Msh6 mutS homolog 6 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Msh6provided by MGI
Official Full Name: mutS homolog 6provided by MGI
Primary source: MGI:MGI:1343961
See related: Ensembl:ENSMUSG00000005370 AllianceGenome:MGI:1343961
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
Also known as: GTBP; Gtmbp
Summary: Enables chromatin binding activity; damaged DNA binding activity; and guanine/thymine mispair binding activity. Acts upstream of or within several processes, including determination of adult lifespan; intrinsic apoptotic signaling pathway in response to DNA damage; and somatic diversification of immunoglobulins. Located in chromatin. Part of MutSalpha complex. Is expressed in several structures, including brain; early conceptus; liver; lung; and oocyte. Human ortholog(s) of this gene implicated in Lynch syndrome; colorectal carcinoma; endometrial cancer; hereditary nonpolyposis colorectal cancer type 5; and mismatch repair cancer syndrome. Orthologous to human MSH6 (mutS homolog 6). [provided by Alliance of Genome Resources, Nov 2024]
Expression: Broad expression in CNS E11.5 (RPKM 17.1), liver E14 (RPKM 9.0) and 23 other tissues See more
Orthologs: human all
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Genomic context

Location:: 17 E4; 17 57.87 cM

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (88282478..88298320)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (87975050..87990892)

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
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?

MSH6 Aggravates the Hypoxic Microenvironment via Regulating HIF1A to Promote the Metastasis of Glioblastoma Multiforme.
Title: MSH6 Aggravates the Hypoxic Microenvironment via Regulating HIF1A to Promote the Metastasis of Glioblastoma Multiforme.
we show that AID binds cooperatively with UNG and the mismatch repair proteins Msh2-Msh6 to Ig Smu and Sgamma3 regions
Title: AID recruits UNG and Msh2 to Ig switch regions dependent upon the AID C terminus [corrected].
Data suggest that MSH6 protects B cells from neoplastic transformation by preserving genomic stability.
Title: Msh6 protects mature B cells from lymphoma by preserving genomic stability.
similar defects on switching in Msh2(-/-), Msh2(-/-)Msh6(-/-) and Msh2(-/-)Msh6(-/-)Msh3(-/-) mice confirm that MutSalpha but not MutSbeta plays an important role in class switch recombination
Title: MSH2/MSH6 complex promotes error-free repair of AID-induced dU:G mispairs as well as error-prone hypermutation of A:T sites.
Synergism between Mgmt and Msh6 can be explained entirely by the suppression of alkylation-induced apoptosis when Msh6 is absent.
Title: Alkylation-induced colon tumorigenesis in mice deficient in the Mgmt and Msh6 proteins.
ablation of either Msh6 or Exo1 function in the Mgmt-null mouse renders these rapidly proliferating tissues alkylation-resistant. The Msh6 defect confers total alkylation resistance
Title: O6-methylguanine-induced cell death involves exonuclease 1 as well as DNA mismatch recognition in vivo.
These findings indicate that MutS alpha reduces spontaneous and IR-induced mutation in a cell type-dependant manner.
Title: Role of the mismatch repair gene, Msh6, in suppressing genome instability and radiation-induced mutations.
p53 and Msh6 are functionally interrelated and these tumor suppressors act together to accelerate tumorigenesis.
Title: The associated contributions of p53 and the DNA mismatch repair protein Msh6 to spontaneous tumorigenesis.
Mice nullizygous for both Msh2 and Msh3 and those nullizygous for both Msh3 and Msh6 displayed the greatest overall increases in mutation frequencies compared with wild-type mice.
Title: Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6.
Msh6 deficiency resulted in somatic instability of a (GTG)84 repeat.
Title: Somatic expansion behaviour of the (CTG)n repeat in myotonic dystrophy knock-in mice is differentially affected by Msh3 and Msh6 mismatch-repair proteins.

Submit: New GeneRIF Correction See all GeneRIFs (14)

Variation

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Alleles

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

Chemically induced (ENU) (1)
Targeted (3) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AW550279 (e-PCR)
- UniSTS:181079

RH140511 (e-PCR)
- UniSTS:222581

RH127753 (e-PCR)
- UniSTS:211063

NoName (e-PCR)
- UniSTS:237725

Gtmbp-rs (e-PCR), detects polymorphism
- UniSTS:143280

AU044881 (e-PCR)
- UniSTS:160706

RH126790 (e-PCR)
- UniSTS:209350

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-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	IGI Inferred from Genetic Interaction more info	PubMed
enables DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables MutLalpha complex binding	IEA Inferred from Electronic Annotation more info
contributes_to MutLalpha complex binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables damaged DNA binding	IGI Inferred from Genetic Interaction more info	PubMed
enables damaged DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
contributes_to double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables enzyme binding	IEA Inferred from Electronic Annotation more info
enables enzyme 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
enables 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 magnesium ion binding	IEA Inferred from Electronic Annotation more info
contributes_to magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables methylated histone binding	ISO Inferred from Sequence Orthology more info
enables methylated histone binding	ISS Inferred from Sequence or Structural Similarity more info
enables mismatched DNA binding	IBA Inferred from Biological aspect of Ancestor more info
contributes_to mismatched DNA binding	ISO Inferred from Sequence Orthology more info
enables mismatched DNA binding	ISO Inferred from Sequence Orthology more info
enables mismatched DNA binding	ISS Inferred from Sequence or Structural Similarity 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 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

Process	Evidence Code	Pubs
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 intrinsic apoptotic signaling pathway	IMP Inferred from Mutant Phenotype 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 isotype switching	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 mismatch repair	IBA Inferred from Biological aspect of Ancestor more info
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 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
involved_in positive regulation of helicase activity	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to UV	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	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
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
located_in chromatin	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology 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	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: DNA mismatch repair protein Msh6

Names: g/T mismatch-binding protein; mutS protein homolog 6; mutS-alpha 160 kDa subunit; p160

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_010830.2 → NP_034960.1 DNA mismatch repair protein Msh6

See identical proteins and their annotated locations for NP_034960.1

Status: VALIDATED

Source sequence(s)

BC051634, CN458717

Consensus CDS

CCDS29021.1

UniProtKB/Swiss-Prot

O54710, P54276, Q6GTK8

UniProtKB/TrEMBL

Q8C2N9

Related

ENSMUSP00000005503.4, ENSMUST00000005503.5

Conserved Domains (8) summary

cd05837
Location:88 → 195

MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...

COG0249
Location:406 → 1330

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

pfam01624
Location:406 → 524

MutS_I; MutS domain I

pfam05188
Location:537 → 689

MutS_II; MutS domain II

pfam05190
Location:929 → 1021

MutS_IV; MutS family domain IV

pfam05192
Location:736 → 824

MutS_III; MutS domain III

pfam14797
Location:224 → 349

SEEEED; Serine-rich region of AP3B1, clathrin-adaptor complex

cl21455
Location:1089 → 1311

P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases