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
Gene location (Mouse)
Chr.	Chromosome 16 (mouse)
End	15,455,264 bp
RNA expression pattern
	Top expressed in
	ganglionic eminence; ; bone marrow cells; ; human penis; ; stromal cell of endometrium; ; oocyte; ; appendix; ; cancellous bone; ; rectum; ; sperm; ; skin of abdomen;
	Top expressed in
	maxillary prominence; ; primitive streak; ; somite; ; external carotid artery; ; Paneth cell; ; abdominal wall; ; internal carotid artery; ; ureter; ; condyle; ; fossa;
	More reference expression data
	; ; ; ;
	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
	4173
	17217
	n/a
	ENSMUSG00000022673
	P33991
	P49717
	NM_005914 ; NM_182746
	NM_008565
	NP_005905 ; NP_877423
	NP_032591
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated August 15, 2023

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]

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]

Related Research Articles

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

Eukaryotic DNA replication is a conserved mechanism that restricts DNA replication to once per cell cycle. Eukaryotic DNA replication of chromosomal DNA is central for the duplication of a cell and is necessary for the maintenance of the eukaryotic genome.

The minichromosome maintenance protein complex (MCM) is a DNA helicase essential for genomic DNA replication. Eukaryotic MCM consists of six gene products, Mcm2–7, which form a heterohexamer. As a critical protein for cell division, MCM is also the target of various checkpoint pathways, such as the S-phase entry and S-phase arrest checkpoints. Both the loading and activation of MCM helicase are strictly regulated and are coupled to cell growth cycles. Deregulation of MCM function has been linked to genomic instability and a variety of carcinomas.

Replication protein A 70 kDa DNA-binding subunit is a protein that in humans is encoded by the RPA1 gene.

DNA replication licensing factor MCM7 is a protein that in humans is encoded by the MCM7 gene.

DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.

DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.

Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.

CDT1 is a protein that in humans is encoded by the CDT1 gene. It is a licensing factor that functions to limit DNA from replicating more than once per cell cycle.

Origin recognition complex subunit 2 is a protein that is encoded by the ORC2 (ORC2L) gene in humans.

DNA replication licensing factor MCM5 is a protein that in humans is encoded by the MCM5 gene.

Cell division cycle 7-related protein kinase is an enzyme that in humans is encoded by the CDC7 gene. The Cdc7 kinase is involved in regulation of the cell cycle at the point of chromosomal DNA replication. The gene CDC7 appears to be conserved throughout eukaryotic evolution; this means that most eukaryotic cells have the Cdc7 kinase protein.

Origin recognition complex subunit 4 is a protein that in humans is encoded by the ORC4 (ORC4L) gene.

Origin recognition complex subunit 6 is a protein that in humans is encoded by the ORC6 (ORC6L) gene.

Protein MCM10 homolog is a protein that in humans is encoded by the MCM10 gene. It is essential for activation of the Cdc45:Mcm2-7:GINS helicase, and thus required for proper DNA replication.

CDC45 is a protein that in humans is encoded by the CDC45L gene.

80 kDa MCM3-associated protein is a protein that in humans is encoded by the MCM3AP gene.

<span class="mw-page-title-main">Cdc6</span>

Cdc6, or cell division cycle 6, is a protein in eukaryotic cells. It is mainly studied in the budding yeast Saccharomyces cerevisiae. It is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle that coordinate S phase and mitosis. It is part of the pre-replicative complex (pre-RC) and is required for loading minichromosome maintenance (MCM) proteins onto the DNA, an essential step in the initiation of DNA synthesis. In addition, it is a member of the family of AAA+ ATPases and highly related to ORC1; both are the same protein in archaea.

Origin recognition complex subunit 1 is a protein that in humans is encoded by the ORC1 gene. It is closely related to CDC6, and both are the same protein in archaea.

Bik Kwoon Yeung Tye is a Chinese-American molecular geneticist and structural biologist. Tye's pioneering work on eukaryotic DNA replication led to the discovery of the minichromosome maintenance (MCM) genes in 1984, which encode the catalytic core of the eukaryotic replisome. Tye also determined the first high-resolution structures of both the MCM complex and the Origin Recognition Complex (ORC) in 2015 and 2018. Tye is currently a Professor Emeritus (2015) at Cornell University and a visiting professor at the Hong Kong University of Science & Technology. She is married to Henry Sze-Hoi Tye and is the mother of Kay Tye and Lynne Tye.

References

1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022673 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ 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.
↑ "Entrez Gene: MCM4 MCM4 minichromosome maintenance deficient 4 (S. cerevisiae)".
1 2 3 4 5 6 7 8 9 10 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.
1 2 3 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.
1 2 3 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.
↑ 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.
1 2 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.
↑ 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.

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.

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[refGRCm38Ensembl-1] 1 2 3 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.

[pmid7601140-4] 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.

[entrez-5] "Entrez Gene: MCM4 MCM4 minichromosome maintenance deficient 4 (S. cerevisiae)".

[pmid12614612-6] 1 2 3 4 5 6 7 8 9 10 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.

[pmid12694531-7] 1 2 3 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.

[pmid8798650-8] 1 2 3 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.

[pmid10567526-9] 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.

[pmid12207017-10] 1 2 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.

[pmid9099751-11] 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.

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MCM4

Contents

Function

See also

Interactions

Related Research Articles

References

Further reading