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 27-MAR-2024, entry version 199. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 341. 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; 4932-YOL090W; -. DR PeptideAtlas; P25847; -. DR EnsemblFungi; YOL090W_mRNA; YOL090W; YOL090W. DR GeneID; 854063; -. DR KEGG; sce:YOL090W; -. DR AGR; SGD:S000005450; -. 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; LVRFPQK; -. DR OrthoDB; 168255at2759; -. DR BioCyc; YEAST:G3O-33490-MONOMER; -. DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR BioGRID-ORCS; 854063; 9 hits in 10 CRISPR screens. 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: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 formation; IGI:SGD. DR CDD; cd03285; ABC_MSH2_euk; 1. DR Gene3D; 1.10.1420.10; -; 2. DR Gene3D; 3.40.1170.10; DNA repair protein MutS, domain I; 1. DR Gene3D; 3.30.420.110; MutS, connector domain; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR011184; DNA_mismatch_repair_Msh2. DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N. DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C. DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp. DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core. DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N. DR InterPro; IPR036187; DNA_mismatch_repair_MutS_sf. DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom. DR InterPro; IPR032642; Msh2_ATP-bd. DR InterPro; IPR036678; MutS_con_dom_sf. DR InterPro; IPR045076; MutS_family. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11361:SF35; DNA MISMATCH REPAIR PROTEIN MSH2; 1. DR PANTHER; PTHR11361; DNA MISMATCH REPAIR PROTEIN MUTS FAMILY MEMBER; 1. DR Pfam; PF01624; MutS_I; 1. DR Pfam; PF05188; MutS_II; 1. DR Pfam; PF05192; MutS_III; 1. DR Pfam; PF05190; MutS_IV; 1. DR Pfam; PF00488; MutS_V; 1. DR PIRSF; PIRSF005813; MSH2; 1. DR SMART; SM00534; MUTSac; 1. DR SMART; SM00533; MUTSd; 1. DR SUPFAM; SSF48334; DNA repair protein MutS, domain III; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1. PE 1: Evidence at protein level; KW 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 //