MSH2 mutS homolog 2 [Homo sapiens (human)] - Gene

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
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: mouse all

Genomic context

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_000002.12 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: 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Hypomethylation of MSH2 gene is associated with chemotolerance of breast carcinoma.
Title: Hypomethylation of mismatch repair genes MLH1 and MSH2 is associated with chemotolerance of breast carcinoma: Clinical significance.
Single-Nucleotide Polymorphisms of the MSH2 is associated with Basal Cell Carcinoma.
Title: Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.
MSH2-MSH3 not only stimulates pol beta to copy through the repeats but also enhances formation of the flap precursor for expansion.
Title: Crosstalk between MSH2-MSH3 and polβ promotes trinucleotide repeat expansion during base excision repair.
Cancer developed more often in mutation carriers, with no consistent difference between MLH1 and MSH2 carriers. More polyps (mostly adenomas) were detected in MLH1 carriers. The majority (13 of 21) of malignant tumours occurred in organs for which there is no recommended surveillance, and were lethal in three patients.
Title: Risk of colorectal polyps and of malignancies in asymptomatic carriers of mutations in the main DNA mismatch repair genes.
SNP Rs2303428 of MSH2 is associated with hepatocellular carcinoma prognosis in a Chinese population.
Title: Rs2303428 of MSH2 Is Associated with Hepatocellular Carcinoma Prognosis in a Chinese Population.
Expression of MSH2 in patients with colon cancer may promote the expression of the obesity gene MC4R, potentially contributing to body weight gains
Title: Correlations of MC4R and MSH2 expression with obesity in colon cancer patients.
An increased risk of breast cancer in MSH2 mutation carriers was demonstrated in a Canadian familial cancer registry.
Title: Association between the Lynch syndrome gene MSH2 and breast cancer susceptibility in a Canadian familial cancer registry.
Loss of MSH2 protein is correlated with MSH2 inactivation, hypermutation, and higher tumor-infiltrating lymphocyte density, and appears most common among very high-grade primary tumors, for which routine screening may be warranted if validated in additional cohorts.
Title: MSH2 Loss in Primary Prostate Cancer.
Immunohistochemistry revealed loss of expression of proteins MSH2 and MSH6, strongly suggesting a diagnosis of MTS.
Title: [Muir-Torre syndrome and Turcot syndrome].
Authors revealed a novel pathologic mutation on the MSH2 gene (G504 splicing) that associates with Lynch syndrome. Systematical comparison of the mutation landscape revealed that multiple cancers in the proband were evolutionarily independent.
Title: Association of a novel point mutation in MSH2 gene with familial multiple primary cancers.

Submit: New GeneRIF Correction See all GeneRIFs (466)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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

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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

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G65627 (e-PCR)
- UniSTS:225564

RH93469 (e-PCR)
- UniSTS:91508

GDB:599286 (e-PCR)
- UniSTS:158114

GDB:599300 (e-PCR)
- UniSTS:158118

GDB:549135 (e-PCR)
- UniSTS:157610

GDB:599318 (e-PCR)
- UniSTS:158122

GDB:599321 (e-PCR)
- UniSTS:158123

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

GDB:599324 (e-PCR)
- UniSTS:158124

GDB:599327 (e-PCR)
- UniSTS:158125

GDB:599341 (e-PCR)
- UniSTS:158128

GDB:599344 (e-PCR)
- UniSTS:158129

GDB:599347 (e-PCR)
- UniSTS:158130

GDB:599356 (e-PCR)
- UniSTS:158131

GDB:599360 (e-PCR)
- UniSTS:158132

GDB:599364 (e-PCR)
- UniSTS:158133

GDB:599367 (e-PCR)
- UniSTS:158134

GDB:599372 (e-PCR)
- UniSTS:158135

GDB:599380 (e-PCR)
- UniSTS:158137

RH70533 (e-PCR)
- UniSTS:52163

D2S2563 (e-PCR)
- UniSTS:27108

SHGC-2762 (e-PCR)
- UniSTS:30458

Homology

Homologs of the MSH2 gene: The MSH2 gene is conserved in dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, and frog.
Orthologs from Annotation Pipeline: 259 organisms have orthologs with human gene MSH2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
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	IDA Inferred from Direct Assay more info	PubMed
centromeric DNA binding	IEA Inferred from Electronic Annotation more info
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
contributes_to double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to four-way junction DNA binding	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
contributes_to magnesium ion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to mismatched DNA binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to oxidized purine DNA binding	IDA Inferred from Direct Assay more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
contributes_to single guanine insertion binding	IDA Inferred from Direct Assay more info	PubMed
contributes_to single thymine insertion binding	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	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
B cell mediated immunity	ISS Inferred from Sequence or Structural Similarity more info
DNA repair	IDA Inferred from Direct Assay more info	PubMed
cell cycle arrest	IEA Inferred from Electronic Annotation more info
determination of adult lifespan	IEA Inferred from Electronic Annotation more info
double-strand break repair	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
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
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
negative regulation of DNA 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
oxidative phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of helicase activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of isotype switching to IgA isotypes	IEA Inferred from Electronic Annotation more info
positive regulation of isotype switching to IgG isotypes	IEA Inferred from Electronic Annotation more info
postreplication repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
postreplication repair	IDA Inferred from Direct Assay more info	PubMed
protein localization to chromatin	IMP Inferred from Mutant Phenotype 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 hypermutation of immunoglobulin genes	IEA Inferred from Electronic Annotation more info
somatic recombination of immunoglobulin gene segments	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
MutSalpha complex	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 more info	PubMed
mismatch repair complex	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nuclear chromosome, telomeric region	HDA more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA mismatch repair protein Msh2

Names: DNA mismatch repair protein Msh2 transcript; mutS homolog 2, colon cancer, nonpolyposis type 1

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.

Genomic

NG_007110.2 RefSeqGene

Range

4944..85105

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_218

mRNA and Protein(s)

NM_000251.2 → NP_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, ENST00000233146.6

Conserved Domains (1) summary

COG0249
Location:23 → 853

MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
NM_001258281.1 → NP_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:58 → 787

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

pfam01624
Location:5 → 66

MutS_I; MutS domain I

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p12 Primary Assembly

Range

47403067..47634501

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011532867.2 → XP_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:633 → 852

ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog

COG0249
Location:23 → 853

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

pfam01624
Location:18 → 132

MutS_I; MutS domain I

pfam05188
Location:158 → 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
XM_005264332.4 → XP_005264389.2 DNA mismatch repair protein Msh2 isoform X1

Conserved Domains (6) summary

cd03285
Location:633 → 852

ABC_MSH2_euk; ATP-binding cassette domain of eukaryotic MutS2 homolog

COG0249
Location:23 → 853

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

pfam01624
Location:18 → 132

MutS_I; MutS domain I

pfam05188
Location:158 → 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