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Function

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.²

See also

• Mini Chromosome Maintenance

Interactions

MCM4 has been shown to interact with:

• Cell division cycle 7-related protein kinase,³
• MCM2,⁴⁵⁶⁷
• MCM6,⁸⁹¹⁰¹¹
• MCM7,^12131415
• ORC1L,¹⁶
• ORC2L,¹⁷
• ORC3L,¹⁸
• ORC4L,¹⁹
• ORC5L,²⁰
• ORC6L,²¹ and
• Replication protein A1.²²

Further reading

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

References

1. Musahl C, Schulte D, Burkhart R, Knippers R (August 1995). "A human homologue of the yeast replication protein Cdc21. Interactions with other Mcm proteins". Eur J Biochem. 230 (3): 1096–101. doi:10.1111/j.1432-1033.1995.tb20660.x (inactive 25 December 2024). PMID 7601140.{{cite journal}}: CS1 maint: DOI inactive as of December 2024 (link) /wiki/Doi_(identifier) ↩

2. "Entrez Gene: MCM4 MCM4 minichromosome maintenance deficient 4 (S. cerevisiae)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4173 ↩

3. 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. /wiki/Doi_(identifier) ↩

4. 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. /wiki/Doi_(identifier) ↩

5. 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. https://doi.org/10.1046%2Fj.1365-2443.2003.00645.x ↩

6. 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. https://doi.org/10.1074%2Fjbc.271.39.24115 ↩

7. 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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC84885 ↩

8. 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. /wiki/Doi_(identifier) ↩

9. 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. https://doi.org/10.1046%2Fj.1365-2443.2003.00645.x ↩

10. 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. https://doi.org/10.1074%2Fjbc.271.39.24115 ↩

11. 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. https://doi.org/10.1074%2Fjbc.M205769200 ↩

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. https://doi.org/10.1046%2Fj.1365-2443.2003.00645.x ↩

13. 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. https://doi.org/10.1074%2Fjbc.271.39.24115 ↩

14. 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. https://doi.org/10.1074%2Fjbc.M205769200 ↩

15. 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. https://doi.org/10.1074%2Fjbc.272.16.10928 ↩

16. 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. /wiki/Doi_(identifier) ↩

17. 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. /wiki/Doi_(identifier) ↩

18. 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. /wiki/Doi_(identifier) ↩

19. 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. /wiki/Doi_(identifier) ↩

20. 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. /wiki/Doi_(identifier) ↩

21. 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. /wiki/Doi_(identifier) ↩

22. 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. /wiki/Doi_(identifier) ↩