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MSH2 mutS homolog 2 [ Homo sapiens (human) ]

Gene ID: 4436, updated on 12-Aug-2018

Summary

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; hMSH2; 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]
Expression
Ubiquitous expression in lymph node (RPKM 3.7), testis (RPKM 3.4) and 25 other tissues See more
Orthologs

Genomic context

See MSH2 in Genome Data Viewer
Location:
2p21-p16.3
Exon count:
21
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 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

Genomic regions, transcripts, and products

Expression

  • 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

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

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

HIV-1 interactions

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

Pathways from BioSystems

  • BRCA1-associated genome surveillance complex (BASC), organism-specific biosystem (from KEGG)
    BRCA1-associated genome surveillance complex (BASC), organism-specific biosystemStructural complex; Genetic information processing; Repair system
  • BRCA1-associated genome surveillance complex (BASC), conserved biosystem (from KEGG)
    BRCA1-associated genome surveillance complex (BASC), conserved biosystemStructural complex; Genetic information processing; Repair system
  • Colorectal cancer, organism-specific biosystem (from KEGG)
    Colorectal cancer, organism-specific biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
  • Colorectal cancer, conserved biosystem (from KEGG)
    Colorectal cancer, conserved biosystemColorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in ...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    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...
  • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • Integrated Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Cancer Pathway, organism-specific biosystem
    Integrated Cancer Pathway
  • 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)
    Mismatch repair, organism-specific biosystemDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preven...
  • 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)
    Mismatch repair, conserved biosystemDNA mismatch repair (MMR) is a highly conserved biological pathway that plays a key role in maintaining genomic stability. MMR corrects DNA mismatches generated during DNA replication, thereby preven...
  • 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)
    Platinum drug resistance, conserved 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...
  • Rac1/Pak1/p38/MMP-2 pathway, organism-specific biosystem (from WikiPathways)
    Rac1/Pak1/p38/MMP-2 pathway, organism-specific biosystemRac1/p38 pathway from Ingenuity Pathway Analysis.
  • TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of DNA Repair Genes, organism-specific biosystemSeveral DNA repair genes contain p53 response elements and their transcription is positively regulated by TP53 (p53). TP53-mediated regulation probably ensures increased protein level of DNA repair g...
  • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
    Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
CONTRIBUTES_TO ADP binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to ADP binding IDA
Inferred from Direct Assay
more info
PubMed 
ATP binding IBA
Inferred from Biological aspect of Ancestor
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 
DNA-dependent ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
CONTRIBUTES_TO MutLalpha complex binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to MutLalpha complex binding IDA
Inferred from Direct Assay
more info
PubMed 
Y-form DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
centromeric DNA binding IEA
Inferred from Electronic Annotation
more info
 
damaged DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to dinucleotide insertion or deletion binding IDA
Inferred from Direct Assay
more info
PubMed 
CONTRIBUTES_TO dinucleotide repeat insertion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to dinucleotide repeat insertion binding IDA
Inferred from Direct Assay
more info
PubMed 
double-strand/single-strand DNA junction binding IBA
Inferred from Biological aspect of Ancestor
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 
four-way junction DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to four-way junction DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
CONTRIBUTES_TO guanine/thymine mispair binding IBA
Inferred from Biological aspect of Ancestor
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 
heteroduplex DNA loop binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
CONTRIBUTES_TO magnesium ion binding IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
CONTRIBUTES_TO single guanine insertion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to single guanine insertion binding IDA
Inferred from Direct Assay
more info
PubMed 
CONTRIBUTES_TO single thymine insertion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
contributes_to single thymine insertion binding IDA
Inferred from Direct Assay
more info
PubMed 
CONTRIBUTES_TO single-stranded DNA binding IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
germ cell development IEA
Inferred from Electronic Annotation
more info
 
in utero embryonic development IEA
Inferred from Electronic Annotation
more info
 
interstrand cross-link repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intra-S DNA damage checkpoint IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
isotype switching ISS
Inferred from Sequence or Structural Similarity
more info
 
maintenance of DNA repeat elements IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
 
meiotic gene conversion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
meiotic mismatch repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mismatch repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
 
mitotic recombination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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
 
negative regulation of reciprocal meiotic recombination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
oxidative phosphorylation IEA
Inferred from Electronic Annotation
more info
 
positive regulation of helicase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
postreplication repair IDA
Inferred from Direct Assay
more info
PubMed 
pyrimidine dimer repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
replication fork arrest IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to UV-B IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to UV-B ISS
Inferred from Sequence or Structural Similarity
more info
 
response to X-ray IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
response to X-ray ISS
Inferred from Sequence or Structural Similarity
more info
 
somatic recombination of immunoglobulin gene segments ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
MutSalpha complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
MutSalpha complex IDA
Inferred from Direct Assay
more info
PubMed 
MutSbeta complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
MutSbeta complex IDA
Inferred from Direct Assay
more info
PubMed 
membrane HDA PubMed 
mismatch repair complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear chromosome IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nuclear chromosome, telomeric region HDA PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
DNA mismatch repair protein Msh2
Names
mutS homolog 2, colon cancer, nonpolyposis type 1

NCBI Reference Sequences (RefSeq)

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 (1) summary
    COG0249
    Location:23853
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
  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 (2) summary
    COG0249
    Location:58787
    MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
    pfam01624
    Location:566
    MutS_I; MutS domain I

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p12 Primary Assembly

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

mRNA and Protein(s)

  1. XM_011532867.2XP_011531169.1  DNA mismatch repair protein Msh2 isoform X2

    See identical proteins and their annotated locations for XP_011531169.1

    Related
    ENSP00000495455.1, ENST00000645506.1
    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_005264332.4XP_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_001738747.2 RNA Sequence

    Related
    ENST00000646415.1
  2. XR_939685.2 RNA Sequence

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