MCM4

MCM4
Identifiers
Aliases	MCM4 , CDC21, CDC54, NKCD, NKGCD, P1-CDC21, hCdc21, minichromosome maintenance complex component 4, IMD54
External IDs	OMIM: 602638; MGI: 103199; HomoloGene: 40496; GeneCards: MCM4; OMA:MCM4 - orthologs
Gene location (Mouse) Chr. Chromosome 16 (mouse) [1] Band 16 A2|16 10.09 cM Start 15,441,761 bp [1] End 15,455,264 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence bone marrow cell human penis stromal cell of endometrium oocyte appendix trabecular bone rectum sperm skin of abdomen Top expressed in mandibular prominence maxillary prominence primitive streak somite external carotid artery Paneth cell abdominal wall internal carotid artery epiblast ureter More reference expression data BioGPS More reference expression data
Gene ontology Molecular function single-stranded DNA binding nucleotide binding DNA helicase activity DNA binding protein binding hydrolase activity ATP binding helicase activity DNA replication origin binding Cellular component MCM complex membrane 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 DNA strand elongation involved in DNA replication mitotic DNA replication initiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4173 17217 Ensembl n/a ENSMUSG00000022673 UniProt P33991 P49717 RefSeq (mRNA) NM_005914 NM_182746 NM_008565 RefSeq (protein) NP_005905 NP_877423 NP_032591 Location (UCSC) n/a Chr 16: 15.44 – 15.46 Mb PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

DNA replication licensing factor MCM4 is a protein that in humans is encoded by the MCM4 gene. ^[4]

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. ^[5]

See also

• Mini Chromosome Maintenance

Interactions

MCM4 has been shown to interact with:

• Cell division cycle 7-related protein kinase, ^[6]
• MCM2, ^{[6] [7] [8] [9]}
• MCM6, ^{[6] [7] [8] [10]}
• MCM7, ^{[7] [8] [10] [11]}
• ORC1L, ^[6]
• ORC2L, ^[6]
• ORC3L, ^[6]
• ORC4L, ^[6]
• ORC5L, ^[6]
• ORC6L, ^[6] and
• Replication protein A1. ^[6]

References

1. GRCm38: Ensembl release 89: ENSMUSG00000022673 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. 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. PMID   7601140.
5. "Entrez Gene: MCM4 MCM4 minichromosome maintenance deficient 4 (S. cerevisiae)".
6. 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. 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.
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. 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.
10. 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.
11. 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

• 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.