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MCM6
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2KLQ, 2LE8
Identifiers
Aliases	MCM6, MCG40308, Mis5, P105MCM, minichromosome maintenance complex component 6
External IDs	OMIM: 601806; MGI: 1298227; HomoloGene: 4322; GeneCards: MCM6; OMA:MCM6 - orthologs
Gene location (Human)
Chr.	Chromosome 2 (human)
End	135,876,443 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	128,287,401 bp
RNA expression pattern
	Top expressed in
	ventricular zone; ; embryo; ; ganglionic eminence; ; trabecular bone; ; endothelial cell; ; gonad; ; glomerulus; ; secondary oocyte; ; metanephric glomerulus; ; bone marrow;
	Top expressed in
	somite; ; Paneth cell; ; mandibular prominence; ; abdominal wall; ; hand; ; maxillary prominence; ; fetal liver hematopoietic progenitor cell; ; primitive streak; ; Gonadal ridge; ; efferent ductule;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	identical protein binding; single-stranded DNA binding; nucleotide binding; DNA helicase activity; DNA binding; protein binding; hydrolase activity; ATP binding; helicase activity; DNA replication origin binding; single-stranded 3'-5' DNA helicase activity;
Cellular component	MCM complex; nucleus; nucleoplasm;
Biological process	G1 phase; DNA replication; cell cycle; DNA replication initiation; DNA unwinding involved in DNA replication; G1/S transition of mitotic cell cycle; double-strand break repair via break-induced replication; pre-replicative complex assembly involved in nuclear cell cycle DNA replication; mitotic DNA replication;
	Sources:Amigo / QuickGO
Orthologs
	4175
	17219
	ENSG00000076003
	ENSMUSG00000026355
	Q14566
	P97311
	NM_005915
	NM_008567; NM_001313695
	NP_005906
	NP_001300624; NP_032593
	Wikidata
View/Edit Human	View/Edit Mouse

DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene.^[5] MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.

Function

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.^[6] 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.^[7]

Gene

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.^[8] 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.^[9]

Mutations in these regions are associated with lactose tolerance into adult life.^[8]^[10]

Interactions

MCM6 has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000076003 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026355 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Harvey CB, Wang Y, Darmoul D, Phillips A, Mantei N, Swallow DM (December 1996). "Characterisation of a human homologue of a yeast cell division cycle gene, MCM6, located adjacent to the 5' end of the lactase gene on chromosome 2q21". FEBS Lett. 398 (2–3): 135–40. doi:10.1016/S0014-5793(96)01189-1. PMID 8977093. S2CID 1323113.
^ "Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)".
^ Wei Z, Liu C, Wu X, Xu N, Zhou B, Liang C, Zhu G (March 2010). "Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6". J Biol Chem. 285 (17): 12469–73. doi:10.1074/jbc.C109.094599. PMC 2857124. PMID 20202939.
^ ^a ^b Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (February 2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828. S2CID 21430931.
^ Olds LC, Sibley E (September 2003). "Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element". Hum. Mol. Genet. 12 (18): 2333–40. doi:10.1093/hmg/ddg244. PMID 12915462.
^ Mattar R, de Campos Mazo DF, Carrilho FJ (2012). "Lactose intolerance: diagnosis, genetic, and clinical factors". Clin Exp Gastroenterol. 5: 113–21. doi:10.2147/CEG.S32368. PMC 3401057. PMID 22826639. " Two variants were associated with lactase persistence..."
^ ^a ^b ^c ^d ^e ^f Kneissl M, Pütter V, Szalay AA, Grummt F (March 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. 327 (1): 111–28. doi:10.1016/s0022-2836(03)00079-2. PMID 12614612.
^ ^a ^b Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H (May 2003). "Mammalian Mcm2/4/6/7 complex forms a toroidal structure". Genes Cells. 8 (5): 413–21. doi:10.1046/j.1365-2443.2003.00645.x. PMID 12694531. S2CID 27707848.
^ ^a ^b ^c You Z, Ishimi Y, Masai H, Hanaoka F (November 2002). "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex". J. Biol. Chem. 277 (45): 42471–9. doi:10.1074/jbc.M205769200. PMID 12207017.
^ 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
^ You Z, Komamura Y, Ishimi Y (December 1999). "Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity". Mol. Cell. Biol. 19 (12): 8003–15. doi:10.1128/MCB.19.12.8003. PMC 84885. PMID 10567526.
^ Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H (September 1996). "Binding of human minichromosome maintenance proteins with histone H3". J. Biol. Chem. 271 (39): 24115–22. doi:10.1074/jbc.271.39.24115. PMID 8798650.
^ Fujita M, Kiyono T, Hayashi Y, Ishibashi M (April 1997). "In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP". J. Biol. Chem. 272 (16): 10928–35. doi:10.1074/jbc.272.16.10928. PMID 9099751.

Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H (1996). "Binding of human minichromosome maintenance proteins with histone H3". J. Biol. Chem. 271 (39): 24115–22. doi:10.1074/jbc.271.39.24115. PMID 8798650.
Holthoff HP, Hameister H, Knippers R (1997). "A novel human Mcm protein: homology to the yeast replication protein Mis5 and chromosomal location". Genomics. 37 (1): 131–4. doi:10.1006/geno.1996.0530. PMID 8921380.
Tsuruga H, Yabuta N, Hosoya S, Tamura K, Endo Y, Nojima H (1997). "HsMCM6: a new member of the human MCM/P1 family encodes a protein homologous to fission yeast Mis5". Genes Cells. 2 (6): 381–99. doi:10.1046/j.1365-2443.1997.1290327.x. PMID 9286856. S2CID 12997515.
Ishimi Y (1997). "A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex". J. Biol. Chem. 272 (39): 24508–13. doi:10.1074/jbc.272.39.24508. PMID 9305914.
Holthoff HP, Baack M, Richter A, Ritzi M, Knippers R (1998). "Human protein MCM6 on HeLa cell chromatin". J. Biol. Chem. 273 (13): 7320–5. doi:10.1074/jbc.273.13.7320. PMID 9516426.
Ohtani K, Iwanaga R, Nakamura M, Ikeda M, Yabuta N, Tsuruga H, Nojima H (1999). "Cell growth-regulated expression of mammalian MCM5 and MCM6 genes mediated by the transcription factor E2F". Oncogene. 18 (14): 2299–309. doi:10.1038/sj.onc.1202544. PMID 10327050.
You Z, Komamura Y, Ishimi Y (2000). "Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity". Mol. Cell. Biol. 19 (12): 8003–15. doi:10.1128/MCB.19.12.8003. PMC 84885. PMID 10567526.
Ishimi Y, Komamura-Kohno Y, You Z, Omori A, Kitagawa M (2000). "Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2". J. Biol. Chem. 275 (21): 16235–41. doi:10.1074/jbc.M909040199. PMID 10748114.
Izumi M, Yanagi K, Mizuno T, Yokoi M, Kawasaki Y, Moon KY, Hurwitz J, Yatagai F, Hanaoka F (2001). "The human homolog of Saccharomyces cerevisiae Mcm10 interacts with replication factors and dissociates from nuclease-resistant nuclear structures in G(2) phase". Nucleic Acids Res. 28 (23): 4769–77. doi:10.1093/nar/28.23.4769. PMC 115166. PMID 11095689.
Lee JK, Hurwitz J (2001). "Processive DNA helicase activity of the minichromosome maintenance proteins 4, 6, and 7 complex requires forked DNA structures". Proc. Natl. Acad. Sci. U.S.A. 98 (1): 54–9. Bibcode:2001PNAS...98...54L. doi:10.1073/pnas.98.1.54. PMC 14543. PMID 11136247.
Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828. S2CID 21430931.
Yanagi K, Mizuno T, You Z, Hanaoka F (2002). "Mouse geminin inhibits not only Cdt1-MCM6 interactions but also a novel intrinsic Cdt1 DNA binding activity". J. Biol. Chem. 277 (43): 40871–80. doi:10.1074/jbc.M206202200. PMID 12192004.
You Z, Ishimi Y, Masai H, Hanaoka F (2003). "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex". J. Biol. Chem. 277 (45): 42471–9. doi:10.1074/jbc.M205769200. PMID 12207017.
Kneissl M, Pütter V, Szalay AA, Grummt F (2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. PMID 12614612.
Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H (2004). "Mammalian Mcm2/4/6/7 complex forms a toroidal structure". Genes Cells. 8 (5): 413–21. doi:10.1046/j.1365-2443.2003.00645.x. PMID 12694531. S2CID 27707848.
Johnson EM, Kinoshita Y, Daniel DC (2003). "A new member of the MCM protein family encoded by the human MCM8 gene, located contrapodal to GCD10 at chromosome band 20p12.3-13". Nucleic Acids Res. 31 (11): 2915–25. doi:10.1093/nar/gkg395. PMC 156728. PMID 12771218.
Ramachandran N, Hainsworth E, Bhullar B, Eisenstein S, Rosen B, Lau AY, Walter JC, LaBaer J (2004). "Self-assembling protein microarrays". Science. 305 (5680): 86–90. Bibcode:2004Sci...305...86R. doi:10.1126/science.1097639. PMID 15232106. S2CID 20936301.
Yu Z, Feng D, Liang C (2004). "Pairwise interactions of the six human MCM protein subunits". J. Mol. Biol. 340 (5): 1197–206. doi:10.1016/j.jmb.2004.05.024. PMID 15236977.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000076003 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026355 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8977093-5] Harvey CB, Wang Y, Darmoul D, Phillips A, Mantei N, Swallow DM (December 1996). "Characterisation of a human homologue of a yeast cell division cycle gene, MCM6, located adjacent to the 5' end of the lactase gene on chromosome 2q21". FEBS Lett. 398 (2–3): 135–40. doi:10.1016/S0014-5793(96)01189-1. PMID 8977093. S2CID 1323113.

[entrez-6] "Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)".

[pmid20202939-7] Wei Z, Liu C, Wu X, Xu N, Zhou B, Liang C, Zhu G (March 2010). "Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6". J Biol Chem. 285 (17): 12469–73. doi:10.1074/jbc.C109.094599. PMC 2857124. PMID 20202939.

[Enattah_2002-8] Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Järvelä I (February 2002). "Identification of a variant associated with adult-type hypolactasia". Nat. Genet. 30 (2): 233–7. doi:10.1038/ng826. PMID 11788828. S2CID 21430931.

[pmid12915462-9] Olds LC, Sibley E (September 2003). "Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element". Hum. Mol. Genet. 12 (18): 2333–40. doi:10.1093/hmg/ddg244. PMID 12915462.

[10] Mattar R, de Campos Mazo DF, Carrilho FJ (2012). "Lactose intolerance: diagnosis, genetic, and clinical factors". Clin Exp Gastroenterol. 5: 113–21. doi:10.2147/CEG.S32368. PMC 3401057. PMID 22826639. " Two variants were associated with lactase persistence..."

[pmid12614612-11] ^ ^a ^b ^c ^d ^e ^f Kneissl M, Pütter V, Szalay AA, Grummt F (March 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. 327 (1): 111–28. doi:10.1016/s0022-2836(03)00079-2. PMID 12614612.

[pmid12694531-12] Yabuta N, Kajimura N, Mayanagi K, Sato M, Gotow T, Uchiyama Y, Ishimi Y, Nojima H (May 2003). "Mammalian Mcm2/4/6/7 complex forms a toroidal structure". Genes Cells. 8 (5): 413–21. doi:10.1046/j.1365-2443.2003.00645.x. PMID 12694531. S2CID 27707848.

[pmid12207017-13] You Z, Ishimi Y, Masai H, Hanaoka F (November 2002). "Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex". J. Biol. Chem. 277 (45): 42471–9. doi:10.1074/jbc.M205769200. PMID 12207017.

[pmid16189514-14] 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 (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid10567526-15] You Z, Komamura Y, Ishimi Y (December 1999). "Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity". Mol. Cell. Biol. 19 (12): 8003–15. doi:10.1128/MCB.19.12.8003. PMC 84885. PMID 10567526.

[pmid8798650-16] Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H (September 1996). "Binding of human minichromosome maintenance proteins with histone H3". J. Biol. Chem. 271 (39): 24115–22. doi:10.1074/jbc.271.39.24115. PMID 8798650.

[pmid9099751-17] Fujita M, Kiyono T, Hayashi Y, Ishibashi M (April 1997). "In vivo interaction of human MCM heterohexameric complexes with chromatin. Possible involvement of ATP". J. Biol. Chem. 272 (16): 10928–35. doi:10.1074/jbc.272.16.10928. PMID 9099751.

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PROFILPELAJAR.COM

MCM6

Function

Gene

Interactions

See also

References

Further reading