Msh2 mutS homolog 2 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Msh2provided by MGI
Official Full Name: mutS homolog 2provided by MGI
Primary source: MGI:MGI:101816
See related: Ensembl:ENSMUSG00000024151 AllianceGenome:MGI:101816
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Summary: Enables ATP hydrolysis activity and DNA binding activity. Contributes to guanine/thymine mispair binding activity. Involved in positive regulation of isotype switching to IgA isotypes and positive regulation of isotype switching to IgG isotypes. Acts upstream of or within several processes, including DNA metabolic process; determination of adult lifespan; and intracellular signal transduction. Located in nucleus. Part of MutSalpha complex. Is expressed in several structures, including genitourinary system; heart; liver; lung; and tail dorsal root ganglion. Used to study Lynch syndrome and colorectal cancer. Human ortholog(s) of this gene implicated in several diseases, including Lynch syndrome (multiple); gastrointestinal system cancer (multiple); lung cancer (multiple); mismatch repair cancer syndrome; and transitional cell carcinoma. Orthologous to human MSH2 (mutS homolog 2). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in CNS E11.5 (RPKM 24.0), CNS E14 (RPKM 14.5) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 E4; 17 57.87 cM

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (87979960..88031141)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (87672532..87723713)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LINC01232 targeting miR-1250-3p/MSH2 axis attenuates mesangial cell proliferation and fibrosis in diabetic nephropathy.
Title: LINC01232 targeting miR-1250-3p/MSH2 axis attenuates mesangial cell proliferation and fibrosis in diabetic nephropathy.
Unexpected moves: a conformational change in MutSalpha enables high-affinity DNA mismatch binding.
Title: Unexpected moves: a conformational change in MutSα enables high-affinity DNA mismatch binding.
Ataxia Telangiectasia Mutated and MSH2 Control Blunt DNA End Joining in Ig Class Switch Recombination.
Title: Ataxia Telangiectasia Mutated and MSH2 Control Blunt DNA End Joining in Ig Class Switch Recombination.
An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient intestinal crypts compared to wild-type epithelium.
Title: Quantifying Microsatellite Mutation Rates from Intestinal Stem Cell Dynamics in Msh2-Deficient Murine Epithelium.
Msh2 deficiency causes dysmyelination of the axonal projections in the corpus callosum. Evoked action potentials in the myelinated corpus callosum projections of Msh2-null mice were smaller than wild-type mice, whereas unmyelinated axons showed no difference.
Title: Msh2 deficiency leads to dysmyelination of the corpus callosum, impaired locomotion, and altered sensory function in mice.
Deletion of the MSH2 C-terminus severely affected the stability of the MSH2/MSH6 heterodimer and consequently strongly attenuated DNA mismatch repair. The C-terminal truncation MSH2 mutant predisposed mice to tumor formation.Mutations deleting the MSH2 C-terminus can therefore unambiguously be considered as pathogenic and a cause of Lynch syndrome.
Title: Truncation of the MSH2 C-terminal 60 amino acids disrupts effective DNA mismatch repair and is causative for Lynch syndrome.
Normal Msh2-deficient organoids showed increased inheritable transient cyst-like growth, which became independent of R-spondin. intestinal stem cell (ISC) proceeded faster in vitro than in vivo independent of the underlying genotype but more under Mutations in mismatch repair deficiency.
Title: Different in vivo and in vitro transformation of intestinal stem cells in mismatch repair deficiency.
Study shows that MSH2-/- mice develop spontaneous thymic lymphomas.
Title: Mismatch repair deficient hematopoietic stem cells are preleukemic stem cells.
Data show that in mutS homolog 2 protein Msh2(+/-) mice, azathioprine (Aza) induced a high incidence of microsatellite instability (MSI) lymphomas in a dose-dependent manner.
Title: Azathioprine induction of tumors with microsatellite instability: risk evaluation using a mouse model.
In Msh2-/- mice, red meat enhanced survival compared to control (p<0.01) and lowered total tumour burden compared to resistant starch (p<0.167).
Title: Role of Red Meat and Resistant Starch in Promutagenic Adduct Formation, MGMT Repair, Thymic Lymphoma and Intestinal Tumourigenesis in Msh2 -Deficient Mice.

Submit: New GeneRIF Correction See all GeneRIFs (51)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3)
Targeted (13) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI788990 (e-PCR)
- UniSTS:181077

WI-18791 (e-PCR)
- UniSTS:28587

BB296288 (e-PCR)
- UniSTS:209349

PMC102144P1 (e-PCR)
- UniSTS:270075

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ADP binding	IEA Inferred from Electronic Annotation more info
contributes_to ADP binding	ISO Inferred from Sequence Orthology more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
contributes_to ATP binding	ISO Inferred from Sequence Orthology more info
enables ATP hydrolysis activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ATP-dependent DNA damage sensor activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent activity, acting on DNA	ISO Inferred from Sequence Orthology more info
enables DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables MutLalpha complex binding	IEA Inferred from Electronic Annotation more info
contributes_to MutLalpha complex binding	ISO Inferred from Sequence Orthology more info
enables centromeric DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables damaged DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to dinucleotide insertion or deletion binding	ISO Inferred from Sequence Orthology more info
enables dinucleotide repeat insertion binding	IEA Inferred from Electronic Annotation more info
contributes_to dinucleotide repeat insertion binding	ISO Inferred from Sequence Orthology more info
enables double-stranded DNA binding	IBA Inferred from Biological aspect of Ancestor more info
contributes_to double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables four-way junction DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to four-way junction DNA binding	ISO Inferred from Sequence Orthology more info
contributes_to guanine/thymine mispair binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to guanine/thymine mispair binding	ISO Inferred from Sequence Orthology more info
enables guanine/thymine mispair binding	ISO Inferred from Sequence Orthology more info	PubMed
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
contributes_to magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables mismatched DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to mismatched DNA binding	ISO Inferred from Sequence Orthology more info
enables oxidized purine DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to oxidized purine DNA binding	ISO Inferred from Sequence Orthology more info
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables protein homodimerization activity	ISO Inferred from Sequence Orthology more info
enables single guanine insertion binding	IEA Inferred from Electronic Annotation more info
contributes_to single guanine insertion binding	ISO Inferred from Sequence Orthology more info
enables single thymine insertion binding	IEA Inferred from Electronic Annotation more info
contributes_to single thymine insertion binding	ISO Inferred from Sequence Orthology more info
enables single-stranded DNA binding	IEA Inferred from Electronic Annotation more info
contributes_to single-stranded DNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within B cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within B cell mediated immunity	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within DNA damage response	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA repair	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within determination of adult lifespan	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within germ cell development	IMP Inferred from Mutant Phenotype more info	PubMed
NOT acts_upstream_of_or_within in utero embryonic development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to DNA damage	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within isotype switching	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of DNA repeat elements	IEA Inferred from Electronic Annotation more info
involved_in maintenance of DNA repeat elements	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within male gonad development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within mismatch repair	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within mismatch repair	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within mismatch repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mismatch repair	ISO Inferred from Sequence Orthology more info	PubMed
involved_in mismatch repair	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within mitotic intra-S DNA damage checkpoint signaling	IGI Inferred from Genetic Interaction more info	PubMed
involved_in mitotic recombination	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within negative regulation of DNA recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of DNA recombination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within oxidative phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of helicase activity	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of isotype switching to IgA isotypes	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of isotype switching to IgG isotypes	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within postreplication repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in postreplication repair	ISO Inferred from Sequence Orthology more info
involved_in postreplication repair	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein localization to chromatin	IEA Inferred from Electronic Annotation more info
involved_in protein localization to chromatin	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to UV-B	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to X-ray	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic hypermutation of immunoglobulin genes	IGI Inferred from Genetic Interaction more info	PubMed
NOT acts_upstream_of_or_within somatic hypermutation of immunoglobulin genes	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic hypermutation of immunoglobulin genes	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within somatic recombination of immunoglobulin gene segments	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within somatic recombination of immunoglobulin gene segments	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in somatic recombination of immunoglobulin genes involved in immune response	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within somatic recombination of immunoglobulin genes involved in immune response	IGI Inferred from Genetic Interaction more info	PubMed

Component	Evidence Code	Pubs
part_of MutSalpha complex	IBA Inferred from Biological aspect of Ancestor more info
part_of MutSalpha complex	IDA Inferred from Direct Assay more info	PubMed
part_of MutSalpha complex	ISO Inferred from Sequence Orthology more info
part_of MutSbeta complex	ISO Inferred from Sequence Orthology more info
located_in chromosome	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	IEA Inferred from Electronic Annotation more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IC Inferred by Curator more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: DNA mismatch repair protein Msh2

Names: mutS protein homolog 2

NCBI Reference Sequences (RefSeq)

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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.

mRNA and Protein(s)

NM_008628.3 → NP_032654.1 DNA mismatch repair protein Msh2

See identical proteins and their annotated locations for NP_032654.1

Status: VALIDATED

Source sequence(s)

AC163652

Consensus CDS

CCDS29019.1

UniProtKB/Swiss-Prot

P43247

UniProtKB/TrEMBL

Q3TZI5, Q80V79

Related

ENSMUSP00000024967.8, ENSMUST00000024967.14

Conserved Domains (6) summary

cd03285
Location:633 → 852

ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog

COG0249
Location:26 → 853

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]

pfam01624
Location:18 → 132

MutS_I; MutS domain I

pfam05188
Location:152 → 284

MutS_II; MutS domain II

pfam05190
Location:473 → 569

MutS_IV; MutS family domain IV

pfam05192
Location:305 → 423

MutS_III; MutS domain III