MCM6

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Minichromosome maintenance complex component 6
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols MCM6 ; MCG40308; Mis5; P105MCM
External IDs OMIM601806 MGI1298227 HomoloGene4322 GeneCards: MCM6 Gene
EC number 3.6.4.12
RNA expression pattern
PBB GE MCM6 201930 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 4175 17219
Ensembl ENSG00000076003 ENSMUSG00000026355
UniProt Q14566 P97311
RefSeq (mRNA) NM_005915 NM_008567
RefSeq (protein) NP_005906 NP_032593
Location (UCSC) Chr 2:
136.6 – 136.63 Mb
Chr 1:
128.33 – 128.36 Mb
PubMed search [1] [2]

DNA replication licensing factor MCM6 is a protein that in humans is encoded by the MCM6 gene.[1] MCM6 is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication.

Function[edit]

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.[2] 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.[3]

Gene[edit]

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 (-13910) and 22 kb (-22018) upstream of LCT.[4] The (-13910) region, in particular, has been shown to function in vitro as an enhancer element capable of differentially activating transcription of LCT promoter.[5]

Mutations in these regions are associated with lactose tolerance into adult life.[4]

Interactions[edit]

MCM6 has been shown to interact with ORC1L,[6] ORC2L,[6] Replication protein A1,[6] ORC4L,[6] MCM4,[7][8][9] MCM7,[9][10] MCM2[6][7][9][11][12] and CDC45-related protein.[6]

See also[edit]

References[edit]

  1. ^ 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. 
  2. ^ "Entrez Gene: MCM6 minichromosome maintenance deficient 6 homolog (S. cerevisiae)". 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. doi:10.1038/nature04209. PMID 16189514. 
  12. ^ 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. PMC 84885. PMID 10567526. 

Further reading[edit]