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MSH3 mutS homolog 3 (E. coli)

Identity

Other namesDUP
hMSH3
MRP1
HGNC (Hugo) MSH3
LocusID (NCBI) 4437
Location 5q14.1
Location_base_pair Starts at 79950467 and ends at 80172634 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Local_order Between the DHFR and RASGRF2 genes.

DNA/RNA

Description The MSH3 gene is composed of 24 exons spanning in a region of 222 Kb.
Transcription There are two major transcripts of 5 kb and 3,8 kb under the control of two different polyadenilation sites.

Protein

Description Amino acids: 1137. Molecular Weight: 127 KDa. MSH3 is a protein involved in the mismatch repair process after DNA replication.
Expression Expression of MSH3 together with the dihydrofolate reductase (DHFR) gene appear to be regulated by a bidirectional promoter composed of multiple GC boxes and two initiator elements. MSH3 is expressed in all human tissues at low levels but with variable intensities, with higher expression in testis and pancreas and lower in small intestine and colon.
Function MSH3 binds to MSH2 to form the MutSb heterodimer, which binds to insertion-deletion mismatches of two or more base pairs. Thereafter the MutS complex associates with the MutL complex and recruits the proteins needed for DNA excision and repair.
Homology MSH3 is homologue to the bacterial MutS gene and to the Msh3 gene in S. cerevisiae. Homology is higher in the C-terminal region.

Mutations

Somatic MSH3 has insertions/deletions in a A(8) repeat in tumours showing microsatellite instability (MSI). As MSH3 is a mismatch repair gene and is mutated in a microsatellite only in MSI tumours is considered to be a secondary mutator that enhances a more severe MSI.

Implicated in

Entity MSI (MicroSatellite Instability).
Note Tumours in which the molecular feature that leads to cancer is the lost of the mismatch repair (MMR) system.
Disease This phenotype is present in 15% of colorectal cancer, gastric cancer and endometrial cancer, and with lower incidence in some other tissues.
Oncogenesis The average frequencies of the microsatellite mutation reported in sporadic MSI from colorectal, gastric and endometrial cancer are 38%, 39% and 25% respectively. In hereditary MSI (or HNPCC) is 51%.
  
Entity Hematological malignancies.
Oncogenesis It has been reported loss of expression of MSH3 at the mRNA level in some hematological malignancies including chronic myelogenous leukemia and acute myelogenous leukemia, acute lymphocytic leukemia and myelodysplastic syndrome.
  

Other Solid tumors implicated (Data extracted from papers in the Atlas)

Solid Tumors AmeloblastomID5945

External links

Nomenclature
HGNC (Hugo)MSH3   7326
Cards
AtlasMSH3ID341ch5q11
Entrez_Gene (NCBI)MSH3  4437  mutS homolog 3
GeneCards (Weizmann)MSH3
Ensembl hg19 (Hinxton)ENSG00000113318 [Gene_View]  chr5:79950467-80172634 [Contig_View]  MSH3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000113318 [Gene_View]  chr5:79950467-80172634 [Contig_View]  MSH3 [Vega]
ICGC DataPortalENSG00000113318
cBioPortalMSH3
AceView (NCBI)MSH3
Genatlas (Paris)MSH3
WikiGenes4437
SOURCE (Princeton)MSH3
Genomic and cartography
GoldenPath hg19 (UCSC)MSH3  -     chr5:79950467-80172634 +  5q11-q12   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)MSH3  -     5q11-q12   [Description]    (hg38-Dec_2013)
EnsemblMSH3 - 5q11-q12 [CytoView hg19]  MSH3 - 5q11-q12 [CytoView hg38]
Mapping of homologs : NCBIMSH3 [Mapview hg19]  MSH3 [Mapview hg38]
OMIM600887   
Gene and transcription
Genbank (Entrez)AA601983 AI817671 AK289856 BC004177 BC011817
RefSeq transcript (Entrez)NM_002439
RefSeq genomic (Entrez)AC_000137 NC_000005 NC_018916 NG_016607 NT_034772 NW_001838951 NW_004929322
Consensus coding sequences : CCDS (NCBI)MSH3
Cluster EST : UnigeneHs.648635 [ NCBI ]
CGAP (NCI)Hs.648635
Alternative Splicing : Fast-db (Paris)GSHG0024068
Alternative Splicing GalleryENSG00000113318
Gene ExpressionMSH3 [ NCBI-GEO ]     MSH3 [ SEEK ]   MSH3 [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP20585 (Uniprot)
NextProtP20585  [Medical]
With graphics : InterProP20585
Splice isoforms : SwissVarP20585 (Swissvar)
Domaine pattern : Prosite (Expaxy)DNA_MISMATCH_REPAIR_2 (PS00486)   
Domains : Interpro (EBI)DNA_mismatch_repair_MutS-lik_N    DNA_mismatch_repair_MutS_C    DNA_mismatch_repair_MutS_clamp    DNA_mismatch_repair_MutS_core    DNA_mismatch_repair_MutS_N    DNA_mmatch_repair_MutS_con_dom    P-loop_NTPase   
Related proteins : CluSTrP20585
Domain families : Pfam (Sanger)MutS_I (PF01624)    MutS_II (PF05188)    MutS_III (PF05192)    MutS_IV (PF05190)    MutS_V (PF00488)   
Domain families : Pfam (NCBI)pfam01624    pfam05188    pfam05192    pfam05190    pfam00488   
Domain families : Smart (EMBL)MUTSac (SM00534)  MUTSd (SM00533)  
DMDM Disease mutations4437
Blocks (Seattle)P20585
PDB (SRS)3THW    3THX    3THY    3THZ   
PDB (PDBSum)3THW    3THX    3THY    3THZ   
PDB (IMB)3THW    3THX    3THY    3THZ   
PDB (RSDB)3THW    3THX    3THY    3THZ   
Human Protein AtlasENSG00000113318
Peptide AtlasP20585
HPRD02931
IPIIPI00329605   IPI01011704   
Protein Interaction databases
DIP (DOE-UCLA)P20585
IntAct (EBI)P20585
FunCoupENSG00000113318
BioGRIDMSH3
IntegromeDBMSH3
STRING (EMBL)MSH3
Ontologies - Pathways
QuickGOP20585
Ontology : AmiGOnuclear chromosome  Y-form DNA binding  heteroduplex DNA loop binding  double-strand/single-strand DNA junction binding  meiotic mismatch repair  single-stranded DNA binding  protein binding  ATP binding  nucleus  ATP catabolic process  DNA repair  mismatch repair  reciprocal meiotic recombination  DNA-dependent ATPase activity  membrane  somatic recombination of immunoglobulin gene segments  centromeric DNA binding  enzyme binding  mismatched DNA binding  guanine/thymine mispair binding  dinucleotide insertion or deletion binding  single guanine insertion binding  dinucleotide repeat insertion binding  MutSbeta complex  oxidized purine DNA binding  protein homodimerization activity  maintenance of DNA repeat elements  negative regulation of DNA recombination  positive regulation of helicase activity  
Ontology : EGO-EBInuclear chromosome  Y-form DNA binding  heteroduplex DNA loop binding  double-strand/single-strand DNA junction binding  meiotic mismatch repair  single-stranded DNA binding  protein binding  ATP binding  nucleus  ATP catabolic process  DNA repair  mismatch repair  reciprocal meiotic recombination  DNA-dependent ATPase activity  membrane  somatic recombination of immunoglobulin gene segments  centromeric DNA binding  enzyme binding  mismatched DNA binding  guanine/thymine mispair binding  dinucleotide insertion or deletion binding  single guanine insertion binding  dinucleotide repeat insertion binding  MutSbeta complex  oxidized purine DNA binding  protein homodimerization activity  maintenance of DNA repeat elements  negative regulation of DNA recombination  positive regulation of helicase activity  
Pathways : KEGGMismatch repair    Pathways in cancer    Colorectal cancer   
Protein Interaction DatabaseMSH3
DoCM (Curated mutations)MSH3
Wikipedia pathwaysMSH3
Gene fusion - rearrangements
Polymorphisms : SNP, variants
NCBI Variation ViewerMSH3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)MSH3
dbVarMSH3
ClinVarMSH3
1000_GenomesMSH3 
Exome Variant ServerMSH3
SNP (GeneSNP Utah)MSH3
SNP : HGBaseMSH3
Genetic variants : HAPMAPMSH3
Genomic VariantsMSH3  MSH3 [DGVbeta]
Mutations
ICGC Data PortalENSG00000113318 
Somatic Mutations in Cancer : COSMICMSH3 
CONAN: Copy Number AnalysisMSH3 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)5:79950467-80172634
Mutations and Diseases : HGMDMSH3
OMIM600887   
MedgenMSH3
NextProtP20585 [Medical]
GENETestsMSH3
Disease Genetic AssociationMSH3
Huge Navigator MSH3 [HugePedia]  MSH3 [HugeCancerGEM]
snp3D : Map Gene to Disease4437
DGIdb (Drug Gene Interaction db)MSH3
General knowledge
Homologs : HomoloGeneMSH3
Homology/Alignments : Family Browser (UCSC)MSH3
Phylogenetic Trees/Animal Genes : TreeFamMSH3
Chemical/Protein Interactions : CTD4437
Chemical/Pharm GKB GenePA31134
Clinical trialMSH3
Cancer Resource (Charite)ENSG00000113318
Other databases
Probes
Litterature
PubMed95 Pubmed reference(s) in Entrez
CoreMineMSH3
GoPubMedMSH3
iHOPMSH3

Bibliography

Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene.
Fujii H, Shimada T
The Journal of biological chemistry. 1989 ; 264 (17) : 10057-10064.
PMID 2722860
 
Loss of expression of the human MSH3 gene in hematological malignancies.
Inokuchi K, Ikejima M, Watanabe A, Nakajima E, Orimo H, Nomura T, Shimada T
Biochemical and biophysical research communications. 1995 ; 214 (1) : 171-179.
PMID 7669036
 
Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair.
Risinger JI, Umar A, Boyd J, Berchuck A, Kunkel TA, Barrett JC
Nature genetics. 1996 ; 14 (1) : 102-105.
PMID 8782829
 
Genomic organization and expression of the human MSH3 gene.
Watanabe A, Ikejima M, Suzuki N, Shimada T
Genomics. 1996 ; 31 (3) : 311-318.
PMID 8838312
 
HNPCC-like cancer predisposition in mice through simultaneous loss of Msh3 and Msh6 mismatch-repair protein functions.
de Wind N, Dekker M, Claij N, Jansen L, van Klink Y, Radman M, Riggins G, van der Valk M, van't Wout K, te Riele H
Nature genetics. 1999 ; 23 (3) : 359-362.
PMID 10545954
 
Mutations at coding repeat sequences in mismatch repair-deficient human cancers: toward a new concept of target genes for instability.
Duval A, Hamelin R
Cancer research. 2002 ; 62 (9) : 2447-2454.
PMID 11980631
 
DNA mismatch repair defects: role in colorectal carcinogenesis.
Jacob S, Praz F
Biochimie. 2002 ; 84 (1) : 27-47.
PMID 11900875
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written07-2006Enric Domingo, Simo Schwartz Jr

Citation

This paper should be referenced as such :
Domingo, E ; Schwartz, S Jr. MSH3 (mutS homolog 3 (E
coli))
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):251-252.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MSH3ID341ch5q11.html

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indexed on : Sun Dec 21 03:13:32 CET 2014

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