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Aliases for MSH6 Gene

Aliases for MSH6 Gene

  • MutS Homolog 6 2 3
  • GTBP 3 4 6
  • G/T Mismatch-Binding Protein 3 4
  • MutS-Alpha 160 KDa Subunit 3 4
  • HNPCC5 3 6
  • GTMBP 3 4
  • P160 3 4
  • DNA Mismatch Repair Protein Msh6 3
  • MutS (E. Coli) Homolog 6 2
  • MutS Homolog 6 (E. Coli) 2
  • Sperm-Associated Protein 3
  • HMSH6 4
  • HSAP 3

External Ids for MSH6 Gene

Previous Symbols for MSH6 Gene

  • GTBP

Summaries for MSH6 Gene

Entrez Gene Summary for MSH6 Gene

  • This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]

GeneCards Summary for MSH6 Gene

MSH6 (MutS Homolog 6) is a Protein Coding gene. Diseases associated with MSH6 include endometrial cancer and colorectal cancer, hereditary nonpolyposis, type 5. Among its related pathways are Pathways in cancer and Glioma. GO annotations related to this gene include protein homodimerization activity and magnesium ion binding.

UniProtKB/Swiss-Prot for MSH6 Gene

  • Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated Lys-36 of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.

Gene Wiki entry for MSH6 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MSH6 Gene

Genomics for MSH6 Gene

Genomic Location for MSH6 Gene

Start:
47,695,530 bp from pter
End:
47,810,101 bp from pter
Size:
114,572 bases
Orientation:
Plus strand

Genomic View for MSH6 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for MSH6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MSH6 Gene

Regulatory Elements for MSH6 Gene

Proteins for MSH6 Gene

  • Protein details for MSH6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P52701-MSH6_HUMAN
    Recommended name:
    DNA mismatch repair protein Msh6
    Protein Accession:
    P52701
    Secondary Accessions:
    • B4DF41
    • B4E3I4
    • F5H2F9
    • O43706
    • O43917
    • Q8TCX4
    • Q9BTB5

    Protein attributes for MSH6 Gene

    Size:
    1360 amino acids
    Molecular mass:
    152786 Da
    Quaternary structure:
    • Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with herpes simplex virus 1 protein UL12 (PubMed:21957315).

    Three dimensional structures from OCA and Proteopedia for MSH6 Gene

    Alternative splice isoforms for MSH6 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MSH6 Gene

Proteomics data for MSH6 Gene at MOPED

Post-translational modifications for MSH6 Gene

  • Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.
  • The N-terminus is blocked
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys334, Lys519, Lys610, Lys632, Lys728, Lys771, Lys824, Lys1296, Lys1315, Lys1325, Lys1352, and Lys1358

No data available for DME Specific Peptides for MSH6 Gene

Domains for MSH6 Gene

Suggested Antigen Peptide Sequences for MSH6 Gene

Graphical View of Domain Structure for InterPro Entry

P52701

UniProtKB/Swiss-Prot:

MSH6_HUMAN
Domain:
  • The PWWP domain specifically recognizes and binds trimethylated Lys-36 of histone H3 (H3K36me3).:
    • P52701
  • Contains 1 PWWP domain.:
    • P52701
Family:
  • Belongs to the DNA mismatch repair MutS family.:
    • P52701
genes like me logo Genes that share domains with MSH6: view

No data available for Gene Families for MSH6 Gene

Function for MSH6 Gene

Molecular function for MSH6 Gene

GENATLAS Biochemistry: must S (E coli) homolog 6,GT binding protein,complexing with MSH2 in mismatch repair (MUTS alpha heterodimer),functioning as a molecular switch between ADP and ATP bound forms,selective for repair or GT mispair and single deplaced bases,with two alternatively spliced isoforms,GTBPN,mutated in gastric carcinomas in association with microsatellite mutator phenotype (MMP),deleted in sporadic colorectal cancer (early onset)
UniProtKB/Swiss-Prot Function: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated Lys-36 of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction.

Gene Ontology (GO) - Molecular Function for MSH6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000287 contributes_to magnesium ion binding IDA 16403449
GO:0000400 contributes_to four-way junction DNA binding IDA 12034830
GO:0003677 DNA binding --
GO:0003682 chromatin binding IEA --
GO:0003684 damaged DNA binding --
genes like me logo Genes that share ontologies with MSH6: view

Phenotypes for MSH6 Gene

genes like me logo Genes that share phenotypes with MSH6: view

Animal Models for MSH6 Gene

MGI Knock Outs for MSH6:

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for MSH6 Gene

Localization for MSH6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MSH6 Gene

Nucleus. Chromosome. Note=Associates with H3K36me3 via its PWWP domain.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for MSH6 Gene COMPARTMENTS Subcellular localization image for MSH6 gene
Compartment Confidence
nucleus 5
cytosol 4
golgi apparatus 4
cytoskeleton 2
plasma membrane 2
extracellular 1
mitochondrion 1
vacuole 1

Gene Ontology (GO) - Cellular Components for MSH6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000228 nuclear chromosome IBA --
GO:0000790 nuclear chromatin IEA --
GO:0005634 nucleus --
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IDA --
genes like me logo Genes that share ontologies with MSH6: view

Pathways for MSH6 Gene

genes like me logo Genes that share pathways with MSH6: view

Pathways by source for MSH6 Gene

Gene Ontology (GO) - Biological Process for MSH6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000710 meiotic mismatch repair ISS --
GO:0006200 obsolete ATP catabolic process --
GO:0006281 DNA repair TAS --
GO:0006298 mismatch repair TAS --
GO:0007131 reciprocal meiotic recombination IBA --
genes like me logo Genes that share ontologies with MSH6: view

Compounds for MSH6 Gene

(11) Novoseek inferred chemical compound relationships for MSH6 Gene

Compound -log(P) Hits PubMed IDs
mononucleotide 77 9
crcs 68.4 4
o6-methylguanine 62.7 2
n-methyl-n-nitrosourea 27.1 1
tyrosine 3.92 1
genes like me logo Genes that share compounds with MSH6: view

Transcripts for MSH6 Gene

Unigene Clusters for MSH6 Gene

MutS homolog 6 (E. coli):
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for MSH6 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b · 8c · 8d ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14
SP1: - - - - -
SP2: - - - - - -
SP3: - - - -
SP4: - - - - -
SP5: - -
SP6: -
SP7: - - -
SP8: - - -
SP9: - - - - - -

Relevant External Links for MSH6 Gene

GeneLoc Exon Structure for
MSH6
ECgene alternative splicing isoforms for
MSH6

Expression for MSH6 Gene

mRNA expression in normal human tissues for MSH6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for MSH6 Gene

SOURCE GeneReport for Unigene cluster for MSH6 Gene Hs.445052

genes like me logo Genes that share expressions with MSH6: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for MSH6 Gene

Orthologs for MSH6 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for MSH6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MSH6 35
  • 99.5 (n)
  • 99.48 (a)
MSH6 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia MSH6 35
  • 90.55 (n)
  • 92.27 (a)
MSH6 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia MSH6 35
  • 91.48 (n)
  • 93.49 (a)
MSH6 36
  • 93 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Msh6 35
  • 84.44 (n)
  • 85.97 (a)
Msh6 16
Msh6 36
  • 86 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia MSH6 36
  • 78 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MSH6 36
  • 65 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia LOC100360342 35
  • 84.37 (n)
  • 86.12 (a)
chicken
(Gallus gallus)
Aves MSH6 35
  • 67.95 (n)
  • 69.81 (a)
MSH6 36
  • 67 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia MSH6 36
  • 64 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia msh6 35
  • 66.42 (n)
  • 68.02 (a)
Str.3583 35
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1092 35
zebrafish
(Danio rerio)
Actinopterygii msh6 35
  • 60.96 (n)
  • 62.08 (a)
msh6 36
  • 59 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP003190 35
  • 50.77 (n)
  • 48.21 (a)
fruit fly
(Drosophila melanogaster)
Insecta Msh6 35
  • 50.23 (n)
  • 45.84 (a)
Msh6 36
  • 42 (a)
OneToOne
CG7003 37
  • 41 (a)
worm
(Caenorhabditis elegans)
Secernentea msh-6 35
  • 49.63 (n)
  • 41.46 (a)
msh-6 36
  • 36 (a)
OneToOne
msh-6 37
  • 40 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_AGR116W 35
  • 45.99 (n)
  • 35.9 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MSH6 35
  • 46.48 (n)
  • 36.52 (a)
MSH6 36
  • 30 (a)
OneToOne
MSH6 38
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0C17732g 35
  • 45.92 (n)
  • 35.59 (a)
thale cress
(Arabidopsis thaliana)
eudicotyledons MSH6 35
  • 49.11 (n)
  • 40.27 (a)
bread mold
(Neurospora crassa)
Ascomycetes NCU08135 35
  • 45.9 (n)
  • 38.62 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes msh6 35
  • 46.59 (n)
  • 36.43 (a)
sea squirt
(Ciona savignyi)
Ascidiacea CSA.1020 36
  • 48 (a)
OneToOne
Species with no ortholog for MSH6:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for MSH6 Gene

ENSEMBL:
Gene Tree for MSH6 (if available)
TreeFam:
Gene Tree for MSH6 (if available)

Paralogs for MSH6 Gene

genes like me logo Genes that share paralogs with MSH6: view

No data available for Paralogs for MSH6 Gene

Variants for MSH6 Gene

Sequence variations from dbSNP and Humsavar for MSH6 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs191332 -- 47,788,859(-) cgcag(G/T)ggctc intron-variant
rs330792 -- 47,781,435(-) tgcat(G/T)tcatc upstream-variant-2KB
rs420594 -- 47,802,737(+) GAACA(A/G/T)AATAA intron-variant
rs728619 - 47,799,596(+) TAAGT(A/C)TCTTC reference, missense
rs811754 -- 47,788,756(-) catct(C/T)tacta intron-variant

Structural Variations from Database of Genomic Variants (DGV) for MSH6 Gene

Variant ID Type Subtype PubMed ID
nsv873999 CNV Gain 21882294

Relevant External Links for MSH6 Gene

HapMap Linkage Disequilibrium report
MSH6
Human Gene Mutation Database (HGMD)
MSH6
Locus Specific Mutation Databases (LSDB)
MSH6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MSH6 Gene

Disorders for MSH6 Gene

(3) OMIM Diseases for MSH6 Gene (600678)

UniProtKB/Swiss-Prot

MSH6_HUMAN
  • Hereditary non-polyposis colorectal cancer 5 (HNPCC5) [MIM:614350]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term suspected HNPCC or incomplete HNPCC can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269 PubMed:10480359, ECO:0000269 PubMed:10521294, ECO:0000269 PubMed:11586295, ECO:0000269 PubMed:12658575, ECO:0000269 PubMed:14974087, ECO:0000269 PubMed:15365995, ECO:0000269 PubMed:9354786}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. {ECO:0000269 PubMed:11153917, ECO:0000269 PubMed:14961575}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
  • Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients. {ECO:0000269 PubMed:17557300}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(42) Novoseek inferred disease relationships for MSH6 Gene

Disease -log(P) Hits PubMed IDs
lynch syndrome 96.2 29
microsatellite instability 94.7 45
colorectal cancer 88 157
endometrial cancer 84.4 32
hereditary nonpolyposis colon cancer 83.1 2

Relevant External Links for MSH6

GeneTests
MSH6
GeneReviews
MSH6
Genetic Association Database (GAD)
MSH6
Human Genome Epidemiology (HuGE) Navigator
MSH6
genes like me logo Genes that share disorders with MSH6: view

Publications for MSH6 Gene

  1. Mutations of GTBP in genetically unstable cells. (PMID: 7604266) Papadopoulos N. … Vogelstein B. (Science 1995) 2 3 4 23
  2. MSH6 germline mutations are rare in colorectal cancer families. (PMID: 14520694) Peterlongo P. … Ellis N.A. (Int. J. Cancer 2003) 3 4 23 48
  3. Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with double primary cancers of the colorectum and the endometrium: a population-based study in northern Sweden. (PMID: 14961575) Cederquist K. … Groenberg H. (Int. J. Cancer 2004) 3 4 23 48
  4. GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells. (PMID: 7604265) Palombo F. … Jiricny J. (Science 1995) 3 4 23
  5. Eight novel MSH6 germline mutations in patients with familial and nonfamilial colorectal cancer selected by loss of protein expression in tumor tissue. (PMID: 14974087) Plaschke J. … Schackert H.K. (Hum. Mutat. 2004) 3 4 23

Products for MSH6 Gene

Sources for MSH6 Gene

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