MSH2_MOUSE
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 03-AUG-2022, entry version 176.
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, Spleen, and
RC 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 -!- 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_008628.2.
DR AlphaFoldDB; P43247; -.
DR SMR; P43247; -.
DR BioGRID; 201525; 10.
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 IntAct; P43247; 4.
DR MINT; P43247; -.
DR STRING; 10090.ENSMUSP00000024967; -.
DR iPTMnet; P43247; -.
DR PhosphoSitePlus; P43247; -.
DR EPD; P43247; -.
DR PaxDb; P43247; -.
DR PeptideAtlas; P43247; -.
DR PRIDE; P43247; -.
DR ProteomicsDB; 290098; -.
DR Antibodypedia; 4037; 736 antibodies from 49 providers.
DR DNASU; 17685; -.
DR Ensembl; ENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
DR GeneID; 17685; -.
DR KEGG; mmu:17685; -.
DR UCSC; uc008dva.1; mouse.
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; LFRIYQV; -.
DR OrthoDB; 138168at2759; -.
DR PhylomeDB; P43247; -.
DR TreeFam; TF351780; -.
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 112 CRISPR screens.
DR ChiTaRS; Msh2; mouse.
DR PRO; PR:P43247; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P43247; protein.
DR Bgee; ENSMUSG00000024151; Expressed in primitive streak and 266 other tissues.
DR ExpressionAtlas; P43247; baseline and differential.
DR Genevisible; P43247; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0032301; C:MutSalpha complex; IDA:MGI.
DR GO; GO:0032302; C:MutSbeta complex; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0043531; F:ADP binding; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0016887; F:ATP hydrolysis activity; IMP:MGI.
DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; ISO:MGI.
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:MGI.
DR GO; GO:0003684; F:damaged DNA binding; IMP:MGI.
DR GO; GO:0032139; F:dinucleotide insertion or deletion binding; ISO:MGI.
DR GO; GO:0032181; F:dinucleotide repeat insertion binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IMP:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0000400; F:four-way junction DNA binding; ISO:MGI.
DR GO; GO:0032137; F:guanine/thymine mispair binding; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; ISO:MGI.
DR GO; GO:0030983; F:mismatched DNA binding; IMP:MGI.
DR GO; GO:0032405; F:MutLalpha complex binding; ISO:MGI.
DR GO; GO:0032357; F:oxidized purine DNA binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0032142; F:single guanine insertion binding; ISO:MGI.
DR GO; GO:0032143; F:single thymine insertion binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0019724; P:B cell mediated immunity; IMP:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0008340; P:determination of adult lifespan; 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:MGI.
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:0051096; P:positive regulation of helicase activity; ISO: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:0006301; P:postreplication repair; IMP:MGI.
DR GO; GO:0071168; P:protein localization to chromatin; ISO:MGI.
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 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 SUPFAM; SSF53150; SSF53150; 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; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome.
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 921
FT /note="Phosphoserine"
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
