MSH2_YEAST
ID MSH2_YEAST Reviewed; 964 AA.
AC P25847; D6W1X8; Q12423;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=DNA mismatch repair protein MSH2;
DE AltName: Full=MutS protein homolog 2;
GN Name=MSH2; OrderedLocusNames=YOL090W; ORFNames=O0935;
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 [GENOMIC DNA].
RX PubMed=1459447; DOI=10.1093/genetics/132.4.963;
RA Reenan R.A.G., Kolodner R.D.;
RT "Isolation and characterization of two Saccharomyces cerevisiae genes
RT encoding homologs of the bacterial HexA and MutS mismatch repair
RT proteins.";
RL Genetics 132:963-973(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 96604 / S288c / FY1679;
RX PubMed=8533473; DOI=10.1002/yea.320111009;
RA Zumstein E., Pearson B.M., Kalogeropoulos A., Schweizer M.;
RT "A 29.425 kb segment on the left arm of yeast chromosome XV contains more
RT than twice as many unknown as known open reading frames.";
RL Yeast 11:975-986(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [4]
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 [5]
RP CHARACTERIZATION.
RX PubMed=1334021; DOI=10.1093/genetics/132.4.975;
RA Reenan R.A.G., Kolodner R.D.;
RT "Characterization of insertion mutations in the Saccharomyces cerevisiae
RT MSH1 and MSH2 genes: evidence for separate mitochondrial and nuclear
RT functions.";
RL Genetics 132:975-985(1992).
RN [6]
RP COMPLEX FORMATION WITH MLH1-PMS1.
RX PubMed=8066446; DOI=10.1126/science.8066446;
RA Prolla T.A., Pang Q., Alani E., Kolodner R.D., Liskay R.M.;
RT "MLH1, PMS1, and MSH2 interactions during the initiation of DNA mismatch
RT repair in yeast.";
RL Science 265:1091-1093(1994).
RN [7]
RP INTERACTION WITH POL30.
RX PubMed=8858149; DOI=10.1016/s0092-8674(00)81323-9;
RA Umar A., Buermeyer A.B., Simon J.A., Thomas D.C., Clark A.B., Liskay R.M.,
RA Kunkel T.A.;
RT "Requirement for PCNA in DNA mismatch repair at a step preceding DNA
RT resynthesis.";
RL Cell 87:65-73(1996).
RN [8]
RP DNA-BINDING SPECIFICITY, AND INTERACTION WITH MSH3.
RX PubMed=8805366; DOI=10.1016/s0960-9822(02)70686-6;
RA Habraken Y., Sung P., Prakash L., Prakash S.;
RT "Binding of insertion/deletion DNA mismatches by the heterodimer of yeast
RT mismatch repair proteins MSH2 and MSH3.";
RL Curr. Biol. 6:1185-1187(1996).
RN [9]
RP FUNCTION, AND INTERACTION WITH MSH3 AND MSH6.
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 [10]
RP CHARACTERIZATION, AND INTERACTION WITH MSH6.
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 [11]
RP FUNCTION, DNA-BINDING SPECIFICITY, AND COMPLEX FORMATION WITH MLH1-PMS1.
RX PubMed=9368761; DOI=10.1016/s0960-9822(06)00337-x;
RA Habraken Y., Sung P., Prakash L., Prakash S.;
RT "Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast MLH1-
RT PMS1 complex.";
RL Curr. Biol. 7:790-793(1997).
RN [12]
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 [13]
RP FUNCTION IN NHTR.
RX PubMed=9256462; DOI=10.1073/pnas.94.17.9214;
RA Sugawara N., Paques F., Colaiacovo M., Haber J.E.;
RT "Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in double-
RT strand break-induced recombination.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:9214-9219(1997).
RN [14]
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 [15]
RP MUTAGENESIS OF GLY-693.
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 [16]
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 [17]
RP MUTAGENESIS OF GLY-317; LEU-402; GLN-430; ASP-524; ARG-542; PRO-640 AND
RP CYS-716.
RX PubMed=10469597; DOI=10.1016/s0960-9822(99)80396-0;
RA Drotschmann K., Clark A.B., Kunkel T.A.;
RT "Mutator phenotypes of common polymorphisms and missense mutations in
RT MSH2.";
RL Curr. Biol. 9:907-910(1999).
RN [18]
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 [19]
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 [20]
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 [21]
RP MUTAGENESIS.
RX PubMed=10523644; DOI=10.1128/mcb.19.11.7558;
RA Studamire B., Price G., Sugawara N., Haber J.E., Alani E.;
RT "Separation-of-function mutations in Saccharomyces cerevisiae MSH2 that
RT confer mismatch repair defects but do not affect nonhomologous-tail removal
RT during recombination.";
RL Mol. Cell. Biol. 19:7558-7567(1999).
RN [22]
RP MUTAGENESIS OF GLY-688; GLY-693; LYS-694 AND SER-695.
RX PubMed=10077621; DOI=10.1073/pnas.96.6.2970;
RA Drotschmann K., Clark A.B., Tran H.T., Resnick M.A., Gordenin D.A.,
RA Kunkel T.A.;
RT "Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:2970-2975(1999).
RN [23]
RP INTERACTION WITH POL30.
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 [24]
RP MUTAGENESIS OF GLY-317; PRO-640 AND HIS-658.
RX PubMed=11555625; DOI=10.1093/hmg/10.18.1889;
RA Ellison A.R., Lofing J., Bitter G.A.;
RT "Functional analysis of human MLH1 and MSH2 missense variants and hybrid
RT human-yeast MLH1 proteins in Saccharomyces cerevisiae.";
RL Hum. Mol. Genet. 10:1889-1900(2001).
RN [25]
RP DNA-BINDING, AND MUTAGENESIS OF TYR-42 AND LYS-65.
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 [26]
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 [27]
RP FUNCTION, AND MUTAGENESIS OF GLU-768.
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 [28]
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 [29]
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 [30]
RP FUNCTION, AND MUTAGENESIS OF SER-561; LYS-564; GLY-566; SER-656 AND
RP ARG-730.
RX PubMed=12875840; DOI=10.1016/s0022-2836(03)00694-6;
RA Kijas A.W., Studamire B., Alani E.;
RT "Msh2 separation of function mutations confer defects in the initiation
RT steps of mismatch repair.";
RL J. Mol. Biol. 331:123-138(2003).
RN [31]
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 [32]
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 [33]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF GLU-768.
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 [34]
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 [35]
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 [36]
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 [37]
RP FUNCTION, AND MUTAGENESIS OF LYS-694 AND GLU-768.
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 [38]
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 [39]
RP FUNCTION, AND MUTAGENESIS OF LYS-694.
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 [40]
RP FUNCTION IN NHTR, AND DNA-BINDING.
RX PubMed=16781730; DOI=10.1016/j.jmb.2006.05.032;
RA Surtees J.A., Alani E.;
RT "Mismatch repair factor MSH2-MSH3 binds and alters the conformation of
RT branched DNA structures predicted to form during genetic recombination.";
RL J. Mol. Biol. 360:523-536(2006).
RN [41]
RP FUNCTION, AND DNA-BINDING.
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 [42]
RP FUNCTION.
RX PubMed=17636021; DOI=10.1128/mcb.00855-07;
RA Harrington J.M., Kolodner R.D.;
RT "Saccharomyces cerevisiae Msh2-Msh3 acts in repair of base-base mispairs.";
RL Mol. Cell. Biol. 27:6546-6554(2007).
RN [43]
RP INTERACTION WITH SAW1.
RX PubMed=18471978; DOI=10.1016/j.molcel.2008.02.028;
RA Li F., Dong J., Pan X., Oum J.-H., Boeke J.D., Lee S.E.;
RT "Microarray-based genetic screen defines SAW1, a gene required for
RT Rad1/Rad10-dependent processing of recombination intermediates.";
RL Mol. Cell 30:325-335(2008).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6
CC heterodimer) and MutS beta (MSH2-MSH3 heterodimer), which bind to DNA
CC mismatches thereby initiating DNA repair. MSH2 seems to act as a
CC scaffold for the other MutS homologs that provide substrate-binding and
CC substrate specificity. When bound, heterodimers bend the DNA helix and
CC shield approximately 20 base pairs. MutS alpha acts mainly to repair
CC base-base and single insertion-deletion mismatches that occur during
CC replication, but can also repair longer insertion-deletion loops
CC (IDLs), although with decreasing efficiency as the size of the
CC extrahelical loop increases. MutS beta acts mainly to repair IDLs from
CC 2 to 13 nucleotides in size, but can also repair base-base and single
CC insertion-deletion mismatches. After mismatch binding, MutS alpha or
CC beta form a ternary complex with a MutL heterodimer, which is thought
CC to be responsible for directing the downstream MMR events, including
CC strand discrimination, excision, and resynthesis. ATP binding and
CC hydrolysis play a pivotal role in mismatch repair functions. Both
CC subunits bind ATP, but with differing affinities, and their ATPase
CC kinetics are also very different. MSH6 binds and hydrolyzes ATP
CC rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate.
CC Binding to a mismatched base pair suppresses MSH6-catalyzed ATP
CC hydrolysis, but not the activity of MSH2. ATP binding to both subunits
CC is necessary to trigger a change in MutS alpha interaction with
CC mismatched DNA, converting MutS alpha into a sliding clamp capable of
CC hydrolysis-independent movement along DNA, and also facilitates
CC formation of ternary complexes containing MutS and MutL proteins and
CC the mismatch. MutS beta also has a role in regulation of heteroduplex
CC formation during mitotic and meiotic recombination. MutS beta binds to
CC DNA flap structures predicted to form during recombination, and is
CC required for 3' non-homologous tail removal (NHTR). MutS beta-binding
CC alters the DNA conformation of its substrate at the ds/ssDNA junction
CC and may facilitate its recognition and/or cleavage by the downstream
CC nucleotide excision repair (NER) RAD1-RAD10 endonuclease.
CC {ECO:0000269|PubMed:10518225, ECO:0000269|PubMed:11237611,
CC ECO:0000269|PubMed:12509278, ECO:0000269|PubMed:12820877,
CC ECO:0000269|PubMed:12875840, ECO:0000269|PubMed:15811858,
CC ECO:0000269|PubMed:16214425, ECO:0000269|PubMed:16337600,
CC ECO:0000269|PubMed:16600868, ECO:0000269|PubMed:16702432,
CC ECO:0000269|PubMed:16781730, ECO:0000269|PubMed:17157869,
CC ECO:0000269|PubMed:17636021, ECO:0000269|PubMed:8600025,
CC ECO:0000269|PubMed:9111357, ECO:0000269|PubMed:9256462,
CC ECO:0000269|PubMed:9368761, 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) or MSH2-MSH3
CC (MutS beta). Both heterodimers form a ternary complex with MutL alpha
CC (MLH1-PMS1). MutS beta also forms a ternary complex with MutL beta
CC (MLH1-MLH3), and possibly with a MLH1-MLH2 heterodimer. Both
CC heterodimers interact with proliferating cell nuclear antigen
CC (PCNA/POL30). This interaction is disrupted upon binding of the MutS
CC heterodimers to mismatch DNA. Interacts with SAW1.
CC {ECO:0000269|PubMed:11005803, ECO:0000269|PubMed:12435741,
CC ECO:0000269|PubMed:18471978, ECO:0000269|PubMed:8600025,
CC ECO:0000269|PubMed:8805366, ECO:0000269|PubMed:8816473,
CC ECO:0000269|PubMed:8858149}.
CC -!- INTERACTION:
CC P25847; P39875: EXO1; NbExp=3; IntAct=EBI-11352, EBI-6738;
CC P25847; P25336: MSH3; NbExp=3; IntAct=EBI-11352, EBI-11362;
CC P25847; Q03834: MSH6; NbExp=6; IntAct=EBI-11352, EBI-11383;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC -!- MISCELLANEOUS: Present with 1230 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; M84170; AAA34802.1; -; Genomic_DNA.
DR EMBL; X83121; CAA58189.1; -; Genomic_DNA.
DR EMBL; Z74832; CAA99102.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10694.1; -; Genomic_DNA.
DR PIR; S57379; S57379.
DR RefSeq; NP_014551.1; NM_001183344.1.
DR AlphaFoldDB; P25847; -.
DR SMR; P25847; -.
DR BioGRID; 34312; 332.
DR ComplexPortal; CPX-1036; DNA mismatch repair MutSbeta complex.
DR ComplexPortal; CPX-1037; DNA mismatch repair MutSalpha complex.
DR DIP; DIP-2415N; -.
DR IntAct; P25847; 38.
DR MINT; P25847; -.
DR STRING; 4932.YOL090W; -.
DR iPTMnet; P25847; -.
DR MaxQB; P25847; -.
DR PaxDb; P25847; -.
DR PRIDE; P25847; -.
DR EnsemblFungi; YOL090W_mRNA; YOL090W; YOL090W.
DR GeneID; 854063; -.
DR KEGG; sce:YOL090W; -.
DR SGD; S000005450; MSH2.
DR VEuPathDB; FungiDB:YOL090W; -.
DR eggNOG; KOG0219; Eukaryota.
DR GeneTree; ENSGT00550000074867; -.
DR HOGENOM; CLU_002472_10_0_1; -.
DR InParanoid; P25847; -.
DR OMA; LFRIYQV; -.
DR BioCyc; YEAST:G3O-33490-MON; -.
DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR Reactome; R-SCE-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR PRO; PR:P25847; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; P25847; protein.
DR GO; GO:0032301; C:MutSalpha complex; IPI:SGD.
DR GO; GO:0032302; C:MutSbeta complex; IPI:SGD.
DR GO; GO:0000228; C:nuclear chromosome; IDA: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:0000406; F:double-strand/single-strand DNA junction binding; IDA:SGD.
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:0006310; P:DNA recombination; IMP:SGD.
DR GO; GO:0036297; P:interstrand cross-link repair; IGI:SGD.
DR GO; GO:0006311; P:meiotic gene conversion; IMP:SGD.
DR GO; GO:0000710; P:meiotic mismatch repair; IMP:SGD.
DR GO; GO:0006298; P:mismatch repair; IDA:ComplexPortal.
DR GO; GO:0006312; P:mitotic recombination; IMP:SGD.
DR GO; GO:0000735; P:removal of nonhomologous ends; IMP:SGD.
DR GO; GO:0043111; P:replication fork arrest; IMP:SGD.
DR GO; GO:0030466; P:silent mating-type cassette heterochromatin assembly; IGI:SGD.
DR Gene3D; 3.30.420.110; -; 1.
DR Gene3D; 3.40.1170.10; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR011184; DNA_mismatch_repair_Msh2.
DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N.
DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C.
DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp.
DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core.
DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N.
DR InterPro; IPR036187; DNA_mismatch_repair_MutS_sf.
DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom.
DR InterPro; IPR032642; Msh2.
DR InterPro; IPR036678; MutS_con_dom_sf.
DR InterPro; IPR045076; MutS_family.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR11361; PTHR11361; 1.
DR PANTHER; PTHR11361:SF35; PTHR11361:SF35; 1.
DR Pfam; PF01624; MutS_I; 1.
DR Pfam; PF05188; MutS_II; 1.
DR Pfam; PF05192; MutS_III; 1.
DR Pfam; PF05190; MutS_IV; 1.
DR Pfam; PF00488; MutS_V; 1.
DR PIRSF; PIRSF005813; MSH2; 1.
DR SMART; SM00534; MUTSac; 1.
DR SMART; SM00533; MUTSd; 1.
DR SUPFAM; SSF48334; SSF48334; 1.
DR SUPFAM; SSF52540; SSF52540; 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; Reference proteome.
FT CHAIN 1..964
FT /note="DNA mismatch repair protein MSH2"
FT /id="PRO_0000115191"
FT REGION 851..964
FT /note="Interaction with MSH6"
FT BINDING 688..695
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT MUTAGEN 42
FT /note="Y->A: Moderately reduced activity in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 65
FT /note="K->A: Defective in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:11641390"
FT MUTAGEN 317
FT /note="G->D: Partially defective in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:11555625"
FT MUTAGEN 402
FT /note="L->F: Partially defective in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10469597"
FT MUTAGEN 430
FT /note="Q->K: Partially defective in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10469597"
FT MUTAGEN 518
FT /note="A->P: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 524
FT /note="D->Y: Partially defective in a mismatch repair
FT assay."
FT /evidence="ECO:0000269|PubMed:10469597"
FT MUTAGEN 542
FT /note="R->P: Defective in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:10469597"
FT MUTAGEN 561
FT /note="S->P: Causes strong defects in MutS alpha mismatch
FT binding. Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:12875840"
FT MUTAGEN 564
FT /note="K->E: Causes strong defects in MutS alpha mismatch
FT binding. Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:12875840"
FT MUTAGEN 566
FT /note="G->D: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:12875840"
FT MUTAGEN 574
FT /note="L->S: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 584
FT /note="L->P: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 640
FT /note="P->L: Defective in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:10469597,
FT ECO:0000269|PubMed:11555625"
FT MUTAGEN 656
FT /note="S->P: Causes defects in ATP-dependent dissociation
FT of MutS alpha from mismatch DNA and in interactions between
FT MutS alpha and MutL alpha. Defective in MMR, but not in
FT NHTR."
FT /evidence="ECO:0000269|PubMed:12875840"
FT MUTAGEN 658
FT /note="H->Y: Fully functional in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:11555625"
FT MUTAGEN 688
FT /note="G->A: Moderately reduced activity in a mismatch
FT repair assay."
FT /evidence="ECO:0000269|PubMed:10077621"
FT MUTAGEN 693
FT /note="G->A,S: Has a dominant negative mutator effect."
FT /evidence="ECO:0000269|PubMed:10077621,
FT ECO:0000269|PubMed:9819445"
FT MUTAGEN 693
FT /note="G->D: Has no defect in mismatch DNA binding, but
FT lacks ATP-induced conformational change. Defective in MMR
FT and in NHTR."
FT /evidence="ECO:0000269|PubMed:10077621,
FT ECO:0000269|PubMed:9819445"
FT MUTAGEN 694
FT /note="K->A: Impairs ATP binding; reduces catalytic
FT activity 1.6-fold for ATP hydrolysis. Has a dominant
FT negative mutator effect."
FT /evidence="ECO:0000269|PubMed:10077621,
FT ECO:0000269|PubMed:16214425, ECO:0000269|PubMed:16600868"
FT MUTAGEN 694
FT /note="K->R: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10077621,
FT ECO:0000269|PubMed:16214425, ECO:0000269|PubMed:16600868"
FT MUTAGEN 695
FT /note="S->A: Has a dominant negative mutator effect."
FT /evidence="ECO:0000269|PubMed:10077621"
FT MUTAGEN 716
FT /note="C->F: Defective in a mismatch repair assay."
FT /evidence="ECO:0000269|PubMed:10469597"
FT MUTAGEN 730
FT /note="R->W: Disrupts MutS alpha ATPase activity, but does
FT not affect ATP binding or interactions with MutL alpha.
FT Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:12875840"
FT MUTAGEN 742
FT /note="S->F: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 742
FT /note="S->P: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 768
FT /note="E->A: Reduces catalytic activity 50-fold for ATP
FT hydrolysis."
FT /evidence="ECO:0000269|PubMed:12509278,
FT ECO:0000269|PubMed:15513922, ECO:0000269|PubMed:16214425"
FT MUTAGEN 773
FT /note="T->I: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 855
FT /note="G->D: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 859
FT /note="A->E: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 862
FT /note="V->D: Defective in MMR, but not in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT MUTAGEN 863..868
FT /note="Missing: Defective in MMR and in NHTR."
FT /evidence="ECO:0000269|PubMed:10523644"
FT CONFLICT 957..964
FT /note="KYIKALLL -> EIYKSPCCYN (in Ref. 1; AAA34802)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 964 AA; 108884 MW; 43FFD8A640138AE4 CRC64;
MSSTRPELKF SDVSEERNFY KKYTGLPKKP LKTIRLVDKG DYYTVIGSDA IFVADSVYHT
QSVLKNCQLD PVTAKNFHEP TKYVTVSLQV LATLLKLCLL DLGYKVEIYD KGWKLIKSAS
PGNIEQVNEL MNMNIDSSII IASLKVQWNS QDGNCIIGVA FIDTTAYKVG MLDIVDNEVY
SNLESFLIQL GVKECLVQDL TSNSNSNAEM QKVINVIDRC GCVVTLLKNS EFSEKDVELD
LTKLLGDDLA LSLPQKYSKL SMGACNALIG YLQLLSEQDQ VGKYELVEHK LKEFMKLDAS
AIKALNLFPQ GPQNPFGSNN LAVSGFTSAG NSGKVTSLFQ LLNHCKTNAG VRLLNEWLKQ
PLTNIDEINK RHDLVDYLID QIELRQMLTS EYLPMIPDIR RLTKKLNKRG NLEDVLKIYQ
FSKRIPEIVQ VFTSFLEDDS PTEPVNELVR SVWLAPLSHH VEPLSKFEEM VETTVDLDAY
EENNEFMIKV EFNEELGKIR SKLDTLRDEI HSIHLDSAED LGFDPDKKLK LENHHLHGWC
MRLTRNDAKE LRKHKKYIEL STVKAGIFFS TKQLKSIANE TNILQKEYDK QQSALVREII
NITLTYTPVF EKLSLVLAHL DVIASFAHTS SYAPIPYIRP KLHPMDSERR THLISSRHPV
LEMQDDISFI SNDVTLESGK GDFLIITGPN MGGKSTYIRQ VGVISLMAQI GCFVPCEEAE
IAIVDAILCR VGAGDSQLKG VSTFMVEILE TASILKNASK NSLIIVDELG RGTSTYDGFG
LAWAIAEHIA SKIGCFALFA THFHELTELS EKLPNVKNMH VVAHIEKNLK EQKHDDEDIT
LLYKVEPGIS DQSFGIHVAE VVQFPEKIVK MAKRKANELD DLKTNNEDLK KAKLSLQEVN
EGNIRLKALL KEWIRKVKEE GLHDPSKITE EASQHKIQEL LRAIANEPEK ENDNYLKYIK
ALLL
