ID   MSH2_MOUSE              Reviewed;         935 AA.
AC   P43247;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   02-SEP-2026, entry version 195.
DE   RecName: Full=DNA mismatch repair protein Msh2;
DE   AltName: Full=MutS protein homolog 2;
GN   Name=Msh2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=BALB/cJ;
RX   PubMed=7838728; DOI=10.1093/nar/22.25.5723;
RA   Varlet I., Pallard C., Radman M., Moreau J., de Wind N.;
RT   "Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair
RT   genes.";
RL   Nucleic Acids Res. 22:5723-5728(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Lipford J.R., Kane M.F., Kolodner R.D.;
RT   "Mouse MutS homolog 2 (mMSH2) c-DNA sequence from -56.";
RL   Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary gland;
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung,
RC   Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [5]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-567, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Embryonic fibroblast;
RX   PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA   Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA   Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT   "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT   pathways.";
RL   Mol. Cell 50:919-930(2013).
CC   -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC       (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6
CC       heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA
CC       mismatches thereby initiating DNA repair. When bound, heterodimers bend
CC       the DNA helix and shields approximately 20 base pairs. MutS alpha
CC       recognizes single base mismatches and dinucleotide insertion-deletion
CC       loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion
CC       loops up to 13 nucleotides long. After mismatch binding, MutS alpha or
CC       beta forms a ternary complex with the MutL alpha heterodimer, which is
CC       thought to be responsible for directing the downstream MMR events,
CC       including strand discrimination, excision, and resynthesis. Recruits
CC       DNA helicase MCM9 to chromatin which unwinds the mismatch containing
CC       DNA strand. ATP binding and hydrolysis play a pivotal role in mismatch
CC       repair functions. The ATPase activity associated with MutS alpha
CC       regulates binding similar to a molecular switch: mismatched DNA
CC       provokes ADP-->ATP exchange, resulting in a discernible conformational
CC       transition that converts MutS alpha into a sliding clamp capable of
CC       hydrolysis-independent diffusion along the DNA backbone. This
CC       transition is crucial for mismatch repair. MutS alpha may also play a
CC       role in DNA homologous recombination repair. In melanocytes may
CC       modulate both UV-B-induced cell cycle regulation and apoptosis.
CC       {ECO:0000250|UniProtKB:P43246}.
CC   -!- SUBUNIT: Component of the DNA mismatch repair (MMR) complex composed at
CC       least of MSH2, MSH3, MSH6, PMS1 and MLH1. Heterodimer consisting of
CC       MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimers form
CC       a ternary complex with MutL alpha (MLH1-PMS1). Interacts with MCM9; the
CC       interaction recruits MCM9 to chromatin. Interacts with MCM8. Interacts
CC       with EXO1. Part of the BRCA1-associated genome surveillance complex
CC       (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the
CC       RAD50-MRE11-NBS1 protein complex. This association could be a dynamic
CC       process changing throughout the cell cycle and within subnuclear
CC       domains. Interacts with ATR. Interacts with SLX4/BTBD12; this
CC       interaction is direct and links MutS beta to SLX4, a subunit of
CC       different structure-specific endonucleases. Interacts with SMARCAD1.
CC       {ECO:0000250|UniProtKB:P43246}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P43246}.
CC       Chromosome {ECO:0000250|UniProtKB:P43246}.
CC   -!- PTM: Sequentially deacetylated and polyubiquitinated by HDAC6, leading
CC       to MSH2 degradation. {ECO:0000250|UniProtKB:P43246}.
CC   -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family.
CC       {ECO:0000305}.
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DR   EMBL; X81143; CAA57049.1; -; mRNA.
DR   EMBL; U21011; AAA75027.1; -; mRNA.
DR   EMBL; BC047117; AAH47117.1; -; mRNA.
DR   CCDS; CCDS29019.1; -.
DR   PIR; S53608; S53608.
DR   RefSeq; NP_032654.1; NM_008628.3.
DR   AlphaFoldDB; P43247; -.
DR   SMR; P43247; -.
DR   BioGRID; 201525; 12.
DR   ComplexPortal; CPX-78; DNA mismatch repair MutSbeta complex.
DR   ComplexPortal; CPX-81; DNA mismatch repair MutSalpha complex.
DR   CORUM; P43247; -.
DR   DIP; DIP-57027N; -.
DR   FunCoup; P43247; 4104.
DR   IntAct; P43247; 4.
DR   MINT; P43247; -.
DR   STRING; 10090.ENSMUSP00000024967; -.
DR   GlyGen; P43247; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P43247; -.
DR   PhosphoSitePlus; P43247; -.
DR   PaxDb; 10090-ENSMUSP00000024967; -.
DR   PeptideAtlas; P43247; -.
DR   ProteomicsDB; 290098; -.
DR   Pumba; P43247; -.
DR   Antibodypedia; 4037; 824 antibodies from 52 providers.
DR   DNASU; 17685; -.
DR   Ensembl; ENSMUST00000024967.14; ENSMUSP00000024967.8; ENSMUSG00000024151.14.
DR   GeneID; 17685; -.
DR   KEGG; mmu:17685; -.
DR   UCSC; uc008dva.1; mouse.
DR   AGR; MGI:101816; -.
DR   CTD; 4436; -.
DR   MGI; MGI:101816; Msh2.
DR   VEuPathDB; HostDB:ENSMUSG00000024151; -.
DR   eggNOG; KOG0219; Eukaryota.
DR   GeneTree; ENSGT00550000074867; -.
DR   HOGENOM; CLU_002472_10_0_1; -.
DR   InParanoid; P43247; -.
DR   OMA; LVRFPQK; -.
DR   OrthoDB; 295033at2759; -.
DR   PhylomeDB; P43247; -.
DR   Reactome; R-MMU-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR   Reactome; R-MMU-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
DR   BioGRID-ORCS; 17685; 15 hits in 117 CRISPR screens.
DR   PRO; PR:P43247; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; P43247; protein.
DR   Bgee; ENSMUSG00000024151; Expressed in primitive streak and 270 other cell types or tissues.
DR   ExpressionAtlas; P43247; baseline and differential.
DR   GO; GO:0005694; C:chromosome; ISS:UniProtKB.
DR   GO; GO:0032301; C:MutSalpha complex; IDA:MGI.
DR   GO; GO:0032302; C:MutSbeta complex; ISO:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; ISO:GO_Central.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0043531; F:ADP binding; IEA:Ensembl.
DR   GO; GO:0005524; F:ATP binding; IEA:Ensembl.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IMP:MGI.
DR   GO; GO:0008094; F:ATP-dependent activity, acting on DNA; ISO:GO_Central.
DR   GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR   GO; GO:0019237; F:centromeric DNA binding; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; ISO:GO_Central.
DR   GO; GO:0003684; F:damaged DNA binding; IMP:MGI.
DR   GO; GO:0032181; F:dinucleotide repeat insertion binding; IEA:Ensembl.
DR   GO; GO:0003677; F:DNA binding; IMP:MGI.
DR   GO; GO:0008047; F:enzyme activator activity; ISO:GO_Central.
DR   GO; GO:0000400; F:four-way junction DNA binding; IEA:Ensembl.
DR   GO; GO:0032137; F:guanine/thymine mispair binding; ISO:MGI.
DR   GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl.
DR   GO; GO:0030983; F:mismatched DNA binding; IMP:MGI.
DR   GO; GO:0032405; F:MutLalpha complex binding; IEA:Ensembl.
DR   GO; GO:0032357; F:oxidized purine DNA binding; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; ISO:GO_Central.
DR   GO; GO:0032142; F:single guanine insertion binding; IEA:Ensembl.
DR   GO; GO:0032143; F:single thymine insertion binding; IEA:Ensembl.
DR   GO; GO:0003697; F:single-stranded DNA binding; IEA:Ensembl.
DR   GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR   GO; GO:0019724; P:B cell mediated immunity; IMP:MGI.
DR   GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR   GO; GO:0006974; P:DNA damage response; IMP:MGI.
DR   GO; GO:0006301; P:DNA damage tolerance; IMP:MGI.
DR   GO; GO:0006281; P:DNA repair; IMP:MGI.
DR   GO; GO:0006302; P:double-strand break repair; IMP:MGI.
DR   GO; GO:0007281; P:germ cell development; IMP:MGI.
DR   GO; GO:0001701; P:in utero embryonic development; IGI:MGI.
DR   GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR   GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IGI:MGI.
DR   GO; GO:0045190; P:isotype switching; IMP:MGI.
DR   GO; GO:0043570; P:maintenance of DNA repeat elements; ISO:GO_Central.
DR   GO; GO:0008584; P:male gonad development; IMP:MGI.
DR   GO; GO:0006298; P:mismatch repair; IDA:MGI.
DR   GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IGI:MGI.
DR   GO; GO:0006312; P:mitotic recombination; IBA:GO_Central.
DR   GO; GO:0045910; P:negative regulation of DNA recombination; IMP:MGI.
DR   GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR   GO; GO:0006119; P:oxidative phosphorylation; IMP:MGI.
DR   GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IMP:CAFA.
DR   GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IMP:CAFA.
DR   GO; GO:0051726; P:regulation of cell cycle; IMP:MGI.
DR   GO; GO:0010224; P:response to UV-B; IMP:MGI.
DR   GO; GO:0010165; P:response to X-ray; IMP:MGI.
DR   GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:MGI.
DR   GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; IMP:MGI.
DR   GO; GO:0002204; P:somatic recombination of immunoglobulin genes involved in immune response; IGI:MGI.
DR   CDD; cd03285; ABC_MSH2_euk; 1.
DR   FunFam; 1.10.1420.10:FF:000003; DNA mismatch repair protein; 1.
DR   FunFam; 1.10.1420.10:FF:000009; DNA mismatch repair protein; 1.
DR   FunFam; 3.30.420.110:FF:000002; DNA mismatch repair protein; 1.
DR   FunFam; 3.40.1170.10:FF:000003; DNA mismatch repair protein; 1.
DR   FunFam; 3.40.50.300:FF:000523; DNA mismatch repair protein; 1.
DR   Gene3D; 1.10.1420.10; -; 2.
DR   Gene3D; 3.40.1170.10; DNA repair protein MutS, domain I; 1.
DR   Gene3D; 3.30.420.110; MutS, connector domain; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR   InterPro; IPR011184; DNA_mismatch_repair_Msh2.
DR   InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N.
DR   InterPro; IPR000432; DNA_mismatch_repair_MutS_C.
DR   InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp.
DR   InterPro; IPR007696; DNA_mismatch_repair_MutS_core.
DR   InterPro; IPR016151; DNA_mismatch_repair_MutS_N.
DR   InterPro; IPR036187; DNA_mismatch_repair_MutS_sf.
DR   InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom.
DR   InterPro; IPR032642; Msh2_ATP-bd.
DR   InterPro; IPR045076; MutS.
DR   InterPro; IPR036678; MutS_con_dom_sf.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   NCBIfam; NF003810; PRK05399.1; 1.
DR   PANTHER; PTHR11361:SF35; DNA MISMATCH REPAIR PROTEIN MSH2; 1.
DR   PANTHER; PTHR11361; DNA MISMATCH REPAIR PROTEIN MUTS FAMILY MEMBER; 1.
DR   Pfam; PF01624; MutS_I; 1.
DR   Pfam; PF05188; MutS_II; 1.
DR   Pfam; PF05192; MutS_III; 1.
DR   Pfam; PF05190; MutS_IV; 1.
DR   Pfam; PF00488; MutS_V; 1.
DR   PIRSF; PIRSF005813; MSH2; 1.
DR   SMART; SM00534; MUTSac; 1.
DR   SMART; SM00533; MUTSd; 1.
DR   SUPFAM; SSF53150; DNA repair protein MutS, domain II; 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   Acetylation; ATP-binding; Cell cycle; Chromosome; DNA damage; DNA repair;
KW   DNA-binding; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CHAIN           2..935
FT                   /note="DNA mismatch repair protein Msh2"
FT                   /id="PRO_0000115184"
FT   REGION          601..671
FT                   /note="Interaction with EXO1"
FT                   /evidence="ECO:0000250"
FT   BINDING         669..676
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         2
FT                   /note="N-acetylalanine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   MOD_RES         567
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:23806337"
FT   MOD_RES         845
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   MOD_RES         847
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   MOD_RES         871
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   MOD_RES         892
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   MOD_RES         921
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CROSSLNK        845
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CROSSLNK        847
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CROSSLNK        871
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CROSSLNK        892
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0000250|UniProtKB:P43246"
FT   CONFLICT        733
FT                   /note="A -> S (in Ref. 2; AAA75027)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   935 AA;  104151 MW;  2111E9D5E3A8548A CRC64;
     MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA LLAAREVFKT
     QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNKAGNK ASKENEWYLA
     FKASPGNLSQ FEDILFGNND MSASVGVMGI KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE
     NDQFSNLEAL LIQIGPKECV LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD
     LNRLLKGKKG EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM
     KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL MDRNRIEERL
     NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPSVIQA
     LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE
     LREVMDGLEK KMQSTLINAA RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS
     TVDIQKNGVK FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
     HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF IPNDVHFEKD
     KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK
     GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISDYI ATKIGAFCMF
     ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV
     IACAKQKALE LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS
     EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP
//