MCM4

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are essential for the initiation of eukaryotic genome replication. The hexameric protein complex formed by 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 MCM complex consisting of this protein and MCM2, 6 and 7 proteins possesses DNA helicase activity, and may act as a DNA unwinding enzyme. The phosphorylation of this protein by CDC2 kinase reduces the DNA helicase activity and chromatin binding of the MCM complex. This gene is mapped to a region on the chromosome 8 head-to-head next to the PRKDC/DNA-PK, a DNA-activated protein kinase involved in the repair of DNA double-strand breaks. Alternatively spliced transcript variants encoding the same protein have been reported.{{cite web | title = Entrez Gene: MCM4 MCM4 minichromosome maintenance deficient 4 (S. cerevisiae)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4173}}

• Mini Chromosome Maintenance

MCM4 has been shown to interact with:

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• Cell division cycle 7-related protein kinase,
• MCM2,{{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}}
• MCM6,{{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 = 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 }}{{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 }}
• 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,
• ORC3L,
• ORC4L,
• ORC5L,
• ORC6L, and
• Replication protein A1.

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• {{cite journal | vauthors = Hu B, Burkhart R, Schulte D, Musahl C, Knippers R | title = The P1 family: a new class of nuclear mammalian proteins related to the yeast Mcm replication proteins | journal = Nucleic Acids Res. | volume = 21 | issue = 23 | pages = 5289–93 | year = 1994 | pmid = 8265339 | pmc = 310560 | doi = 10.1093/nar/21.23.5289-a }}
• {{cite journal | vauthors = Schulte D, Richter A, Burkhart R, Musahl C, Knippers R | title = Properties of the human nuclear protein p85Mcm. Expression, nuclear localization and interaction with other Mcm proteins | journal = Eur. J. Biochem. | volume = 235 | issue = 1–2 | pages = 144–51 | year = 1996 | pmid = 8631321 | doi = 10.1111/j.1432-1033.1996.00144.x | 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 | year = 1996 | pmid = 8798650 | doi = 10.1074/jbc.271.39.24115 | doi-access = free }}
• {{cite journal | vauthors = Ladenburger EM, Fackelmayer FO, Hameister H, Knippers R | title = MCM4 and PRKDC, human genes encoding proteins MCM4 and DNA-PKcs, are close neighbours located on chromosome 8q12→q13 | journal = Cytogenet. Cell Genet. | volume = 77 | issue = 3–4 | pages = 268–70 | year = 1997 | pmid = 9284934 | doi = 10.1159/000134594 }}
• {{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 = Connelly MA, Zhang H, Kieleczawa J, Anderson CW | title = The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed genes located at chromosome 8 band q11 | journal = Genomics | volume = 47 | issue = 1 | pages = 71–83 | year = 1998 | pmid = 9465298 | doi = 10.1006/geno.1997.5076 }}
• {{cite journal | vauthors = Fujita M, Yamada C, Tsurumi T, Hanaoka F, Matsuzawa K, Inagaki M | title = Cell cycle- and chromatin binding state-dependent phosphorylation of human MCM heterohexameric complexes. A role for cdc2 kinase | journal = J. Biol. Chem. | volume = 273 | issue = 27 | pages = 17095–101 | year = 1998 | pmid = 9642275 | doi = 10.1074/jbc.273.27.17095 | 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 G2 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 = Ishimi Y, Komamura-Kohno Y | title = Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4,6,7 helicase activity | journal = J. Biol. Chem. | volume = 276 | issue = 37 | pages = 34428–33 | year = 2001 | pmid = 11454864 | doi = 10.1074/jbc.M104480200 | 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 = Ishimi Y, Komamura-Kohno Y, Kwon HJ, Yamada K, Nakanishi M | title = Identification of MCM4 as a target of the DNA replication block checkpoint system | journal = J. Biol. Chem. | volume = 278 | issue = 27 | pages = 24644–50 | year = 2003 | pmid = 12714602 | doi = 10.1074/jbc.M213252200 | 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 }}

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