
RL Biochem. Biophys. Res. Commun. 236:248-252(1997).
RN [58]
RP VARIANTS LYNCH1 THR-110; ARG-639; LYS-647; HIS-656; THR-679; VAL-729 AND
RP ILE-732.
RX PubMed=9419403;
RA Nakahara M., Yokozaki H., Yasui W., Dohi K., Tahara E.;
RT "Identification of concurrent germ-line mutations in hMSH2 and/or hMLH1 in
RT Japanese hereditary nonpolyposis colorectal cancer kindreds.";
RL Cancer Epidemiol. Biomarkers Prev. 6:1057-1064(1997).
RN [59]
RP VARIANT SER-596.
RX PubMed=8993976;
RX DOI=10.1002/(sici)1098-2264(199701)18:1<8::aid-gcc2>3.0.co;2-7;
RA Viel A., Genuardi M., Capozzi E., Leonardi F., Bellacosa A.,
RA Paravatou-Petsotas M., Pomponi M.G., Fornasarig M., Percesepe A.,
RA Roncucci L., Tamassia M.G., Benatti P., Ponz de Leon M., Valenti A.,
RA Covino M., Anti M., Foletto M., Boiocchi M., Neri G.;
RT "Characterization of MSH2 and MLH1 mutations in Italian families with
RT hereditary nonpolyposis colorectal cancer.";
RL Genes Chromosomes Cancer 18:8-18(1997).
RN [60]
RP VARIANT ASP-322.
RX PubMed=9087566;
RX DOI=10.1002/(sici)1098-2264(199704)18:4<269::aid-gcc4>3.3.co;2-9;
RA Wu Y., Nystroem-Lahti M., Osinga J., Looman M.W.G., Peltomaeki P.,
RA Aaltonen L.A., de la Chapelle A., Hofstra R.M.W., Buys C.H.C.M.;
RT "MSH2 and MLH1 mutations in sporadic replication error-positive colorectal
RT carcinoma as assessed by two-dimensional DNA electrophoresis.";
RL Genes Chromosomes Cancer 18:269-278(1997).
RN [61]
RP VARIANT LYNCH1 VAL-562.
RX PubMed=9048925; DOI=10.1007/s004390050343;
RA Beck N.E., Tomlinson I.P.M., Homfray T., Frayling I., Hodgson S.V.,
RA Harocopos C.J., Bodmer W.F.;
RT "Use of SSCP analysis to identify germline mutations in HNPCC families
RT fulfilling the Amsterdam criteria.";
RL Hum. Genet. 99:219-224(1997).
RN [62]
RP VARIANT LYNCH1 PHE-697, AND VARIANT ASP-322.
RX PubMed=9298827;
RX DOI=10.1002/(sici)1098-1004(1997)10:3<241::aid-humu12>3.0.co;2-#;
RA Wehner M., Buschhausen L., Lamberti C., Kruse R., Caspari R., Propping P.,
RA Friedl W.;
RT "Hereditary nonpolyposis colorectal cancer (HNPCC): eight novel germline
RT mutations in hMSH2 or hMLH1 genes.";
RL Hum. Mutat. 10:241-244(1997).
RN [63]
RP VARIANT LYNCH1 265-VAL--GLN-314 DEL, AND VARIANTS GLY-641 AND VAL-770.
RX PubMed=9718327; DOI=10.1086/301996;
RA Farrington S.M., Lin-Goerke J., Ling J., Wang Y., Burczak J.D.,
RA Robbins D.J., Dunlop M.G.;
RT "Systematic analysis of hMSH2 and hMLH1 in young colon cancer patients and
RT controls.";
RL Am. J. Hum. Genet. 63:749-759(1998).
RN [64]
RP VARIANT GLIOMA ARG-199.
RX PubMed=9777949; DOI=10.1016/s0002-9440(10)65662-3;
RA Leung S.Y., Chan T.L., Chung L.P., Chan A.S.Y., Fan Y.W., Hung K.N.,
RA Kwong W.K., Ho J.W.C., Yuen S.T.;
RT "Microsatellite instability and mutation of DNA mismatch repair genes in
RT gliomas.";
RL Am. J. Pathol. 153:1181-1188(1998).
RN [65]
RP VARIANT CRC TYR-506, AND VARIANT LYNCH1 ILE-688.
RX PubMed=9559627; DOI=10.1007/bf02235756;
RA Yuan Y., Han H.-J., Zheng S., Park J.-G.;
RT "Germline mutations of hMLH1 and hMSH2 genes in patients with suspected
RT hereditary nonpolyposis colorectal cancer and sporadic early-onset
RT colorectal cancer.";
RL Dis. Colon Rectum 41:434-440(1998).
RN [66]
RP VARIANT ASP-322.
RX PubMed=10023327; DOI=10.1016/s0959-8049(98)00217-2;
RA Liu T., Stathopoulos P., Lindblom P., Rubio C., Wasteson Arver B.,
RA Iselius L., Holmberg E., Groenberg H., Lindblom A.;
RT "MSH2 codon 322 Gly to Asp seems not to confer an increased risk for
RT colorectal cancer susceptibility.";
RL Eur. J. Cancer 34:1981-1981(1998).
RN [67]
RP VARIANT LYNCH1 PHE-390.
RX PubMed=9621522; DOI=10.1007/s100380050057;
RA Okamura S., Koyama K., Miyoshi Y., Monden M., Takami M.;
RT "Novel germline mutations of hMSH2 in a patient with hereditary
RT nonpolyposis colorectal cancer 'HNPCC' and in a patient with six primary
RT cancers.";
RL J. Hum. Genet. 43:143-145(1998).
RN [68]
RP VARIANTS LYNCH1 SER-336 AND ASN-596 DEL.
RX PubMed=10375096;
RX DOI=10.1002/(sici)1097-0142(19990615)85:12<2512::aid-cncr4>3.0.co;2-g;
RA Heinimann K., Scott R.J., Buerstedde J.-M., Weber W., Siebold K.,
RA Attenhofer M., Mueller H., Dobbie Z.;
RT "Influence of selection criteria on mutation detection in patients with
RT hereditary nonpolyposis colorectal cancer.";
RL Cancer 85:2512-2518(1999).
RN [69]
RP CHARACTERIZATION OF VARIANTS ASP-322; PHE-390; LYS-419; TYR-506; PRO-524;
RP LEU-622 AND PHE-697.
RX PubMed=10469597; DOI=10.1016/s0960-9822(99)80396-0;
RA Drotschmann K., Clark A.B., Kunkel T.A.;
RT "Mutator phenotypes of common polymorphisms and missense mutations in
RT MSH2.";
RL Curr. Biol. 9:907-910(1999).
RN [70]
RP VARIANTS LYNCH1 GLN-246; SER-596 AND THR-834, AND VARIANT ASP-322.
RX PubMed=10573010; DOI=10.1038/sj.ejhg.5200363;
RA Genuardi M., Carrara S., Anti M., Ponz de Leon M., Viel A.;
RT "Assessment of pathogenicity criteria for constitutional missense mutations
RT of the hereditary nonpolyposis colorectal cancer genes MLH1 and MSH2.";
RL Eur. J. Hum. Genet. 7:778-782(1999).
RN [71]
RP VARIANT LYNCH1 PHE-390.
RX PubMed=10386556; DOI=10.1001/jama.281.24.2316;
RA Weber T.K., Chin H.-M., Rodriguez-Bigas M., Keitz B., Gilligan R.,
RA O'Malley L., Urf E., Diba N., Pazik J., Petrelli N.J.;
RT "Novel hMLH1 and hMSH2 germline mutations in African Americans with
RT colorectal cancer.";
RL JAMA 281:2316-2320(1999).
RN [72]
RP VARIANT LYNCH1 PRO-636.
RX PubMed=10528862; DOI=10.1136/jmg.36.10.792;
RA Yuan Z.Q., Wong N., Foulkes W.D., Alpert L., Manganaro F.,
RA Andreutti-Zaugg C., Iggo R., Anthony K., Hsieh E., Redston M., Pinsky L.,
RA Trifiro M., Gordon P.H., Lasko D.;
RT "A missense mutation in both hMSH2 and APC in an Ashkenazi Jewish HNPCC
RT kindred: implications for clinical screening.";
RL J. Med. Genet. 36:790-793(1999).
RN [73]
RP VARIANTS LYNCH1 ILE-688 AND GLU-845, AND VARIANT MET-8.
RX PubMed=10777691; DOI=10.1006/bbrc.2000.2547;
RA Nomura S., Sugano K., Kashiwabara H., Taniguchi T., Fukayama N., Fujita S.,
RA Akasu T., Moriya Y., Ohhigashi S., Kakizoe T., Sekiya T.;
RT "Enhanced detection of deleterious and other germline mutations of hMSH2
RT and hMLH1 in Japanese hereditary nonpolyposis colorectal cancer kindreds.";
RL Biochem. Biophys. Res. Commun. 271:120-129(2000).
RN [74]
RP VARIANT ASP-322.
RX PubMed=10713887; DOI=10.1038/sj.ejhg.5200393;
RA Fidalgo P., Almeida M.R., West S., Gaspar C., Maia L., Wijnen J.,
RA Albuquerque C., Curtis A., Cravo M., Fodde R., Leitao C.N., Burn J.;
RT "Detection of mutations in mismatch repair genes in Portuguese families
RT with hereditary non-polyposis colorectal cancer (HNPCC) by a multi-method
RT approach.";
RL Eur. J. Hum. Genet. 8:49-53(2000).
RN [75]
RP VARIANTS LYNCH1 ARG-692 AND ARG-697.
RX PubMed=10612836;
RX DOI=10.1002/(sici)1098-1004(200001)15:1<116::aid-humu24>3.0.co;2-q;
RA Isidro G., Veiga I., Matos P., Almeida S., Bizarro S., Marshall B.,
RA Baptista M., Leite J., Regateiro F., Soares J., Castedo S., Boavida M.G.;
RT "Four novel MSH2 / MLH1 gene mutations in Portuguese HNPCC families.";
RL Hum. Mutat. 15:116-116(2000).
RN [76]
RP VARIANT LYNCH1 ASN-603, AND VARIANT ASP-322.
RX PubMed=10829038; DOI=10.1200/jco.2000.18.11.2193;
RA Salovaara R., Loukola A., Kristo P., Kaeaeriaeinen H., Ahtola H.,
RA Eskelinen M., Haerkoenen N., Julkunen R., Kangas E., Ojala S.,
RA Tulikoura J., Valkamo E., Jaervinen H., Mecklin J.-P., Aaltonen L.A.,
RA de la Chapelle A.;
RT "Population-based molecular detection of hereditary nonpolyposis colorectal
RT cancer.";
RL J. Clin. Oncol. 18:2193-2200(2000).
RN [77]
RP ERRATUM OF PUBMED:10829038.
RA Salovaara R., Loukola A., Kristo P., Kaeaeriaeinen H., Ahtola H.,
RA Eskelinen M., Haerkoenen N., Julkunen R., Kangas E., Ojala S.,
RA Tulikoura J., Valkamo E., Jaervinen H., Mecklin J.-P., Aaltonen L.A.,
RA de la Chapelle A.;
RL J. Clin. Oncol. 18:3456-3456(2000).
RN [78]
RP VARIANTS GASTRIC CANCER PHE-17; GLU-824; ALA-868; GLY-870 AND GLY-873, AND
RP VARIANTS LYNCH1 CYS-98; TYR-323; ILE-335; ARG-629 AND VAL-714.
RX PubMed=12132870;
RA Kim J.C., Kim H.C., Roh S.A., Koo K.H., Lee D.H., Yu C.S., Lee J.H.,
RA Kim T.W., Lee H.I., Beck N.E., Bodmer W.F.;
RT "hMLH1 and hMSH2 mutations in families with familial clustering of gastric
RT cancer and hereditary non-polyposis colorectal cancer.";
RL Cancer Detect. Prev. 25:503-510(2001).
RN [79]
RP VARIANTS LYNCH1 ASP-161; VAL-216 AND ARG-554.
RX PubMed=11726306;
RA Mueller-Koch Y., Kopp R., Lohse P., Baretton G., Stoetzer A., Aust D.,
RA Daum J., Kerker B., Gross M., Dietmeier W., Holinski-Feder E.;
RT "Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a
RT cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer)
RT patients: mutations or polymorphisms?";
RL Eur. J. Med. Res. 6:473-482(2001).
RN [80]
RP CHARACTERIZATION OF VARIANTS ASP-322; LEU-622 AND TYR-639.
RX PubMed=11555625; DOI=10.1093/hmg/10.18.1889;
RA Ellison A.R., Lofing J., Bitter G.A.;
RT "Functional analysis of human MLH1 and MSH2 missense variants and hybrid
RT human-yeast MLH1 proteins in Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 10:1889-1900(2001).
RN [81]
RP VARIANT LYNCH1 VAL-813.
RX PubMed=12373605; DOI=10.1038/sj.bjc.6600565;
RA Gille J.J.P., Hogervorst F.B.L., Pals G., Wijnen J.T., van Schooten R.J.,
RA Dommering C.J., Meijer G.A., Craanen M.E., Nederlof P.M., de Jong D.,
RA McElgunn C.J., Schouten J.P., Menko F.H.;
RT "Genomic deletions of MSH2 and MLH1 in colorectal cancer families detected
RT by a novel mutation detection approach.";
RL Br. J. Cancer 87:892-897(2002).
RN [82]
RP VARIANTS LYNCH1 VAL-600 AND PHE-723.
RX PubMed=11920458; DOI=10.1002/cncr.10332.abs;
RA Furukawa T., Konishi F., Shitoh K., Kojima M., Nagai H., Tsukamoto T.;
RT "Evaluation of screening strategy for detecting hereditary nonpolyposis
RT colorectal carcinoma.";
RL Cancer 94:911-920(2002).
RN [83]
RP VARIANTS LYNCH1 HIS-167; MET-393; PRO-524; ASN-596 DEL; LEU-622; SER-674
RP AND ARG-905, AND CHARACTERIZATION OF VARIANTS LYNCH1 HIS-167; MET-393;
RP PRO-524; ASN-596 DEL; LEU-622; SER-674 AND ARG-905.
RX PubMed=12124176; DOI=10.1016/s1535-6108(02)00073-9;
RA Heinen C.D., Wilson T., Mazurek A., Berardini M., Butz C., Fishel R.;
RT "HNPCC mutations in hMSH2 result in reduced hMSH2-hMSH6 molecular switch
RT functions.";
RL Cancer Cell 1:469-478(2002).
RN [84]
RP INVOLVEMENT IN MULTIPLE CAFE-AU-LAIT SPOTS WITH LEUKEMIA.
RX PubMed=11809679;
RA Whiteside D., McLeod R., Graham G., Steckley J.L., Booth K.,
RA Somerville M.J., Andrew S.E.;
RT "A homozygous germ-line mutation in the human MSH2 gene predisposes to
RT hematological malignancy and multiple cafe-au-lait spots.";
RL Cancer Res. 62:359-362(2002).
RN [85]
RP VARIANT ASP-322.
RX PubMed=11839723; DOI=10.1136/gut.50.3.405;
RA Cravo M., Afonso A.J., Lage P., Albuquerque C., Maia L., Lacerda C.,
RA Fidalgo P., Chaves P., Cruz C., Nobre-Leitao C.;
RT "Pathogenicity of missense and splice site mutations in hMSH2 and hMLH1
RT mismatch repair genes: implications for genetic testing.";
RL Gut 50:405-412(2002).
RN [86]
RP VARIANTS LYNCH1 MET-44; VAL-45; ASN-596 DEL; GLY-886 AND GLU-923.
RX PubMed=12112654; DOI=10.1002/humu.10083;
RA Bisgaard M.L., Jaeger A.C., Myrhoej T., Bernstein I., Nielsen F.C.;
RT "Hereditary non-polyposis colorectal cancer (HNPCC): phenotype-genotype
RT correlation between patients with and without identified mutation.";
RL Hum. Mutat. 20:20-27(2002).
RN [87]
RP VARIANTS LYNCH1 ILE-102; ASP-163 AND ALA-564, AND VARIANT ASP-322.
RX PubMed=12200596; DOI=10.1007/s00432-002-0361-2;
RA Ward R., Meldrum C., Williams R., Mokany E., Scott R., Turner J.,
RA Hawkins N., Burgess B., Groombridge C., Spigelman A.;
RT "Impact of microsatellite testing and mismatch repair protein expression on
RT the clinical interpretation of genetic testing in hereditary non-polyposis
RT colorectal cancer.";
RL J. Cancer Res. Clin. Oncol. 128:403-411(2002).
RN [88]
RP VARIANTS LYNCH1 HIS-167 AND SER-359.
RX PubMed=11870161; DOI=10.1200/jco.2002.20.5.1203;
RA Scartozzi M., Bianchi F., Rosati S., Galizia E., Antolini A., Loretelli C.,
RA Piga A., Bearzi I., Cellerino R., Porfiri E.;
RT "Mutations of hMLH1 and hMSH2 in patients with suspected hereditary
RT nonpolyposis colorectal cancer: correlation with microsatellite instability
RT and abnormalities of mismatch repair protein expression.";
RL J. Clin. Oncol. 20:1203-1208(2002).
RN [89]
RP VARIANTS LYNCH1 LEU-92 DEL AND ALA-853, AND VARIANT ASP-322.
RX PubMed=12362047; DOI=10.1136/jmg.39.10.e65;
RA Kurzawski G., Suchy J., Kladny J., Safranow K., Jakubowska A., Elsakov P.,
RA Kucinskas V., Gardovski J., Irmejs A., Sibul H., Huzarski T., Byrski T.,
RA Debniak T., Cybulski C., Gronwald J., Oszurek O., Clark J., Gozdz S.,
RA Niepsuj S., Slomski R., Plawski A., Lacka-Wojciechowska A., Rozmiarek A.,
RA Fiszer-Maliszewska L., Bebenek M., Sorokin D., Stawicka M., Godlewski D.,
RA Richter P., Brozek I., Wysocka B., Jawien A., Banaszkiewicz Z.,
RA Kowalczyk J., Czudowska D., Goretzki P.E., Moeslein G., Lubinski J.;
RT "Germline MSH2 and MLH1 mutational spectrum in HNPCC families from Poland
RT and the Baltic States.";
RL J. Med. Genet. 39:E65-E65(2002).
RN [90]
RP VARIANTS LYNCH1 PRO-552; SER-583 AND PRO-636.
RX PubMed=12658575; DOI=10.1086/373963;
RA Wagner A., Barrows A., Wijnen J.T., van der Klift H., Franken P.F.,
RA Verkuijlen P., Nakagawa H., Geugien M., Jaghmohan-Changur S., Breukel C.,
RA Meijers-Heijboer H., Morreau H., van Puijenbroek M., Burn J., Coronel S.,
RA Kinarski Y., Okimoto R., Watson P., Lynch J.F., de la Chapelle A.,
RA Lynch H.T., Fodde R.;
RT "Molecular analysis of hereditary nonpolyposis colorectal cancer in the
RT United States: high mutation detection rate among clinically selected
RT families and characterization of an American founder genomic deletion of
RT the MSH2 gene.";
RL Am. J. Hum. Genet. 72:1088-1100(2003).
RN [91]
RP VARIANTS CRC ILE-13 AND ILE-342, AND VARIANT ASP-322.
RX PubMed=14504054; DOI=10.1093/annonc/mdg402;
RA Colombino M., Cossu A., Arba A., Manca A., Curci A., Avallone A.,
RA Comella G., Botti G., Scintu F., Amoruso M., D'Abbicco D., d'Agnessa M.R.,
RA Spanu A., Tanda F., Palmieri G.;
RT "Microsatellite instability and mutation analysis among southern Italian
RT patients with colorectal carcinoma: detection of different alterations
RT accounting for MLH1 and MSH2 inactivation in familial cases.";
RL Ann. Oncol. 14:1530-1536(2003).
RN [92]
RP VARIANT LYNCH1 SER-127.
RX PubMed=12655564; DOI=10.1002/humu.9123;
RA Chen-Shtoyerman R., Theodor L., Harmati E., Friedman E., Dacka S.,
RA Kopelman Y., Sternberg A., Zarivach R., Bar-Meir S., Fireman Z.;
RT "Genetic analysis of familial colorectal cancer in Israeli Arabs.";
RL Hum. Mutat. 21:446-447(2003).
RN [93]
RP VARIANT LYNCH1 PRO-175.
RX PubMed=12655568; DOI=10.1002/humu.9127;
RA Bartosova Z., Fridrichova I., Bujalkova M., Wolf B., Ilencikova D.,
RA Krizan P., Hlavcak P., Palaj J., Lukac L., Lukacova M., Boeoer A.,
RA Haider R., Jiricny J., Nystroem-Lahti M., Marra G.;
RT "Novel MLH1 and MSH2 germline mutations in the first HNPCC families
RT identified in Slovakia.";
RL Hum. Mutat. 21:449-449(2003).
RN [94]
RP VARIANTS LYNCH1 GLY-163 AND GLY-660.
RX PubMed=14635101; DOI=10.1002/humu.10291;
RA Taylor C.F., Charlton R.S., Burn J., Sheridan E., Taylor G.R.;
RT "Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-
RT polyposis colorectal cancer: identification of novel and recurrent
RT deletions by MLPA.";
RL Hum. Mutat. 22:428-433(2003).
RN [95]
RP VARIANTS CRC SER-40; VAL-169; ARG-203; PHE-390; LYS-419; CYS-619 AND
RP ARG-629, AND VARIANT MET-8.
RX PubMed=12792735;
RA Yamada K., Zhong X., Kanazawa S., Koike J., Tsujita K., Hemmi H.;
RT "Oncogenic pathway of sporadic colorectal cancer with novel germline
RT missense mutations in the hMSH2 gene.";
RL Oncol. Rep. 10:859-866(2003).
RN [96]
RP VARIANT LYNCH1 THR-931.
RX PubMed=15046096;
RA Sun M.H., Cai Q., Fu G., Ren S., Mo S., Xu Y., Ding C., Zhang T., Zhu X.,
RA Xu X., Min D., Cai S., Luo D., Shi Y., Shi D.;
RT "Gene symbol: hMSH2. Disease: hereditary nonpolyposis colorectal cancer.";
RL Hum. Genet. 114:409-409(2004).
RN [97]
RP VARIANT LYNCH1 TYR-671.
RX PubMed=15300854; DOI=10.1002/humu.9267;
RA Sharp A., Pichert G., Lucassen A., Eccles D.;
RT "RNA analysis reveals splicing mutations and loss of expression defects in
RT MLH1 and BRCA1.";
RL Hum. Mutat. 24:272-272(2004).
RN [98]
RP VARIANTS LYNCH1 LEU-440 DEL; TYR-506; ARG-629 AND ILE-688.
RX PubMed=15365995; DOI=10.1002/humu.9277;
RA Shin Y.-K., Heo S.-C., Shin J.-H., Hong S.-H., Ku J.-L., Yoo B.-C.,
RA Kim I.-J., Park J.-G.;
RT "Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non-
RT polyposis colorectal cancer families.";
RL Hum. Mutat. 24:351-351(2004).
RN [99]
RP VARIANT LYNCH1 ARG-839, AND VARIANT ARG-629.
RX PubMed=15613555; DOI=10.1093/jjco/hyh121;
RA Yuan Y., Huang Y.-Q., Cai S.-R., Song Y.-M., Zheng S., Zhang S.-Z.;
RT "Genetic characterization of Chinese hereditary non-polyposis colorectal
RT cancer by DHPLC and multiplex PCR.";
RL Jpn. J. Clin. Oncol. 34:660-666(2004).
RN [100]
RP VARIANTS LYNCH1 LEU-349 AND ASN-596 DEL.
RX PubMed=15342696; DOI=10.1136/jmg.2004.020651;
RA Domingo E., Laiho P., Ollikainen M., Pinto M., Wang L., French A.J.,
RA Westra J., Frebourg T., Espin E., Armengol M., Hamelin R., Yamamoto H.,
RA Hofstra R.M.W., Seruca R., Lindblom A., Peltomaeki P., Thibodeau S.N.,
RA Aaltonen L.A., Schwartz S. Jr.;
RT "BRAF screening as a low-cost effective strategy for simplifying HNPCC
RT genetic testing.";
RL J. Med. Genet. 41:664-668(2004).
RN [101]
RP VARIANT LYNCH1 PHE-93.
RX PubMed=15896463; DOI=10.1016/j.canlet.2004.09.051;
RA Baudi F., Fersini G., Lavecchia A., Terracciano R., Leone F., Quaresima B.,
RA Faniello M.C., De Paola L., Doldo P., Cuda G., Costanzo F., Venuta S.;
RT "A novel missense germline mutation in exon 2 of the hMSH2 gene in a HNPCC
RT family from Southern Italy.";
RL Cancer Lett. 223:285-291(2005).
RN [102]
RP VARIANTS LYNCH1 VAL-169; PHE-390; ALA-564 AND ARG-629, AND VARIANT CRC
RP LYS-419.
RX PubMed=15996210; DOI=10.1111/j.1399-0004.2005.00469.x;
RA Lee S.-C., Guo J.-Y., Lim R., Soo R., Koay E., Salto-Tellez M., Leong A.,
RA Goh B.-C.;
RT "Clinical and molecular characteristics of hereditary non-polyposis
RT colorectal cancer families in Southeast Asia.";
RL Clin. Genet. 68:137-145(2005).
RN [103]
RP VARIANT LYNCH1 TYR-283.
RX PubMed=15870828; DOI=10.1038/sj.ejhg.5201421;
RA Wehner M., Mangold E., Sengteller M., Friedrichs N., Aretz S., Friedl W.,
RA Propping P., Pagenstecher C.;
RT "Hereditary nonpolyposis colorectal cancer: pitfalls in deletion screening
RT in MSH2 and MLH1 genes.";
RL Eur. J. Hum. Genet. 13:983-986(2005).
RN [104]
RP VARIANT LYNCH1 ARG-162.
RX PubMed=15991316;
RA Kohonen-Corish M.R.J., Otway R., Tetlow N., Hornby J., Doe W.F.;
RT "Gene symbol: MSH2. Disease: hereditary nonpolyposis colorectal cancer.";
RL Hum. Genet. 116:539-539(2005).
RN [105]
RP VARIANTS LYNCH1 THR-2; LEU-92 DEL; MET-145; PHE-390 AND ALA-853, AND
RP VARIANT ASP-322.
RX PubMed=16451135; DOI=10.1111/j.1399-0004.2006.00550.x;
RA Kurzawski G., Suchy J., Lener M., Klujszo-Grabowska E., Kladny J.,
RA Safranow K., Jakubowska K., Jakubowska A., Huzarski T., Byrski T.,
RA Debniak T., Cybulski C., Gronwald J., Oszurek O., Oszutowska D.,
RA Kowalska E., Gozdz S., Niepsuj S., Slomski R., Plawski A.,
RA Lacka-Wojciechowska A., Rozmiarek A., Fiszer-Maliszewska L., Bebenek M.,
RA Sorokin D., Sasiadek M.M., Stembalska A., Grzebieniak Z., Kilar E.,
RA Stawicka M., Godlewski D., Richter P., Brozek I., Wysocka B., Limon J.,
RA Jawien A., Banaszkiewicz Z., Janiszewska H., Kowalczyk J., Czudowska D.,
RA Scott R.J., Lubinski J.;
RT "Germline MSH2 and MLH1 mutational spectrum including large rearrangements
RT in HNPCC families from Poland (update study).";
RL Clin. Genet. 69:40-47(2006).
RN [106]
RP VARIANTS LYNCH1 PRO-33; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187;
RP TYR-333; ASN-603; PRO-636; PHE-697; 745-ILE-ILE-746 DEL AND LYS-749,
RP VARIANTS VAL-272; THR-834 AND GLU-923, CHARACTERIZATION OF VARIANTS LYNCH1
RP PRO-33; ASP-161; ARG-162; ARG-164; PRO-173; PRO-187; TYR-333; ASN-603;
RP PRO-636; PHE-697; 745-ILE-ILE-746 DEL AND LYS-749, AND CHARACTERIZATION OF
RP VARIANTS VAL-272; THR-834 AND GLU-923.
RX PubMed=17101317; DOI=10.1053/j.gastro.2006.08.044;
RA Ollila S., Sarantaus L., Kariola R., Chan P., Hampel H., Holinski-Feder E.,
RA Macrae F., Kohonen-Corish M., Gerdes A.-M., Peltomaeki P., Mangold E.,
RA de la Chapelle A., Greenblatt M., Nystroem M.;
RT "Pathogenicity of MSH2 missense mutations is typically associated with
RT impaired repair capability of the mutated protein.";
RL Gastroenterology 131:1408-1417(2006).
RN [107]
RP VARIANT LYNCH1 ALA-162.
RX PubMed=17128465;
RA Leonardis D.;
RT "Gene symbol: msh2. Disease: hereditary nonpolyposis colorectal cancer.";
RL Hum. Genet. 119:675-675(2006).
RN [108]
RP VARIANT LYNCH1 ARG-674.
RX PubMed=18625694; DOI=10.1136/gut.2008.156695;
RA Ramsoekh D., Wagner A., van Leerdam M.E., Dinjens W.N., Steyerberg E.W.,
RA Halley D.J., Kuipers E.J., Dooijes D.;
RT "A high incidence of MSH6 mutations in Amsterdam criteria II-negative
RT families tested in a diagnostic setting.";
RL Gut 57:1539-1544(2008).
RN [109]
RP VARIANTS GLN-46; LYS-106; ASP-322; SER-596; LEU-670; ILE-779; SER-807;
RP HIS-835 AND ARG-911.
RX PubMed=18033691; DOI=10.1002/humu.20635;
RA Barnetson R.A., Cartwright N., van Vliet A., Haq N., Drew K.,
RA Farrington S., Williams N., Warner J., Campbell H., Porteous M.E.,
RA Dunlop M.G.;
RT "Classification of ambiguous mutations in DNA mismatch repair genes
RT identified in a population-based study of colorectal cancer.";
RL Hum. Mutat. 29:367-374(2008).
RN [110]
RP CHARACTERIZATION OF VARIANTS LYNCH1 PRO-33; SER-127; ASP-161; ARG-162;
RP ARG-164; PRO-173; PRO-187; VAL-272; TYR-333; ASN-603; PRO-636; ALA-674;
RP PHE-697; 745-ILE-ILE-746 DEL; LYS-749; THR-834 AND GLU-923, AND
RP CHARACTERIZATION OF VARIANT ASP-322.
RX PubMed=18951462; DOI=10.1002/humu.20893;
RA Ollila S., Dermadi Bebek D., Jiricny J., Nystroem M.;
RT "Mechanisms of pathogenicity in human MSH2 missense mutants.";
RL Hum. Mutat. 29:1355-1363(2008).
RN [111]
RP VARIANTS LYNCH1 LEU-92 DEL; ARG-199; ASP-331; GLU-470; ASN-610; GLY-638;
RP GLU-645; LEU-696; TYR-748 AND GLN-839, VARIANTS VAL-272; ASN-596 DEL;
RP TYR-671; ARG-697 AND PHE-723, CHARACTERIZATION OF VARIANTS LYNCH1 LEU-92
RP DEL; ARG-199; ASP-331; GLU-470; ASN-610; GLY-638; GLU-645; LEU-696; TYR-748
RP AND GLN-839, AND CHARACTERIZATION OF VARIANTS VAL-272; ASN-596 DEL;
RP TYR-671; ARG-697 AND PHE-723.
RX PubMed=18561205; DOI=10.1002/humu.20796;
RA Tournier I., Vezain M., Martins A., Charbonnier F., Baert-Desurmont S.,
RA Olschwang S., Wang Q., Buisine M.P., Soret J., Tazi J., Frebourg T.,
RA Tosi M.;
RT "A large fraction of unclassified variants of the mismatch repair genes
RT MLH1 and MSH2 is associated with splicing defects.";
RL Hum. Mutat. 29:1412-1424(2008).
RN [112]
RP CHARACTERIZATION OF VARIANTS LYNCH1 ARG-162; HIS-167 AND SER-359.
RX PubMed=18781619; DOI=10.1002/humu.20875;
RA Belvederesi L., Bianchi F., Galizia E., Loretelli C., Bracci R.,
RA Catalani R., Amati M., Cellerino R.;
RT "MSH2 missense mutations and HNPCC syndrome: pathogenicity assessment in a
RT human expression system.";
RL Hum. Mutat. 29:E296-E309(2008).
RN [113]
RP CHARACTERIZATION OF VARIANTS LYNCH1 HIS-167; THR-305: LEU-622; ARG-639;
RP ARG-674; PHE-697 AND THR-834.
RX PubMed=18822302; DOI=10.1016/j.mrfmmm.2008.08.015;
RA Lutzen A., de Wind N., Georgijevic D., Nielsen F.C., Rasmussen L.J.;
RT "Functional analysis of HNPCC-related missense mutations in MSH2.";
RL Mutat. Res. 645:44-55(2008).
RN [114]
RP CHARACTERIZATION OF VARIANTS LYNCH1 MET-44; VAL-45; HIS-167; THR-305;
RP PHE-390; ASN-596 DEL; ARG-639; ARG-674; PHE-697; PHE-723 AND GLY-886, AND
RP CHARACTERIZATION OF VARIANTS ASP-165; HIS-177; VAL-272; LEU-385; LEU-519;
RP ALA-675; GLU-759; VAL-805; GLY-843 AND LEU-860.
RX PubMed=22102614; DOI=10.1002/humu.22000;
RA Drost M., Zonneveld J.B., van Hees S., Rasmussen L.J., Hofstra R.M.,
RA de Wind N.;
RT "A rapid and cell-free assay to test the activity of lynch syndrome-
RT associated MSH2 and MSH6 missense variants.";
RL Hum. Mutat. 33:488-494(2012).
RN [115]
RP CHARACTERIZATION OF VARIANTS SER-127; MET-145; GLN-205; ASP-322; PRO-328;
RP ILE-367; GLU-487 AND ILE-909.
RX PubMed=22581703; DOI=10.1002/humu.22119;
RA Kantelinen J., Kansikas M., Candelin S., Hampel H., Smith B., Holm L.,
RA Kariola R., Nystrom M.;
RT "Mismatch repair analysis of inherited MSH2 and/or MSH6 variation pairs
RT found in cancer patients.";
RL Hum. Mutat. 33:1294-1301(2012).
RN [116]
RP VARIANT LYNCH1 ARG-669.
RX PubMed=22371642; DOI=10.3748/wjg.v18.i8.814;
RA Zahary M.N., Kaur G., Abu Hassan M.R., Singh H., Naik V.R., Ankathil R.;
RT "Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome
RT patients.";
RL World J. Gastroenterol. 18:814-820(2012).
RN [117]
RP VARIANTS GLN-5; GLY-55; PRO-534; ILE-813 AND ARG-839, AND CHARACTERIZATION
RP OF VARIANTS GLN-5; GLY-55; PRO-534; ILE-813 AND ARG-839.
RX PubMed=28494185; DOI=10.1080/15384047.2017.1326439;
RA Arora S., Huwe P.J., Sikder R., Shah M., Browne A.J., Lesh R., Nicolas E.,
RA Deshpande S., Hall M.J., Dunbrack R.L. Jr., Golemis E.A.;
RT "Functional analysis of rare variants in mismatch repair proteins augments
RT results from computation-based predictive methods.";
RL Cancer Biol. Ther. 18:519-533(2017).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6
CC heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA
CC mismatches thereby initiating DNA repair. When bound, heterodimers bend
CC the DNA helix and shields approximately 20 base pairs. MutS alpha
CC recognizes single base mismatches and dinucleotide insertion-deletion
CC loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion
CC loops up to 13 nucleotides long. After mismatch binding, MutS alpha or
CC beta forms a ternary complex with the MutL alpha heterodimer, which is
CC thought to be responsible for directing the downstream MMR events,
CC including strand discrimination, excision, and resynthesis. Recruits
CC DNA helicase MCM9 to chromatin which unwinds the mismatch containing
CC DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal
CC role in mismatch repair functions. The ATPase activity associated with
CC MutS alpha regulates binding similar to a molecular switch: mismatched
CC DNA provokes ADP-->ATP exchange, resulting in a discernible
CC conformational transition that converts MutS alpha into a sliding clamp
CC capable of hydrolysis-independent diffusion along the DNA backbone.
CC This transition is crucial for mismatch repair. MutS alpha may also
CC play a role in DNA homologous recombination repair. In melanocytes may
CC modulate both UV-B-induced cell cycle regulation and apoptosis.
CC {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545,
CC ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:17611581,
CC ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:26300262,
CC ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679,
CC ECO:0000269|PubMed:9822680}.
CC -!- SUBUNIT: Component of the DNA mismatch repair (MMR) complex composed at
CC least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer
CC consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta)
CC (PubMed:8942985). Both heterodimers form a ternary complex with MutL
CC alpha (MLH1-PMS1) (PubMed:9788596, PubMed:10856833, PubMed:11427529,
CC PubMed:11429708, PubMed:12414623, PubMed:14676842). Interacts with
CC MCM9; the interaction recruits MCM9 to chromatin (PubMed:26300262).
CC Interacts with MCM8 (PubMed:26300262). Interacts with EXO1
CC (PubMed:9788596, PubMed:10856833, PubMed:11427529, PubMed:11429708,
CC PubMed:12414623, PubMed:14676842). Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex
CC (PubMed:10783165). This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains
CC (PubMed:10783165). Interacts with ATR (PubMed:14657349). Interacts with
CC SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a
CC subunit of different structure-specific endonucleases
CC (PubMed:19596235). Interacts with SMARCAD1 (PubMed:18675275).
CC {ECO:0000269|PubMed:10783165, ECO:0000269|PubMed:10856833,
CC ECO:0000269|PubMed:11427529, ECO:0000269|PubMed:11429708,
CC ECO:0000269|PubMed:12414623, ECO:0000269|PubMed:14657349,
CC ECO:0000269|PubMed:14676842, ECO:0000269|PubMed:18675275,
CC ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:26300262,
CC ECO:0000269|PubMed:8942985, ECO:0000269|PubMed:9788596}.
CC -!- INTERACTION:
CC P43246; Q92624: APPBP2; NbExp=3; IntAct=EBI-355888, EBI-743771;
CC P43246; Q9UQ84-1: EXO1; NbExp=3; IntAct=EBI-355888, EBI-944694;
CC P43246; P09429: HMGB1; NbExp=2; IntAct=EBI-355888, EBI-389432;
CC P43246; P20585: MSH3; NbExp=12; IntAct=EBI-355888, EBI-1164205;
CC P43246; P52701: MSH6; NbExp=9; IntAct=EBI-355888, EBI-395529;
CC P43246; Q8IY92: SLX4; NbExp=5; IntAct=EBI-355888, EBI-2370740;
CC P43246; P39875: EXO1; Xeno; NbExp=2; IntAct=EBI-355888, EBI-6738;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26300262}. Chromosome
CC {ECO:0000269|PubMed:26300262}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P43246-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P43246-2; Sequence=VSP_045536;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10856833}.
CC -!- PTM: Phosphorylated by PRKCZ, which may prevent MutS alpha degradation
CC by the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:15808853}.
CC -!- DISEASE: Lynch syndrome 1 (LYNCH1) [MIM:120435]: A form of Lynch
CC syndrome, an autosomal dominant disease associated with marked increase
CC in cancer susceptibility. It is characterized by a familial
CC predisposition to early-onset colorectal carcinoma (CRC) and extra-
CC colonic tumors of the gastrointestinal, urological and female
CC reproductive tracts. Lynch syndrome is reported to be the most common
CC form of inherited colorectal cancer in the Western world. Clinically,
CC it is often divided into two subgroups. Type I is characterized by
CC hereditary predisposition to colorectal cancer, a young age of onset,
CC and carcinoma observed in the proximal colon. Type II is characterized
CC by increased risk for cancers in certain tissues such as the uterus,
CC ovary, breast, stomach, small intestine, skin, and larynx in addition
CC to the colon. Diagnosis of classical Lynch syndrome is based on the
CC Amsterdam criteria: 3 or more relatives affected by colorectal cancer,
CC one a first degree relative of the other two; 2 or more generation
CC affected; 1 or more colorectal cancers presenting before 50 years of
CC age; exclusion of hereditary polyposis syndromes. The term 'suspected
CC Lynch syndrome' or 'incomplete Lynch syndrome' can be used to describe
CC families who do not or only partially fulfill the Amsterdam criteria,
CC but in whom a genetic basis for colon cancer is strongly suspected.
CC {ECO:0000269|PubMed:10375096, ECO:0000269|PubMed:10386556,
CC ECO:0000269|PubMed:10528862, ECO:0000269|PubMed:10573010,
CC ECO:0000269|PubMed:10612836, ECO:0000269|PubMed:10777691,
CC ECO:0000269|PubMed:10829038, ECO:0000269|PubMed:11726306,
CC ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:11920458,
CC ECO:0000269|PubMed:12112654, ECO:0000269|PubMed:12124176,
CC ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596,
CC ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605,
CC ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:12655568,
CC ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14635101,
CC ECO:0000269|PubMed:15046096, ECO:0000269|PubMed:15300854,
CC ECO:0000269|PubMed:15342696, ECO:0000269|PubMed:15365995,
CC ECO:0000269|PubMed:15613555, ECO:0000269|PubMed:15870828,
CC ECO:0000269|PubMed:15896463, ECO:0000269|PubMed:15991316,
CC ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:16451135,
CC ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:17128465,
CC ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:18625694,
CC ECO:0000269|PubMed:18781619, ECO:0000269|PubMed:18822302,
CC ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944,
CC ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:22371642,
CC ECO:0000269|PubMed:7874129, ECO:0000269|PubMed:8261515,
CC ECO:0000269|PubMed:8700523, ECO:0000269|PubMed:8797773,
CC ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9048925,
CC ECO:0000269|PubMed:9240418, ECO:0000269|PubMed:9298827,
CC ECO:0000269|PubMed:9311737, ECO:0000269|PubMed:9419403,
CC ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9621522,
CC ECO:0000269|PubMed:9718327, ECO:0000269|PubMed:9889267}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal
CC dominant disorder characterized by sebaceous neoplasms and visceral
CC malignancy. {ECO:0000269|PubMed:7713503}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of
CC endometrium, the mucous lining of the uterus. Most endometrial cancers
CC are adenocarcinomas, cancers that begin in cells that make and release
CC mucus and other fluids. {ECO:0000305|PubMed:11306449,
CC ECO:0000305|PubMed:21642682}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Mismatch repair cancer syndrome 2 (MMRCS2) [MIM:619096]: An
CC autosomal recessive form of mismatch repair cancer syndrome, a
CC childhood cancer predisposition syndrome encompassing a broad tumor
CC spectrum. This includes hematological malignancies, central nervous
CC system tumors, Lynch syndrome-associated malignancies such as
CC colorectal tumors as well as multiple intestinal polyps, embryonic
CC tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature
CC reminiscent of neurofibromatosis type 1, are often found as first
CC manifestation of the underlying cancer. {ECO:0000269|PubMed:12549480,
CC ECO:0000269|PubMed:16372347}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease
CC characterized by malignant lesions arising from the inner wall of the
CC large intestine (the colon) and the rectum. Genetic alterations are
CC often associated with progression from premalignant lesion (adenoma) to
CC invasive adenocarcinoma. Risk factors for cancer of the colon and
CC rectum include colon polyps, long-standing ulcerative colitis, and
CC genetic family history. {ECO:0000269|PubMed:12792735,
CC ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:15996210,
CC ECO:0000269|PubMed:9559627}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC27930.1; Type=Frameshift; Note=The frameshift is caused by a single nucleotide deletion which is found in a HNPCC kindred.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/340/MSH2";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/msh2/";
CC ---------------------------------------------------------------------------
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DR EMBL; U03911; AAA18643.1; -; mRNA.
DR EMBL; U04045; AAA61870.1; -; mRNA.
DR EMBL; U41221; AAA82080.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U41206; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41207; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41208; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41210; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41211; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41212; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41213; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41214; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41215; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41216; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41217; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41218; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41219; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; U41220; AAA82080.1; JOINED; Genomic_DNA.
DR EMBL; L47583; AAB59564.1; -; mRNA.
DR EMBL; L47582; AAB59565.1; -; mRNA.
DR EMBL; L47581; AAA76858.1; -; mRNA.
DR EMBL; AY601851; AAS99351.1; -; Genomic_DNA.
DR EMBL; AK304496; BAG65304.1; -; mRNA.
DR EMBL; BX649122; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC079775; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC138655; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021566; AAH21566.1; -; mRNA.
DR EMBL; AF066081; AAC27930.1; ALT_FRAME; Genomic_DNA.
DR CCDS; CCDS1834.1; -. [P43246-1]
DR CCDS; CCDS58709.1; -. [P43246-2]
DR PIR; I64819; I64819.
DR RefSeq; NP_000242.1; NM_000251.2. [P43246-1]
DR RefSeq; NP_001245210.1; NM_001258281.1. [P43246-2]
DR PDB; 2O8B; X-ray; 2.75 A; A=1-934.
DR PDB; 2O8C; X-ray; 3.37 A; A=1-934.
DR PDB; 2O8D; X-ray; 3.00 A; A=1-934.
DR PDB; 2O8E; X-ray; 3.30 A; A=1-934.
DR PDB; 2O8F; X-ray; 3.25 A; A=1-934.
DR PDB; 3THW; X-ray; 3.09 A; A=1-934.
DR PDB; 3THX; X-ray; 2.70 A; A=1-934.
DR PDB; 3THY; X-ray; 2.89 A; A=1-934.
DR PDB; 3THZ; X-ray; 4.30 A; A=1-934.
DR PDB; 8AG6; EM; 2.80 A; A=1-934.
DR PDB; 8OLX; EM; 3.10 A; A=1-934.
DR PDB; 8OM5; EM; 3.52 A; A=1-934.
DR PDB; 8OM9; EM; 3.32 A; A=1-934.
DR PDB; 8OMA; EM; 3.29 A; A=1-934.
DR PDB; 8OMO; EM; 3.43 A; A=1-934.
DR PDB; 8OMQ; EM; 3.11 A; A=1-934.
DR PDBsum; 2O8B; -.
DR PDBsum; 2O8C; -.
DR PDBsum; 2O8D; -.
DR PDBsum; 2O8E; -.
DR PDBsum; 2O8F; -.
DR PDBsum; 3THW; -.
DR PDBsum; 3THX; -.
DR PDBsum; 3THY; -.
DR PDBsum; 3THZ; -.
DR PDBsum; 8AG6; -.
DR PDBsum; 8OLX; -.
DR PDBsum; 8OM5; -.
DR PDBsum; 8OM9; -.
DR PDBsum; 8OMA; -.
DR PDBsum; 8OMO; -.
DR PDBsum; 8OMQ; -.
DR AlphaFoldDB; P43246; -.
DR EMDB; EMD-15417; -.
DR EMDB; EMD-15518; -.
DR EMDB; EMD-15519; -.
DR EMDB; EMD-16964; -.
DR EMDB; EMD-16969; -.
DR EMDB; EMD-16971; -.
DR EMDB; EMD-16972; -.
DR EMDB; EMD-16973; -.
DR EMDB; EMD-16974; -.
DR SMR; P43246; -.
DR BioGRID; 110573; 306.
DR ComplexPortal; CPX-77; DNA mismatch repair MutSbeta complex.
DR ComplexPortal; CPX-80; DNA mismatch repair MutSalpha complex.
DR CORUM; P43246; -.
DR DIP; DIP-35054N; -.
DR IntAct; P43246; 77.
DR MINT; P43246; -.
DR STRING; 9606.ENSP00000233146; -.
DR ChEMBL; CHEMBL4296019; -.
DR GlyGen; P43246; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P43246; -.
DR PhosphoSitePlus; P43246; -.
DR SwissPalm; P43246; -.
DR BioMuta; MSH2; -.
DR DMDM; 1171032; -.
DR EPD; P43246; -.
DR jPOST; P43246; -.
DR MassIVE; P43246; -.
DR MaxQB; P43246; -.
DR PaxDb; 9606-ENSP00000233146; -.
DR PeptideAtlas; P43246; -.
DR ProteomicsDB; 55601; -. [P43246-1]
DR ProteomicsDB; 5866; -.
DR Pumba; P43246; -.
DR Antibodypedia; 4037; 882 antibodies from 49 providers.
DR CPTC; P43246; 1 antibody.
DR DNASU; 4436; -.
DR Ensembl; ENST00000233146.7; ENSP00000233146.2; ENSG00000095002.15. [P43246-1]
DR Ensembl; ENST00000543555.6; ENSP00000442697.1; ENSG00000095002.15. [P43246-2]
DR GeneID; 4436; -.
DR KEGG; hsa:4436; -.
DR MANE-Select; ENST00000233146.7; ENSP00000233146.2; NM_000251.3; NP_000242.1.
DR UCSC; uc002rvy.3; human. [P43246-1]
DR AGR; HGNC:7325; -.
DR CTD; 4436; -.
DR DisGeNET; 4436; -.
DR GeneCards; MSH2; -.
DR GeneReviews; MSH2; -.
DR HGNC; HGNC:7325; MSH2.
DR HPA; ENSG00000095002; Low tissue specificity.
DR MalaCards; MSH2; -.
DR MIM; 114500; phenotype.
DR MIM; 120435; phenotype.
DR MIM; 158320; phenotype.
DR MIM; 608089; phenotype.
DR MIM; 609309; gene.
DR MIM; 619096; phenotype.
DR neXtProt; NX_P43246; -.
DR OpenTargets; ENSG00000095002; -.
DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome.
DR Orphanet; 144; Lynch syndrome.
DR PharmGKB; PA31133; -.
DR VEuPathDB; HostDB:ENSG00000095002; -.
DR eggNOG; KOG0219; Eukaryota.
DR GeneTree; ENSGT00550000074867; -.
DR HOGENOM; CLU_002472_10_0_1; -.
DR InParanoid; P43246; -.
DR OMA; LVRFPQK; -.
DR OrthoDB; 168255at2759; -.
DR PhylomeDB; P43246; -.
DR TreeFam; TF351780; -.
DR PathwayCommons; P43246; -.
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-5632927; Defective Mismatch Repair Associated With MSH3.
DR Reactome; R-HSA-5632928; Defective Mismatch Repair Associated With MSH2.
DR Reactome; R-HSA-5632968; Defective Mismatch Repair Associated With MSH6.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR SignaLink; P43246; -.
DR SIGNOR; P43246; -.
DR BioGRID-ORCS; 4436; 27 hits in 1168 CRISPR screens.
DR ChiTaRS; MSH2; human.
DR EvolutionaryTrace; P43246; -.
DR GeneWiki; MSH2; -.
DR GenomeRNAi; 4436; -.
DR Pharos; P43246; Tbio.
DR PRO; PR:P43246; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P43246; Protein.
DR Bgee; ENSG00000095002; Expressed in secondary oocyte and 194 other cell types or tissues.
DR ExpressionAtlas; P43246; baseline and differential.
DR Genevisible; P43246; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0032301; C:MutSalpha complex; IDA:UniProtKB.
DR GO; GO:0032302; C:MutSbeta complex; IDA:HGNC-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:Ensembl.
DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:HGNC-UCL.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0019237; F:centromeric DNA binding; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0032137; F:guanine/thymine mispair binding; IMP:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:HGNC-UCL.
DR GO; GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
DR GO; GO:0019724; P:B cell mediated immunity; ISS:BHF-UCL.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; IDA:BHF-UCL.
DR GO; GO:0006302; P:double-strand break repair; IEA:Ensembl.
DR GO; GO:0007281; P:germ cell development; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl.
DR GO; GO:0045190; P:isotype switching; ISS:BHF-UCL.
DR GO; GO:0043570; P:maintenance of DNA repeat elements; IMP:HGNC-UCL.
DR GO; GO:0008584; P:male gonad development; ISS:BHF-UCL.
DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB.
DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IEA:Ensembl.
DR GO; GO:0006312; P:mitotic recombination; IBA:GO_Central.
DR GO; GO:0045910; P:negative regulation of DNA recombination; IDA:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:BHF-UCL.
DR GO; GO:0006119; P:oxidative phosphorylation; IEA:Ensembl.
DR GO; GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IEA:Ensembl.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IEA:Ensembl.
DR GO; GO:0006301; P:postreplication repair; IDA:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IMP:UniProtKB.
DR GO; GO:0010224; P:response to UV-B; ISS:BHF-UCL.
DR GO; GO:0010165; P:response to X-ray; ISS:BHF-UCL.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IEA:Ensembl.
DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; ISS:BHF-UCL.
DR GO; GO:0002204; P:somatic recombination of immunoglobulin genes involved in immune response; IBA:GO_Central.
DR CDD; cd03285; ABC_MSH2_euk; 1.
DR Gene3D; 1.10.1420.10; -; 2.
DR Gene3D; 3.40.1170.10; DNA repair protein MutS, domain I; 1.
DR Gene3D; 3.30.420.110; MutS, connector domain; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR IDEAL; IID00048; -.
DR InterPro; IPR011184; DNA_mismatch_repair_Msh2.
DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N.
DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C.
DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp.
DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core.
DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N.
DR InterPro; IPR036187; DNA_mismatch_repair_MutS_sf.
DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom.
DR InterPro; IPR032642; Msh2_ATP-bd.
DR InterPro; IPR036678; MutS_con_dom_sf.
DR InterPro; IPR045076; MutS_family.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11361:SF35; DNA MISMATCH REPAIR PROTEIN MSH2; 1.
DR PANTHER; PTHR11361; DNA MISMATCH REPAIR PROTEIN MUTS FAMILY MEMBER; 1.
DR Pfam; PF01624; MutS_I; 1.
DR Pfam; PF05188; MutS_II; 1.
DR Pfam; PF05192; MutS_III; 1.
DR Pfam; PF05190; MutS_IV; 1.
DR Pfam; PF00488; MutS_V; 1.
DR PIRSF; PIRSF005813; MSH2; 1.
DR SMART; SM00534; MUTSac; 1.
DR SMART; SM00533; MUTSd; 1.
DR SUPFAM; SSF48334; DNA repair protein MutS, domain III; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chromosome;
KW Disease variant; DNA damage; DNA repair; DNA-binding;
KW Hereditary nonpolyposis colorectal cancer; Isopeptide bond;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Tumor suppressor; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..934
FT /note="DNA mismatch repair protein Msh2"
FT /id="PRO_0000115183"
FT REGION 601..671
FT /note="Interaction with EXO1"
FT BINDING 669..676
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 555
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 567
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P43247"
FT MOD_RES 921
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 430
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..66
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_045536"
FT VARIANT 2
FT /note="A -> T (in LYNCH1; dbSNP:rs63750466)"
FT /evidence="ECO:0000269|PubMed:16451135"
FT /id="VAR_054511"
FT VARIANT 5
FT /note="P -> Q (decreases protein levels; dbSNP:rs56170584)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079822"
FT VARIANT 8
FT /note="T -> M (in dbSNP:rs17217716)"
FT /evidence="ECO:0000269|PubMed:10777691,
FT ECO:0000269|PubMed:12792735, ECO:0000269|Ref.9"
FT /id="VAR_013171"
FT VARIANT 13
FT /note="S -> I (in CRC; uncertain significance;
FT dbSNP:rs63749907)"
FT /evidence="ECO:0000269|PubMed:14504054"
FT /id="VAR_043736"
FT VARIANT 17
FT /note="V -> F (in gastric cancer; uncertain significance;
FT cryptic acceptor splice site suppressed on ex vivo splicing
FT assay; dbSNP:rs63750966)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043737"
FT VARIANT 33
FT /note="T -> P (in LYNCH1; decreased mismatch repair
FT activity; dbSNP:rs63751107)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043738"
FT VARIANT 40
FT /note="G -> S (in CRC; uncertain significance;
FT dbSNP:rs63751260)"
FT /evidence="ECO:0000269|PubMed:12792735"
FT /id="VAR_043739"
FT VARIANT 43
FT /note="Y -> C (in dbSNP:rs17217723)"
FT /evidence="ECO:0000269|Ref.9"
FT /id="VAR_019233"
FT VARIANT 44
FT /note="T -> M (in LYNCH1; uncertain significance; no
FT decrease in mismatch repair activity; dbSNP:rs587779085)"
FT /evidence="ECO:0000269|PubMed:12112654,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614"
FT /id="VAR_043740"
FT VARIANT 45
FT /note="A -> V (in LYNCH1; uncertain significance; no
FT decrease in mismatch repair activity; dbSNP:rs63750285)"
FT /evidence="ECO:0000269|PubMed:12112654,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614"
FT /id="VAR_043741"
FT VARIANT 46
FT /note="H -> Q (in LYNCH1; dbSNP:rs33946261)"
FT /evidence="ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:8700523"
FT /id="VAR_004470"
FT VARIANT 55
FT /note="R -> G (decreases protein levels;
FT dbSNP:rs587782354)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079823"
FT VARIANT 92
FT /note="Missing (in LYNCH1; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:18561205"
FT /id="VAR_043742"
FT VARIANT 93
FT /note="L -> F (in LYNCH1; dbSNP:rs63751429)"
FT /evidence="ECO:0000269|PubMed:15896463"
FT /id="VAR_043743"
FT VARIANT 96
FT /note="R -> H (in dbSNP:rs63750002)"
FT /evidence="ECO:0000269|PubMed:7726159"
FT /id="VAR_004471"
FT VARIANT 98
FT /note="Y -> C (in LYNCH1; uncertain significance;
FT dbSNP:rs63750887)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043744"
FT VARIANT 102
FT /note="V -> I (in LYNCH1; dbSNP:rs193922373)"
FT /evidence="ECO:0000269|PubMed:12200596"
FT /id="VAR_043745"
FT VARIANT 106
FT /note="R -> K (in dbSNP:rs41295286)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038026"
FT VARIANT 110
FT /note="K -> T (in LYNCH1; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043746"
FT VARIANT 127
FT /note="N -> S (in LYNCH1; presumed to enhance cancer risk
FT considerably when associated with P-328; shows
FT significantly decreased repair efficiency when associated
FT with variant P-328; dbSNP:rs17217772)"
FT /evidence="ECO:0000269|PubMed:12655564,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22581703, ECO:0000269|Ref.9"
FT /id="VAR_019234"
FT VARIANT 139
FT /note="N -> S (in LYNCH1; dbSNP:rs1553350676)"
FT /id="VAR_004472"
FT VARIANT 145
FT /note="I -> M (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; dbSNP:rs63750124)"
FT /evidence="ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22581703"
FT /id="VAR_004473"
FT VARIANT 161
FT /note="V -> D (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63750126)"
FT /evidence="ECO:0000269|PubMed:11726306,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_012936"
FT VARIANT 162
FT /note="G -> A (in LYNCH1; dbSNP:rs63750773)"
FT /evidence="ECO:0000269|PubMed:17128465"
FT /id="VAR_054512"
FT VARIANT 162
FT /note="G -> R (in LYNCH1; decreased mismatch repair
FT activity; associated with an abnormal subcellular
FT localization pattern; affects protein stability; loss of
FT protein expression; dbSNP:rs63750624)"
FT /evidence="ECO:0000269|PubMed:15991316,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18781619,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043747"
FT VARIANT 163
FT /note="V -> D (in LYNCH1; dbSNP:rs63750214)"
FT /evidence="ECO:0000269|PubMed:12200596"
FT /id="VAR_043748"
FT VARIANT 163
FT /note="V -> G (in LYNCH1; dbSNP:rs63750214)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022670"
FT VARIANT 164
FT /note="G -> R (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63750582)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043749"
FT VARIANT 165
FT /note="Y -> D (in LYNCH1; uncertain significance; decreased
FT mismatch repair activity; dbSNP:rs587779163)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067284"
FT VARIANT 167
FT /note="D -> H (in LYNCH1; shows reduced mismatch binding;
FT does not show a decreased expression level of the MutS
FT alpha complex; not associated with an abnormal subcellular
FT localization pattern; normal mismatch repair activity;
FT dbSNP:rs63750255)"
FT /evidence="ECO:0000269|PubMed:11870161,
FT ECO:0000269|PubMed:12124176, ECO:0000269|PubMed:18781619,
FT ECO:0000269|PubMed:18822302, ECO:0000269|PubMed:22102614,
FT ECO:0000269|PubMed:8872463"
FT /id="VAR_004474"
FT VARIANT 169
FT /note="I -> V (in LYNCH1 and CRC; uncertain significance;
FT dbSNP:rs63750716)"
FT /evidence="ECO:0000269|PubMed:12792735,
FT ECO:0000269|PubMed:15996210"
FT /id="VAR_043750"
FT VARIANT 173
FT /note="L -> P (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63750070)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043751"
FT VARIANT 175
FT /note="L -> P (in LYNCH1; dbSNP:rs63751291)"
FT /evidence="ECO:0000269|PubMed:12655568"
FT /id="VAR_043752"
FT VARIANT 177
FT /note="E -> H (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067285"
FT VARIANT 187
FT /note="L -> P (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63751444)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043753"
FT VARIANT 187
FT /note="L -> R (in LYNCH1; decreased mismatch repair
FT activity; loss of protein expression; dbSNP:rs63751444)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076352"
FT VARIANT 198
FT /note="E -> G (in LYNCH1; dbSNP:rs63750327)"
FT /id="VAR_054513"
FT VARIANT 199
FT /note="C -> R (in glioma; also associated with LYNCH1; no
FT effect on MSH2 splicing; dbSNP:rs63751110)"
FT /evidence="ECO:0000269|PubMed:18561205,
FT ECO:0000269|PubMed:9777949"
FT /id="VAR_012937"
FT VARIANT 203
FT /note="G -> R (in CRC; uncertain significance; somatic
FT mutation; dbSNP:rs587779973)"
FT /evidence="ECO:0000269|PubMed:12792735"
FT /id="VAR_043754"
FT VARIANT 205
FT /note="E -> Q (shows no defects; normal mismatch repair
FT activity; dbSNP:rs63749984)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068705"
FT VARIANT 216
FT /note="I -> V (in LYNCH1; uncertain significance; shows
FT slightly reduced mismatch binding or release efficiency;
FT dbSNP:rs63749936)"
FT /evidence="ECO:0000269|PubMed:11726306"
FT /id="VAR_012938"
FT VARIANT 246
FT /note="K -> Q (in LYNCH1; uncertain significance;
FT dbSNP:rs63750881)"
FT /evidence="ECO:0000269|PubMed:10573010"
FT /id="VAR_043755"
FT VARIANT 265..314
FT /note="Missing (in LYNCH1)"
FT /evidence="ECO:0000269|PubMed:9718327"
FT /id="VAR_004475"
FT VARIANT 272
FT /note="A -> V (in LYNCH1; uncertain significance; shows
FT slightly reduced mismatch binding or release efficiency;
FT results in partial MSH2 exon 5 skipping; normal mismatch
FT repair activity; dbSNP:rs34136999)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614"
FT /id="VAR_043756"
FT VARIANT 283
FT /note="D -> Y (in LYNCH1; dbSNP:rs63750381)"
FT /evidence="ECO:0000269|PubMed:15870828"
FT /id="VAR_043757"
FT VARIANT 305
FT /note="A -> T (in LYNCH1; normal mismatch repair activity;
FT dbSNP:rs63751454)"
FT /evidence="ECO:0000269|PubMed:22102614,
FT ECO:0000269|PubMed:9311737"
FT /id="VAR_004476"
FT VARIANT 322
FT /note="G -> D (in dbSNP:rs4987188)"
FT /evidence="ECO:0000269|PubMed:10023327,
FT ECO:0000269|PubMed:10469597, ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:10713887, ECO:0000269|PubMed:10829038,
FT ECO:0000269|PubMed:11555625, ECO:0000269|PubMed:11839723,
FT ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22581703,
FT ECO:0000269|PubMed:8566964, ECO:0000269|PubMed:9087566,
FT ECO:0000269|PubMed:9298827, ECO:0000269|Ref.9"
FT /id="VAR_004477"
FT VARIANT 323
FT /note="S -> C (in LYNCH1; uncertain significance;
FT dbSNP:rs63750732)"
FT /evidence="ECO:0000269|PubMed:9240418"
FT /id="VAR_012939"
FT VARIANT 323
FT /note="S -> Y (in LYNCH1; uncertain significance;
FT dbSNP:rs63750732)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043758"
FT VARIANT 328
FT /note="A -> P (shows significantly decreased repair
FT efficiency when associated with variant S-127; presumed to
FT enhance cancer risk considerably when associated with
FT variant S-127; dbSNP:rs753237286)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068706"
FT VARIANT 331
FT /note="N -> D (in LYNCH1; no effect on MSH2 splicing;
FT dbSNP:rs267607938)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054514"
FT VARIANT 333
FT /note="C -> Y (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63750828)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043759"
FT VARIANT 335
FT /note="T -> I (in LYNCH1; uncertain significance;
FT dbSNP:rs63750602)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043760"
FT VARIANT 336
FT /note="P -> S (in LYNCH1; dbSNP:rs63751062)"
FT /evidence="ECO:0000269|PubMed:10375096"
FT /id="VAR_043761"
FT VARIANT 342
FT /note="V -> I (in CRC; uncertain significance;
FT dbSNP:rs63749879)"
FT /evidence="ECO:0000269|PubMed:14504054"
FT /id="VAR_043762"
FT VARIANT 349
FT /note="P -> L (in LYNCH1; dbSNP:rs587779067)"
FT /evidence="ECO:0000269|PubMed:15342696"
FT /id="VAR_043763"
FT VARIANT 359
FT /note="R -> S (in LYNCH1; shows a decreased expression
FT level of the MutS alpha complex; associated with an
FT abnormal subcellular localization pattern;
FT dbSNP:rs63751617)"
FT /evidence="ECO:0000269|PubMed:11870161,
FT ECO:0000269|PubMed:18781619"
FT /id="VAR_043764"
FT VARIANT 367
FT /note="V -> I (shows no defects; normal mismatch repair
FT activity; dbSNP:rs80285180)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068707"
FT VARIANT 385
FT /note="P -> L (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; dbSNP:rs564736113)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067286"
FT VARIANT 390
FT /note="L -> F (in LYNCH1 and CRC; uncertain significance;
FT may decrease mismatch repair activity; dbSNP:rs17224367)"
FT /evidence="ECO:0000269|PubMed:10386556,
FT ECO:0000269|PubMed:10469597, ECO:0000269|PubMed:12792735,
FT ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:16451135,
FT ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:8690195,
FT ECO:0000269|PubMed:9621522, ECO:0000269|Ref.9"
FT /id="VAR_004478"
FT VARIANT 393
FT /note="K -> M (in LYNCH1; dbSNP:rs1558478490)"
FT /evidence="ECO:0000269|PubMed:12124176"
FT /id="VAR_043765"
FT VARIANT 419
FT /note="Q -> K (in CRC; uncertain significance; decreased
FT mismatch repair activity; dbSNP:rs63750006)"
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:12792735, ECO:0000269|PubMed:15996210,
FT ECO:0000269|PubMed:8690195"
FT /id="VAR_012940"
FT VARIANT 440
FT /note="Missing (in LYNCH1)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043766"
FT VARIANT 470
FT /note="V -> E (in LYNCH1; has no effect on ex vivo splicing
FT assay; dbSNP:rs267607959)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054515"
FT VARIANT 487
FT /note="D -> E (decreased mismatch repair activity;
FT dbSNP:rs35107951)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068708"
FT VARIANT 492
FT /note="M -> V (in LYNCH1)"
FT /id="VAR_043767"
FT VARIANT 506
FT /note="D -> Y (in LYNCH1 and CRC; sporadic early-onset CRC;
FT decreased mismatch repair activity; dbSNP:rs63750492)"
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:8797773,
FT ECO:0000269|PubMed:9559627"
FT /id="VAR_012941"
FT VARIANT 519
FT /note="F -> L (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; dbSNP:rs1371291280)"
FT /evidence="ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_067287"
FT VARIANT 524
FT /note="R -> P (in LYNCH1; decreased mismatch repair
FT activity; dbSNP:rs63751207)"
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:12124176, ECO:0000269|PubMed:9889267"
FT /id="VAR_004479"
FT VARIANT 534
FT /note="R -> P (no effect on protein levels;
FT dbSNP:rs587778523)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079824"
FT VARIANT 552
FT /note="T -> P (in LYNCH1; dbSNP:rs63750838)"
FT /evidence="ECO:0000269|PubMed:12658575"
FT /id="VAR_043768"
FT VARIANT 554
FT /note="S -> R (in LYNCH1; uncertain significance;
FT dbSNP:rs63751656)"
FT /evidence="ECO:0000269|PubMed:11726306"
FT /id="VAR_012942"
FT VARIANT 562
FT /note="E -> V (in LYNCH1; dbSNP:rs63750997)"
FT /evidence="ECO:0000269|PubMed:9048925"
FT /id="VAR_004480"
FT VARIANT 564
FT /note="T -> A (in LYNCH1; uncertain significance;
FT dbSNP:rs55778204)"
FT /evidence="ECO:0000269|PubMed:12200596,
FT ECO:0000269|PubMed:15996210"
FT /id="VAR_043769"
FT VARIANT 583
FT /note="N -> S (in LYNCH1; dbSNP:rs201118107)"
FT /evidence="ECO:0000269|PubMed:12658575"
FT /id="VAR_043770"
FT VARIANT 596
FT /note="N -> S (in LYNCH1; uncertain significance;
FT dbSNP:rs41295288)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:18033691, ECO:0000269|PubMed:8993976"
FT /id="VAR_012943"
FT VARIANT 596
FT /note="Missing (in LYNCH1; decreased mismatch repair
FT activity; has no effect on MSH2 splicing;
FT dbSNP:rs63749831)"
FT /evidence="ECO:0000269|PubMed:10375096,
FT ECO:0000269|PubMed:12112654, ECO:0000269|PubMed:12124176,
FT ECO:0000269|PubMed:15342696, ECO:0000269|PubMed:18561205,
FT ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:7874129,
FT ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9311737"
FT /id="VAR_004481"
FT VARIANT 600
FT /note="A -> V (in LYNCH1; dbSNP:rs63751236)"
FT /evidence="ECO:0000269|PubMed:11920458"
FT /id="VAR_043771"
FT VARIANT 603
FT /note="D -> N (in LYNCH1; decreased mismatch repair
FT activity; affects protein stability; loss of protein
FT expression; dbSNP:rs63750657)"
FT /evidence="ECO:0000269|PubMed:10829038,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043772"
FT VARIANT 610
FT /note="H -> N (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs267607980)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054516"
FT VARIANT 619
FT /note="Y -> C (in CRC; uncertain significance;
FT dbSNP:rs63749982)"
FT /evidence="ECO:0000269|PubMed:12792735"
FT /id="VAR_043773"
FT VARIANT 622
FT /note="P -> L (in LYNCH1; decreased mismatch repair
FT activity; confers multiple biochemical defects;
FT dbSNP:rs28929483)"
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:11555625, ECO:0000269|PubMed:12124176,
FT ECO:0000269|PubMed:18822302, ECO:0000269|PubMed:8261515"
FT /id="VAR_004482"
FT VARIANT 629
FT /note="Q -> R (in LYNCH1; uncertain significance;
FT dbSNP:rs61756468)"
FT /evidence="ECO:0000269|PubMed:12132870,
FT ECO:0000269|PubMed:12792735, ECO:0000269|PubMed:15365995,
FT ECO:0000269|PubMed:15613555, ECO:0000269|PubMed:15996210"
FT /id="VAR_043774"
FT VARIANT 636
FT /note="A -> P (in LYNCH1; decreased mismatch binding
FT activity; dbSNP:rs63750875)"
FT /evidence="ECO:0000269|PubMed:10528862,
FT ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_012944"
FT VARIANT 638
FT /note="R -> G (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs267607981)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054517"
FT VARIANT 639
FT /note="H -> R (in LYNCH1; decreased mismatch repair
FT activity; dbSNP:rs587779116)"
FT /evidence="ECO:0000269|PubMed:18822302,
FT ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:9419403"
FT /id="VAR_043775"
FT VARIANT 639
FT /note="H -> Y (in LYNCH1; the equivalent substitution in
FT yeast does not affect mismatch repair efficiency in vitro;
FT dbSNP:rs28929484)"
FT /evidence="ECO:0000269|PubMed:11555625,
FT ECO:0000269|PubMed:8261515"
FT /id="VAR_004483"
FT VARIANT 641
FT /note="C -> G (in dbSNP:rs63749946)"
FT /evidence="ECO:0000269|PubMed:9718327"
FT /id="VAR_004484"
FT VARIANT 645
FT /note="Q -> E (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs267607982)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054518"
FT VARIANT 647
FT /note="E -> K (in LYNCH1)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043776"
FT VARIANT 656
FT /note="Y -> H (in LYNCH1; somatic mutation;
FT dbSNP:rs1573567393)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043777"
FT VARIANT 660
FT /note="D -> G (in LYNCH1; dbSNP:rs1085308057)"
FT /evidence="ECO:0000269|PubMed:14635101"
FT /id="VAR_022671"
FT VARIANT 669
FT /note="G -> R (in LYNCH1; dbSNP:rs63751668)"
FT /evidence="ECO:0000269|PubMed:22371642"
FT /id="VAR_067761"
FT VARIANT 670
FT /note="P -> L (in dbSNP:rs41294982)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038027"
FT VARIANT 671
FT /note="N -> Y (in LYNCH1; uncertain significance;
FT dbSNP:rs63751232)"
FT /evidence="ECO:0000269|PubMed:15300854,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_043778"
FT VARIANT 674
FT /note="G -> A (in LYNCH1; decreased mismatch repair
FT activity; dbSNP:rs267607996)"
FT /evidence="ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_076353"
FT VARIANT 674
FT /note="G -> R (in LYNCH1; decreased mismatch repair
FT activity; dbSNP:rs63750234)"
FT /evidence="ECO:0000269|PubMed:18625694,
FT ECO:0000269|PubMed:18822302, ECO:0000269|PubMed:22102614"
FT /id="VAR_067288"
FT VARIANT 674
FT /note="G -> S (in LYNCH1; somatic mutation;
FT dbSNP:rs63750234)"
FT /evidence="ECO:0000269|PubMed:12124176"
FT /id="VAR_004485"
FT VARIANT 675
FT /note="K -> A (in LYNCH1; uncertain significance; decreased
FT mismatch repair activity; requires 2 nucleotide
FT substitutions; dbSNP:rs587779128)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067289"
FT VARIANT 679
FT /note="I -> T (in LYNCH1; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043779"
FT VARIANT 688
FT /note="M -> I (in LYNCH1; dbSNP:rs63750790)"
FT /evidence="ECO:0000269|PubMed:10777691,
FT ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:9559627"
FT /id="VAR_012945"
FT VARIANT 688
FT /note="M -> V (in LYNCH1; loss of protein expression)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076354"
FT VARIANT 692
FT /note="G -> R (in LYNCH1; dbSNP:rs63750232)"
FT /evidence="ECO:0000269|PubMed:10612836"
FT /id="VAR_009250"
FT VARIANT 696
FT /note="P -> L (in LYNCH1; has no effect on ex vivo splicing
FT assay; dbSNP:rs267607994)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054519"
FT VARIANT 697
FT /note="C -> F (in LYNCH1; decreased mismatch repair
FT activity; loss of protein expression; confers multiple
FT biochemical defects; dbSNP:rs63750398)"
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18822302,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:9298827"
FT /id="VAR_004486"
FT VARIANT 697
FT /note="C -> R (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs63750961)"
FT /evidence="ECO:0000269|PubMed:10612836,
FT ECO:0000269|PubMed:18561205"
FT /id="VAR_009251"
FT VARIANT 714
FT /note="A -> V (in LYNCH1; uncertain significance;
FT dbSNP:rs63751224)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043780"
FT VARIANT 722
FT /note="V -> I (in LYNCH1; dbSNP:rs587781996)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076355"
FT VARIANT 723
FT /note="S -> F (in LYNCH1; decreased mismatch repair
FT activity; has no effect on MSH2 splicing;
FT dbSNP:rs63750794)"
FT /evidence="ECO:0000269|PubMed:11920458,
FT ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:22102614"
FT /id="VAR_043781"
FT VARIANT 729
FT /note="M -> V (in LYNCH1; somatic mutation;
FT dbSNP:rs1558520059)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043782"
FT VARIANT 732
FT /note="T -> I (in LYNCH1; somatic mutation;
FT dbSNP:rs730881765)"
FT /evidence="ECO:0000269|PubMed:9419403"
FT /id="VAR_043783"
FT VARIANT 745..746
FT /note="Missing (in LYNCH1; decreased mismatch repair
FT activity)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043784"
FT VARIANT 748
FT /note="D -> Y (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs267608007)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054520"
FT VARIANT 749
FT /note="E -> K (in LYNCH1; decreased mismatch repair
FT activity; no loss of protein expression; dbSNP:rs63751477)"
FT /evidence="ECO:0000269|PubMed:17101317,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944"
FT /id="VAR_043785"
FT VARIANT 759
FT /note="G -> E (in LYNCH1; uncertain significance; decreased
FT mismatch repair activity; dbSNP:rs386833406)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067290"
FT VARIANT 770
FT /note="I -> V (in dbSNP:rs63750684)"
FT /evidence="ECO:0000269|PubMed:9718327"
FT /id="VAR_004487"
FT VARIANT 779
FT /note="M -> I (in dbSNP:rs41295292)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038028"
FT VARIANT 805
FT /note="L -> V (in LYNCH1; uncertain significance; normal
FT mismatch repair activity)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067291"
FT VARIANT 807
FT /note="T -> S (in dbSNP:rs41295294)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038029"
FT VARIANT 813
FT /note="M -> I (no effect on protein levels;
FT dbSNP:rs587781678)"
FT /evidence="ECO:0000269|PubMed:28494185"
FT /id="VAR_079825"
FT VARIANT 813
FT /note="M -> V (in LYNCH1; dbSNP:rs63749841)"
FT /evidence="ECO:0000269|PubMed:12373605"
FT /id="VAR_043786"
FT VARIANT 824
FT /note="Q -> E (in gastric cancer; uncertain significance;
FT dbSNP:rs63750623)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043787"
FT VARIANT 834
FT /note="A -> T (in LYNCH1; decreased mismatch repair
FT activity; shows no functional defects in gel shift assay;
FT dbSNP:rs63750757)"
FT /evidence="ECO:0000269|PubMed:10573010,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18822302,
FT ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944,
FT ECO:0000269|PubMed:9311737"
FT /id="VAR_004488"
FT VARIANT 835
FT /note="N -> H (in dbSNP:rs41295296)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038030"
FT VARIANT 839
FT /note="H -> Q (in LYNCH1; has no effect on MSH2 splicing;
FT dbSNP:rs267608016)"
FT /evidence="ECO:0000269|PubMed:18561205"
FT /id="VAR_054521"
FT VARIANT 839
FT /note="H -> R (in LYNCH1; decreases protein levels;
FT dbSNP:rs63750027)"
FT /evidence="ECO:0000269|PubMed:15613555,
FT ECO:0000269|PubMed:28494185"
FT /id="VAR_043788"
FT VARIANT 843
FT /note="C -> G (in LYNCH1; uncertain significance; normal
FT mismatch repair activity)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067292"
FT VARIANT 845
FT /note="K -> E (in LYNCH1; dbSNP:rs63750571)"
FT /evidence="ECO:0000269|PubMed:10777691"
FT /id="VAR_013172"
FT VARIANT 853
FT /note="E -> A (in LYNCH1; uncertain significance;
FT dbSNP:rs63750797)"
FT /evidence="ECO:0000269|PubMed:12362047,
FT ECO:0000269|PubMed:16451135"
FT /id="VAR_043789"
FT VARIANT 860
FT /note="S -> L (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; dbSNP:rs63750849)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067293"
FT VARIANT 868
FT /note="P -> A (in gastric cancer; uncertain significance;
FT dbSNP:rs63751400)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043790"
FT VARIANT 870
FT /note="A -> G (in gastric cancer; uncertain significance;
FT dbSNP:rs63750709)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043791"
FT VARIANT 873
FT /note="C -> G (in gastric cancer; uncertain significance;
FT dbSNP:rs63750795)"
FT /evidence="ECO:0000269|PubMed:12132870"
FT /id="VAR_043792"
FT VARIANT 886
FT /note="E -> G (in LYNCH1; uncertain significance; normal
FT mismatch repair activity; dbSNP:rs63750350)"
FT /evidence="ECO:0000269|PubMed:12112654,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614"
FT /id="VAR_043793"
FT VARIANT 905
FT /note="T -> R (in LYNCH1; uncertain significance;
FT dbSNP:rs267608022)"
FT /evidence="ECO:0000269|PubMed:12124176"
FT /id="VAR_004489"
FT VARIANT 909
FT /note="K -> I (found in a colorectal cancer sample; normal
FT mismatch repair activity; dbSNP:rs34319539)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068709"
FT VARIANT 911
FT /note="L -> R (in dbSNP:rs41295182)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038031"
FT VARIANT 923
FT /note="V -> E (in LYNCH1; uncertain significance;
FT dbSNP:rs146421227)"
FT /evidence="ECO:0000269|PubMed:12112654,
FT ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:18951462,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043794"
FT VARIANT 931
FT /note="K -> T (in LYNCH1; dbSNP:rs267608023)"
FT /evidence="ECO:0000269|PubMed:15046096"
FT /id="VAR_043795"
FT MUTAGEN 675
FT /note="K->R: No effect on mismatch binding, complete loss
FT of DNA repair function when associated with MSH6 mutant R-
FT 1140."
FT /evidence="ECO:0000269|PubMed:9564049"
FT CONFLICT 784
FT /note="F -> I (in Ref. 7; BX649122)"
FT /evidence="ECO:0000305"
FT CONFLICT 836
FT /note="F -> S (in Ref. 7; BX649122)"
FT /evidence="ECO:0000305"
FT HELIX 14..24
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 40..46
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 48..56
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 82..94
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 99..105
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 129..131
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 132..135
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:8AG6"
FT STRAND 147..152
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 160..167
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 168..171
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 172..179
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 185..194
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 197..204
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 208..220
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 223..227
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 229..232
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 237..244
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 252..254
FT /evidence="ECO:0007829|PDB:2O8E"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 259..262
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 264..277
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 279..281
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 289..293
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 296..298
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 304..309
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 336..347
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 353..367
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 370..377
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 378..380
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 381..383
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 387..395
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 401..411
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 414..423
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 424..426
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 432..435
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 437..455
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 462..464
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 472..474
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 476..502
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 507..509
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 512..515
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 517..519
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 521..525
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 527..530
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 531..535
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 540..544
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 549..552
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 556..563
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 564..567
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 568..585
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 586..588
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 589..613
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 615..617
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 623..625
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 631..637
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 640..644
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 653..658
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 659..661
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 664..668
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 675..691
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 695..703
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 706..711
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 724..738
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 744..749
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 756..772
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 777..783
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 785..792
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 797..807
FT /evidence="ECO:0007829|PDB:3THX"
FT STRAND 810..820
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 827..833
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 838..850
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 851..855
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 875..892
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 896..898
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 901..917
FT /evidence="ECO:0007829|PDB:3THX"
FT HELIX 921..928
FT /evidence="ECO:0007829|PDB:3THX"
FT TURN 931..933
FT /evidence="ECO:0007829|PDB:8AG6"
SQ SEQUENCE 934 AA; 104743 MW; 664A058C78242E05 CRC64;
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT
QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA
YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD
NDQFSNLEAL LIQIGPKECV LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD
LNRLLKGKKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL
NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA
LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE
LREIMNDLEK KMQSTLISAA RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF IPNDVYFEKD
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV
IECAKQKALE LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT
//
