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MSH2 Gene

protein-coding   GIFtS: 73
GCID: GC02P047630

MutS Homolog 2

(Previous names: mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type...)
(Previous symbol: COCA1)
  See MSH2-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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This gene clusters with an RNA gene
Subcategory (RNA class): antisense

Quality score for the ORGUL clustered with this gene is 3

Aliases
MutS Homolog 21 2     MutS Homolog 2, Colon Cancer, Nonpolyposis Type 1 (E. Coli)1
COCA11 2 5     HNPCC2
hMSH22 3     LCFS22
FCC12 5     DNA Mismatch Repair Protein Msh22
HNPCC12 5     MutS Homolog 2, Colon Cancer, Nonpolyposis Type 12
MutS (E. Coli) Homolog 2 (Colon Cancer, Nonpolyposis Type 1)1     MutS Protein Homolog 23

External Ids:    HGNC: 73251   Entrez Gene: 44362   Ensembl: ENSG000000950027   OMIM: 6093095   UniProtKB: P432463   
ORGUL members:         

Export aliases for MSH2 gene to outside databases

Previous GC identifers: GC02P047648 GC02P047798 GC02P047604 GC02P047541 GC02P047367


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for MSH2 Gene:
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)

GeneCards Summary for MSH2 Gene:
MSH2 (mutS homolog 2) is a protein-coding gene. Diseases associated with MSH2 include msh2-related muir-torre syndrome, and msh2-related turcot syndrome. GO annotations related to this gene include enzyme binding and protein homodimerization activity.

UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246
Function: 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

Gene Wiki entry for MSH2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NT_022184.16  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the MSH2 gene promoter:
         AREB6   GATA-3   AP-1   ATF-2   c-Jun   NF-Y   CBF(2)   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidMSH2 promoter sequence
   Search Chromatin IP Primers for MSH2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat MSH2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p21   Ensembl cytogenetic band:  2p21   HGNC cytogenetic band: 2p21

MSH2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
MSH2 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02P047630:  view genomic region     (about GC identifiers)

Start:
47,630,108 bp from pter      End:
47,789,450 bp from pter
Size:
159,343 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246 (See protein sequence)
Recommended Name: DNA mismatch repair protein Msh2  
Size: 934 amino acids; 104743 Da
Subunit: 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. Interacts with SMARCAD1
Sequence caution: Sequence=AAC27930.1; Type=Frameshift; Positions=417; Note=The frameshift is caused by a single
nucleotide deletion which is found in a HNPCC kindred;
Selected PDB 3D structures from and Proteopedia for MSH2 (see all 9):
2O8B (3D)        2O8C (3D)        2O8D (3D)        2O8E (3D)        2O8F (3D)        3THW (3D)    
Secondary accessions: B4E2Z2 O75488
Alternative splicing: 2 isoforms:  P43246-1   P43246-2   

Explore the universe of human proteins at neXtProt for MSH2: NX_P43246

Explore proteomics data for MSH2 at MOPED

Post-translational modifications: 

  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway1
  • Ubiquitination2 at Lys73, Lys882
  • Modification sites at PhosphoSitePlus

  • See MSH2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_000242.1  NP_001245210.1  

    ENSEMBL proteins: 
     ENSP00000233146   ENSP00000411482   ENSP00000384199   ENSP00000442697  

    MSH2 Human Recombinant Protein Products:

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    Novus Biologicals MSH2 Proteins
    Novus Biologicals MSH2 Lysates
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    Cloud-Clone Corp. Proteins for MSH2

     
    Search eBioscience for Proteins for MSH2 

    MSH2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of MSH2
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    MSH2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Cloud-Clone Corp. ELISAs for MSH2
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    Search eBioscience for ELISAs for MSH2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 7):
     IPR007861 DNA_mismatch_repair_MutS_clamp
     IPR007696 DNA_mismatch_repair_MutS_core
     IPR007695 DNA_mismatch_repair_MutS-lik_N
     IPR011184 DNA_mismatch_repair_MSH2
     IPR007860 DNA_mmatch_repair_MutS_con_dom

    Graphical View of Domain Structure for InterPro Entry P43246

    ProtoNet protein and cluster: P43246

    1 Blocks protein domain: IPB007696 MutS III

    UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246
    Similarity: Belongs to the DNA mismatch repair MutS family


    Find genes that share domains with MSH2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: MSH2_HUMAN, P43246
    Function: 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

         Genatlas biochemistry entry for MSH2:
    yeast mutator gene homolog (bacterial mutS),several spliced isoforms,complexing with GTBP (MUTS alpha
    heterodimer),also interacting with HEX1,involved in mismatch repair of displaced loops of 2 to 4 bases,deleted in
    sporadic colorectal cancer and in hepatocellular carcinoma with poor prognosis

         Gene Ontology (GO): Selected molecular function terms (see all 27):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000287contributes to magnesium ion binding IDA16403449
    GO:0000400contributes to four-way junction DNA binding IDA12034830
    GO:0000403Y-form DNA binding IBA--
    GO:0000404loop DNA binding IBA--
    GO:0000406double-strand/single-strand DNA junction binding IBA--
         
    Find genes that share ontologies with MSH2           About GenesLikeMe


    Phenotypes:
         5 GenomeRNAi human phenotypes for MSH2:
     Decreased Salmonella enterica   Decreased Salmonella enterica   Decreased Salmonella-containin  Increased cell death in breast 
     Upregulation of Wnt/beta-caten 

         9 MGI mutant phenotypes (inferred from 10 alleles(MGI details for Msh2):
     cellular  digestive/alimentary  hematopoietic system  homeostasis/metabolism  immune system 
     integument  mortality/aging  nervous system  tumorigenesis 

    Find genes that share phenotypes with MSH2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for MSH2: Msh2tm1Htr Msh2tm2.2Rak Msh2tm1Rak Msh2tm1Tts Msh2tm1Whl Msh2tm1Mak

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for MSH2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for MSH2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for MSH2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for MSH2

    miRNA
    Products:
        
    miRTarBase miRNAs that target MSH2:
    hsa-mir-15a-5p (MIRT000880), hsa-mir-101-3p (MIRT027251), hsa-mir-21-5p (MIRT005429), hsa-mir-1 (MIRT023691), hsa-mir-16-5p (MIRT000879), hsa-mir-183-5p (MIRT047085), hsa-mir-155-5p (MIRT000460)

    Block miRNA regulation of human, mouse, rat MSH2 using miScript Target Protectors
    3 qRT-PCR Assays for microRNAs that regulate MSH2:
    hsa-miR-3163 hsa-miR-590-5p hsa-miR-21
    SwitchGear 3'UTR luciferase reporter plasmidMSH2 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for MSH2
    Predesigned siRNA for gene silencing in human, mouse, rat MSH2

    Gene Editing
    Products:
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    Clone
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    OriGene clones in human, mouse for MSH2 (see all 7)
    OriGene ORF clones in mouse, rat for MSH2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: MSH2 (NM_000251)
    Sino Biological Human cDNA Clone for MSH2
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MSH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH2
    Addgene plasmids for MSH2 

    Cell Line
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    In Situ Assay
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for MSH2


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    MSH2_HUMAN, P43246: Nucleus (Potential)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    nucleus4
    mitochondrion2

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000228nuclear chromosome IBA--
    GO:0005634nucleus ----
    GO:0032301MutSalpha complex IDA--
    GO:0032302MutSbeta complex IDA8942985

    Find genes that share ontologies with MSH2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for MSH2 About   (see all 13)  
    See pathways by source

    SuperPathContained pathways About
    1Telomere C-strand (Lagging Strand) Synthesis
    Mismatch repair0.56
    Mismatch repair0.00
    Mismatch Repair in Eukaryotes0.54
    2Prostate Cancer
    Prostate Cancer0.32
    Integrated Cancer pathway0.32
    3Cell Cycle / Checkpoint Control
    Cell Cycle / Checkpoint Control0.32
    DNA Damage0.32
    4Doxorubicin Pathway, Pharmacokinetics
    Doxorubicin Pathway (Cancer Cell), Pharmacodynamics0.43
    5Endometrial cancer
    Colorectal cancer0.42


    Find genes that share SuperPaths with MSH2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    4 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for MSH2
        Mismatch Repair in Eukaryotes
    BRCA1 Pathway
    DNA Repair Mechanisms
    Colorectal Cancer Metastasis

    2 Cell Signaling Technology (CST) Pathways for MSH2
        Cell Cycle / Checkpoint Control
    DNA Damage

    1 GeneGo (Thomson Reuters) Pathway for MSH2
        DNA damage Role of Brca1 and Brca2 in DNA repair

    5 BioSystems Pathways for MSH2
        Mismatch repair
    Integrated Breast Cancer Pathway
    Prostate Cancer
    Direct p53 effectors
    Integrated Cancer pathway


    2 PharmGKB Pathways for MSH2
        Busulfan Pathway, Pharmacodynamics
    Doxorubicin Pathway (Cancer Cell), Pharmacodynamics

    3 Kegg Pathways  (Kegg details for MSH2):
        Mismatch repair
    Pathways in cancer
    Colorectal cancer

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MSH2 (see all 8): 
              DNA Damage Signaling Pathway in human mouse rat
              Liver Cancer in human mouse rat
              Cell Cycle in human mouse rat
              Telomeres & Telomerase in human mouse rat
              p53 Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for MSH2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for MSH2 (P432461, 2, 3 ENSP000002331464) via UniProtKB, MINT, STRING, and/or I2D (see all 1002)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    SMN1Q166372, 3MINT-7945693 MINT-8271333 MINT-7947479 I2D: score=2 
    SMN2Q166372, 3MINT-7945693 MINT-8271333 MINT-7947479 I2D: score=2 
    NBNO609342, 3, ENSP000002654334MINT-7945693 MINT-7947479 I2D: score=1 STRING: ENSP00000265433
    SNW1Q135732, 3, ENSP000002615314MINT-7945693 MINT-7947479 I2D: score=1 STRING: ENSP00000261531
    MLH1P406922, 3, ENSP000002317904MINT-7945693 I2D: score=5 STRING: ENSP00000231790
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 31):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000710meiotic mismatch repair IBA--
    GO:0001701in utero embryonic development IEA--
    GO:0002204somatic recombination of immunoglobulin genes involved in immune response ----
    GO:0006119oxidative phosphorylation IEA--
    GO:0006200ATP catabolic process IDA16403449

    Find genes that share ontologies with MSH2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for MSH2

    Selected Novoseek inferred chemical compound relationships for MSH2 gene (see all 22)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    crcs 77.9 6 8137274 (1), 11208710 (1), 20388775 (1), 15887099 (1) (see all 5)
    mononucleotide 76.4 6 17504984 (2), 14871813 (1), 10918391 (1), 9674699 (1) (see all 5)
    o6-methylguanine 55 4 10954713 (2), 19047896 (1), 18670349 (1)
    6 thioguanine 35.8 3 17616687 (1), 17426439 (1)
    temozolomide 29.2 3 11138465 (1), 19741564 (1), 19127257 (1)
    mnng 25.9 4 14657349 (2), 16085492 (1), 15647386 (1)
    n-methyl-n'-nitrosourea 25.8 1 10954713 (1)
    paraffin 10.8 2 11376026 (1), 12400605 (1)
    cisplatin 7.78 11 16690105 (2), 15044851 (2), 19484784 (2), 14706347 (2) (see all 5)
    serine 4.64 2 14576825 (1), 17165155 (1)



    Find genes that share compounds with MSH2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for MSH2 gene (2 alternative transcripts): 
    NM_000251.2  NM_001258281.1  

    Unigene Cluster for MSH2:

    MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
    Hs.597656  [show with all ESTs]
    Unigene Representative Sequence: NM_000251
    6 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000233146(uc010fbf.1 uc002rvy.1) ENST00000454849 ENST00000406134(uc002rvz.3)
    ENST00000461394 ENST00000467323 ENST00000543555(uc010fbh.1 uc010fbi.1 uc010yoh.1 uc010fbg.2)

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    SwitchGear 3'UTR luciferase reporter plasmidMSH2 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector: MSH2 (NM_000251)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MSH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH2
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      QuantiFast Probe-based Assays in human, mouse, rat MSH2

    Additional mRNA sequence: 

    AK222860.1 AK296831.1 AK297763.1 AK299667.1 AK304496.1 AK310679.1 AK311330.1 BC001122.1 
    BC012599.1 BC021566.1 BX649122.1 DQ648894.1 DQ648895.1 DQ648896.1 DQ648897.1 L47574.1 
    L47575.1 L47576.1 L47577.1 L47578.1 L47579.1 L47580.1 L47581.1 L47582.1 
    L47583.1 U03911.1 U04045.1 

    9 DOTS entries:

    DT.416491  DT.100807952  DT.100807950  DT.92436431  DT.102824275  DT.120985251  DT.206918  DT.416492 
    DT.95135588 

    Selected AceView cDNA sequences (see all 204):

    AU154692 L47583 AU133333 BM784479 AU133361 CN483366 BM475467 AA502616 
    AU125592 BQ422633 BQ322983 BC001122 L47576 AU118136 CD655479 L47582 
    BQ225922 U04045 AA679697 AW576363 F02380 AA286682 BP349795 U03911 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    MSH2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TAGTTTGTGG
    MSH2 Expression
    About this image


    MSH2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 6) fully expand
     
     Brain (Nervous System)    fully expand to see all 4 entries
             Cerebral Cortex
     
     Inner Cell Mass (Early Embryonic Tissues)    fully expand to see all 2 entries
             Human embryonic stem cells (family)
     
     Trophoblast (Extraembryonic Tissues)
             Trophoblast Cells Trophoblast
     
     Pancreas (Endocrine System)
             Islets of Langerhans
     
     Ovary (Reproductive System)
             Ovarian Mesenchymal Stroma Cells Ovary Interstitium
    MSH2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    MSH2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.597656

    UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246
    Tissue specificity: Ubiquitously expressed

        Pathway & Disease-focused RT2 Profiler PCR Arrays including MSH2 (see all 8): 
              DNA Damage Signaling Pathway in human mouse rat
              Liver Cancer in human mouse rat
              Cell Cycle in human mouse rat
              Telomeres & Telomerase in human mouse rat
              p53 Signaling Pathway in human mouse rat

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of eukaryotes.

    Orthologs for MSH2 gene from Selected species (see all 25)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Msh21 , 5 mutS homolog 2 (E. coli)1, 5 86.97(n)1
    92.8(a)1
      17 (57.87 cM)5
    176851  NM_008628.21  NP_032654.11 
     876723305 
    chicken
    (Gallus gallus)
    Aves MSH21 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. more 76.41(n)
    81.84(a)
      378799  XM_426110.4  XP_426110.4 
    lizard
    (Anolis carolinensis)
    Reptilia MSH26
    mutS homolog 2
    70(a)
    1 ↔ 1
    1(254690159-254808123)
    African clawed frog
    (Xenopus laevis)
    Amphibia BX853729.12   -- 72.01(n)    BX853729.1 
    zebrafish
    (Danio rerio)
    Actinopterygii BC044370.12   -- 73.78(n)    BC044370.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta spel11 , 3 mismatch repair3
    spellchecker11
    43(a)3
    51.02(n)1
    45.97(a)1
      348421  NM_001259102.21  NP_001246031.11 
    worm
    (Caenorhabditis elegans)
    Secernentea msh-23 DNA mismatch repair protein 30(a)   I(3694373-3697537)   --
    baker's yeast
    (Saccharomyces cerevisiae)
    Saccharomycetes MSH2(YOL090W)4
    MSH21
    Protein that forms heterodimers with Msh3p and Msh6p more4
    MSH21
    53.54(n)1
    44.64(a)1
      15(147382-150276)4
    8540631, 4  NP_014551.11, 4 
    thale cress
    (Arabidopsis thaliana)
    eudicotyledons MSH21 MSH2 51.24(n)
    43.69(a)
      821383  NM_113607.3  NP_566804.3 
    barley
    (Hordeum vulgare)
    Liliopsida Hv.21992 Transcribed sequence with moderate similarity to protein more 80.28(n)    BF618221.3 


    ENSEMBL Gene Tree for MSH2 (if available)
    TreeFam Gene Tree for MSH2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for MSH2 gene
    2 SIMAP similar genes for MSH2 using alignment to 18 protein entries:     MSH2_HUMAN (see all proteins):
    MSH6    DKFZp434C1615

    Find genes that share paralogs with MSH2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for MSH2 (see all 3130)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs339462611,2,,4
    CHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 untested147497573(+) GCGCAC/GGGCGA 3 H Q mis1 int12Minor allele frequency- G:0.00NA EU 1733
    rs172177721,2,,4
    C,F,HHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 probable-non-pathogenic147504350(+) TGGCAA/GTCTCT 4 N S mis115Minor allele frequency- G:0.04NS NA CSA WA 6284
    rs637501241,2,,4
    C,FHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 untested147504405(+) TCCATT/GGGTGT 4 /M /I mis11Minor allele frequency- G:0.00NA 4552
    rs289294831,2,,4
    CHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 pathogenic147569733(+) ACGACC/TAGCCA 4 P L mis1 ese30--------
    rs289294841,2,,4
    CHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 pathogenic147569783(+) CCAGGC/TATGCT 4 H Y mis10--------
    rs637507901,2,,4
    CHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 untested147571028(+) CTCATA/GGCCCA 4 I M mis10--------
    rs637505711,2,,4
    CHereditary non-polyposis colorectal cancer 1 (HNPCC1)4 untested147575373(+) GTGCTA/GAACAG 4 K E mis10--------
    VAR_0437474
    Hereditary non-polyposis colorectal cancer 1 (HNPCC1)4--see VAR_0437472 G R mis40--------
    VAR_0437624
    Colorectal cancer4--see VAR_0437622 V I mis40--------
    VAR_0044744
    Hereditary non-polyposis colorectal cancer 1 (HNPCC1)4--see VAR_0044742 D H mis40--------

    HapMap Linkage Disequilibrium report for MSH2 (47630108 - 47789450 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 7 variations for MSH2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv995811CNV Deletion20482838
    esv2291090CNV Deletion18987734
    esv2720025CNV Deletion23290073
    esv1070809CNV Deletion17803354
    esv2720024CNV Deletion23290073
    esv3890CNV Deletion18987735
    nsv527823CNV Gain19592680

    Human Gene Mutation Database (HGMD): MSH2
    Locus Specific Mutation Databases (LSDB): MSH2

    3 Site Specific Mutation Identification with PCR Assays for MSH2:
    Cosmic IdAA Change
    26860p.R711*
    27628p.R680*
    26122p.L787fs*11
    SeqTarget long-range PCR primers for resequencing MSH2
    DNA2.0 Custom Variant and Variant Library Synthesis for MSH2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 609309   
    OMIM disorders: 120435  158320  276300  
    UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246
  • Hereditary non-polyposis colorectal cancer 1 (HNPCC1) [MIM:120435]: An autosomal dominant disease
    associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to
    early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female
    reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western
    world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary
    predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II
    is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach,
    small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the
    Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other
    two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of
    hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families
    who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is
    strongly suspected. Note=The disease is caused by mutations affecting the gene represented in this entry
  • Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous
    neoplasms and visceral malignancy. Note=The disease is caused by mutations affecting the gene represented in this
    entry
  • Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus.
    Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other
    fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry

  • 18 diseases for MSH2:    
    About MalaCards
    msh2-related muir-torre syndrome    msh2-related turcot syndrome    colorectal cancer, hereditary nonpolyposis, type 1    msh2-related lynch syndrome
    muir-torre syndrome    colorectal cancer 1    sebaceous adenoma    anal fistula
    cerebral primitive neuroectodermal tumor    lynch syndrome    turcot syndrome    in situ carcinoma
    keratoacanthoma    attenuated familial adenomatous polyposis    colon cancer    familial adenomatous polyposis
    vipoma    colorectal cancer

    8 diseases from the University of Copenhagen DISEASES database for MSH2:
    Lynch syndrome     Colorectal cancer     Endometrial cancer     Carcinoma
    Familial adenomatous polyposis     Adenoma     Ovarian cancer     Sebaceous adenoma

    Find genes that share disorders with MSH2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for MSH2 gene (see all 77)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    lynch syndrome 96.6 103 20388775 (8), 19459153 (3), 18999873 (2), 19911012 (2) (see all 61)
    microsatellite instability 96.2 145 11601928 (4), 8993979 (3), 10190329 (2), 15945244 (2) (see all 99)
    colorectal cancer 92.2 573 16331552 (5), 15782118 (5), 8993979 (5), 15943554 (4) (see all 99)
    muir-torre syndrome 90.8 20 17051350 (2), 11231323 (2), 18270343 (2), 16826164 (1) (see all 16)
    hereditary nonpolyposis colon cancer 86.8 10 18999873 (1), 11409565 (1), 16237223 (1), 16395668 (1) (see all 10)
    endometrial cancer 83.7 47 16803540 (3), 16985024 (3), 17925543 (2), 9071575 (2) (see all 31)
    germ-line mutation 80.5 34 11093816 (3), 18331697 (3), 9709044 (2), 15872200 (2) (see all 24)
    colorectal carcinoma 75 27 9087566 (3), 15025965 (2), 19398597 (1), 11391585 (1) (see all 23)
    cancer 70.7 171 9841970 (5), 16106253 (5), 11600610 (4), 11376026 (3) (see all 99)
    colon cancer 69.6 26 8880570 (2), 15059910 (1), 15780936 (1), 15837969 (1) (see all 22)

    GeneTests: MSH2
    GeneReviews: MSH2
    Genetic Association Database (GAD): MSH2
    Human Genome Epidemiology (HuGE) Navigator: MSH2 (185 documents)

    Export disorders for MSH2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

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    PubMed articles for MSH2 gene, integrated from 10 sources (see all 1162):
    (articles sorted by number of sources associating them with MSH2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. BRAF screening as a low-cost effective strategy for simplifying HNPCC genetic testing. (PubMed id 15342696)1, 2, 4, 9 Domingo E.... Schwartz S. Jr. (J. Med. Genet. 2004)
    2. Genomic deletions in MSH2 or MLH1 are a frequent cause of hereditary non-polyposis colorectal cancer: identification of novel and recurrent deletions by MLPA. (PubMed id 14635101)1, 2, 4, 9 Taylor C.F.... Taylor G.R. (Hum. Mutat. 2003)
    3. Classification of ambiguous mutations in DNA mismatch repair genes identified in a population-based study of colorectal cancer. (PubMed id 18033691)1, 2, 4, 9 Barnetson R.A....Dunlop M.G. (Hum. Mutat. 2008)
    4. Sixteen rare sequence variants of the hMLH1 and hMSH2 genes found in a cohort of 254 suspected HNPCC (hereditary non-polyposis colorectal cancer) patients: mutations or polymorphisms? (PubMed id 11726306)1, 2, 4 Mueller-Koch Y.... Holinski-Feder E. (Eur. J. Med. Res. 2001)
    5. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. (PubMed id 8156592)1, 2, 4 Fishel R....Kolodner R. (Cell 1994)
    6. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. (PubMed id 8252616)1, 2, 4 Fishel R.... Kolodner R.D. (Cell 1993)
    7. Detection of mismatch repair gene germline mutation carrier among Chinese population with colorectal cancer. (PubMed id 18257912)1, 4, 9 Jin H.Y....Zhao R. (BMC Cancer 2008)
    8. The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers. (PubMed id 16106253)1, 4, 9 Lawes D.A....Boulos P.B. (Br. J. Cancer 2005)
    9. Efficient detection of hereditary nonpolyposis colorectal cancer gene carriers by screening for tumor microsatellite instability before germline genetic testing. (PubMed id 11208710)1, 4, 9 Terdiman J.P....Kim Y.S. (Gastroenterology 2001)
    10. Gene-related cancer spectrum in families with hereditary non-polyposis colorectal cancer (HNPCC). (PubMed id 17939062)1, 4, 9 Geary J....Hodgson S.V. (Fam. Cancer 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 4436 HGNC: 7325 AceView: MSH2 Ensembl:ENSG00000095002 euGenes: HUgn4436
    ECgene: MSH2 Kegg: 4436 H-InvDB: MSH2

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for MSH2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for MSH2 Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=MSH2[genesymbol]
    Hereditary non-polyposis colorectal cancer dbhttp://www.nfdht.nl/
    NIEHS-SNPshttp://egp.gs.washington.edu/data/msh2/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for MSH2 gene:
    Search GeneIP for patents involving MSH2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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