MSH6

MutS homolog 6 (E. coli)
PDB rendering based on 2gfu.
Available structures PDB 2GFU, 2O8B, 2O8C, 2O8D, 2O8E, 2O8F
Identifiers
Symbols	MSH6; GTBP; HNPCC5; HSAP
External IDs	OMIM: 600678 MGI: 1343961 HomoloGene: 149 GeneCards: MSH6 Gene
Gene Ontology Molecular function • nucleotide binding • magnesium ion binding • four-way junction DNA binding • chromatin binding • damaged DNA binding • double-stranded DNA binding • protein binding • protein binding • ATP binding • DNA-dependent ATPase activity • ATPase activity • mismatched DNA binding • guanine/thymine mispair binding • single guanine insertion binding • single thymine insertion binding • oxidized purine DNA binding • MutLalpha complex binding • protein homodimerization activity • ADP binding Cellular component • nuclear chromosome • nuclear chromatin • nucleus • MutSalpha complex Biological process • meiotic mismatch repair • meiotic mismatch repair • ATP catabolic process • DNA repair • mismatch repair • mismatch repair • reciprocal meiotic recombination • determination of adult lifespan • induction of apoptosis by intracellular signals • DNA damage response, signal transduction resulting in induction of apoptosis • DNA damage response, signal transduction resulting in induction of apoptosis • response to UV • response to UV • somatic hypermutation of immunoglobulin genes • somatic hypermutation of immunoglobulin genes • somatic recombination of immunoglobulin gene segments • maintenance of DNA repeat elements • isotype switching • isotype switching • negative regulation of DNA recombination • positive regulation of helicase activity Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2956	17688
Ensembl	ENSG00000116062	ENSMUSG00000005370
UniProt	P52701	Q61061
RefSeq (mRNA)	NM_000179.2	NM_010830.2
RefSeq (protein)	NP_000170.1	NP_034960.1
Location (UCSC)	Chr 2: 48.01 – 48.03 Mb	Chr 17: 88.37 – 88.39 Mb
PubMed search	[1]	[2]

MSH6 is a gene commonly associated with hereditary nonpolyposis colorectal cancer.

Function

MSH6 contributes to ADP and ATP binding.^[1] It also contributes to ATPase activity.^[2] The product of this gene plays a role in binding double-stranded DNA and in four-way junction DNA Binding.^[3][4]

Interactions

MSH6 has been shown to interact with MSH2,^{[5][6][7][8][9]} PCNA^[10][11][12] and BRCA1.^[5][13]

See also

• Mismatch_repair#MutS

References

1. ^ Martik, D; Baitinger, C, Modrich, P (2004-07-02). "Differential specificities and simultaneous occupancy of human MutSalpha nucleotide binding sites.". The Journal of biological chemistry 279 (27): 28402–10. PMID 15105434. 
2. ^ Plotz, G; Piiper, A, Wormek, M, Zeuzem, S, Raedle, J (2006-02-17). "Analysis of the human MutLalpha.MutSalpha complex.". Biochemical and biophysical research communications 340 (3): 852–9. doi:10.1016/j.bbrc.2005.12.096. PMID 16403449. 
3. ^ Subramanian, D; Griffith, JD (2002-06-01). "Interactions between p53, hMSH2-hMSH6 and HMG I(Y) on Holliday junctions and bulged bases.". Nucleic Acids Research 30 (11): 2427–34. doi:10.1093/nar/30.11.2427. PMC 117204. PMID 12034830. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=117204. 
4. ^ Plotz, G; Raedle, J, Brieger, A, Trojan, J, Zeuzem, S (2002-02-01). "hMutSalpha forms an ATP-dependent complex with hMutLalpha and hMutLbeta on DNA.". Nucleic Acids Research 30 (3): 711–8. doi:10.1093/nar/30.3.711. PMC 100294. PMID 11809883. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=100294. 
5. ^ ^{a b} Wang, Y; Cortez D, Yazdi P, Neff N, Elledge S J, Qin J (Apr. 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. (UNITED STATES) 14 (8): 927–39. ISSN 0890-9369. PMC 316544. PMID 10783165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316544. 
6. ^ Wang, Yi; Qin Jun (Dec. 2003). "MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (26): 15387–92. doi:10.1073/pnas.2536810100. ISSN 0027-8424. PMC 307577. PMID 14657349. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=307577. 
7. ^ Guerrette, S; Wilson T, Gradia S, Fishel R (Nov. 1998). "Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer". Mol. Cell. Biol. (UNITED STATES) 18 (11): 6616–23. ISSN 0270-7306. PMC 109246. PMID 9774676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109246. 
8. ^ Bocker, T; Barusevicius A, Snowden T, Rasio D, Guerrette S, Robbins D, Schmidt C, Burczak J, Croce C M, Copeland T, Kovatich A J, Fishel R (Feb. 1999). "hMSH5: a human MutS homologue that forms a novel heterodimer with hMSH4 and is expressed during spermatogenesis". Cancer Res. (UNITED STATES) 59 (4): 816–22. ISSN 0008-5472. PMID 10029069. 
9. ^ Acharya, S; Wilson T, Gradia S, Kane M F, Guerrette S, Marsischky G T, Kolodner R, Fishel R (Nov. 1996). "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 93 (24): 13629–34. doi:10.1073/pnas.93.24.13629. ISSN 0027-8424. PMC 19374. PMID 8942985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19374. 
10. ^ Kleczkowska, H E; Marra G, Lettieri T, Jiricny J (Mar. 2001). "hMSH3 and hMSH6 interact with PCNA and colocalize with it to replication foci". Genes Dev. (United States) 15 (6): 724–36. doi:10.1101/gad.191201. ISSN 0890-9369. PMC 312660. PMID 11274057. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=312660. 
11. ^ Clark, A B; Valle F, Drotschmann K, Gary R K, Kunkel T A (Nov. 2000). "Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes". J. Biol. Chem. (UNITED STATES) 275 (47): 36498–501. doi:10.1074/jbc.C000513200. ISSN 0021-9258. PMID 11005803. 
12. ^ Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (Oct. 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". J. Biol. Chem. (United States) 277 (43): 40362–7. doi:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929. 
13. ^ Wang, Q; Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene M I (Aug. 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene (England) 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. ISSN 0950-9232. PMID 11498787. 

External links

• FAQs on HNPCC from the National Institute of Health
• GeneReviews/NCBI/NIH/UW entry on Lynch syndrome
• MeSH MSH6+protein,+human

Further reading

• Drummond JT, Li GM, Longley MJ, Modrich P (1995). "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.". Science 268 (5219): 1909–12. doi:10.1126/science.7604264. PMID 7604264. 
• Palombo F, Gallinari P, Iaccarino I, et al. (1995). "GTBP, a 160-kilodalton protein essential for mismatch-binding activity in human cells.". Science 268 (5219): 1912–4. doi:10.1126/science.7604265. PMID 7604265. 
• Papadopoulos N, Nicolaides NC, Liu B, et al. (1995). "Mutations of GTBP in genetically unstable cells.". Science 268 (5219): 1915–7. doi:10.1126/science.7604266. PMID 7604266. 
• Risinger JI, Umar A, Boyd J, et al. (1996). "Mutation of MSH3 in endometrial cancer and evidence for its functional role in heteroduplex repair.". Nat. Genet. 14 (1): 102–5. doi:10.1038/ng0996-102. PMID 8782829. 
• Nicolaides NC, Palombo F, Kinzler KW, et al. (1997). "Molecular cloning of the N-terminus of GTBP.". Genomics 31 (3): 395–7. doi:10.1006/geno.1996.0067. PMID 8838326. 
• Acharya S, Wilson T, Gradia S, et al. (1997). "hMSH2 forms specific mispair-binding complexes with hMSH3 and hMSH6.". Proc. Natl. Acad. Sci. U.S.A. 93 (24): 13629–34. doi:10.1073/pnas.93.24.13629. PMC 19374. PMID 8942985. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=19374. 
• Miyaki M, Konishi M, Tanaka K, et al. (1997). "Germline mutation of MSH6 as the cause of hereditary nonpolyposis colorectal cancer.". Nat. Genet. 17 (3): 271–2. doi:10.1038/ng1197-271. PMID 9354786. 
• Yin J, Kong D, Wang S, et al. (1998). "Mutation of hMSH3 and hMSH6 mismatch repair genes in genetically unstable human colorectal and gastric carcinomas.". Hum. Mutat. 10 (6): 474–8. doi:10.1002/(SICI)1098-1004(1997)10:6<474::AID-HUMU9>3.0.CO;2-D. PMID 9401011. 
• Gradia S, Acharya S, Fishel R (1998). "The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.". Cell 91 (7): 995–1005. doi:10.1016/S0092-8674(00)80490-0. PMID 9428522. 
• Shiwaku HO, Wakatsuki S, Mori Y, et al. (1998). "Alternative splicing of GTBP in normal human tissues.". DNA Res. 4 (5): 359–62. doi:10.1093/dnares/4.5.359. PMID 9455487. 
• Wei Q, Guan Y, Cheng L, et al. (1998). "Expression of five selected human mismatch repair genes simultaneously detected in normal and cancer cell lines by a nonradioactive multiplex reverse transcription-polymerase chain reaction.". Pathobiology 65 (6): 293–300. doi:10.1159/000164141. PMID 9491849. 
• Guerrette S, Wilson T, Gradia S, Fishel R (1998). "Interactions of human hMSH2 with hMSH3 and hMSH2 with hMSH6: examination of mutations found in hereditary nonpolyposis colorectal cancer.". Mol. Cell. Biol. 18 (11): 6616–23. PMC 109246. PMID 9774676. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=109246. 
• Wang Q, Lasset C, Desseigne F, et al. (1999). "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and hMSH6 genes in 75 French kindreds with nonpolyposis colorectal cancer.". Hum. Genet. 105 (1–2): 79–85. doi:10.1007/s004390051067. PMID 10480359. 
• Wijnen J, de Leeuw W, Vasen H, et al. (1999). "Familial endometrial cancer in female carriers of MSH6 germline mutations". Nat. Genet. 23 (2): 142–4. doi:10.1038/13773. PMID 10508506. 
• Wu Y, Berends MJ, Mensink RG, et al. (1999). "Association of hereditary nonpolyposis colorectal cancer-related tumors displaying low microsatellite instability with MSH6 germline mutations". Am. J. Hum. Genet. 65 (5): 1291–8. doi:10.1086/302612. PMC 1288281. PMID 10521294. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1288281. 
• Kolodner RD, Tytell JD, Schmeits JL, et al. (1999). "Germ-line msh6 mutations in colorectal cancer families". Cancer Res. 59 (20): 5068–74. PMID 10537275. 
• Wang Y, Cortez D, Yazdi P, et al. (2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. PMC 316544. PMID 10783165. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=316544. 
• Ceccotti S, Ciotta C, Fronza G, et al. (2000). "Multiple mutations and frameshifts are the hallmark of defective hPMS2 in pZ189-transfected human tumor cells". Nucleic Acids Res. 28 (13): 2577–84. doi:10.1093/nar/28.13.2577. PMC 102707. PMID 10871409. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=102707. 
• Christmann M, Kaina B (2000). "Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents". J. Biol. Chem. 275 (46): 36256–62. doi:10.1074/jbc.M005377200. PMID 10954713. 
• Clark AB, Valle F, Drotschmann K, et al. (2001). "Functional interaction of proliferating cell nuclear antigen with MSH2-MSH6 and MSH2-MSH3 complexes". J. Biol. Chem. 275 (47): 36498–501. doi:10.1074/jbc.C000513200. PMID 11005803.