MSH6_HUMAN
ID MSH6_HUMAN Reviewed; 1360 AA.
AC P52701; B4DF41; B4E3I4; F5H2F9; O43706; O43917; Q8TCX4; Q9BTB5;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=DNA mismatch repair protein Msh6 {ECO:0000250|UniProtKB:P54276};
DE Short=hMSH6 {ECO:0000303|PubMed:8942985};
DE AltName: Full=G/T mismatch-binding protein {ECO:0000303|PubMed:7604265};
DE Short=GTBP {ECO:0000303|PubMed:9455487};
DE Short=GTMBP {ECO:0000250|UniProtKB:P54276};
DE AltName: Full=MutS protein homolog 6 {ECO:0000312|HGNC:HGNC:7329};
DE AltName: Full=MutS-alpha 160 kDa subunit;
DE Short=p160 {ECO:0000303|PubMed:7604264};
GN Name=MSH6 {ECO:0000312|HGNC:HGNC:7329}; Synonyms=GTBP;
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 [GENOMIC DNA / MRNA], VARIANT GLU-39, AND SUBUNIT.
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 [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
RX PubMed=9455487; DOI=10.1093/dnares/4.5.359;
RA Shiwaku H.O., Wakatsuki S., Mori Y., Fukushige S., Horii A.;
RT "Alternative splicing of GTBP in normal human tissues.";
RL DNA Res. 4:359-362(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4).
RC TISSUE=Cerebellum, and 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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-39; VAL-396; ALA-623
RP AND VAL-886.
RG NIEHS SNPs program;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-1360, AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=7604265; DOI=10.1126/science.7604265;
RA Palombo F., Gallinari P., Iaccarino I., Lettieri T., Hughes M.,
RA D'Arrigo A., Truong O., Hsuan J.J., Jiricny J.;
RT "GTBP, a 160-kilodalton protein essential for mismatch-binding activity in
RT human cells.";
RL Science 268:1912-1914(1995).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-116.
RX PubMed=8838326; DOI=10.1006/geno.1996.0067;
RA Nicolaides N.C., Palombo F., Kinzler K.W., Vogelstein B., Jiricny J.;
RT "Molecular cloning of the N-terminus of GTBP.";
RL Genomics 31:395-397(1996).
RN [9]
RP CHARACTERIZATION, PARTIAL PROTEIN SEQUENCE, AND SUBUNIT.
RX PubMed=7604264; DOI=10.1126/science.7604264;
RA Drummond J.T., Li G.-M., Longley M.J., Modrich P.;
RT "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair
RT to tumor cells.";
RL Science 268:1909-1912(1995).
RN [10]
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 [11]
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 [12]
RP FUNCTION, AND MUTAGENESIS OF LYS-1140.
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 [13]
RP MISMATCH-BINDING.
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
RP IDENTIFICATION OF MSH6 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 [19]
RP INVOLVEMENT IN HNPCC5.
RX PubMed=9354786; DOI=10.1038/ng1197-271;
RA Miyaki M., Konishi M., Tanaka K., Kikuchi-Yanoshita R., Muraoka M.,
RA Yasuno M., Igari T., Koike M., Chiba M., Mori T.;
RT "Germline mutation of MSH6 as the cause of hereditary nonpolyposis
RT colorectal cancer.";
RL Nat. Genet. 17:271-272(1997).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219; SER-227 AND SER-261, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-41 AND SER-43,
RP VARIANT [LARGE SCALE ANALYSIS] GLU-39, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [22]
RP INVOLVEMENT IN MMRCS.
RX PubMed=17557300; DOI=10.1002/humu.20569;
RA Auclair J., Leroux D., Desseigne F., Lasset C., Saurin J.C., Joly M.O.,
RA Pinson S., Xu X.L., Montmain G., Ruano E., Navarro C., Puisieux A.,
RA Wang Q.;
RT "Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as a
RT likely cause of PMS2 gene inactivation.";
RL Hum. Mutat. 28:1084-1090(2007).
RN [23]
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 [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-79; SER-91; SER-137;
RP SER-200; SER-227; SER-252; SER-254; SER-256 AND SER-261, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70 AND LYS-504, AND
RP IDENTIFICATION BY MASS 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 [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-137; SER-227 AND
RP SER-830, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [29]
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 [30]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-137; SER-219;
RP SER-227; SER-252; SER-261; THR-269; SER-274; SER-275; SER-279; SER-280 AND
RP SER-309, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-137; SER-227;
RP SER-252; SER-309; THR-488; SER-830; SER-935 AND THR-1010, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP CHARACTERIZATION OF VARIANTS HNPCC5 LEU-128; ILE-144; ARG-566; LEU-623;
RP THR-728; GLY-881 DELINS LYS-SER; THR-1087; HIS-1095; LYS-1193 AND GLN-1354,
RP CHARACTERIZATION OF VARIANT ARG-1087, 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 [33]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12 (MICROBIAL INFECTION).
RX PubMed=21957315; DOI=10.1128/jvi.05487-11;
RA Mohni K.N., Mastrocola A.S., Bai P., Weller S.K., Heinen C.D.;
RT "DNA mismatch repair proteins are required for efficient herpes simplex
RT virus 1 replication.";
RL J. Virol. 85:12241-12253(2011).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-103 AND
RP 105-TRP-TRP-106.
RX PubMed=23622243; DOI=10.1016/j.cell.2013.03.025;
RA Li F., Mao G., Tong D., Huang J., Gu L., Yang W., Li G.M.;
RT "The histone mark H3K36me3 regulates human DNA mismatch repair through its
RT interaction with MutSalpha.";
RL Cell 153:590-600(2013).
RN [35]
RP IDENTIFICATION IN THE MMR COMPLEX, AND INTERACTION WITH MCM9.
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 [36]
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 [37]
RP VARIANTS VAL-1213 AND ILE-1260.
RX PubMed=7604266; DOI=10.1126/science.7604266;
RA Papadopoulos N., Nicolaides N.C., Liu B., Parsons R., Lengauer C.,
RA Palombo F., D'Arrigo A., Markowitz S., Willson J.K.V., Kinzler K.W.,
RA Jiricny J., Vogelstein B.;
RT "Mutations of GTBP in genetically unstable cells.";
RL Science 268:1915-1917(1995).
RN [38]
RP VARIANTS HNPCC5 ILE-144 AND CYS-850.
RX PubMed=10521294; DOI=10.1086/302612;
RA Wu Y., Berends M.J.W., Mensink R.G.J., Kempinga C., Sijmons R.H.,
RA van Der Zee A.G.J., Hollema H., Kleibeuker J.H., Buys C.H.C.M.,
RA Hofstra R.M.W.;
RT "Association of hereditary nonpolyposis colorectal cancer-related tumors
RT displaying low microsatellite instability with MSH6 germline mutations.";
RL Am. J. Hum. Genet. 65:1291-1298(1999).
RN [39]
RP VARIANTS CRC ILE-285; ARG-566; GLY-803 AND THR-1087, AND VARIANTS GLU-39;
RP ASP-220; VAL-396 AND LEU-800.
RX PubMed=10537275;
RA Kolodner R.D., Tytell J.D., Schmeits J.L., Kane M.F., Das Gupta R.,
RA Weger J., Wahlberg S., Fox E.A., Peel D., Ziogas A., Garber J.E.,
RA Syngal S., Anton-Culver H., Li F.P.;
RT "Germ-line msh6 mutations in colorectal cancer families.";
RL Cancer Res. 59:5068-5074(1999).
RN [40]
RP VARIANT HNPCC5 GLU-698.
RX PubMed=10480359; DOI=10.1007/s004399900064;
RA Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., Navarro C.,
RA Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., Puisieux A.;
RT "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6
RT genes in 75 French kindreds with nonpolyposis colorectal cancer.";
RL Hum. Genet. 105:79-85(1999).
RN [41]
RP VARIANT CRC MET-1284.
RX PubMed=10413423; DOI=10.1093/jnci/91.14.1221;
RA Chan T.L., Yuen S.T., Chung L.P., Ho J.W.C., Kwan K.Y.M., Chan A.S.Y.,
RA Ho J.C.Y., Leung S.Y., Wyllie A.H.;
RT "Frequent microsatellite instability and mismatch repair gene mutations in
RT young Chinese patients with colorectal cancer.";
RL J. Natl. Cancer Inst. 91:1221-1226(1999).
RN [42]
RP VARIANTS CRC VAL-20; ALA-878 AND HIS-901, AND VARIANTS ENDMC VAL-20;
RP ALA-878 AND HIS-901.
RX PubMed=11153917; DOI=10.1007/s004390000417;
RA Charames G.S., Millar A.L., Pal T., Narod S., Bapat B.;
RT "Do MSH6 mutations contribute to double primary cancers of the colorectum
RT and endometrium?";
RL Hum. Genet. 107:623-629(2000).
RN [43]
RP VARIANT CRC SER-340, AND VARIANT GLU-39.
RX PubMed=10699937;
RX DOI=10.1002/(sici)1097-0215(20000301)85:5<606::aid-ijc2>3.0.co;2-b;
RA Plaschke J., Kruppa C., Tischler R., Bocker T., Pistorius S., Dralle H.,
RA Rueschoff J., Saeger H.D., Fishel R., Schackert H.K.;
RT "Sequence analysis of the mismatch repair gene hMSH6 in the germline of
RT patients with familial and sporadic colorectal cancer.";
RL Int. J. Cancer 85:606-613(2000).
RN [44]
RP VARIANTS CRC ALA-685; GLN-772; ALA-800; MET-854; ALA-878; VAL-1031 AND
RP ARG-1158.
RX PubMed=11470537; DOI=10.1016/s0378-1119(01)00517-0;
RA Ohmiya N., Matsumoto S., Yamamoto H., Baranovskaya S., Malkhosyan S.R.,
RA Perucho M.;
RT "Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal
RT cancers of the microsatellite mutator phenotype.";
RL Gene 272:301-313(2001).
RN [45]
RP VARIANT HNPCC5 ALA-878.
RX PubMed=11586295; DOI=10.1038/ng1001-137;
RA Wu Y., Berends M.J.W., Sijmons R.H., Mensink R.G.J., Verlind E., Kooi K.A.,
RA van der Sluis T., Kempinga C., van der Zee A.G.J., Hollema H.,
RA Buys C.H.C.M., Kleibeuker J.H., Hofstra R.M.W.;
RT "A role for MLH3 in hereditary nonpolyposis colorectal cancer.";
RL Nat. Genet. 29:137-138(2001).
RN [46]
RP VARIANTS CRC ILE-144; ARG-522; MET-725; CYS-850; ALA-878; ASP-1021;
RP MET-1100; ILE-1219 AND ASP-1248.
RX PubMed=11709755; DOI=10.1086/337944;
RA Berends M.J.W., Wu Y., Sijmons R.H., Mensink R.G.J., van der Sluis T.,
RA Hordijk-Hos J.M., de Vries E.G.E., Hollema H., Karrenbeld A.,
RA Buys C.H.C.M., van der Zee A.G.J., Hofstra R.M.W., Kleibeuker J.H.;
RT "Molecular and clinical characteristics of MSH6 variants: an analysis of 25
RT index carriers of a germline variant.";
RL Am. J. Hum. Genet. 70:26-37(2002).
RN [47]
RP VARIANT CRC HIS-976.
RX PubMed=11807791; DOI=10.1002/ijc.10097;
RA Plaschke J., Krueger S., Pistorius S., Theissig F., Saeger H.D.,
RA Schackert H.K.;
RT "Involvement of hMSH6 in the development of hereditary and sporadic
RT colorectal cancer revealed by immunostaining is based on germline
RT mutations, but rarely on somatic inactivation.";
RL Int. J. Cancer 97:643-648(2002).
RN [48]
RP VARIANT HNPCC5 VAL-492.
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 [49]
RP VARIANTS CRC HIS-1095 AND GLN-1354.
RX PubMed=12522549; DOI=10.1007/s00439-002-0866-4;
RA Kariola R., Otway R., Loennqvist K.E., Raevaara T.E., Macrae F., Vos Y.J.,
RA Kohonen-Corish M., Hofstra R.M.W., Nystroem-Lahti M.;
RT "Two mismatch repair gene mutations found in a colon cancer patient - which
RT one is pathogenic?";
RL Hum. Genet. 112:105-109(2003).
RN [50]
RP VARIANT CRC ALA-54, AND VARIANTS GLU-39; ALA-509; MET-854 AND ALA-878.
RX PubMed=14520694; DOI=10.1002/ijc.11415;
RA Peterlongo P., Nafa K., Lerman G.S., Glogowski E., Shia J., Ye T.Z.,
RA Markowitz A.J., Guillem J.G., Kolachana P., Boyd J.A., Offit K.,
RA Ellis N.A.;
RT "MSH6 germline mutations are rare in colorectal cancer families.";
RL Int. J. Cancer 107:571-579(2003).
RN [51]
RP VARIANTS LEU-128; LEU-623; THR-728 AND LYS-1193, AND CHARACTERIZATION OF
RP VARIANTS LEU-128; LEU-623; THR-728 AND LYS-1193.
RX PubMed=15354210; DOI=10.1038/sj.bjc.6602129;
RA Kariola R., Hampel H., Frankel W.L., Raevaara T.E., de la Chapelle A.,
RA Nystroem-Lahti M.;
RT "MSH6 missense mutations are often associated with no or low cancer
RT susceptibility.";
RL Br. J. Cancer 91:1287-1292(2004).
RN [52]
RP VARIANT HNPCC5 TRP-772.
RX PubMed=14974087; DOI=10.1002/humu.9217;
RG The German HNPCC consortium;
RA Plaschke J., Krueger S., Dietmaier W., Gebert J., Sutter C., Mangold E.,
RA Pagenstecher C., Holinski-Feder E., Schulmann K., Moeslein G.,
RA Rueschoff J., Engel C., Evans G., Schackert H.K.;
RT "Eight novel MSH6 germline mutations in patients with familial and
RT nonfamilial colorectal cancer selected by loss of protein expression in
RT tumor tissue.";
RL Hum. Mutat. 23:285-285(2004).
RN [53]
RP VARIANT HNPCC5 VAL-1163.
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 [54]
RP VARIANT CRC PRO-449, AND VARIANT ENDMC PRO-449.
RX PubMed=14961575; DOI=10.1002/ijc.11718;
RA Cederquist K., Emanuelsson M., Goeransson I., Holinski-Feder E.,
RA Mueller-Koch Y., Golovleva I., Groenberg H.;
RT "Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double
RT primary cancers of the colorectum and the endometrium: a population-based
RT study in northern Sweden.";
RL Int. J. Cancer 109:370-376(2004).
RN [55]
RP VARIANTS CRC ASN-99; ASP-619; VAL-787; ALA-878 AND CYS-1076.
RX PubMed=15483016; DOI=10.1200/jco.2004.02.033;
RA Plaschke J., Engel C., Krueger S., Holinski-Feder E., Pagenstecher C.,
RA Mangold E., Moeslein G., Schulmann K., Gebert J., von Knebel Doeberitz M.,
RA Rueschoff J., Loeffler M., Schackert H.K.;
RT "Lower incidence of colorectal cancer and later age of disease onset in 27
RT families with pathogenic MSH6 germline mutations compared with families
RT with MLH1 or MSH2 mutations: the German hereditary nonpolyposis colorectal
RT cancer consortium.";
RL J. Clin. Oncol. 22:4486-4494(2004).
RN [56]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-221 AND VAL-492.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [57]
RP VARIANTS THR-13; LEU-65; ILE-144; HIS-468; CYS-503; LEU-580; ALA-878;
RP LEU-1232 AND GLY-1321.
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 [58]
RP CHARACTERIZATION OF VARIANT HNPCC5 VAL-20, CHARACTERIZATION OF VARIANTS CRC
RP HIS-976 AND ASP-1021, AND CHARACTERIZATION OF VARIANTS SER-25; VAL-326;
RP VAL-396; VAL-492; CYS-503; ARG-522; ASN-610; CYS-850; ALA-878; TYR-1026;
RP SER-1087 AND MET-1225.
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 [59]
RP CHARACTERIZATION OF VARIANTS PRO-435; PRO-585; THR-677; ALA-878; HIS-1095
RP AND GLN-1354.
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).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA
CC mismatches thereby initiating DNA repair. When bound, MutS alpha bends
CC the DNA helix and shields approximately 20 base pairs, and recognizes
CC single base mismatches and dinucleotide insertion-deletion loops (IDL)
CC in the DNA. After mismatch binding, forms a ternary complex with the
CC MutL alpha heterodimer, which is thought to be responsible for
CC directing the downstream MMR events, including strand discrimination,
CC excision, and resynthesis. 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. Recruited on
CC chromatin in G1 and early S phase via its PWWP domain that specifically
CC binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early
CC recruitment to chromatin to be replicated allowing a quick
CC identification of mismatch repair to initiate the DNA mismatch repair
CC reaction. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545,
CC ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944,
CC ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049,
CC ECO:0000269|PubMed:9822679, 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) (PubMed:8942985, PubMed:7604264).
CC Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with
CC MCM9 (PubMed:26300262). Part of the BRCA1-associated genome
CC surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1,
CC ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex
CC (PubMed:10783165). This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains
CC (PubMed:10783165). {ECO:0000269|PubMed:10783165,
CC ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:7604264,
CC ECO:0000269|PubMed:8942985}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC protein UL12. {ECO:0000269|PubMed:21957315}.
CC -!- INTERACTION:
CC P52701; Q9NXL9: MCM9; NbExp=2; IntAct=EBI-395529, EBI-2804985;
CC P52701; P43246: MSH2; NbExp=7; IntAct=EBI-395529, EBI-355888;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23622243}. Chromosome
CC {ECO:0000269|PubMed:23622243}. Note=Associates with H3K36me3 via its
CC PWWP domain.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=GTBP-N;
CC IsoId=P52701-1; Sequence=Displayed;
CC Name=GTBP-alt;
CC IsoId=P52701-2; Sequence=VSP_003291, VSP_003292;
CC Name=3;
CC IsoId=P52701-3; Sequence=VSP_054419;
CC Name=4;
CC IsoId=P52701-4; Sequence=VSP_055020;
CC -!- DOMAIN: The PWWP domain specifically recognizes and binds trimethylated
CC 'Lys-36' of histone H3 (H3K36me3). {ECO:0000269|PubMed:23622243}.
CC -!- PTM: The N-terminus is blocked.
CC -!- PTM: Phosphorylated by PRKCZ, which may prevent MutS alpha degradation
CC by the ubiquitin-proteasome pathway. {ECO:0000269|PubMed:15808853}.
CC -!- DISEASE: Hereditary non-polyposis colorectal cancer 5 (HNPCC5)
CC [MIM:614350]: An autosomal dominant disease associated with marked
CC increase 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. HNPCC is reported to be the most common form of
CC inherited colorectal cancer in the Western world. Clinically, HNPCC is
CC often divided into two subgroups. Type I is characterized by hereditary
CC predisposition to colorectal cancer, a young age of onset, and
CC carcinoma observed in the proximal colon. Type II is characterized by
CC 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 HNPCC is based on the Amsterdam
CC criteria: 3 or more relatives affected by colorectal cancer, one a
CC first degree relative of the other two; 2 or more generation affected;
CC 1 or more colorectal cancers presenting before 50 years of age;
CC exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC'
CC or 'incomplete HNPCC' can be used to describe families who do not or
CC only partially fulfill the Amsterdam criteria, but in whom a genetic
CC basis for colon cancer is strongly suspected.
CC {ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10521294,
CC ECO:0000269|PubMed:11586295, ECO:0000269|PubMed:12658575,
CC ECO:0000269|PubMed:14974087, ECO:0000269|PubMed:15365995,
CC ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614,
CC ECO:0000269|PubMed:9354786}. Note=The disease is caused by variants
CC 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:0000269|PubMed:11153917,
CC ECO:0000269|PubMed:14961575}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Mismatch repair cancer syndrome 3 (MMRCS3) [MIM:619097]: 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:17557300}.
CC Note=The disease is caused by variants affecting the gene represented
CC 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:10413423,
CC ECO:0000269|PubMed:10537275, ECO:0000269|PubMed:10699937,
CC ECO:0000269|PubMed:11153917, ECO:0000269|PubMed:11470537,
CC ECO:0000269|PubMed:11709755, ECO:0000269|PubMed:11807791,
CC ECO:0000269|PubMed:12522549, ECO:0000269|PubMed:14520694,
CC ECO:0000269|PubMed:14961575, ECO:0000269|PubMed:15483016,
CC ECO:0000269|PubMed:22102614}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MSH6ID344ch2p16.html";
CC -!- WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db;
CC URL="http://www.nfdht.nl/";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/msh6/";
CC ---------------------------------------------------------------------------
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DR EMBL; U73737; AAB47425.1; -; Genomic_DNA.
DR EMBL; U73732; AAB47425.1; JOINED; Genomic_DNA.
DR EMBL; U73733; AAB47425.1; JOINED; Genomic_DNA.
DR EMBL; U73734; AAB47425.1; JOINED; Genomic_DNA.
DR EMBL; U73736; AAB47425.1; JOINED; Genomic_DNA.
DR EMBL; D89645; BAA23674.1; -; Genomic_DNA.
DR EMBL; D89646; BAA23675.1; -; mRNA.
DR EMBL; AK293921; BAG57302.1; -; mRNA.
DR EMBL; AK304735; BAG65496.1; -; mRNA.
DR EMBL; AY082894; AAL87401.1; -; Genomic_DNA.
DR EMBL; AC006509; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004246; AAH04246.1; -; mRNA.
DR EMBL; U54777; AAB39212.2; -; mRNA.
DR EMBL; U28946; AAC50461.1; -; mRNA.
DR CCDS; CCDS1836.1; -. [P52701-1]
DR CCDS; CCDS62906.1; -. [P52701-3]
DR CCDS; CCDS62907.1; -. [P52701-4]
DR PIR; JC5839; JC5839.
DR RefSeq; NP_000170.1; NM_000179.2. [P52701-1]
DR RefSeq; NP_001268421.1; NM_001281492.1. [P52701-3]
DR RefSeq; NP_001268422.1; NM_001281493.1. [P52701-4]
DR RefSeq; NP_001268423.1; NM_001281494.1. [P52701-4]
DR PDB; 2GFU; NMR; -; A=68-201.
DR PDB; 2O8B; X-ray; 2.75 A; B=341-1360.
DR PDB; 2O8C; X-ray; 3.37 A; B=341-1360.
DR PDB; 2O8D; X-ray; 3.00 A; B=341-1360.
DR PDB; 2O8E; X-ray; 3.30 A; B=341-1360.
DR PDB; 2O8F; X-ray; 3.25 A; B=341-1360.
DR PDB; 6OQM; X-ray; 2.20 A; A=87-198.
DR PDBsum; 2GFU; -.
DR PDBsum; 2O8B; -.
DR PDBsum; 2O8C; -.
DR PDBsum; 2O8D; -.
DR PDBsum; 2O8E; -.
DR PDBsum; 2O8F; -.
DR PDBsum; 6OQM; -.
DR AlphaFoldDB; P52701; -.
DR SMR; P52701; -.
DR BioGRID; 109211; 182.
DR ComplexPortal; CPX-80; DNA mismatch repair MutSalpha complex.
DR CORUM; P52701; -.
DR DIP; DIP-32972N; -.
DR ELM; P52701; -.
DR IntAct; P52701; 64.
DR MINT; P52701; -.
DR STRING; 9606.ENSP00000234420; -.
DR ChEMBL; CHEMBL4739849; -.
DR CarbonylDB; P52701; -.
DR GlyGen; P52701; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P52701; -.
DR MetOSite; P52701; -.
DR PhosphoSitePlus; P52701; -.
DR SwissPalm; P52701; -.
DR BioMuta; MSH6; -.
DR DMDM; 68067672; -.
DR CPTAC; CPTAC-544; -.
DR EPD; P52701; -.
DR jPOST; P52701; -.
DR MassIVE; P52701; -.
DR MaxQB; P52701; -.
DR PaxDb; P52701; -.
DR PeptideAtlas; P52701; -.
DR PRIDE; P52701; -.
DR ProteomicsDB; 25957; -.
DR ProteomicsDB; 4004; -.
DR ProteomicsDB; 56502; -. [P52701-1]
DR ProteomicsDB; 56503; -. [P52701-2]
DR ABCD; P52701; 6 sequenced antibodies.
DR Antibodypedia; 3963; 753 antibodies from 45 providers.
DR CPTC; P52701; 1 antibody.
DR DNASU; 2956; -.
DR Ensembl; ENST00000234420.11; ENSP00000234420.5; ENSG00000116062.18. [P52701-1]
DR Ensembl; ENST00000538136.1; ENSP00000438580.1; ENSG00000116062.18. [P52701-4]
DR Ensembl; ENST00000540021.6; ENSP00000446475.1; ENSG00000116062.18. [P52701-3]
DR Ensembl; ENST00000614496.4; ENSP00000477844.1; ENSG00000116062.18. [P52701-4]
DR GeneID; 2956; -.
DR KEGG; hsa:2956; -.
DR MANE-Select; ENST00000234420.11; ENSP00000234420.5; NM_000179.3; NP_000170.1.
DR UCSC; uc002rwd.5; human. [P52701-1]
DR CTD; 2956; -.
DR DisGeNET; 2956; -.
DR GeneCards; MSH6; -.
DR GeneReviews; MSH6; -.
DR HGNC; HGNC:7329; MSH6.
DR HPA; ENSG00000116062; Low tissue specificity.
DR MalaCards; MSH6; -.
DR MIM; 114500; phenotype.
DR MIM; 600678; gene.
DR MIM; 608089; phenotype.
DR MIM; 614350; phenotype.
DR MIM; 619097; phenotype.
DR neXtProt; NX_P52701; -.
DR OpenTargets; ENSG00000116062; -.
DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome.
DR Orphanet; 144; Lynch syndrome.
DR Orphanet; 587; Muir-Torre syndrome.
DR PharmGKB; PA184; -.
DR VEuPathDB; HostDB:ENSG00000116062; -.
DR eggNOG; KOG0217; Eukaryota.
DR GeneTree; ENSGT00550000075024; -.
DR HOGENOM; CLU_002472_1_3_1; -.
DR InParanoid; P52701; -.
DR OMA; TPMMAQY; -.
DR OrthoDB; 138168at2759; -.
DR PhylomeDB; P52701; -.
DR TreeFam; TF105842; -.
DR PathwayCommons; P52701; -.
DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-HSA-5632928; Defective Mismatch Repair Associated With MSH2.
DR Reactome; R-HSA-5632968; Defective Mismatch Repair Associated With MSH6.
DR SignaLink; P52701; -.
DR SIGNOR; P52701; -.
DR BioGRID-ORCS; 2956; 14 hits in 1083 CRISPR screens.
DR ChiTaRS; MSH6; human.
DR EvolutionaryTrace; P52701; -.
DR GeneWiki; MSH6; -.
DR GenomeRNAi; 2956; -.
DR Pharos; P52701; Tbio.
DR PRO; PR:P52701; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P52701; protein.
DR Bgee; ENSG00000116062; Expressed in ventricular zone and 218 other tissues.
DR ExpressionAtlas; P52701; baseline and differential.
DR Genevisible; P52701; HS.
DR GO; GO:0000785; C:chromatin; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0032301; C:MutSalpha complex; IDA:UniProtKB.
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: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:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0032137; F:guanine/thymine mispair binding; IEA:Ensembl.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0030983; F:mismatched DNA binding; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; ISS:BHF-UCL.
DR GO; GO:0006281; P:DNA repair; IDA:BHF-UCL.
DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:BHF-UCL.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:BHF-UCL.
DR GO; GO:0045190; P:isotype switching; ISS:BHF-UCL.
DR GO; GO:0000710; P:meiotic mismatch repair; ISS:BHF-UCL.
DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB.
DR GO; GO:0045910; P:negative regulation of DNA recombination; IDA:BHF-UCL.
DR GO; GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL.
DR GO; GO:0009411; P:response to UV; ISS:BHF-UCL.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS:BHF-UCL.
DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; ISS:BHF-UCL.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR Gene3D; 3.30.420.110; -; 1.
DR Gene3D; 3.40.1170.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR IDEAL; IID00054; -.
DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N.
DR InterPro; IPR017261; DNA_mismatch_repair_MutS/MSH.
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; IPR036678; MutS_con_dom_sf.
DR InterPro; IPR045076; MutS_family.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000313; PWWP_dom.
DR PANTHER; PTHR11361; PTHR11361; 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 Pfam; PF00855; PWWP; 1.
DR PIRSF; PIRSF037677; DNA_mis_repair_Msh6; 1.
DR SMART; SM00534; MUTSac; 1.
DR SMART; SM00533; MUTSd; 1.
DR SMART; SM00293; PWWP; 1.
DR SUPFAM; SSF48334; SSF48334; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF55271; SSF55271; 1.
DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1.
DR PROSITE; PS50812; PWWP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; Chromosome;
KW Direct protein sequencing; Disease variant; DNA damage; DNA repair;
KW DNA-binding; Hereditary nonpolyposis colorectal cancer;
KW Host-virus interaction; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1360
FT /note="DNA mismatch repair protein Msh6"
FT /id="PRO_0000115207"
FT DOMAIN 92..154
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT REGION 1..84
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..362
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 247..277
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 320..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 1134..1141
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 41
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243"
FT MOD_RES 70
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 137
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 200
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 254
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692"
FT MOD_RES 269
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 279
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 309
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 488
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 504
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 830
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 935
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1010
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..302
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055020"
FT VAR_SEQ 80..209
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054419"
FT VAR_SEQ 1058..1068
FT /note="DVLLCLANYSR -> GKTLNKLVLRL (in isoform GTBP-alt)"
FT /evidence="ECO:0000305"
FT /id="VSP_003291"
FT VAR_SEQ 1069..1360
FT /note="Missing (in isoform GTBP-alt)"
FT /evidence="ECO:0000305"
FT /id="VSP_003292"
FT VARIANT 13
FT /note="K -> T (in dbSNP:rs41294988)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038032"
FT VARIANT 20
FT /note="A -> V (in HNPCC5, CRC and ENDMC; unknown
FT pathological significance; normal mismatch repair activity;
FT dbSNP:rs63750664)"
FT /evidence="ECO:0000269|PubMed:11153917,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_043943"
FT VARIANT 25
FT /note="A -> S (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs267608026)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067294"
FT VARIANT 25
FT /note="A -> V (in dbSNP:rs35462442)"
FT /id="VAR_038033"
FT VARIANT 39
FT /note="G -> E (in dbSNP:rs1042821)"
FT /evidence="ECO:0000269|PubMed:10537275,
FT ECO:0000269|PubMed:10699937, ECO:0000269|PubMed:14520694,
FT ECO:0000269|PubMed:8942985, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:16964243"
FT /id="VAR_004490"
FT VARIANT 54
FT /note="G -> A (in CRC; unknown pathological significance;
FT dbSNP:rs63751098)"
FT /evidence="ECO:0000269|PubMed:14520694"
FT /id="VAR_043944"
FT VARIANT 65
FT /note="S -> L (in dbSNP:rs41294984)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038034"
FT VARIANT 99
FT /note="K -> N (in CRC; unknown pathological significance;
FT dbSNP:rs63751258)"
FT /evidence="ECO:0000269|PubMed:15483016"
FT /id="VAR_043945"
FT VARIANT 128
FT /note="R -> L (in HNPCC5; unknown pathological
FT significance; no impairment of heterodimerization with
FT MSH2; normal mismatch repair activity; dbSNP:rs63750143)"
FT /evidence="ECO:0000269|PubMed:15354210,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043946"
FT VARIANT 144
FT /note="S -> I (in HNPCC5 and CRC; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs3211299)"
FT /evidence="ECO:0000269|PubMed:10521294,
FT ECO:0000269|PubMed:11709755, ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_012955"
FT VARIANT 220
FT /note="E -> D (in dbSNP:rs1800938)"
FT /evidence="ECO:0000269|PubMed:10537275"
FT /id="VAR_012956"
FT VARIANT 221
FT /note="E -> D (in dbSNP:rs41557217)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042274"
FT VARIANT 285
FT /note="S -> I (in CRC; unknown pathological significance;
FT dbSNP:rs63750878)"
FT /evidence="ECO:0000269|PubMed:10537275"
FT /id="VAR_012957"
FT VARIANT 295
FT /note="K -> R (in multiple colorectal adenoma;
FT dbSNP:rs267608051)"
FT /id="VAR_043947"
FT VARIANT 326
FT /note="A -> V (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs587779323)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067295"
FT VARIANT 340
FT /note="F -> S (in CRC, breast cancer and leukemia; unknown
FT pathological significance; dbSNP:rs61753793)"
FT /evidence="ECO:0000269|PubMed:10699937"
FT /id="VAR_043948"
FT VARIANT 396
FT /note="L -> V (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs2020908)"
FT /evidence="ECO:0000269|PubMed:10537275,
FT ECO:0000269|PubMed:22102614, ECO:0000269|Ref.4"
FT /id="VAR_012958"
FT VARIANT 435
FT /note="L -> P (decreased mismatch repair activity;
FT dbSNP:rs63751405)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068710"
FT VARIANT 449
FT /note="L -> P (in CRC and ENDMC; unknown pathological
FT significance; dbSNP:rs63750741)"
FT /evidence="ECO:0000269|PubMed:14961575"
FT /id="VAR_043949"
FT VARIANT 468
FT /note="R -> H (in dbSNP:rs41295268)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038035"
FT VARIANT 492
FT /note="M -> V (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs61754783)"
FT /evidence="ECO:0000269|PubMed:12658575,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:22102614"
FT /id="VAR_042275"
FT VARIANT 503
FT /note="S -> C (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63750897)"
FT /evidence="ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_038036"
FT VARIANT 509
FT /note="V -> A (in dbSNP:rs63751005)"
FT /evidence="ECO:0000269|PubMed:14520694"
FT /id="VAR_043950"
FT VARIANT 522
FT /note="Q -> R (in CRC; unknown pathological significance;
FT normal mismatch repair activity; dbSNP:rs63751009)"
FT /evidence="ECO:0000269|PubMed:11709755,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_043951"
FT VARIANT 538
FT /note="Y -> S (in dbSNP:rs728619)"
FT /id="VAR_038037"
FT VARIANT 566
FT /note="G -> R (in CRC and HNPCC5; decreased mismatch repair
FT activity; loss of protein expression; dbSNP:rs63749973)"
FT /evidence="ECO:0000269|PubMed:10537275,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_012959"
FT VARIANT 580
FT /note="S -> L (in dbSNP:rs41295270)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038038"
FT VARIANT 585
FT /note="L -> P (decreased mismatch repair activity;
FT dbSNP:rs587779220)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068711"
FT VARIANT 610
FT /note="K -> N (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs201735525)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067296"
FT VARIANT 619
FT /note="E -> D (in CRC; unknown pathological significance;
FT dbSNP:rs63751121)"
FT /evidence="ECO:0000269|PubMed:15483016"
FT /id="VAR_043952"
FT VARIANT 623
FT /note="P -> A (in dbSNP:rs3136334)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_029244"
FT VARIANT 623
FT /note="P -> L (in HNPCC5; unknown pathological
FT significance; no impairment of heterodimerization with
FT MSH2; normal mismatch repair activity; dbSNP:rs63750462)"
FT /evidence="ECO:0000269|PubMed:15354210,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043953"
FT VARIANT 677
FT /note="S -> T (normal mismatch repair activity;
FT dbSNP:rs587779224)"
FT /evidence="ECO:0000269|PubMed:22581703"
FT /id="VAR_068712"
FT VARIANT 685
FT /note="G -> A (in CRC; unknown pathological significance;
FT dbSNP:rs63750358)"
FT /evidence="ECO:0000269|PubMed:11470537"
FT /id="VAR_043954"
FT VARIANT 698
FT /note="Q -> E (in HNPCC; unknown pathological significance;
FT dbSNP:rs63750832)"
FT /evidence="ECO:0000269|PubMed:10480359"
FT /id="VAR_012960"
FT VARIANT 725
FT /note="I -> M (in CRC; unknown pathological significance;
FT dbSNP:rs63750304)"
FT /evidence="ECO:0000269|PubMed:11709755"
FT /id="VAR_043955"
FT VARIANT 728
FT /note="K -> T (in HNPCC5; unknown pathological
FT significance; no impairment of heterodimerization with
FT MSH2; normal mismatch repair activity; dbSNP:rs35552856)"
FT /evidence="ECO:0000269|PubMed:15354210,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043956"
FT VARIANT 772
FT /note="R -> Q (in CRC; unknown pathological significance;
FT dbSNP:rs63750725)"
FT /evidence="ECO:0000269|PubMed:11470537"
FT /id="VAR_043957"
FT VARIANT 772
FT /note="R -> W (in HNPCC5; dbSNP:rs63750138)"
FT /evidence="ECO:0000269|PubMed:14974087"
FT /id="VAR_043958"
FT VARIANT 787
FT /note="A -> V (in CRC; unknown pathological significance;
FT dbSNP:rs63750637)"
FT /evidence="ECO:0000269|PubMed:15483016"
FT /id="VAR_043959"
FT VARIANT 800
FT /note="V -> A (in CRC; somatic mutation; dbSNP:rs63750895)"
FT /evidence="ECO:0000269|PubMed:11470537"
FT /id="VAR_043960"
FT VARIANT 800
FT /note="V -> L (in dbSNP:rs61748083)"
FT /evidence="ECO:0000269|PubMed:10537275"
FT /id="VAR_012961"
FT VARIANT 803
FT /note="D -> G (in CRC; unknown pathological significance;
FT dbSNP:rs63751450)"
FT /evidence="ECO:0000269|PubMed:10537275"
FT /id="VAR_012962"
FT VARIANT 850
FT /note="Y -> C (in HNPCC5 and CRC; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63750389)"
FT /evidence="ECO:0000269|PubMed:10521294,
FT ECO:0000269|PubMed:11709755, ECO:0000269|PubMed:22102614"
FT /id="VAR_012963"
FT VARIANT 854
FT /note="K -> M (in CRC; unknown pathological significance;
FT dbSNP:rs34374438)"
FT /evidence="ECO:0000269|PubMed:11470537,
FT ECO:0000269|PubMed:14520694"
FT /id="VAR_043961"
FT VARIANT 878
FT /note="V -> A (in HNPCC5, CRC and ENDMC; unknown
FT pathological significance; normal mismatch repair activity;
FT dbSNP:rs2020912)"
FT /evidence="ECO:0000269|PubMed:11153917,
FT ECO:0000269|PubMed:11470537, ECO:0000269|PubMed:11586295,
FT ECO:0000269|PubMed:11709755, ECO:0000269|PubMed:14520694,
FT ECO:0000269|PubMed:15483016, ECO:0000269|PubMed:18033691,
FT ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:22581703"
FT /id="VAR_012964"
FT VARIANT 881
FT /note="G -> KS (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076356"
FT VARIANT 886
FT /note="I -> V (in dbSNP:rs2020914)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_014902"
FT VARIANT 901
FT /note="R -> H (in CRC and ENDMC; unknown pathological
FT significance; dbSNP:rs63749889)"
FT /evidence="ECO:0000269|PubMed:11153917"
FT /id="VAR_043962"
FT VARIANT 976
FT /note="R -> H (in CRC; sporadic; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63751113)"
FT /evidence="ECO:0000269|PubMed:11807791,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_012965"
FT VARIANT 1021
FT /note="A -> D (in CRC; unknown pathological significance;
FT normal mismatch repair activity; dbSNP:rs63750287)"
FT /evidence="ECO:0000269|PubMed:11709755,
FT ECO:0000269|PubMed:22102614"
FT /id="VAR_043963"
FT VARIANT 1026
FT /note="D -> Y (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs267608054)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067297"
FT VARIANT 1031
FT /note="D -> V (in CRC; unknown pathological significance;
FT somatic mutation; dbSNP:rs63750804)"
FT /evidence="ECO:0000269|PubMed:11470537"
FT /id="VAR_043964"
FT VARIANT 1076
FT /note="R -> C (in CRC; unknown pathological significance;
FT dbSNP:rs63750617)"
FT /evidence="ECO:0000269|PubMed:15483016"
FT /id="VAR_043965"
FT VARIANT 1087
FT /note="P -> R (in dbSNP:rs63750753)"
FT /evidence="ECO:0000269|PubMed:21120944"
FT /id="VAR_076357"
FT VARIANT 1087
FT /note="P -> S (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63750998)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067298"
FT VARIANT 1087
FT /note="P -> T (in CRC and HNPCC5; unknown pathological
FT significance; dbSNP:rs63750998)"
FT /evidence="ECO:0000269|PubMed:10537275,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_012966"
FT VARIANT 1095
FT /note="R -> H (in CRC and HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63750253)"
FT /evidence="ECO:0000269|PubMed:12522549,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22581703"
FT /id="VAR_043966"
FT VARIANT 1100
FT /note="T -> M (in CRC; unknown pathological significance;
FT dbSNP:rs63750442)"
FT /evidence="ECO:0000269|PubMed:11709755"
FT /id="VAR_043967"
FT VARIANT 1158
FT /note="C -> R (in CRC; unknown pathological significance;
FT somatic mutation; dbSNP:rs63750157)"
FT /evidence="ECO:0000269|PubMed:11470537"
FT /id="VAR_043968"
FT VARIANT 1163
FT /note="E -> V (in HNPCC5; dbSNP:rs63750252)"
FT /evidence="ECO:0000269|PubMed:15365995"
FT /id="VAR_043969"
FT VARIANT 1193
FT /note="E -> K (in HNPCC5; decreased mismatch repair
FT activity; displays marked impairment of heterodimerization
FT with MSH2; dbSNP:rs63751328)"
FT /evidence="ECO:0000269|PubMed:15354210,
FT ECO:0000269|PubMed:21120944"
FT /id="VAR_043970"
FT VARIANT 1213
FT /note="D -> V"
FT /evidence="ECO:0000269|PubMed:7604266"
FT /id="VAR_004491"
FT VARIANT 1219
FT /note="T -> I (in CRC; unknown pathological significance;
FT dbSNP:rs63750949)"
FT /evidence="ECO:0000269|PubMed:11709755"
FT /id="VAR_043971"
FT VARIANT 1225
FT /note="T -> M (in HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs63750370)"
FT /evidence="ECO:0000269|PubMed:22102614"
FT /id="VAR_067299"
FT VARIANT 1232
FT /note="V -> L (in dbSNP:rs41295276)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038039"
FT VARIANT 1234
FT /note="E -> Q (in dbSNP:rs35717727)"
FT /id="VAR_038040"
FT VARIANT 1248
FT /note="H -> D (in CRC; unknown pathological significance;
FT dbSNP:rs63750882)"
FT /evidence="ECO:0000269|PubMed:11709755"
FT /id="VAR_043972"
FT VARIANT 1260
FT /note="V -> I (in dbSNP:rs63750673)"
FT /evidence="ECO:0000269|PubMed:7604266"
FT /id="VAR_004492"
FT VARIANT 1284
FT /note="T -> M (in CRC; unknown pathological significance;
FT dbSNP:rs63750836)"
FT /evidence="ECO:0000269|PubMed:10413423"
FT /id="VAR_043973"
FT VARIANT 1321
FT /note="R -> G (in dbSNP:rs41295278)"
FT /evidence="ECO:0000269|PubMed:18033691"
FT /id="VAR_038041"
FT VARIANT 1354
FT /note="L -> Q (in CRC and HNPCC5; unknown pathological
FT significance; normal mismatch repair activity;
FT dbSNP:rs267608140)"
FT /evidence="ECO:0000269|PubMed:12522549,
FT ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22581703"
FT /id="VAR_043974"
FT MUTAGEN 103
FT /note="Y->A: Abolishes binding to H3K36me3 and DNA mismatch
FT repair activity."
FT /evidence="ECO:0000269|PubMed:23622243"
FT MUTAGEN 105..106
FT /note="WW->AA: Abolishes binding to H3K36me3 and DNA
FT mismatch repair activity."
FT /evidence="ECO:0000269|PubMed:23622243"
FT MUTAGEN 1140
FT /note="K->R: No effect on mismatch binding, complete loss
FT of DNA repair function when associated with MSH2 mutant R-
FT 675."
FT /evidence="ECO:0000269|PubMed:9564049"
FT CONFLICT 36..57
FT /note="AAPGASPSPGGDAAWSEAGPGP -> GCPRGLSFPRRGCGLERGWAWA (in
FT Ref. 2; BAA23674/BAA23675)"
FT /evidence="ECO:0000305"
FT CONFLICT 868
FT /note="M -> V (in Ref. 3; BAG65496)"
FT /evidence="ECO:0000305"
FT CONFLICT 1358..1360
FT /note="KEL -> D (in Ref. 4; AAL87401)"
FT /evidence="ECO:0000305"
FT STRAND 74..79
FT /evidence="ECO:0007829|PDB:2GFU"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 106..110
FT /evidence="ECO:0007829|PDB:6OQM"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 128..133
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 139..144
FT /evidence="ECO:0007829|PDB:6OQM"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:6OQM"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:6OQM"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:6OQM"
FT HELIX 170..183
FT /evidence="ECO:0007829|PDB:6OQM"
FT HELIX 187..191
FT /evidence="ECO:0007829|PDB:2GFU"
FT TURN 192..195
FT /evidence="ECO:0007829|PDB:2GFU"
FT STRAND 197..199
FT /evidence="ECO:0007829|PDB:2GFU"
FT HELIX 366..369
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 371..373
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 400..403
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 408..419
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 423..429
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 432..436
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 437..447
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 453..456
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 458..462
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 466..475
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 480..485
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 489..497
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 511..517
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 519..521
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 526..528
FT /evidence="ECO:0007829|PDB:2O8D"
FT STRAND 538..546
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 554..561
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 563..565
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 568..575
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 580..588
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 591..597
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 598..600
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 603..609
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 610..615
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 616..621
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 624..626
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 630..639
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 640..643
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 644..647
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 657..661
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 667..669
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 671..673
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 675..677
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 678..693
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 697..701
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 706..708
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 712..715
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 737..742
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 750..753
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 758..762
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 768..779
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 785..799
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 802..812
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 818..829
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 831..836
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 838..841
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 847..879
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 885..890
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 894..896
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 897..900
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 906..913
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 918..923
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 936..955
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 959..961
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 968..970
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 973..975
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 978..981
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 983..986
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 995..999
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1002..1005
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1008..1010
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1011..1041
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1044..1066
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1070..1072
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1082..1084
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1089..1094
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1111..1116
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1120..1122
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 1129..1133
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1136..1138
FT /evidence="ECO:0007829|PDB:2O8F"
FT HELIX 1140..1154
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1155..1157
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1160..1167
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1171..1176
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1189..1203
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1209..1213
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1215..1218
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1221..1237
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1242..1246
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1250..1255
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1256..1258
FT /evidence="ECO:0007829|PDB:2O8F"
FT STRAND 1260..1269
FT /evidence="ECO:0007829|PDB:2O8B"
FT STRAND 1285..1292
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1298..1305
FT /evidence="ECO:0007829|PDB:2O8B"
FT HELIX 1310..1322
FT /evidence="ECO:0007829|PDB:2O8B"
FT TURN 1323..1326
FT /evidence="ECO:0007829|PDB:2O8F"
FT TURN 1330..1332
FT /evidence="ECO:0007829|PDB:2O8B"
SQ SEQUENCE 1360 AA; 152786 MW; 4A4AA9F8ECB8FFE9 CRC64;
MSRQSTLYSF FPKSPALSDA NKASARASRE GGRAAAAPGA SPSPGGDAAW SEAGPGPRPL
ARSASPPKAK NLNGGLRRSV APAAPTSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI
REKGKSVRVH VQFFDDSPTR GWVSKRLLKP YTGSKSKEAQ KGGHFYSAKP EILRAMQRAD
EALNKDKIKR LELAVCDEPS EPEEEEEMEV GTTYVTDKSE EDNEIESEEE VQPKTQGSRR
SSRQIKKRRV ISDSESDIGG SDVEFKPDTK EEGSSDEISS GVGDSESEGL NSPVKVARKR
KRMVTGNGSL KRKSSRKETP SATKQATSIS SETKNTLRAF SAPQNSESQA HVSGGGDDSS
RPTVWYHETL EWLKEEKRRD EHRRRPDHPD FDASTLYVPE DFLNSCTPGM RKWWQIKSQN
FDLVICYKVG KFYELYHMDA LIGVSELGLV FMKGNWAHSG FPEIAFGRYS DSLVQKGYKV
ARVEQTETPE MMEARCRKMA HISKYDRVVR REICRIITKG TQTYSVLEGD PSENYSKYLL
SLKEKEEDSS GHTRAYGVCF VDTSLGKFFI GQFSDDRHCS RFRTLVAHYP PVQVLFEKGN
LSKETKTILK SSLSCSLQEG LIPGSQFWDA SKTLRTLLEE EYFREKLSDG IGVMLPQVLK
GMTSESDSIG LTPGEKSELA LSALGGCVFY LKKCLIDQEL LSMANFEEYI PLDSDTVSTT
RSGAIFTKAY QRMVLDAVTL NNLEIFLNGT NGSTEGTLLE RVDTCHTPFG KRLLKQWLCA
PLCNHYAIND RLDAIEDLMV VPDKISEVVE LLKKLPDLER LLSKIHNVGS PLKSQNHPDS
RAIMYEETTY SKKKIIDFLS ALEGFKVMCK IIGIMEEVAD GFKSKILKQV ISLQTKNPEG
RFPDLTVELN RWDTAFDHEK ARKTGLITPK AGFDSDYDQA LADIRENEQS LLEYLEKQRN
RIGCRTIVYW GIGRNRYQLE IPENFTTRNL PEEYELKSTK KGCKRYWTKT IEKKLANLIN
AEERRDVSLK DCMRRLFYNF DKNYKDWQSA VECIAVLDVL LCLANYSRGG DGPMCRPVIL
LPEDTPPFLE LKGSRHPCIT KTFFGDDFIP NDILIGCEEE EQENGKAYCV LVTGPNMGGK
STLMRQAGLL AVMAQMGCYV PAEVCRLTPI DRVFTRLGAS DRIMSGESTF FVELSETASI
LMHATAHSLV LVDELGRGTA TFDGTAIANA VVKELAETIK CRTLFSTHYH SLVEDYSQNV
AVRLGHMACM VENECEDPSQ ETITFLYKFI KGACPKSYGF NAARLANLPE EVIQKGHRKA
REFEKMNQSL RLFREVCLAS ERSTVDAEAV HKLLTLIKEL
