| Written | 2006-07 | Enric Domingo, Simo Schwartz Jr |
| Oncologia Molecular i Envelliment, Centre d'Investigacions en Bioqumica i Biologia Molecular (CIBBIM) Hospital Universitari Vall d'Hebron Passeig Vall d'Hebron 119-129 Barcelona 08035, Catalonia, Spain |
| Identity |
| Alias_names | mutS (E. coli) homolog 3 |
| mutS homolog 3 (E. coli) | |
| Alias_symbol (synonym) | DUP |
| MRP1 | |
| Other alias | hMSH3 |
| HGNC (Hugo) | MSH3 |
| LocusID (NCBI) | 4437 |
| Atlas_Id | 341 |
| Location | 5q14.1 [Link to chromosome band 5q14] |
| Location_base_pair | Starts at 80654648 and ends at 80876815 bp from pter ( according to hg19-Feb_2009) [Mapping MSH3.png] |
| Local_order | Between the DHFR and RASGRF2 genes. |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| MSH3 (5q14.1) / MSH3 (5q14.1) |
| 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 |
| Note | |
| 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. |
| Bibliography |
| 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 |
| 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 |
| DNA mismatch repair defects: role in colorectal carcinogenesis. |
| Jacob S, Praz F |
| Biochimie. 2002 ; 84 (1) : 27-47. |
| PMID 11900875 |
| 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 |
| 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 journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/MSH3ID341ch5q11.html |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 4 ] |
|
Breast tumors : an overview
Colon: Colorectal adenocarcinoma Breast: Ductal carcinoma Gastric Tumors: an overview |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon May 14 12:47:30 CEST 2018 |
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