MSH2 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli) [Homo sapiens] - Gene

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Summary

Official Symbol: MSH2provided by HGNC
Official Full Name: mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)provided by HGNC
Primary source: HGNC:7325
See related: Ensembl:ENSG00000095002; HPRD:00389; 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; 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]

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Genomic context

Location :: 2p21

Sequence :: Chromosome: 2; NC_000002.11 (47630263..47710360)

See MSH2 in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

MSH2(wt)-MSH6(T1219D) fails to couple nucleotide binding and mismatch recognition, whereas MSH2(G674A)-MSH6(wt) has a partial defect in nucleotide binding.
Title: Biochemical analysis of the human mismatch repair proteins hMutSα MSH2(G674A)-MSH6 and MSH2-MSH6(T1219D).
Single nucleotide polymorphisms in MSH2 is associated with esophageal cancer.
Title: Esophageal cancer risk is associated with polymorphisms of DNA repair genes MSH2 and WRN in Chinese population.
Mutations in MSH2 is associated with neoplasms.
Title: Colorectal and other cancer risks for carriers and noncarriers from families with a DNA mismatch repair gene mutation: a prospective cohort study.
study focuses on evaluating incidence of epigenetic aberrations in MSH2 genes and its clinical impact on the development of esophageal squamous cell carcinoma in a middle incidence area of China; suggested that MSH2 methylation in plasma would be a goo...
Title: MSH2 promoter hypermethylation in circulating tumor DNA is a valuable predictor of disease-free survival for patients with esophageal squamous cell carcinoma.
Germline mutations of MLH1 and MSH2 were identified in four Malaysian Lynch syndrome patients.
Title: Germline mutation analysis of MLH1 and MSH2 in Malaysian Lynch syndrome patients.
Approximately 50-80% of individuals who carry an MSH2 gene mutation are likely to develop a colon cancer by the age of 70 years
Title: Challenges in the diagnosis and management of Lynch Syndrome in an Indigenous family living in a remote West Australian community.
Studies indicate thar eukaryotes MutSbeta, a heterodimer of Msh2 and Msh3, recognizes insertion-deletion loops (IDLs) of 1-15 nucleotides, as well as DNA with a 3' single-stranded overhang.
Title: Mechanism of mismatch recognition revealed by human MutSβ bound to unpaired DNA loops.
Study adds new information about MSH2 gene mutations and contribute to better characterize Lynch Syndrome. High rate of novel mutations demonstrates the importance of defining MSH2 mutations in distinct Lynch Syndrome populations.
Title: Characterization of germline mutations of MLH1 and MSH2 in unrelated south American suspected Lynch syndrome individuals.
missense mutation in exon 12 at codon 600 of the MSH2 gene in Lynch syndrome
Title: Pathogenicity of A600V variant in exon 12 of the MSH2 gene detected in a Japanese kindred with Lynch syndrome.
Alu-mediated rearrangements in MSH2 gene is associated with a Lynch syndrome phenotype.
Title: Characterization of new founder Alu-mediated rearrangements in MSH2 gene associated with a Lynch syndrome phenotype.

Submit: New GeneRIF Correction See all (314)

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Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Products	Interactant	Other Gene	Source	Pubs	Description
NC_000002.9	NP_005216.1	E2F1	BIND	PubMed	The 5'MSH2 promoter region interacts with E2F1.
NC_000002.9	NP_005216.1	E2F1	BIND	PubMed	E2F1 interacts with the MSH2 promoter.
NC_000002.9	NP_001940.1	E2F3	BIND	PubMed	E2F3 interacts with the MSH2 promoter.
NC_000002.9	NP_001941.2	E2F4	BIND	PubMed	E2F4 interacts with the MSH2 promoter.
NP_000242.1	NP_009227.1	BRCA1	BIND	PubMed	BRCA1 interacts with MSH2 in the absence of ADP-MSH2 interaction.
NP_000242.1	NP_003677.3	EXO1	BIND	PubMed	The exonuclease HEX1 interacts with the mismatch repair protein hMSH2.
NP_000242.1	NP_006018.3	EXO1	BIND	PubMed	The exonuclease hEXO1b interacts with the mismatch repair protein hMSH2.
NP_000242.1	NP_002373.3	MAX	BIND	PubMed	Max interacts with MSH2. This is a modeled interaction between Max from an unspecified source and human MSH2.
NP_000242.1	NP_002430.1	MSH3	BIND	PubMed	MSH2/HNPCC interacts with MSH3
NP_000242.1	NP_000170.1	MSH6	BIND	PubMed	MSH2 interacts with MSH6.
NP_000242.1	NP_000170.1	MSH6	BIND	PubMed	MSH2 interacts with MSH6.
P43246	Q13535	ATR	HPRD	PubMed
P43246	Q8WXE1	ATRIP	HPRD	PubMed
P43246	Q99728	BARD1	HPRD	PubMed
P43246	O96017	CHEK2	HPRD	PubMed
P43246	Q92793	CREBBP	HPRD	PubMed
P43246	Q9UQ84	EXO1	HPRD	PubMed
P43246	P61244	MAX	HPRD	PubMed
P43246	P20585	MSH3	HPRD	PubMed
P43246	P52701	MSH6	HPRD	PubMed
P43246	P12004	PCNA	HPRD	PubMed
P43246	Q14683	SMC1A	HPRD	PubMed
BioGRID:110573	BioGRID:106823	AIRE	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:106807	ANXA7	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:106962	ATM	BioGRID	PubMed	Co-purification
BioGRID:110573	BioGRID:107027	ATR	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-localization; Reconstituted Complex
BioGRID:110573	BioGRID:313463	ATRIP	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:107056	BARD1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110573	BioGRID:107110	BLM	BioGRID	PubMed	Affinity Capture-Western; Co-purification
BioGRID:110573	BioGRID:107140	BRCA1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-purification; Reconstituted Complex; Two-hybrid
BioGRID:110573	BioGRID:107459	CDK9	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:107460	CDKN1A	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:107536	CHEK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:116369	CHEK2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110573	BioGRID:117421	COBRA1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:107777	CREBBP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:119582	DTL	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:108403	ESR1	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex
BioGRID:110573	BioGRID:108404	ESR2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110573	BioGRID:114602	EXO1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110573	BioGRID:108472	FANCA	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:109143	GRB7	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:108918	KAT2A	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:110319	MAX	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:110573	BioGRID:110411	MGMT	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:110438	MLH1	BioGRID	PubMed	Affinity Capture-Western; Co-purification
BioGRID:110573	BioGRID:110501	MRE11A	BioGRID	PubMed	Co-purification
BioGRID:110573	BioGRID:110573	MSH2	BioGRID	PubMed	Reconstituted Complex
BioGRID:110573	BioGRID:110574	MSH3	BioGRID	PubMed	Affinity Capture-MS; Reconstituted Complex
BioGRID:110573	BioGRID:109211	MSH6	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-purification; Reconstituted Complex
BioGRID:110573	BioGRID:110694	MYC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110573	BioGRID:110763	NBN	BioGRID	PubMed	Co-purification
BioGRID:110573	BioGRID:120751	OTUB1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:111142	PCNA	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:111391	PMS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:111404	PMS2	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110573	BioGRID:111576	PRKCZ	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:116327	PTP4A3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:115417	RAD50	BioGRID	PubMed	Co-purification
BioGRID:110573	BioGRID:111825	RAD51	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:111913	RFC1	BioGRID	PubMed	Co-purification
BioGRID:110573	BioGRID:118975	RPA4	BioGRID	PubMed	Reconstituted Complex
BioGRID:110573	BioGRID:116283	RPP14	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:124097	SLX4	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Two-hybrid
BioGRID:110573	BioGRID:121244	SMARCAD1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:112490	SMN1	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:116597	SNW1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110573	BioGRID:112938	TK1	BioGRID	PubMed	Two-hybrid
BioGRID:110573	BioGRID:113010	TP53	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110573	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110573	BioGRID:113344	XPA	BioGRID	PubMed	Reconstituted Complex

Function	Evidence Code	Pubs
contributes_to ADP binding	IDA Inferred from Direct Assay 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
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
centromeric DNA binding	IEA Inferred from Electronic Annotation more info
damaged DNA binding	IEA Inferred from Electronic Annotation more info
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
double-strand/single-strand DNA junction binding	IBA Inferred from Biological aspect of Ancestor more info
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	IDA Inferred from Direct Assay 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
loop DNA binding	IBA Inferred from Biological aspect of Ancestor more info
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
nucleotide binding	IEA Inferred from Electronic Annotation more info
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	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
ATP catabolic process	IDA Inferred from Direct Assay more info	PubMed
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 damage response, signal transduction by p53 class mediator resulting in induction of apoptosis	IBA Inferred from Biological aspect of Ancestor 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
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
isotype switching	IBA Inferred from Biological aspect of Ancestor more info
isotype switching	ISS Inferred from Sequence or Structural Similarity more info
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
meiotic mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
mismatch repair	IDA Inferred from Direct Assay 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 apoptosis	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of reciprocal meiotic recombination	IBA Inferred from Biological aspect of Ancestor more info
oxidative phosphorylation	IEA Inferred from Electronic Annotation more info
positive regulation of helicase activity	IDA Inferred from Direct Assay more info	PubMed
postreplication repair	IDA Inferred from Direct Assay more info	PubMed
response to UV-B	IBA Inferred from Biological aspect of Ancestor more info
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
response to X-ray	ISS Inferred from Sequence or Structural Similarity more info
response to amino acid stimulus	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info
somatic hypermutation of immunoglobulin genes	IBA Inferred from Biological aspect of Ancestor more info
somatic recombination of immunoglobulin gene segments	ISS Inferred from Sequence or Structural Similarity more info
spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
MutSalpha complex	IDA Inferred from Direct Assay more info	PubMed
MutSbeta complex	IDA Inferred from Direct Assay more info	PubMed
nuclear chromosome	IBA Inferred from Biological aspect of Ancestor more info
nucleus	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: DNA mismatch repair protein Msh2

Names: DNA mismatch repair protein Msh2; hMSH2

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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

NG_007110.2 RefSeqGene

Range

4944..85105

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000251.2 → NP_000242.1 DNA mismatch repair protein Msh2 isoform 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, OTTHUMP00000159084, ENST00000233146, OTTHUMT00000250805

Conserved Domains (5) summary

COG0249
Location:19 – 853
Blast Score: 1332

MutS; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]

cd03285
Location:633 – 852
Blast Score: 1031

ABC_MSH2_euk; MutS2 homolog in eukaryotes. The MutS protein initiates DNA mismatch repair by recognizing mispaired and unpaired bases embedded in duplex DNA and activating endo- and exonucleases to remove the mismatch. Members of the MutS family possess C-terminal ...

pfam01624
Location:18 – 132
Blast Score: 278

MutS_I; MutS domain I

pfam05188
Location:158 – 284
Blast Score: 214

MutS_II; MutS domain II

pfam05190
Location:473 – 559
Blast Score: 184

MutS_IV; MutS family domain IV
NM_001258281.1 → NP_001245210.1 DNA mismatch repair protein Msh2 isoform 2

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

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000002.11 Reference GRCh37.p5 Primary Assembly

Range

47630263..47710360

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1 Alternate HuRef

Range

47367227..47445833

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC079775.6	AAY15096.1
genomic	AC138655.1	None
genomic	AF066081.1	AAC27930.1
genomic	AY344477.1	AAQ23475.1
genomic	AY601851.1	AAS99351.1
genomic	CH471053.2	EAX00213.1
		EAX00214.1
		EAX00215.1
genomic	U41221.1	AAA82080.1
mRNA	AK222860.1	BAD96580.1
mRNA	AK223284.1	BAD97004.1
mRNA	AK296831.1	BAG59401.1
mRNA	AK297763.1	BAG60111.1
mRNA	AK299667.1	BAG61581.1
mRNA	AK304496.1	BAG65304.1
mRNA	AK311330.1	None
mRNA	BC001122.1	None
mRNA	BC012599.1	None
mRNA	BC021566.1	AAH21566.1
mRNA	BX649122.1	None
mRNA	CB250419.1	None
mRNA	DC342099.1	None
mRNA	DQ648894.1	ABG49489.1
mRNA	DQ648895.1	ABG49490.1
mRNA	DQ648896.1	ABG49491.1
mRNA	DQ648897.1	ABG49492.1
mRNA	L47574.1	AAB59566.1
mRNA	L47575.1	AAB59567.1
mRNA	L47576.1	AAB59568.1
mRNA	L47577.1	AAB59569.1
mRNA	L47578.1	AAB59570.1
mRNA	L47579.1	AAB59571.1
mRNA	L47580.1	AAB59572.1
mRNA	L47581.1	AAA76858.1
mRNA	L47582.1	AAB59565.1
mRNA	L47583.1	AAB59564.1
mRNA	U03911.1	AAA18643.1
mRNA	U04045.1	AAA61870.1
other-genetic	DQ892558.2	ABM83484.1
other-genetic	DQ895772.2	ABM86698.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P43246.1	GenPept	UniProtKB/Swiss-Prot:P43246
Q0ZAI9	GenPept	UniProtKB/TrEMBL:Q0ZAI9
Q0ZAJ0	GenPept	UniProtKB/TrEMBL:Q0ZAJ0
Q0ZAJ1	GenPept	UniProtKB/TrEMBL:Q0ZAJ1
Q0ZAJ2	GenPept	UniProtKB/TrEMBL:Q0ZAJ2
Q53FK0	GenPept	UniProtKB/TrEMBL:Q53FK0
Q53GS1	GenPept	UniProtKB/TrEMBL:Q53GS1
Q53RU4	GenPept	UniProtKB/TrEMBL:Q53RU4
Q6VBB7	GenPept	UniProtKB/TrEMBL:Q6VBB7