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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

MSH2 Gene

protein-coding   GIFtS: 71
GCID: GC02P047630

mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)

(Previous names: mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type...)
(Previous symbol: COCA1)
 Explore 140 diseases affiliated with
MSH2 via
MalaCards
our new
 Human Malady Compendium 
Biological research products
for MSH2    

Aliases
for MSH2 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
MutS Homolog 2, Colon Cancer, Nonpolyposis Type 1 (E. Coli)1 2     FCC12 5
COCA11 2 5     MutS (E. Coli) Homolog 2 (Colon Cancer, Nonpolyposis Type 1)1
HNPCC11 2 5     LCFS22
HNPCC1 2     DNA Mismatch Repair Protein Msh22
HMSH21     MutS Protein Homolog 23

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

Export aliases for MSH2 gene to outside databases

Previous GC identifers: GC02P047648 GC02P047798 GC02P047604 GC02P047541 GC02P047367


Summaries
for MSH2 gene

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

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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NC_018913.1  NT_022184.15  
Regulatory elements:
   SABiosciences 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 plasmid: MSH2 promoter sequence
   Search SABiosciences Chromatin IP Primers for MSH2

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for MSH2 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: Nucleus (Potential)
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;
6/9 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

Post-translational modifications:

  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P43246

    • MSH2 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

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

    ENSEMBL proteins: 
     ENSP00000233146   ENSP00000411482   ENSP00000384199   ENSP00000442697  

    Human Recombinant Protein Products: 
    Browse Purified and Recombinant Proteins at EMD Millipore
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Protein: MSH2
    OriGene Protein Over-expression Lysate: MSH2
    OriGene Custom Protein Services for MSH2 
    GenScript Custom Purified and Recombinant Proteins Services for MSH2
    Novus Biologicals MSH2 Proteins
    Novus Biologicals MSH2 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for MSH2

    Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view):    About this table

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


    MSH2 for ontologies           About GeneDecksing



    MSH2 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of MSH2
    R&D Systems Antibodies for MSH2
    Cell Signaling Technology (CST) Antibodies for MSH2 
    OriGene Antibodies (see all 2): MSH2
    OriGene Custom Antibody Services for MSH2 
    GenScript Custom Superior Antibodies Services for MSH2
    Novus Biologicals MSH2 Antibodies
    Abcam antibodies for MSH2 
    Uscn Antibodies for MSH2
    ThermoFisher Antibody for MSH2

    Assay Products for MSH2: 
    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Immunoassay Development
    Browse OriGene Fluorogenic Cell Assay Kits
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for MSH2
    Browse Enzo Life Sciences for kits & assays
    Uscn ELISAs and CLIAs for MSH2

    Protein Domains /
    Families
    for MSH2 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    MSH2 for domains           About GeneDecksing

    5/6 InterPro domains/families (see all 6):
     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 family: IPB007696 MutS III

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


    Function
    for MSH2 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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

         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

    miRNA
    Products:            		miRTarBase miRNAs that target MSH2:
    hsa-mir-21 (MIRT005429), hsa-mir-155 (MIRT000460)

    OriGene 3'-UTR Clone: MSH2
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MSH2
    3 QIAGEN miScript miRNA Assays for microRNAs that regulate MSH2:
    hsa-miR-3163 hsa-miR-590-5p hsa-miR-21
    SwitchGear 3'UTR luciferase reporter plasmid: MSH2 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MSH2 (see all 7)
    OriGene shRNA RFP: MSH2
    OriGene siRNA: MSH2
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MSH2

    Gene Editing
    Products:    		DNA2.0 Custom Protein Engineering Service for MSH2

    Clone
    Products:             		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MSH2 (see all 3)
    OriGene untagged cDNA clones in CMV expression vector in human, 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)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MSH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH2 

    Cell Line
    Products:             		GenScript Custom overexpressing Cell Line Services for MSH2
    Search LifeMap BioReagents cell lines for MSH2

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

    Gene Ontology (GO): 5/27 molecular function terms (GO ID links to tree view) (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--


    MSH2 for ontologies           About GeneDecksing


    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 

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

    MSH2 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for MSH2 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/14 super-pathways (see all 14) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Lagging Strand Synthesis
    		Mismatch repair0.48
    		Mismatch repair0.17
    		Mismatch Repair in Eukaryotes0.33
    2Formation of RNA Pol II elongation complex
    		DNA damage_Role of Brca1 and Brca2 in DNA repair0.17
    		DNA damage Role of Brca1 and Brca2 in DNA repair0.17
    3DNA Damage
    		DNA Damage1.00
    4Cell Cycle / Checkpoint Control
    		Cell Cycle / Checkpoint Control1.00
    5Busulfan Pathway, Pharmacodynamics
    		Busulfan Pathway, Pharmacodynamics1.00

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    1 EMD Millipore Pathway for MSH2
        DNA damage Role of Brca1 and Brca2 in DNA repair

    4 Downloadable PowerPoint Slides of QIAGEN 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

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

    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


    MSH2 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for MSH2

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

    5/874 Interacting proteins for MSH2 (P432461, 2, 3 ENSP000002331464) via UniProtKB, MINT, STRING, and/or I2D (see all 874)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    MSH6P527011, 2, 3, ENSP000002344204EBI-355888,EBI-395529 MINT-7945693 MINT-7947479 I2D: score=12 STRING: ENSP00000234420
    SMN1Q166372, 3MINT-7945693 MINT-8271333 MINT-7947479 I2D: score=2 
    SMN2Q166372, 3MINT-7945693 MINT-8271333 MINT-7947479 I2D: score=2 
    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): 5/35 biological process terms (GO ID links to tree view) (see all 35):    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


    MSH2 for ontologies           About GeneDecksing



    Drugs & Compounds
    for MSH2 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    MSH2 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for MSH2
    10/22 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about MSH2 

    Transcripts
    for MSH2 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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)


    miRNA
    Products:             		 OriGene 3'-UTR Clone: MSH2
    Browse OriGene MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat MSH2
    3 QIAGEN miScript miRNA Assays for microRNAs that regulate MSH2:
    hsa-miR-3163 hsa-miR-590-5p hsa-miR-21
    SwitchGear 3'UTR luciferase reporter plasmid: MSH2 3' UTR sequence
    Inhib. RNA
    Products:             		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for MSH2 (see all 7)
    OriGene shRNA RFP: MSH2
    OriGene siRNA: MSH2
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat MSH2
    Clone
    Products:             		 OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for MSH2 (see all 3)
    OriGene untagged cDNA clones in CMV expression vector in human, 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)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for MSH2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat MSH2 
    Primer
    Products:            		 OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for MSH2
    Browse OriGene validated miRNA SYBR primer pairs
    SABiosciences RT2 qPCR Primer Assay in human, mouse, rat MSH2
      QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat MSH2
      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat MSH2

    Additional cDNA 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 

    24/204 AceView cDNA sequences (see all 204):

    BM763059 BM457765 AU131477 BP349795 F02380 L47582 BM784479 F04850 
    AU126323 L47581 CB250419 BM987298 AI792246 CB135120 AA286682 CN483366 
    BQ422633 BM796343 AU118136 AA502616 BM834569 BE671648 NM_000251 BQ322983 

    GeneLoc Exon Structure


    Expression
    for MSH2 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    MSH2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: TAGTTTGTGG

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    MSH2 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    Stem Cell Differentiation: 1 LifeMap Cell 
    NameCategory
    HSF-1 (UC01) (Embryonic Stem Cell)Early Embryo, Inner Cell Mass
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization

    See MSH2 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for MSH2

    SOURCE GeneReport for Unigene cluster: Hs.597656

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

        SABiosciences Expression via Pathway-Focused 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

    Primer
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    In Situ
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    Orthologs
    for MSH2 gene

    (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)
    About This Section
    This gene was present in the last universal common ancestor (LUCA).

    Orthologs for MSH2 gene from 10/38 species (see all 38)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves MSH21 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. more 76.41(n)
    81.84(a)    		   378799  XM_426110.3  XP_426110.3 
    lizard
    (Anolis carolinensis)    		 Reptilia MSH26
    		 --
    		 71(a)
    		 1 ↔ 1
    		 1(254690509-254808123)
    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
    50.9(n)1
    45.73(a)1    		   348421  NM_078841.41  NP_523565.21 
    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
    Msh2p1    		 53.06(n)1
    43.76(a)1    		   15(147382-150276)4
    8540631, 4  NP_014551.11, 4 
    thale cress
    (Arabidopsis thaliana)    		 eudicotyledons MSH21 DNA mismatch repair protein Msh2 51.27(n)
    43.6(a)    		   821383  NM_113607.3  NP_566804.3 
    rice
    (Oryza sativa)    		 Liliopsida --
    		 MSH-like DNA mismatch repair protein, putative, ex...
    		 40(a)
    		 1 ↔ 1
    		 5(11189344-11198004)
    E. coli
    (Escherichia coli)    		 Gamma proteobacteria mutS6
    		 methyl-directed mismatch repair protein
    		 24(a)
    		 possible ortholog
    		 Chromosome(2855115-2857676)


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

    Paralogs
    for MSH2 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    		  --

    Genomic Variants
    for MSH2 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/2612 NCBI SNPs in MSH2 are shown (see all 2612)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 2 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs23034261,2
    		C,F,non-pathogenic47630550(+) AGGGCG/CGGGAC 2 -- int114Minor allele frequency- C:0.30EA NS NA WA CSA EU 1937
    rs172243601,2
    		C,F,non-pathogenic47656871(+) GTTAAT/CTTATT 2 -- int14Minor allele frequency- C:0.02NS NA 296
    rs129988371,2
    		C,F,H,non-pathogenic47693788(+) TCTTGA/TTTATC 2 -- int19Minor allele frequency- T:0.09NS EA NA EU 2027
    rs37321831,2
    		C,F,A,H,non-pathogenic47693959(+) AAGTCG/ATTATT 2 -- int142Minor allele frequency- A:0.46NS NA EA WA CSA EU 5087
    rs1939223761,2
    		Cpathogenic47641560(+) CAGGTA/TAAAAA 2 -- int10--------
    rs637502451,2
    		Cpathogenic47643522(+) TTAACC/TAGTGG 4 Q * stg10--------
    rs637511081,2
    		Cpathogenic47657020(+) GTTACC/TGACTC 4 R * stg10--------
    rs637512071,2
    		Cpathogenic47693857(+) CTTTCC/G/TTGTAA 6 P R L mis10--------
    rs637503931,2
    		Cpathogenic47698147(+) AAACA-/GAATATG 4 I E fra10--------
    rs637500471,2
    		Cpathogenic47702205(+) TAGCTC/TAGCTA 4 Q * stg10--------

    HapMap Linkage Disequilibrium report for MSH2 (47630108 - 47789450 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
    Database of Genomic Variants (DGV): 1 variation for MSH2
         1 Indel: 41311
    Human Gene Mutation Database (HGMD): MSH2

    Locus Specific Mutation Databases (LSDB): MSH2

    3 SABiosciences Cancer Mutation PCR Assays for MSH2:
    Cosmic IdAA Change
    26860p.R711*
    27628p.R680*
    26122p.L787fs*11
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing MSH2
    DNA2.0 Custom Variant and Variant Library Synthesis for MSH2

    Disorders / Diseases
    for MSH2 gene

    (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.)
    About This Section
    MSH2 for disorders           About GeneDecksing

    OMIM gene information: 609309   
    OMIM disorders: 120435  158320  276300  
    UniProtKB/Swiss-Prot: MSH2_HUMAN, P43246
  • Defects in MSH2 are the cause of hereditary non-polyposis colorectal cancer type 1 (HNPCC1) [MIM:120435].
    • Mutations in more than one gene locus can be involved alone or in combination in the production of the HNPCC phenotype
    (also called Lynch syndrome). Most families with clinically recognized HNPCC have mutations in either MLH1 or MSH2
    genes. HNPCC is an autosomal, dominantly inherited disease associated with marked increase in cancer susceptibility.
    It is characterized by a familial predisposition to early onset colorectal carcinoma (CRC) and extra-colonic cancers
    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. Cancers in HNPCC originate within benign neoplastic polyps termed
    adenomas. Clinically, HNPCC is often divided into two subgroups. Type I: hereditary predisposition to colorectal
    cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II: patients have an 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. MSH2 mutations may predispose to
    hematological malignancies and multiple cafe-au-lait spots
  • Defects in MSH2 are a cause of Muir-Torre syndrome (MRTES) [MIM:158320]. Rare autosomal dominant disorder
    • characterized by sebaceous neoplasms and visceral malignancy
  • Defects in MSH2 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089]

    • 20/140 diseases for MSH2 (see all 140):    About MalaCards
    cafe-au-lait spots    colon cancer    muir-torre syndrome    hemolytic-uremic syndrome
    atypical hemolytic-uremic syndrome    li-fraumeni syndrome    familial adenomatous polyposis    attenuated familial adenomatous polyposis
    alveolar soft part sarcoma    colorectal cancer, hereditary nonpolyposis, type 1    malignant fibrous histiocytoma    fibrous histiocytoma
    diffuse large b-cell lymphoma    primitive neuroectodermal tumor    cerebral primitive neuroectodermal tumor    non-small cell lung carcinoma
    actinic cheilitis    adenomatous polyposis coli    b-cell lymphomas    acoustic neuroma

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

    10/77 Novoseek 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
    Hereditary Non-Polyposis Colon Cancer

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

    Export disorders for MSH2 gene to outside databases

    Publications
    for MSH2 gene

    (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

    PubMed articles for MSH2 gene, integrated from 9 sources (see all 1125):
    (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. (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. (2003)
    3. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. (PubMed id 8156592)1, 2, 4 Fishel R....Kolodner R. (1994)
    4. 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. (1993)
    5. 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. (2005)
    6. 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. (2001)
    7. Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer. (PubMed id 15849733)1, 4, 9 Mangold E....Propping P. (2005)
    8. Germline MSH2 and MLH1 mutational spectrum including large rearrangements in HNPCC families from Poland (update study). (PubMed id 16451135)1, 2, 9 Kurzawski G....Lubinski J. (2006)
    9. MSH2 mutation carriers are at higher risk of cancer than MLH1 mutation carriers: a study of hereditary nonpolyposis colorectal cancer families. (PubMed id 11600610)1, 4, 9 Vasen H.F....Wijnen J.T. (2001)
    10. Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden. (PubMed id 14961575)1, 4, 9 Cederquist K.... Groenberg H. (2004)

    External Searches for MSH2 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
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      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing MSH2 gene

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

    Other Databases showing MSH2 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing MSH2 gene

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    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/sites/GeneTests/lab/gene/MSH2
    Hereditary non-polyposis colorectal cancer dbhttp://www.nfdht.nl/
    NIEHS-SNPshttp://egp.gs.washington.edu/data/msh2/

    Intellectual Property
    for MSH2 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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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