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 28-JAN-2026, entry version 255. 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 SUBCELLULAR LOCATION, ACETYLATION AT LYS-845; LYS-847; LYS-871 AND LYS-892, RP DEACETYLATION BY HDAC6, UBIQUITINATION AT LYS-845; LYS-847; LYS-871 AND RP LYS-892, AND MUTAGENESIS OF LYS-845; LYS-847; LYS-871 AND LYS-892. RX PubMed=24882211; DOI=10.1016/j.molcel.2014.04.028; RA Zhang M., Xiang S., Joo H.Y., Wang L., Williams K.A., Liu W., Hu C., RA Tong D., Haakenson J., Wang C., Zhang S., Pavlovicz R.E., Jones A., RA Schmidt K.H., Tang J., Dong H., Shan B., Fang B., Radhakrishnan R., RA Glazer P.M., Matthias P., Koomen J., Seto E., Bepler G., Nicosia S.V., RA Chen J., Li C., Gu L., Li G.M., Bai W., Wang H., Zhang X.; RT "HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of RT MutSalpha."; RL Mol. Cell 55:31-46(2014). RN [41] 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 [42] 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 [43] 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] 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 [63] 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 [64] 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 [65] RP VARIANT 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 [66] 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 [67] 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 does not seem to confer an increased risk for RT colorectal cancer susceptibility."; RL Eur. J. Cancer 34:1981-1981(1998). RN [68] 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 [69] 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 [70] 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 [71] 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 [72] 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 [73] 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 [74] 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 [75] 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 [76] 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 [77] 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 [78] 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 [79] 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 [80] 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 [81] 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 [82] 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 [83] 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 [84] 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 [85] 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 [86] 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 [87] 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 [88] 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 [89] 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 [90] 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 [91] 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 [92] 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 [93] 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 [94] 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 [95] 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 [96] 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 [97] 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 [98] 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 [99] 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 [100] 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 [101] 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 [102] 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 [103] 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 [104] 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 [105] 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 [106] 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 [107] 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 [108] 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 [109] 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 [110] 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 [111] 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 [112] 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 [113] 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 [114] 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 [115] 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 [116] 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 [117] 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 [118] 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:10856833, PubMed:11427529, PubMed:11429708, CC PubMed:12414623, PubMed:14676842, PubMed:9788596). Interacts with MCM9; CC the interaction recruits MCM9 to chromatin (PubMed:26300262). Interacts CC with MCM8 (PubMed:26300262). Interacts with EXO1 (PubMed:10856833, CC PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842, CC PubMed:9788596). Part of the BRCA1-associated genome surveillance CC complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 CC and the RAD50-MRE11-NBS1 protein complex (PubMed:10783165). This CC association could be a dynamic process changing throughout the cell CC cycle and within subnuclear domains (PubMed:10783165). Interacts with CC ATR (PubMed:14657349). Interacts with SLX4/BTBD12; this interaction is CC direct and links MutS beta to SLX4, a subunit of different structure- CC specific endonucleases (PubMed:19596235). Interacts with SMARCAD1 CC (PubMed:18675275). {ECO:0000269|PubMed:10783165, CC ECO:0000269|PubMed:10856833, ECO:0000269|PubMed:11427529, CC ECO:0000269|PubMed:11429708, ECO:0000269|PubMed:12414623, CC ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14676842, CC ECO:0000269|PubMed:18675275, ECO:0000269|PubMed:19596235, CC ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:8942985, CC 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=14; IntAct=EBI-355888, EBI-1164205; CC P43246; P52701: MSH6; NbExp=11; 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:24882211, CC ECO:0000269|PubMed:26300262}. Chromosome {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 -!- PTM: Sequentially deacetylated and polyubiquitinated by HDAC6, leading CC to MSH2 degradation. {ECO:0000269|PubMed:24882211}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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_000251.3. [P43246-1] DR RefSeq; NP_001245210.1; NM_001258281.1. [P43246-2] DR RefSeq; NP_001393570.1; NM_001406641.1. [P43246-1] 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 PDB; 8R7C; X-ray; 2.82 A; A/E=1-930. DR PDB; 8R7E; X-ray; 2.78 A; A/E=1-930. DR PDB; 8R7V; EM; 3.12 A; A=1-934. DR PDB; 8RAU; X-ray; 2.33 A; A=1-934. DR PDB; 8RAV; X-ray; 2.63 A; A=1-934. DR PDB; 8RAW; X-ray; 2.69 A; A=1-934. DR PDB; 8RAX; X-ray; 3.16 A; A=1-934. DR PDB; 8RAZ; X-ray; 2.84 A; A=1-934. DR PDB; 8RB0; X-ray; 2.67 A; A=1-934. DR PDB; 8RB1; X-ray; 2.08 A; A=1-934. DR PDB; 8RB2; X-ray; 2.53 A; A/E=1-934. DR PDB; 8RZ7; EM; 3.37 A; A=1-934. DR PDB; 8RZ8; EM; 3.06 A; A=1-934. DR PDB; 8RZ9; EM; 3.02 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 PDBsum; 8R7C; -. DR PDBsum; 8R7E; -. DR PDBsum; 8R7V; -. DR PDBsum; 8RAU; -. DR PDBsum; 8RAV; -. DR PDBsum; 8RAW; -. DR PDBsum; 8RAX; -. DR PDBsum; 8RAZ; -. DR PDBsum; 8RB0; -. DR PDBsum; 8RB1; -. DR PDBsum; 8RB2; -. DR PDBsum; 8RZ7; -. DR PDBsum; 8RZ8; -. DR PDBsum; 8RZ9; -. 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 EMDB; EMD-18992; -. DR EMDB; EMD-19605; -. DR EMDB; EMD-19606; -. DR EMDB; EMD-19607; -. DR SMR; P43246; -. DR BioGRID; 110573; 329. 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 FunCoup; P43246; 3266. DR IntAct; P43246; 111. DR MINT; P43246; -. DR STRING; 9606.ENSP00000233146; -. DR ChEMBL; CHEMBL4296019; -. DR GlyGen; P43246; 3 sites, 2 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P43246; -. DR PhosphoSitePlus; P43246; -. DR SwissPalm; P43246; -. DR BioMuta; MSH2; -. DR DMDM; 1171032; -. DR jPOST; P43246; -. DR MassIVE; P43246; -. DR PaxDb; 9606-ENSP00000233146; -. DR PeptideAtlas; P43246; -. DR ProteomicsDB; 55601; -. [P43246-1] DR ProteomicsDB; 5866; -. DR Pumba; P43246; -. DR Antibodypedia; 4037; 803 antibodies from 50 providers. DR CPTC; P43246; 1 antibody. DR DNASU; 4436; -. DR Ensembl; ENST00000233146.7; ENSP00000233146.2; ENSG00000095002.17. [P43246-1] DR Ensembl; ENST00000543555.6; ENSP00000442697.1; ENSG00000095002.17. [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 CIViC; 4436; 8 evidence items across 9 molecular profiles. DR ClinPGx; PA31133; -. 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 OpenTargets; ENSG00000095002; -. DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome. DR Orphanet; 144; Lynch syndrome. 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; 295033at2759; -. DR PAN-GO; P43246; 5 GO annotations based on evolutionary models. DR PhylomeDB; P43246; -. 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 Agora; ENSG00000095002; -. 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 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:0008047; F:enzyme activator activity; IDA:BHF-UCL. 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:0006301; P:DNA damage tolerance; IDA:UniProtKB. 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: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: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 FunFam; 1.10.1420.10:FF:000003; DNA mismatch repair protein; 1. DR FunFam; 1.10.1420.10:FF:000009; DNA mismatch repair protein; 1. DR FunFam; 3.30.420.110:FF:000002; DNA mismatch repair protein; 1. DR FunFam; 3.40.1170.10:FF:000003; DNA mismatch repair protein; 1. DR FunFam; 3.40.50.300:FF:000523; DNA mismatch repair protein; 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; IPR045076; MutS. DR InterPro; IPR036678; MutS_con_dom_sf. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; NF003810; PRK05399.1; 1. 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; Proteomics identification; KW Reference proteome; 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 845 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24882211" FT MOD_RES 847 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24882211" FT MOD_RES 871 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24882211" FT MOD_RES 892 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:24882211" 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 CROSSLNK 845 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:24882211" FT CROSSLNK 847 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:24882211" FT CROSSLNK 871 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:24882211" FT CROSSLNK 892 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:24882211" 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; likely benign; 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; likely benign; 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; likely benign; FT 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; benign; presumed to enhance FT cancer risk 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; decreased mismatch repair FT activity; dbSNP:rs587779163)" FT /evidence="ECO:0000269|PubMed:22102614" FT /id="VAR_067284" FT VARIANT 167 FT /note="D -> H (in LYNCH1; benign; shows reduced mismatch FT binding; does not show a decreased expression level of the FT MutS alpha complex; not associated with an abnormal FT subcellular localization pattern; normal mismatch repair FT activity; 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; likely benign; 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 dbSNP:rs63750327)" FT /id="VAR_054513" FT VARIANT 199 FT /note="C -> R (in LYNCH1; also found in a patient with FT glioma; no 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; benign; shows slightly reduced FT mismatch binding or release efficiency; results in partial FT MSH2 exon 5 skipping; normal mismatch repair activity; FT 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; uncertain significance; no effect FT on MSH2 splicing; 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; benign; may decrease FT 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; likely benign; decreased mismatch FT 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; benign; 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; uncertain significance; decreased FT mismatch repair activity; affects protein stability; loss FT of protein 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; benign; 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; uncertain significance; FT 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 dbSNP:rs1573569964)" 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; dbSNP:rs779182536)" 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; uncertain significance; FT 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; likely benign; decreased mismatch FT repair activity; shows no functional defects in gel shift FT assay; 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; dbSNP:rs1667495338)" 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; likely benign; normal mismatch FT 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; likely benign; 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 MUTAGEN 845 FT /note="K->R: Reduces interaction with MSH6. Reduces FT acetylation; when associated with R-847, R-871 and R-892." FT /evidence="ECO:0000269|PubMed:24882211" FT MUTAGEN 847 FT /note="K->R: Reduces interaction with MSH6. Reduces FT acetylation; when associated with R-845, R-871 and R-892." FT /evidence="ECO:0000269|PubMed:24882211" FT MUTAGEN 871 FT /note="K->R: Does not affect interaction with MSH6. Reduces FT acetylation; when associated with R-845, R-847 and R-892." FT /evidence="ECO:0000269|PubMed:24882211" FT MUTAGEN 892 FT /note="K->R: Does not affect interaction with MSH6. Reduces FT acetylation; when associated with R-845, R-847 and R-871." FT /evidence="ECO:0000269|PubMed:24882211" 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 STRAND 234..236 FT /evidence="ECO:0007829|PDB:8OLX" FT HELIX 237..244 FT /evidence="ECO:0007829|PDB:3THX" FT STRAND 249..251 FT /evidence="ECO:0007829|PDB:8OLX" 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 TURN 286..288 FT /evidence="ECO:0007829|PDB:8R7E" 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 STRAND 321..323 FT /evidence="ECO:0007829|PDB:8OMA" 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 536..538 FT /evidence="ECO:0007829|PDB:8OMO" FT STRAND 540..544 FT /evidence="ECO:0007829|PDB:3THX" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:8OMQ" 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 645..647 FT /evidence="ECO:0007829|PDB:8R7C" 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 STRAND 671..674 FT /evidence="ECO:0007829|PDB:8OMO" 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 TURN 718..721 FT /evidence="ECO:0007829|PDB:8OMQ" FT HELIX 724..738 FT /evidence="ECO:0007829|PDB:3THX" FT STRAND 744..749 FT /evidence="ECO:0007829|PDB:3THX" FT TURN 750..753 FT /evidence="ECO:0007829|PDB:8R7E" 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 //