MSH6_YEAST
ID MSH6_YEAST Reviewed; 1242 AA.
AC Q03834; D6VS82;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=DNA mismatch repair protein MSH6;
DE AltName: Full=MutS protein homolog 6;
DE AltName: Full=Postmeiotic segregation protein 3;
GN Name=MSH6; Synonyms=PMS3; OrderedLocusNames=YDR097C; ORFNames=YD8557.04C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP CHARACTERIZATION.
RX PubMed=8723353; DOI=10.1016/s0960-9822(02)00516-x;
RA Iaccarino I., Palombo F., Drummond J.T., Totty N.F., Hsuan J.J.,
RA Modrich P., Jiricny J.;
RT "MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as a
RT heterodimer with MSH2.";
RL Curr. Biol. 6:484-486(1996).
RN [4]
RP FUNCTION, INTERACTION WITH MSH2, AND MUTAGENESIS OF GLY-421.
RX PubMed=8600025; DOI=10.1101/gad.10.4.407;
RA Marsischky G.T., Filosi N., Kane M.F., Kolodner R.D.;
RT "Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2-dependent
RT mismatch repair.";
RL Genes Dev. 10:407-420(1996).
RN [5]
RP CHARACTERIZATION, AND INTERACTION WITH MSH2.
RX PubMed=8816473; DOI=10.1128/mcb.16.10.5604;
RA Alani E.;
RT "The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that
RT specifically binds to duplex oligonucleotides containing mismatched DNA
RT base pairs.";
RL Mol. Cell. Biol. 16:5604-5615(1996).
RN [6]
RP FUNCTION IN MMR.
RX PubMed=9111357; DOI=10.1128/mcb.17.5.2851;
RA Sia E.A., Kokoska R.J., Dominska M., Greenwell P., Petes T.D.;
RT "Microsatellite instability in yeast: dependence on repeat unit size and
RT DNA mismatch repair genes.";
RL Mol. Cell. Biol. 17:2851-2858(1997).
RN [7]
RP FUNCTION, DNA-BINDING, AND COMPLEX FORMATION WITH MLH1-PMS1.
RX PubMed=9545323; DOI=10.1074/jbc.273.16.9837;
RA Habraken Y., Sung P., Prakash L., Prakash S.;
RT "ATP-dependent assembly of a ternary complex consisting of a DNA mismatch
RT and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes.";
RL J. Biol. Chem. 273:9837-9841(1998).
RN [8]
RP MUTAGENESIS OF GLY-987.
RX PubMed=9819445; DOI=10.1128/mcb.18.12.7590;
RA Studamire B., Quach T., Alani E.;
RT "Saccharomyces cerevisiae Msh2p and Msh6p ATPase activities are both
RT required during mismatch repair.";
RL Mol. Cell. Biol. 18:7590-7601(1998).
RN [9]
RP FUNCTION.
RX PubMed=9770499; DOI=10.1073/pnas.95.21.12404;
RA Flores-Rozas H., Kolodner R.D.;
RT "The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent
RT suppression of frameshift mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12404-12409(1998).
RN [10]
RP MUTAGENESIS OF LEU-301 AND GLY-477.
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 [11]
RP DNA-BINDING SPECIFICITY.
RX PubMed=10066781; DOI=10.1074/jbc.274.11.7200;
RA Marsischky G.T., Lee S., Griffith J., Kolodner R.D.;
RT "Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday junctions
RT and facilitates their cleavage by phage resolution enzymes.";
RL J. Biol. Chem. 274:7200-7206(1999).
RN [12]
RP MUTAGENESIS OF PHE-337.
RX PubMed=10347163; DOI=10.1074/jbc.274.23.16115;
RA Bowers J., Sokolsky T., Quach T., Alani E.;
RT "A mutation in the MSH6 subunit of the Saccharomyces cerevisiae MSH2-MSH6
RT complex disrupts mismatch recognition.";
RL J. Biol. Chem. 274:16115-16125(1999).
RN [13]
RP DNA-BINDING SPECIFICITY.
RX PubMed=10480869; DOI=10.1074/jbc.274.38.26668;
RA Marsischky G.T., Kolodner R.D.;
RT "Biochemical characterization of the interaction between the Saccharomyces
RT cerevisiae MSH2-MSH6 complex and mispaired bases in DNA.";
RL J. Biol. Chem. 274:26668-26682(1999).
RN [14]
RP FUNCTION.
RX PubMed=10518225; DOI=10.1016/s1097-2765(00)80346-9;
RA Ni T.T., Marsischky G.T., Kolodner R.D.;
RT "MSH2 and MSH6 are required for removal of adenine misincorporated opposite
RT 8-oxo-guanine in S. cerevisiae.";
RL Mol. Cell 4:439-444(1999).
RN [15]
RP INTERACTION WITH POL30, AND MUTAGENESIS OF 26-LYS-GLN-27 AND 33-PHE-PHE-34.
RX PubMed=11005803; DOI=10.1074/jbc.c000513200;
RA Clark A.B., Valle F., Drotschmann K., Gary R.K., Kunkel T.A.;
RT "Functional interaction of proliferating cell nuclear antigen with MSH2-
RT MSH6 and MSH2-MSH3 complexes.";
RL J. Biol. Chem. 275:36498-36501(2000).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF PHE-337.
RX PubMed=10970737; DOI=10.1006/jmbi.2000.4081;
RA Bowers J., Tran P.T., Liskay R.M., Alani E.;
RT "Analysis of yeast MSH2-MSH6 suggests that the initiation of mismatch
RT repair can be separated into discrete steps.";
RL J. Mol. Biol. 302:327-338(2000).
RN [17]
RP MUTAGENESIS.
RX PubMed=10615127; DOI=10.1038/71684;
RA Das Gupta R., Kolodner R.D.;
RT "Novel dominant mutations in Saccharomyces cerevisiae MSH6.";
RL Nat. Genet. 24:53-56(2000).
RN [18]
RP INTERACTION WITH POL30, AND MUTAGENESIS OF 33-PHE-PHE-34.
RX PubMed=11062484; DOI=10.1038/81708;
RA Flores-Rozas H., Clark D., Kolodner R.D.;
RT "Proliferating cell nuclear antigen and Msh2p-Msh6p interact to form an
RT active mispair recognition complex.";
RL Nat. Genet. 26:375-378(2000).
RN [19]
RP DNA-BINDING, AND MUTAGENESIS OF PRO-313; PHE-337; GLU-339; GLY-368;
RP PRO-370; GLN-393; ARG-412; LYS-848 AND ARG-852.
RX PubMed=11641390; DOI=10.1074/jbc.c100450200;
RA Drotschmann K., Yang W., Brownewell F.E., Kool E.T., Kunkel T.A.;
RT "Asymmetric recognition of DNA local distortion. Structure-based functional
RT studies of eukaryotic Msh2-Msh6.";
RL J. Biol. Chem. 276:46225-46229(2001).
RN [20]
RP FUNCTION, AND COMPLEX FORMATION WITH MLH1-PMS1.
RX PubMed=11237611; DOI=10.1006/jmbi.2001.4467;
RA Bowers J., Tran P.T., Joshi A., Liskay R.M., Alani E.;
RT "MSH-MLH complexes formed at a DNA mismatch are disrupted by the PCNA
RT sliding clamp.";
RL J. Mol. Biol. 306:957-968(2001).
RN [21]
RP FUNCTION, AND MUTAGENESIS OF GLU-1062.
RX PubMed=12509278; DOI=10.1016/s1568-7864(02)00081-2;
RA Drotschmann K., Yang W., Kunkel T.A.;
RT "Evidence for sequential action of two ATPase active sites in yeast Msh2-
RT Msh6.";
RL DNA Repair 1:743-753(2002).
RN [22]
RP MUTAGENESIS OF SER-1036; GLY-1067; HIS-1096 AND GLY-1142.
RX PubMed=11986324; DOI=10.1074/jbc.m202282200;
RA Hess M.T., Das Gupta R., Kolodner R.D.;
RT "Dominant Saccharomyces cerevisiae msh6 mutations cause increased mispair
RT binding and decreased dissociation from mispairs by Msh2-Msh6 in the
RT presence of ATP.";
RL J. Biol. Chem. 277:25545-25553(2002).
RN [23]
RP FUNCTION.
RX PubMed=12820877; DOI=10.1021/bi034602h;
RA Antony E., Hingorani M.M.;
RT "Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP-bound
RT state at the initiation of DNA repair.";
RL Biochemistry 42:7682-7693(2003).
RN [24]
RP INTERACTION WITH POL30.
RX PubMed=12435741; DOI=10.1074/jbc.c200627200;
RA Lau P.J., Kolodner R.D.;
RT "Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen
RT to mispaired bases in DNA.";
RL J. Biol. Chem. 278:14-17(2003).
RN [25]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [26]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [27]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-1062.
RX PubMed=15513922; DOI=10.1074/jbc.c400495200;
RA Clark A.B., Kunkel T.A.;
RT "Cadmium inhibits the functions of eukaryotic MutS complexes.";
RL J. Biol. Chem. 279:53903-53906(2004).
RN [28]
RP FUNCTION, AND COMPLEX FORMATION WITH MLH1-PMS1.
RX PubMed=15811858; DOI=10.1074/jbc.m407545200;
RA Mendillo M.L., Mazur D.J., Kolodner R.D.;
RT "Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6
RT and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking
RT system.";
RL J. Biol. Chem. 280:22245-22257(2005).
RN [29]
RP FUNCTION.
RX PubMed=16337600; DOI=10.1016/j.molcel.2005.10.014;
RA Jiang J., Bai L., Surtees J.A., Gemici Z., Wang M.D., Alani E.;
RT "Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by
RT single-molecule unzipping force analysis.";
RL Mol. Cell 20:771-781(2005).
RN [30]
RP ACTIVITY REGULATION.
RX PubMed=15746000; DOI=10.1093/nar/gki291;
RA Banerjee S., Flores-Rozas H.;
RT "Cadmium inhibits mismatch repair by blocking the ATPase activity of the
RT MSH2-MSH6 complex.";
RL Nucleic Acids Res. 33:1410-1419(2005).
RN [31]
RP FUNCTION, AND MUTAGENESIS OF LYS-988 AND GLU-1062.
RX PubMed=16214425; DOI=10.1016/j.dnarep.2005.08.016;
RA Antony E., Khubchandani S., Chen S., Hingorani M.M.;
RT "Contribution of Msh2 and Msh6 subunits to the asymmetric ATPase and DNA
RT mismatch binding activities of Saccharomyces cerevisiae Msh2-Msh6 mismatch
RT repair protein.";
RL DNA Repair 5:153-162(2006).
RN [32]
RP FUNCTION.
RX PubMed=16702432; DOI=10.1534/genetics.106.055616;
RA Stone J.E., Petes T.D.;
RT "Analysis of the proteins involved in the in vivo repair of base-base
RT mismatches and four-base loops formed during meiotic recombination in the
RT yeast Saccharomyces cerevisiae.";
RL Genetics 173:1223-1239(2006).
RN [33]
RP FUNCTION, AND MUTAGENESIS OF LYS-988.
RX PubMed=16600868; DOI=10.1016/j.molcel.2006.02.010;
RA Mazur D.J., Mendillo M.L., Kolodner R.D.;
RT "Inhibition of Msh6 ATPase activity by mispaired DNA induces a Msh2(ATP)-
RT Msh6(ATP) state capable of hydrolysis-independent movement along DNA.";
RL Mol. Cell 22:39-49(2006).
RN [34]
RP FUNCTION, AND MUTAGENESIS OF SER-1036; GLY-1067 AND GLY-1142.
RX PubMed=16407100; DOI=10.1073/pnas.0510078103;
RA Hess M.T., Mendillo M.L., Mazur D.J., Kolodner R.D.;
RT "Biochemical basis for dominant mutations in the Saccharomyces cerevisiae
RT MSH6 gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:558-563(2006).
RN [35]
RP FUNCTION, AND MUTAGENESIS OF GLU-339.
RX PubMed=17141577; DOI=10.1016/j.dnarep.2006.10.023;
RA Holmes S.F., Scarpinato K.D., McCulloch S.D., Schaaper R.M., Kunkel T.A.;
RT "Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif of
RT yeast Msh6.";
RL DNA Repair 6:293-303(2007).
RN [36]
RP FUNCTION.
RX PubMed=17157869; DOI=10.1016/j.jmb.2006.10.099;
RA Lee S.D., Surtees J.A., Alani E.;
RT "Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display
RT distinct requirements for DNA binding domain I in mismatch recognition.";
RL J. Mol. Biol. 366:53-66(2007).
RN [37]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145 AND SER-150, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [38]
RP FUNCTION, AND DNA-BINDING DOMAIN.
RX PubMed=17567610; DOI=10.1093/nar/gkm409;
RA Clark A.B., Deterding L., Tomer K.B., Kunkel T.A.;
RT "Multiple functions for the N-terminal region of Msh6.";
RL Nucleic Acids Res. 35:4114-4123(2007).
RN [39]
RP FUNCTION.
RX PubMed=17573527; DOI=10.1073/pnas.0704148104;
RA Shell S.S., Putnam C.D., Kolodner R.D.;
RT "Chimeric Saccharomyces cerevisiae Msh6 protein with an Msh3 mispair-
RT binding domain combines properties of both proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:10956-10961(2007).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; SER-145; SER-150 AND
RP THR-451, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145; SER-150 AND SER-201, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
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. MSH6 provides substrate-
CC binding and substrate specificity to the complex. When bound, MutS
CC alpha bends the DNA helix and shields approximately 20 base pairs. Acts
CC mainly to repair base-base and single insertion-deletion mismatches
CC that occur during replication, but can also repair longer insertion-
CC deletion loops (IDLs), although with decreasing efficiency as the size
CC of the extrahelical loop increases. After mismatch binding, forms a
CC ternary complex with the MutL alpha heterodimer, which is thought to be
CC responsible for directing the downstream MMR events, including strand
CC discrimination, excision, and resynthesis. ATP binding and hydrolysis
CC by the MutS alpha complex is crucial for MMR. Both subunits bind ATP,
CC but with differing affinities, and their ATPase kinetics are also very
CC different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2
CC catalyzes ATP at a substantially slower rate. Binding to a mismatched
CC base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the
CC activity of MSH2. ATP binding to both subunits is necessary to trigger
CC a change in MutS alpha interaction with mismatched DNA, converting MutS
CC alpha into a sliding clamp capable of hydrolysis-independent movement
CC along DNA, and also facilitates formation of ternary complexes
CC containing MutS and MutL proteins and the mismatch. May also be
CC involved in resolution of recombination intermediates.
CC {ECO:0000269|PubMed:10518225, ECO:0000269|PubMed:10970737,
CC ECO:0000269|PubMed:11237611, ECO:0000269|PubMed:12509278,
CC ECO:0000269|PubMed:12820877, ECO:0000269|PubMed:15811858,
CC ECO:0000269|PubMed:16214425, ECO:0000269|PubMed:16337600,
CC ECO:0000269|PubMed:16407100, ECO:0000269|PubMed:16600868,
CC ECO:0000269|PubMed:16702432, ECO:0000269|PubMed:17141577,
CC ECO:0000269|PubMed:17157869, ECO:0000269|PubMed:17567610,
CC ECO:0000269|PubMed:17573527, ECO:0000269|PubMed:8600025,
CC ECO:0000269|PubMed:9111357, ECO:0000269|PubMed:9545323,
CC ECO:0000269|PubMed:9770499}.
CC -!- ACTIVITY REGULATION: Inhibited by Cd(2+). {ECO:0000269|PubMed:15513922,
CC ECO:0000269|PubMed:15746000}.
CC -!- SUBUNIT: Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a
CC ternary complex with MutL alpha (MLH1-PMS1). MutS alpha interacts with
CC proliferating cell nuclear antigen (PCNA/POL30). This interaction is
CC disrupted upon binding of MutS alpha to mismatch DNA.
CC {ECO:0000269|PubMed:11005803, ECO:0000269|PubMed:11062484,
CC ECO:0000269|PubMed:12435741, ECO:0000269|PubMed:8600025,
CC ECO:0000269|PubMed:8816473}.
CC -!- INTERACTION:
CC Q03834; P25847: MSH2; NbExp=6; IntAct=EBI-11383, EBI-11352;
CC Q03834; P15873: POL30; NbExp=5; IntAct=EBI-11383, EBI-12993;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC -!- DOMAIN: The PIP box serves as a PCNA(POL30)-recognition and -binding
CC motif.
CC -!- MISCELLANEOUS: Present with 5330 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family.
CC {ECO:0000305}.
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DR EMBL; Z47746; CAA87671.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11942.1; -; Genomic_DNA.
DR PIR; S51246; S51246.
DR RefSeq; NP_010382.3; NM_001180405.3.
DR AlphaFoldDB; Q03834; -.
DR SMR; Q03834; -.
DR BioGRID; 32152; 123.
DR ComplexPortal; CPX-1037; DNA mismatch repair MutSalpha complex.
DR DIP; DIP-2423N; -.
DR ELM; Q03834; -.
DR IntAct; Q03834; 35.
DR MINT; Q03834; -.
DR STRING; 4932.YDR097C; -.
DR iPTMnet; Q03834; -.
DR MaxQB; Q03834; -.
DR PaxDb; Q03834; -.
DR PRIDE; Q03834; -.
DR EnsemblFungi; YDR097C_mRNA; YDR097C; YDR097C.
DR GeneID; 851671; -.
DR KEGG; sce:YDR097C; -.
DR SGD; S000002504; MSH6.
DR VEuPathDB; FungiDB:YDR097C; -.
DR eggNOG; KOG0217; Eukaryota.
DR GeneTree; ENSGT00550000075024; -.
DR HOGENOM; CLU_002472_1_0_1; -.
DR InParanoid; Q03834; -.
DR OMA; TPMMAQY; -.
DR BioCyc; YEAST:G3O-29700-MON; -.
DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR PRO; PR:Q03834; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; Q03834; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0032301; C:MutSalpha complex; IPI:SGD.
DR GO; GO:0005634; C:nucleus; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; IDA:SGD.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003690; F:double-stranded DNA binding; IBA:GO_Central.
DR GO; GO:0000400; F:four-way junction DNA binding; IDA:SGD.
DR GO; GO:0030983; F:mismatched DNA binding; IBA:GO_Central.
DR GO; GO:0036297; P:interstrand cross-link repair; IGI:SGD.
DR GO; GO:0000710; P:meiotic mismatch repair; IMP:SGD.
DR GO; GO:0006298; P:mismatch repair; IDA:SGD.
DR GO; GO:0043111; P:replication fork arrest; IMP:SGD.
DR DisProt; DP01623; -.
DR Gene3D; 3.30.420.110; -; 1.
DR Gene3D; 3.40.1170.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
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 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 PIRSF; PIRSF037677; DNA_mis_repair_Msh6; 1.
DR SMART; SM00534; MUTSac; 1.
DR SMART; SM00533; MUTSd; 1.
DR SUPFAM; SSF48334; SSF48334; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF53150; SSF53150; 1.
DR SUPFAM; SSF55271; SSF55271; 1.
DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; DNA damage; DNA repair; DNA-binding; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..1242
FT /note="DNA mismatch repair protein MSH6"
FT /id="PRO_0000115213"
FT DNA_BIND 228..299
FT REGION 1..271
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 305..421
FT /note="Mispair-binding domain"
FT MOTIF 27..34
FT /note="PIP box"
FT COMPBIAS 9..67
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 129..168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 169..190
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 213..234
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..268
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 982..989
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MOD_RES 102
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 150
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 451
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MUTAGEN 26..27
FT /note="KQ->AA: Partially functional in a mismatch repair
FT assay; when associated with 33-AA-34."
FT /evidence="ECO:0000269|PubMed:11005803"
FT MUTAGEN 33..34
FT /note="FF->AA: Abolishes interaction with PCNA (POL30), but
FT only causes a moderate mismatch repair defect. Partially
FT functional in a mismatch repair assay; when associated with
FT 26-AA-27."
FT /evidence="ECO:0000269|PubMed:11005803,
FT ECO:0000269|PubMed:11062484"
FT MUTAGEN 301
FT /note="L->V: Fully functional in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:10537275"
FT MUTAGEN 313
FT /note="P->A: Fully functional in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 337
FT /note="F->A: Shows defects in both homoduplex and mispair
FT DNA binding and is only partially functional in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:10347163,
FT ECO:0000269|PubMed:10970737, ECO:0000269|PubMed:11641390"
FT MUTAGEN 337
FT /note="F->H,I,Y: Partially functional in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10347163,
FT ECO:0000269|PubMed:10970737, ECO:0000269|PubMed:11641390"
FT MUTAGEN 337
FT /note="F->K: Completely abolishes mismatch repair."
FT /evidence="ECO:0000269|PubMed:10347163,
FT ECO:0000269|PubMed:10970737, ECO:0000269|PubMed:11641390"
FT MUTAGEN 337
FT /note="F->S: In MSH6-6; partially functional in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:10347163,
FT ECO:0000269|PubMed:10970737, ECO:0000269|PubMed:11641390"
FT MUTAGEN 339
FT /note="E->A: Defective in repairing 8-oxo-G-A mismatches."
FT /evidence="ECO:0000269|PubMed:11641390,
FT ECO:0000269|PubMed:17141577"
FT MUTAGEN 340..343
FT /note="LYEK->CFAE: In MSH6-340; shows defects in mispair
FT DNA binding, but not in homoduplex DNA binding."
FT /evidence="ECO:0000269|PubMed:10615127"
FT MUTAGEN 368
FT /note="G->A: Moderately reduced activity in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 370
FT /note="P->A: Partially functional in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 393
FT /note="Q->A: Moderately reduced activity in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 393
FT /note="Q->R: In MSH6-5; partially functional in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 412
FT /note="R->A: Completely abolishes mismatch repair."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 412
FT /note="R->G: In MSH6-7; partially functional in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 421
FT /note="G->D: In PMS3-1; completely abolishes mismatch
FT repair."
FT /evidence="ECO:0000269|PubMed:8600025"
FT MUTAGEN 477
FT /note="G->R: Partially functional in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10537275"
FT MUTAGEN 848
FT /note="K->A: Fully functional in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 852
FT /note="R->A: Moderately reduced activity in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 987
FT /note="G->D: Has no defect in mismatch DNA binding, but
FT lacks ATP-induced conformational change."
FT /evidence="ECO:0000269|PubMed:9819445"
FT MUTAGEN 988
FT /note="K->A: Impairs ATP binding; reduces catalytic
FT activity 13-fold for ATP hydrolysis."
FT /evidence="ECO:0000269|PubMed:16214425,
FT ECO:0000269|PubMed:16600868"
FT MUTAGEN 1036
FT /note="S->P: In MSH6-4; defective for ATP-induced sliding
FT clamp formation and assembly of ternary complexes with MutL
FT alpha."
FT /evidence="ECO:0000269|PubMed:11986324,
FT ECO:0000269|PubMed:16407100"
FT MUTAGEN 1062
FT /note="E->A: Reduces catalytic activity 13-fold for ATP
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:12509278,
FT ECO:0000269|PubMed:15513922, ECO:0000269|PubMed:16214425"
FT MUTAGEN 1067
FT /note="G->D: In MSH6-3; defective for ATP-induced sliding
FT clamp formation and assembly of ternary complexes with MutL
FT alpha."
FT /evidence="ECO:0000269|PubMed:11986324,
FT ECO:0000269|PubMed:16407100"
FT MUTAGEN 1096
FT /note="H->A: In MSH6-9; shows normal mispair binding and
FT dissociation, but fails to show complete mispair activation
FT of the ATPase."
FT /evidence="ECO:0000269|PubMed:11986324"
FT MUTAGEN 1142
FT /note="G->D: In MSH6-2; defective for ATP-induced sliding
FT clamp formation, but assembles ternary complexes with MutL
FT alpha."
FT /evidence="ECO:0000269|PubMed:11986324,
FT ECO:0000269|PubMed:16407100"
SQ SEQUENCE 1242 AA; 140080 MW; 11A6883AADCFA222 CRC64;
MAPATPKTSK TAHFENGSTS SQKKMKQSSL LSFFSKQVPS GTPSKKVQKP TPATLENTAT
DKITKNPQGG KTGKLFVDVD EDNDLTIAEE TVSTVRSDIM HSQEPQSDTM LNSNTTEPKS
TTTDEDLSSS QSRRNHKRRV NYAESDDDDS DTTFTAKRKK GKVVDSESDE DEYLPDKNDG
DEDDDIADDK EDIKGELAED SGDDDDLISL AETTSKKKFS YNTSHSSSPF TRNISRDNSK
KKSRPNQAPS RSYNPSHSQP SATSKSSKFN KQNEERYQWL VDERDAQRRP KSDPEYDPRT
LYIPSSAWNK FTPFEKQYWE IKSKMWDCIV FFKKGKFFEL YEKDALLANA LFDLKIAGGG
RANMQLAGIP EMSFEYWAAQ FIQMGYKVAK VDQRESMLAK EMREGSKGIV KRELQCILTS
GTLTDGDMLH SDLATFCLAI REEPGNFYNE TQLDSSTIVQ KLNTKIFGAA FIDTATGELQ
MLEFEDDSEC TKLDTLMSQV RPMEVVMERN NLSTLANKIV KFNSAPNAIF NEVKAGEEFY
DCDKTYAEII SSEYFSTEED WPEVLKSYYD TGKKVGFSAF GGLLYYLKWL KLDKNLISMK
NIKEYDFVKS QHSMVLDGIT LQNLEIFSNS FDGSDKGTLF KLFNRAITPM GKRMMKKWLM
HPLLRKNDIE SRLDSVDSLL QDITLREQLE ITFSKLPDLE RMLARIHSRT IKVKDFEKVI
TAFETIIELQ DSLKNNDLKG DVSKYISSFP EGLVEAVKSW TNAFERQKAI NENIIVPQRG
FDIEFDKSMD RIQELEDELM EILMTYRKQF KCSNIQYKDS GKEIYTIEIP ISATKNVPSN
WVQMAANKTY KRYYSDEVRA LARSMAEAKE IHKTLEEDLK NRLCQKFDAH YNTIWMPTIQ
AISNIDCLLA ITRTSEYLGA PSCRPTIVDE VDSKTNTQLN GFLKFKSLRH PCFNLGATTA
KDFIPNDIEL GKEQPRLGLL TGANAAGKST ILRMACIAVI MAQMGCYVPC ESAVLTPIDR
IMTRLGANDN IMQGKSTFFV ELAETKKILD MATNRSLLVV DELGRGGSSS DGFAIAESVL
HHVATHIQSL GFFATHYGTL ASSFKHHPQV RPLKMSILVD EATRNVTFLY KMLEGQSEGS
FGMHVASMCG ISKEIIDNAQ IAADNLEHTS RLVKERDLAA NNLNGEVVSV PGGLQSDFVR
IAYGDGLKNT KLGSGEGVLN YDWNIKRNVL KSLFSIIDDL QS
