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P43247

- MSH2_MOUSE

UniProt

P43247 - MSH2_MOUSE

Protein

DNA mismatch repair protein Msh2

Gene

Msh2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
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    Functioni

    Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi669 – 6768ATPSequence Analysis

    GO - Molecular functioni

    1. ADP binding Source: Ensembl
    2. ATPase activity Source: MGI
    3. ATP binding Source: UniProtKB-KW
    4. centromeric DNA binding Source: MGI
    5. damaged DNA binding Source: MGI
    6. dinucleotide repeat insertion binding Source: Ensembl
    7. DNA binding Source: UniProtKB
    8. DNA-dependent ATPase activity Source: RefGenome
    9. double-strand/single-strand DNA junction binding Source: RefGenome
    10. four-way junction DNA binding Source: RefGenome
    11. guanine/thymine mispair binding Source: MGI
    12. heteroduplex DNA loop binding Source: RefGenome
    13. magnesium ion binding Source: Ensembl
    14. mismatched DNA binding Source: MGI
    15. oxidized purine DNA binding Source: Ensembl
    16. single base insertion or deletion binding Source: RefGenome
    17. single guanine insertion binding Source: Ensembl
    18. single-stranded DNA binding Source: Ensembl
    19. single thymine insertion binding Source: Ensembl
    20. Y-form DNA binding Source: RefGenome

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. B cell differentiation Source: MGI
    3. B cell mediated immunity Source: MGI
    4. cell cycle arrest Source: MGI
    5. cellular response to DNA damage stimulus Source: MGI
    6. determination of adult lifespan Source: MGI
    7. DNA repair Source: MGI
    8. double-strand break repair Source: MGI
    9. germ cell development Source: MGI
    10. intra-S DNA damage checkpoint Source: MGI
    11. intrinsic apoptotic signaling pathway in response to DNA damage Source: MGI
    12. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: MGI
    13. in utero embryonic development Source: MGI
    14. isotype switching Source: MGI
    15. maintenance of DNA repeat elements Source: RefGenome
    16. male gonad development Source: MGI
    17. meiotic gene conversion Source: RefGenome
    18. meiotic mismatch repair Source: RefGenome
    19. mismatch repair Source: MGI
    20. negative regulation of DNA recombination Source: MGI
    21. negative regulation of neuron apoptotic process Source: MGI
    22. negative regulation of reciprocal meiotic recombination Source: RefGenome
    23. oxidative phosphorylation Source: MGI
    24. positive regulation of helicase activity Source: Ensembl
    25. postreplication repair Source: UniProtKB
    26. response to UV-B Source: MGI
    27. response to X-ray Source: MGI
    28. somatic hypermutation of immunoglobulin genes Source: MGI
    29. somatic recombination of immunoglobulin gene segments Source: MGI
    30. somatic recombination of immunoglobulin genes involved in immune response Source: MGI

    Keywords - Biological processi

    Cell cycle, DNA damage, DNA repair

    Keywords - Ligandi

    ATP-binding, DNA-binding, Nucleotide-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    DNA mismatch repair protein Msh2
    Alternative name(s):
    MutS protein homolog 2
    Gene namesi
    Name:Msh2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 17

    Organism-specific databases

    MGIiMGI:101816. Msh2.

    Subcellular locationi

    Nucleus Curated

    GO - Cellular componenti

    1. MutSalpha complex Source: MGI
    2. MutSbeta complex Source: RefGenome
    3. nuclear chromosome Source: RefGenome
    4. nucleus Source: MGI

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 935934DNA mismatch repair protein Msh2PRO_0000115184Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei567 – 5671N6-acetyllysine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP43247.
    PaxDbiP43247.
    PRIDEiP43247.

    PTM databases

    PhosphoSiteiP43247.

    Expressioni

    Gene expression databases

    ArrayExpressiP43247.
    BgeeiP43247.
    CleanExiMM_MSH2.
    GenevestigatoriP43247.

    Interactioni

    Subunit structurei

    Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases By similarity. Interacts with SMARCAD1 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi201525. 4 interactions.
    DIPiDIP-57027N.
    IntActiP43247. 1 interaction.
    STRINGi10090.ENSMUSP00000024967.

    Structurei

    3D structure databases

    ProteinModelPortaliP43247.
    SMRiP43247. Positions 1-930.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni601 – 67171Interaction with EXO1By similarityAdd
    BLAST

    Sequence similaritiesi

    Belongs to the DNA mismatch repair MutS family.Curated

    Phylogenomic databases

    eggNOGiCOG0249.
    HOGENOMiHOG000196498.
    HOVERGENiHBG006399.
    InParanoidiP43247.
    KOiK08735.
    OMAiLNKCRTP.
    OrthoDBiEOG76DTRW.
    PhylomeDBiP43247.
    TreeFamiTF351780.

    Family and domain databases

    Gene3Di3.30.420.110. 1 hit.
    3.40.50.300. 1 hit.
    InterProiIPR011184. DNA_mismatch_repair_MSH2.
    IPR007695. DNA_mismatch_repair_MutS-lik_N.
    IPR000432. DNA_mismatch_repair_MutS_C.
    IPR007861. DNA_mismatch_repair_MutS_clamp.
    IPR007696. DNA_mismatch_repair_MutS_core.
    IPR007860. DNA_mmatch_repair_MutS_con_dom.
    IPR027417. P-loop_NTPase.
    [Graphical view]
    PfamiPF01624. MutS_I. 1 hit.
    PF05188. MutS_II. 1 hit.
    PF05192. MutS_III. 1 hit.
    PF05190. MutS_IV. 1 hit.
    PF00488. MutS_V. 1 hit.
    [Graphical view]
    PIRSFiPIRSF005813. MSH2. 1 hit.
    SMARTiSM00534. MUTSac. 1 hit.
    SM00533. MUTSd. 1 hit.
    [Graphical view]
    SUPFAMiSSF48334. SSF48334. 1 hit.
    SSF52540. SSF52540. 1 hit.
    SSF53150. SSF53150. 2 hits.
    PROSITEiPS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P43247-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA    50
    LLAAREVFKT QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV 100
    EVYKNKAGNK ASKENEWYLA FKASPGNLSQ FEDILFGNND MSASVGVMGI 150
    KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE NDQFSNLEAL LIQIGPKECV 200
    LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD LNRLLKGKKG 250
    EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM 300
    KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL 350
    MDRNRIEERL NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN 400
    LQDCYRLYQG INQLPSVIQA LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF 450
    QEMIETTLDM DQVENHEFLV KPSFDPNLSE LREVMDGLEK KMQSTLINAA 500
    RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK 550
    FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 600
    HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF 650
    IPNDVHFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA 700
    EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL 750
    GRGTSTYDGF GLAWAISDYI ATKIGAFCMF ATHFHELTAL ANQIPTVNNL 800
    HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV IACAKQKALE 850
    LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS 900
    EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP 935
    Length:935
    Mass (Da):104,151
    Last modified:November 1, 1995 - v1
    Checksum:i2111E9D5E3A8548A
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti733 – 7331A → S in AAA75027. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X81143 mRNA. Translation: CAA57049.1.
    U21011 mRNA. Translation: AAA75027.1.
    BC047117 mRNA. Translation: AAH47117.1.
    CCDSiCCDS29019.1.
    PIRiS53608.
    RefSeqiNP_032654.1. NM_008628.2.
    UniGeneiMm.4619.

    Genome annotation databases

    EnsembliENSMUST00000024967; ENSMUSP00000024967; ENSMUSG00000024151.
    GeneIDi17685.
    KEGGimmu:17685.
    UCSCiuc008dva.1. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X81143 mRNA. Translation: CAA57049.1 .
    U21011 mRNA. Translation: AAA75027.1 .
    BC047117 mRNA. Translation: AAH47117.1 .
    CCDSi CCDS29019.1.
    PIRi S53608.
    RefSeqi NP_032654.1. NM_008628.2.
    UniGenei Mm.4619.

    3D structure databases

    ProteinModelPortali P43247.
    SMRi P43247. Positions 1-930.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201525. 4 interactions.
    DIPi DIP-57027N.
    IntActi P43247. 1 interaction.
    STRINGi 10090.ENSMUSP00000024967.

    PTM databases

    PhosphoSitei P43247.

    Proteomic databases

    MaxQBi P43247.
    PaxDbi P43247.
    PRIDEi P43247.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000024967 ; ENSMUSP00000024967 ; ENSMUSG00000024151 .
    GeneIDi 17685.
    KEGGi mmu:17685.
    UCSCi uc008dva.1. mouse.

    Organism-specific databases

    CTDi 4436.
    MGIi MGI:101816. Msh2.

    Phylogenomic databases

    eggNOGi COG0249.
    HOGENOMi HOG000196498.
    HOVERGENi HBG006399.
    InParanoidi P43247.
    KOi K08735.
    OMAi LNKCRTP.
    OrthoDBi EOG76DTRW.
    PhylomeDBi P43247.
    TreeFami TF351780.

    Miscellaneous databases

    NextBioi 292252.
    PROi P43247.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P43247.
    Bgeei P43247.
    CleanExi MM_MSH2.
    Genevestigatori P43247.

    Family and domain databases

    Gene3Di 3.30.420.110. 1 hit.
    3.40.50.300. 1 hit.
    InterProi IPR011184. DNA_mismatch_repair_MSH2.
    IPR007695. DNA_mismatch_repair_MutS-lik_N.
    IPR000432. DNA_mismatch_repair_MutS_C.
    IPR007861. DNA_mismatch_repair_MutS_clamp.
    IPR007696. DNA_mismatch_repair_MutS_core.
    IPR007860. DNA_mmatch_repair_MutS_con_dom.
    IPR027417. P-loop_NTPase.
    [Graphical view ]
    Pfami PF01624. MutS_I. 1 hit.
    PF05188. MutS_II. 1 hit.
    PF05192. MutS_III. 1 hit.
    PF05190. MutS_IV. 1 hit.
    PF00488. MutS_V. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF005813. MSH2. 1 hit.
    SMARTi SM00534. MUTSac. 1 hit.
    SM00533. MUTSd. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48334. SSF48334. 1 hit.
    SSF52540. SSF52540. 1 hit.
    SSF53150. SSF53150. 2 hits.
    PROSITEi PS00486. DNA_MISMATCH_REPAIR_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning and expression of the Xenopus and mouse Msh2 DNA mismatch repair genes."
      Varlet I., Pallard C., Radman M., Moreau J., de Wind N.
      Nucleic Acids Res. 22:5723-5728(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
    2. "Mouse MutS homolog 2 (mMSH2) c-DNA sequence from -56."
      Lipford J.R., Kane M.F., Kolodner R.D.
      Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    4. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-567, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiMSH2_MOUSE
    AccessioniPrimary (citable) accession number: P43247
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 120 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3