MCM6
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesMCM6, MCG40308, Mis5, P105MCM, minichromosome maintenance complex component 6
External IDsOMIM: 601806 MGI: 1298227 HomoloGene: 4322 GeneCards: MCM6
Orthologs
SpeciesHumanMouse
Entrez

4175

17219

Ensembl

ENSG00000076003

ENSMUSG00000026355

UniProt

Q14566

P97311

RefSeq (mRNA)

NM_005915

NM_008567
NM_001313695

RefSeq (protein)

NP_005906

NP_001300624
NP_032593

Location (UCSC)Chr 2: 135.84 – 135.88 MbChr 1: 128.26 – 128.29 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000076003 - Ensembl, May 2017
  2. ^ a b c 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.
  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.
  6. ^ "Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)".
  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.
  8. ^ 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.
  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..."
  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.
  12. ^ 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.
  13. ^ 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.
  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.
  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.
  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.
  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.

Further reading

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