MCM6

The MCM complex consisting of MCM6 (this protein) and MCM2, 4 and 7 possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The hexameric protein complex formed by the MCM proteins is a key component of the pre-replication complex (pre-RC) and may be involved in the formation of replication forks and in the recruitment of other DNA replication related proteins. The phosphorylation of the complex by CDC2 kinase reduces the helicase activity, suggesting a role in the regulation of DNA replication.{{cite web | title = Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4175}} Mcm 6 has recently been shown to interact strongly Cdt1 at defined residues, by mutating these target residues Wei et al. observed lack of Cdt1 recruitment of Mcm2-7 to the pre-RC.{{cite journal | vauthors = Wei Z, Liu C, Wu X, Xu N, Zhou B, Liang C, Zhu G | title = Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6 | journal = J Biol Chem | volume = 285 | issue = 17 | pages = 12469–73 | date = March 2010 | pmid = 20202939 | pmc = 2857124 | doi = 10.1074/jbc.C109.094599 | doi-access = free }}

The MCM6 gene, MCM6, is expressed at very high level. MCM6 contains 18 introns. There are 2 non overlapping alternative last exons. The transcripts appear to differ by truncation of the 3' end, presence or absence of 2 cassette exons, common exons with different boundaries.

MCM6 produces, by alternative splicing, 3 different transcripts, all with introns, putatively encoding 3 different protein isoforms.

MCM6 contains two of the regulatory regions for LCT, the gene encoding the protein lactase, located in two of the MCM6 introns, approximately 14 kb and 22 kb upstream of LCT.{{cite journal | vauthors = Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I | title = Identification of a variant associated with adult-type hypolactasia | journal = Nat. Genet. | volume = 30 | issue = 2 | pages = 233–7 | date = February 2002 | pmid = 11788828 | doi = 10.1038/ng826 | s2cid = 21430931 }} A substitution of thymine for cytosine in the first region (at -13910), in particular, has been shown to function in vitro as an enhancer element capable of differentially activating transcription of LCT promoter.{{cite journal | vauthors = Olds LC, Sibley E | title = Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element | journal = Hum. Mol. Genet. | volume = 12 | issue = 18 | pages = 2333–40 | date = September 2003 | pmid = 12915462 | doi = 10.1093/hmg/ddg244 | doi-access = free }}

Mutations in these regions are associated with lactose tolerance into adult life.{{cite journal | pmc = 3401057 |doi=10.2147/CEG.S32368 | pmid=22826639 | volume=5 | title=Lactose intolerance: diagnosis, genetic, and clinical factors | year=2012 | journal=Clin Exp Gastroenterol | pages=113–21 | vauthors=Mattar R, de Campos Mazo DF, Carrilho FJ |doi-access=free }} " Two variants were associated with lactase persistence..."

MCM6 has been shown to interact with:

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• CDC45-related protein,
• MCM2,{{cite journal | vauthors = Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M | title = Towards a proteome-scale map of the human protein-protein interaction network | journal = Nature | volume = 437 | issue = 7062 | pages = 1173–8 | date = October 2005 | pmid = 16189514 | doi = 10.1038/nature04209 | bibcode = 2005Natur.437.1173R | s2cid = 4427026 }}{{cite journal | vauthors = You Z, Komamura Y, Ishimi Y | title = Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity | journal = Mol. Cell. Biol. | volume = 19 | issue = 12 | pages = 8003–15 | date = December 1999 | pmid = 10567526 | pmc = 84885 | doi = 10.1128/MCB.19.12.8003}}
• MCM4,{{cite journal | vauthors = Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H | title = Mammalian Mcm2/4/6/7 complex forms a toroidal structure | journal = Genes Cells | volume = 8 | issue = 5 | pages = 413–21 | date = May 2003 | pmid = 12694531 | doi = 10.1046/j.1365-2443.2003.00645.x| s2cid = 27707848 | doi-access = free }}{{cite journal | vauthors = You Z, Ishimi Y, Masai H, Hanaoka F | title = Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex | journal = J. Biol. Chem. | volume = 277 | issue = 45 | pages = 42471–9 | date = November 2002 | pmid = 12207017 | doi = 10.1074/jbc.M205769200 | doi-access = free }}{{cite journal | vauthors = Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H | title = Binding of human minichromosome maintenance proteins with histone H3 | journal = J. Biol. Chem. | volume = 271 | issue = 39 | pages = 24115–22 | date = September 1996 | pmid = 8798650 | doi = 10.1074/jbc.271.39.24115| doi-access = free }}
• MCM7,{{cite journal | vauthors = Fujita M, Kiyono T, Hayashi Y, Ishibashi M | title = In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP | journal = J. Biol. Chem. | volume = 272 | issue = 16 | pages = 10928–35 | date = April 1997 | pmid = 9099751 | doi = 10.1074/jbc.272.16.10928| doi-access = free }}
• ORC1L,{{cite journal | vauthors = Kneissl M, Pütter V, Szalay AA, Grummt F | title = Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells | journal = J. Mol. Biol. | volume = 327 | issue = 1 | pages = 111–28 | date = March 2003 | pmid = 12614612 | doi = 10.1016/s0022-2836(03)00079-2}}
• ORC2L,
• ORC4L, and
• Replication protein A1.

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• Mini Chromosome Maintenance

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• {{cite journal | vauthors = Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H | title = Binding of human minichromosome maintenance proteins with histone H3 | journal = J. Biol. Chem. | volume = 271 | issue = 39 | pages = 24115–22 | year = 1996 | pmid = 8798650 | doi = 10.1074/jbc.271.39.24115 | doi-access = free }}
• {{cite journal | vauthors = Holthoff HP, Hameister H, Knippers R | title = A novel human Mcm protein: homology to the yeast replication protein Mis5 and chromosomal location | journal = Genomics | volume = 37 | issue = 1 | pages = 131–4 | year = 1997 | pmid = 8921380 | doi = 10.1006/geno.1996.0530 }}
• {{cite journal | vauthors = Tsuruga H, Yabuta N, Hosoya S, Tamura K, Endo Y, Nojima H | title = HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5 | journal = Genes Cells | volume = 2 | issue = 6 | pages = 381–99 | year = 1997 | pmid = 9286856 | doi = 10.1046/j.1365-2443.1997.1290327.x | s2cid = 12997515 | doi-access = free }}
• {{cite journal | vauthors = Ishimi Y | title = A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex | journal = J. Biol. Chem. | volume = 272 | issue = 39 | pages = 24508–13 | year = 1997 | pmid = 9305914 | doi = 10.1074/jbc.272.39.24508 | doi-access = free }}
• {{cite journal | vauthors = Holthoff HP, Baack M, Richter A, Ritzi M, Knippers R | title = Human protein MCM6 on HeLa cell chromatin | journal = J. Biol. Chem. | volume = 273 | issue = 13 | pages = 7320–5 | year = 1998 | pmid = 9516426 | doi = 10.1074/jbc.273.13.7320 | doi-access = free }}
• {{cite journal | vauthors = Ohtani K, Iwanaga R, Nakamura M, Ikeda M, Yabuta N, Tsuruga H, Nojima H | title = Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F | journal = Oncogene | volume = 18 | issue = 14 | pages = 2299–309 | year = 1999 | pmid = 10327050 | doi = 10.1038/sj.onc.1202544 | doi-access = free }}
• {{cite journal | vauthors = You Z, Komamura Y, Ishimi Y | title = Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity | journal = Mol. Cell. Biol. | volume = 19 | issue = 12 | pages = 8003–15 | year = 2000 | pmid = 10567526 | pmc = 84885 | doi = 10.1128/MCB.19.12.8003}}
• {{cite journal | vauthors = Ishimi Y, Komamura-Kohno Y, You Z, Omori A, Kitagawa M | title = Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2 | journal = J. Biol. Chem. | volume = 275 | issue = 21 | pages = 16235–41 | year = 2000 | pmid = 10748114 | doi = 10.1074/jbc.M909040199 | doi-access = free }}
• {{cite journal | vauthors = Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F | title = The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase | journal = Nucleic Acids Res. | volume = 28 | issue = 23 | pages = 4769–77 | year = 2001 | pmid = 11095689 | pmc = 115166 | doi = 10.1093/nar/28.23.4769 }}
• {{cite journal | vauthors = Lee JK, Hurwitz J | title = Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 98 | issue = 1 | pages = 54–9 | year = 2001 | pmid = 11136247 | pmc = 14543 | doi = 10.1073/pnas.98.1.54 | bibcode = 2001PNAS...98...54L | doi-access = free }}
• {{cite journal | vauthors = Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I | title = Identification of a variant associated with adult-type hypolactasia | journal = Nat. Genet. | volume = 30 | issue = 2 | pages = 233–7 | year = 2002 | pmid = 11788828 | doi = 10.1038/ng826 | s2cid = 21430931 }}
• {{cite journal | vauthors = Yanagi K, Mizuno T, You Z, Hanaoka F | title = Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity | journal = J. Biol. Chem. | volume = 277 | issue = 43 | pages = 40871–80 | year = 2002 | pmid = 12192004 | doi = 10.1074/jbc.M206202200 | doi-access = free }}
• {{cite journal | vauthors = You Z, Ishimi Y, Masai H, Hanaoka F | title = Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex | journal = J. Biol. Chem. | volume = 277 | issue = 45 | pages = 42471–9 | year = 2003 | pmid = 12207017 | doi = 10.1074/jbc.M205769200 | doi-access = free }}
• {{cite journal | vauthors = Kneissl M, Pütter V, Szalay AA, Grummt F | title = Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells | journal = J. Mol. Biol. | volume = 327 | issue = 1 | pages = 111–28 | year = 2003 | pmid = 12614612 | doi = 10.1016/S0022-2836(03)00079-2 }}
• {{cite journal | vauthors = Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H | title = Mammalian Mcm2/4/6/7 complex forms a toroidal structure | journal = Genes Cells | volume = 8 | issue = 5 | pages = 413–21 | year = 2004 | pmid = 12694531 | doi = 10.1046/j.1365-2443.2003.00645.x | s2cid = 27707848 | doi-access = free }}
• {{cite journal | vauthors = Johnson EM, Kinoshita Y, Daniel DC | title = A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13 | journal = Nucleic Acids Res. | volume = 31 | issue = 11 | pages = 2915–25 | year = 2003 | pmid = 12771218 | pmc = 156728 | doi = 10.1093/nar/gkg395 }}
• {{cite journal | vauthors = Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J | title = Self-assembling protein microarrays | journal = Science | volume = 305 | issue = 5680 | pages = 86–90 | year = 2004 | pmid = 15232106 | doi = 10.1126/science.1097639 | bibcode = 2004Sci...305...86R | s2cid = 20936301 }}
• {{cite journal | vauthors = Yu Z, Feng D, Liang C | title = Pairwise interactions of the six human MCM protein subunits | journal = J. Mol. Biol. | volume = 340 | issue = 5 | pages = 1197–206 | year = 2004 | pmid = 15236977 | doi = 10.1016/j.jmb.2004.05.024 }}

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Category:Proteins