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    MSH2 mutS homolog 2 [ Homo sapiens (human) ]

    Gene ID: 4436, updated on 25-May-2017
    Official Symbol
    MSH2provided by HGNC
    Official Full Name
    mutS homolog 2provided by HGNC
    Primary source
    HGNC:HGNC:7325
    See related
    Ensembl:ENSG00000095002 MIM:609309; Vega:OTTHUMG00000128861
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    FCC1; COCA1; HNPCC; LCFS2; HNPCC1
    Summary
    This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
    Orthologs
    Location:
    2p21-p16.3
    Exon count:
    21
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (47403067..47634501)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (47630206..47739716)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene RNA, 7SK small nuclear pseudogene 119 Neighboring gene epithelial cell adhesion molecule Neighboring gene microRNA 559 Neighboring gene uncharacterized LOC644093 Neighboring gene potassium two pore domain channel subfamily K member 12 Neighboring gene NME/NM23 nucleoside diphosphate kinase 2 pseudogene Neighboring gene ribosomal protein L18a pseudogene 6 Neighboring gene uncharacterized LOC440864

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in MSH2 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    Lynch syndrome I
    MedGen: C2936783 OMIM: 120435 GeneReviews: Lynch Syndrome
    Compare labs
    Muir-Torre syndrome
    MedGen: C1321489 OMIM: 158320 GeneReviews: Lynch Syndrome
    Compare labs
    Turcot syndrome
    MedGen: C0265325 OMIM: 276300 GeneReviews: Lynch Syndrome
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2015-07-09)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2015-07-09)

    ClinGen Genome Curation PagePubMed

    Protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with mutS homolog 2, colon cancer, nonpolyposis type 1 (MSH2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

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    • Colorectal cancer, conserved biosystem (from KEGG)
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      DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
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      Direct p53 effectors, organism-specific biosystem
      Direct p53 effectors
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    • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
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    • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
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    • Mismatch Repair, organism-specific biosystem (from REACTOME)
      Mismatch Repair, organism-specific biosystemThe mismatch repair (MMR) system corrects single base mismatches and small insertion and deletion loops (IDLs) of unpaired bases. MMR is primarily associated with DNA replication and is highly conser...
    • Mismatch repair, organism-specific biosystem (from KEGG)
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    • Mismatch repair, organism-specific biosystem (from WikiPathways)
      Mismatch repair, organism-specific biosystemDNA mismatch repair is a system for recognizing and repairing erroneous insertion, deletion and mis-incorporation of bases that can arise during DNA replication and recombination, as well as repairin...
    • Mismatch repair, conserved biosystem (from KEGG)
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    • Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta), organism-specific biosystem (from REACTOME)
      Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta), organism-specific biosystemMSH2:MSH3 (MutSbeta) binds unpaired loops of 2 or more nucleotides (Palombo et al. 1996, Genschel et al. 1998). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta) and an imbala...
    • Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha), organism-specific biosystem (from REACTOME)
      Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha), organism-specific biosystemMSH2:MSH6 (MutSalpha) binds single base mismatches and unpaired loops of 1-2 nucleotides (reviewed in Edelbrock et al. 2013). Human cells contain about 6-fold more MSH2:MSH6 than MSH2:MSH3 (MutSbeta)...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Platinum drug resistance, organism-specific biosystem (from KEGG)
      Platinum drug resistance, organism-specific biosystemPlatinum-based drugs cisplatin, carboplatin and oxaliplatin are widely used in the therapy of solid malignancies, including testicular, ovarian, head and neck, colorectal, bladder and lung cancers. T...
    • Platinum drug resistance, conserved biosystem (from KEGG)
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    • Rac1/Pak1/p38/MMP-2 pathway, organism-specific biosystem (from WikiPathways)
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    • TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystem (from REACTOME)
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    • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to ADP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to ATPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to MutLalpha complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    centromeric DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    contributes_to dinucleotide insertion or deletion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to dinucleotide repeat insertion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to four-way junction DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to guanine/thymine mispair binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    guanine/thymine mispair binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    contributes_to magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to mismatched DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to oxidized purine DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein C-terminus binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to single guanine insertion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to single thymine insertion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to single-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    B cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    B cell mediated immunity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    DNA repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell cycle arrest IEA
    Inferred from Electronic Annotation
    more info
     
    determination of adult lifespan IEA
    Inferred from Electronic Annotation
    more info
     
    double-strand break repair IEA
    Inferred from Electronic Annotation
    more info
     
    germ cell development IEA
    Inferred from Electronic Annotation
    more info
     
    in utero embryonic development IEA
    Inferred from Electronic Annotation
    more info
     
    intra-S DNA damage checkpoint IEA
    Inferred from Electronic Annotation
    more info
     
    intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IEA
    Inferred from Electronic Annotation
    more info
     
    isotype switching ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    maintenance of DNA repeat elements IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    male gonad development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    mismatch repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mismatch repair IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    mismatch repair TAS
    Traceable Author Statement
    more info
     
    negative regulation of DNA recombination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of DNA recombination ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of neuron apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    oxidative phosphorylation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of helicase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of isotype switching to IgA isotypes IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of isotype switching to IgG isotypes IEA
    Inferred from Electronic Annotation
    more info
     
    postreplication repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to UV-B ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    response to X-ray ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    somatic hypermutation of immunoglobulin genes IEA
    Inferred from Electronic Annotation
    more info
     
    somatic recombination of immunoglobulin gene segments ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    MutSalpha complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MutSbeta complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nuclear chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    DNA mismatch repair protein Msh2
    Names
    hMSH2
    mutS homolog 2, colon cancer, nonpolyposis type 1

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007110.2 RefSeqGene

      Range
      4944..85105
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_218

    mRNA and Protein(s)

    1. NM_000251.2NP_000242.1  DNA mismatch repair protein Msh2 isoform 1

      See identical proteins and their annotated locations for NP_000242.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AK304496, CB250419, DC342099, U04045
      Consensus CDS
      CCDS1834.1
      UniProtKB/Swiss-Prot
      P43246
      Related
      ENSP00000233146.2, OTTHUMP00000159084, ENST00000233146.6, OTTHUMT00000250805
      Conserved Domains (6) summary
      cd03285
      Location:633852
      ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog
      COG0249
      Location:23853
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:18132
      MutS_I; MutS domain I
      pfam05188
      Location:158284
      MutS_II; MutS domain II
      pfam05190
      Location:473569
      MutS_IV; MutS family domain IV
      pfam05192
      Location:305423
      MutS_III; MutS domain III
    2. NM_001258281.1NP_001245210.1  DNA mismatch repair protein Msh2 isoform 2

      See identical proteins and their annotated locations for NP_001245210.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate segment of the first exon, including the translation start site, compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.
      Source sequence(s)
      AK304496, CB250419, DC342099
      Consensus CDS
      CCDS58709.1
      UniProtKB/Swiss-Prot
      P43246
      Related
      ENSP00000442697.1, ENST00000543555.5
      Conserved Domains (6) summary
      cd03285
      Location:567786
      ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog
      smart00533
      Location:257579
      MUTSd; DNA-binding domain of DNA mismatch repair MUTS family
      pfam01624
      Location:566
      MutS_I; MutS domain I
      pfam05188
      Location:92218
      MutS_II; MutS domain II
      pfam05190
      Location:407503
      MutS_IV; MutS family domain IV
      pfam05192
      Location:239357
      MutS_III; MutS domain III

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

      Range
      47403067..47634501
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011532867.1XP_011531169.1  DNA mismatch repair protein Msh2 isoform X2

      See identical proteins and their annotated locations for XP_011531169.1

      Conserved Domains (6) summary
      cd03285
      Location:633852
      ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog
      COG0249
      Location:23853
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:18132
      MutS_I; MutS domain I
      pfam05188
      Location:158284
      MutS_II; MutS domain II
      pfam05190
      Location:473569
      MutS_IV; MutS family domain IV
      pfam05192
      Location:305423
      MutS_III; MutS domain III
    2. XM_005264332.3XP_005264389.2  DNA mismatch repair protein Msh2 isoform X1

      Conserved Domains (6) summary
      cd03285
      Location:633852
      ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog
      COG0249
      Location:23853
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:18132
      MutS_I; MutS domain I
      pfam05188
      Location:158284
      MutS_II; MutS domain II
      pfam05190
      Location:473569
      MutS_IV; MutS family domain IV
      pfam05192
      Location:305423
      MutS_III; MutS domain III

    RNA

    1. XR_001738747.1 RNA Sequence

    2. XR_939685.1 RNA Sequence

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      47560266..47640762
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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