MCM3

Minichromosome maintenance complex component 3
Identifiers
Symbols	MCM3 ; HCC5; P1-MCM3; P1.h; RLFB
External IDs	OMIM: 602693 MGI: 101845 HomoloGene: 1791 GeneCards: MCM3 Gene
EC number	3.6.4.12
Gene ontology Molecular function • DNA binding • DNA helicase activity • protein binding • ATP binding Cellular component • nucleus • nucleoplasm • alpha DNA polymerase:primase complex • centrosome • membrane • MCM complex • intracellular membrane-bounded organelle • perinuclear region of cytoplasm Biological process • G1/S transition of mitotic cell cycle • mitotic cell cycle • DNA replication • DNA replication initiation • DNA strand elongation involved in DNA replication • DNA duplex unwinding Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4172	17215
Ensembl	ENSG00000112118	ENSMUSG00000041859
UniProt	P25205	P25206
RefSeq (mRNA)	NM_001270472	NM_008563
RefSeq (protein)	NP_001257401	NP_032589
Location (UCSC)	Chr 6: 52.26 – 52.28 Mb	Chr 1: 20.8 – 20.82 Mb
PubMed search

DNA replication licensing factor MCM3 is a protein that in humans is encoded by the MCM3 gene.^[1]

Function

The protein encoded by this gene is one of the highly conserved mini-chromosome maintenance proteins (MCM) that are involved in 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. This protein is a subunit of the protein complex that consists of MCM2-7. It has been shown to interact directly with MCM5/CDC46. This protein also interacts with, and thus is acetlyated by MCM3AP, a chromatin-associated acetyltransferase. The acetylation of this protein inhibits the initiation of DNA replication and cell cycle progression.^[2]

Interactions

MCM3 has been shown to interact with:

• CDC45-related protein,^[3]
• CDC6,^[4][5]
• DBF4,^[3]
• MCM2^[3]
• MCM3AP,^[6][7][8]
• MCM5,^[3][9]
• MCM7,^{[3][4][10][11]}
• ORC4L,^[3] and
• ORC5L.^[3]

See also

• Mini Chromosome Maintenance

References

1. Thömmes P, Fett R, Schray B, Burkhart R, Barnes M, Kennedy C, Brown NC, Knippers R (April 1992). "Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein". Nucleic Acids Res 20 (5): 1069–74. doi:10.1093/nar/20.5.1069. PMC 312092. PMID 1549468.
2. "Entrez Gene: MCM3 MCM3 minichromosome maintenance deficient 3 (S. cerevisiae)".
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.
4. Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T (September 1999). "Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation". J. Biol. Chem. 274 (36): 25927–32. doi:10.1074/jbc.274.36.25927. PMID 10464337.
5. Méndez J, Stillman B (November 2000). "Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis". Mol. Cell. Biol. 20 (22): 8602–12. doi:10.1128/mcb.20.22.8602-8612.2000. PMC 102165. PMID 11046155.
6. Takei Y, Assenberg M, Tsujimoto G, Laskey R (November 2002). "The MCM3 acetylase MCM3AP inhibits initiation, but not elongation, of DNA replication via interaction with MCM3". J. Biol. Chem. 277 (45): 43121–5. doi:10.1074/jbc.C200442200. PMID 12226073.
7. Kuwahara K, Yoshida M, Kondo E, Sakata A, Watanabe Y, Abe E, Kouno Y, Tomiyasu S, Fujimura S, Tokuhisa T, Kimura H, Ezaki T, Sakaguchi N (April 2000). "A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication". Blood 95 (7): 2321–8. PMID 10733502.
8. Takei Y, Tsujimoto G (August 1998). "Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization". J. Biol. Chem. 273 (35): 22177–80. doi:10.1074/jbc.273.35.22177. PMID 9712829.
9. DaFonseca CJ, Shu F, Zhang JJ (March 2001). "Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3034–9. doi:10.1073/pnas.061487598. PMC 30602. PMID 11248027.
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. Fujita M, Ishimi Y, Nakamura H, Kiyono T, Tsurumi T (March 2002). "Nuclear organization of DNA replication initiation proteins in mammalian cells". J. Biol. Chem. 277 (12): 10354–61. doi:10.1074/jbc.M111398200. PMID 11779870.

Further reading

• Musahl C, Schulte D, Burkhart R, Knippers R (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.
• Schulte D, Burkhart R, Musahl C, Hu B, Schlatterer C, Hameister H, Knippers R (1995). "Expression, phosphorylation and nuclear localization of the human P1 protein, a homologue of the yeast Mcm 3 replication protein". J. Cell. Sci. 108 (4): 1381–9. PMID 7615659.
• Starborg M, Brundell E, Gell K, Larsson C, White I, Daneholt B, Höög C (1995). "A murine replication protein accumulates temporarily in the heterochromatic regions of nuclei prior to initiation of DNA replication". J. Cell. Sci. 108 (3): 927–34. PMID 7622621.
• Burkhart R, Schulte D, Hu D, Musahl C, Göhring F, Knippers R (1995). "Interactions of human nuclear proteins P1Mcm3 and P1Cdc46". Eur. J. Biochem. 228 (2): 431–8. doi:10.1111/j.1432-1033.1995.tb20281.x. PMID 7705359.
• Kubota Y, Mimura S, Nishimoto S, Takisawa H, Nojima H (1995). "Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor". Cell 81 (4): 601–9. doi:10.1016/0092-8674(95)90081-0. PMID 7758114.
• Madine MA, Khoo CY, Mills AD, Laskey RA (1995). "MCM3 complex required for cell cycle regulation of DNA replication in vertebrate cells". Nature 375 (6530): 421–4. doi:10.1038/375421a0. PMID 7760938.
• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• 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.
• Sato N, Arai K, Masai H (1997). "Human and Xenopus cDNAs encoding budding yeast Cdc7-related kinases: in vitro phosphorylation of MCM subunits by a putative human homologue of Cdc7". EMBO J. 16 (14): 4340–51. doi:10.1093/emboj/16.14.4340. PMC 1170060. PMID 9250678.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Takei Y, Tsujimoto G (1998). "Identification of a novel MCM3-associated protein that facilitates MCM3 nuclear localization". J. Biol. Chem. 273 (35): 22177–80. doi:10.1074/jbc.273.35.22177. PMID 9712829.
• Zhang JJ, Zhao Y, Chait BT, Lathem WW, Ritzi M, Knippers R, Darnell JE (1999). "Ser727-dependent recruitment of MCM5 by Stat1alpha in IFN-gamma-induced transcriptional activation". EMBO J. 17 (23): 6963–71. doi:10.1093/emboj/17.23.6963. PMC 1171044. PMID 9843502.
• Yankulov K, Todorov I, Romanowski P, Licatalosi D, Cilli K, McCracken S, Laskey R, Bentley DL (1999). "MCM Proteins Are Associated with RNA Polymerase II Holoenzyme". Mol. Cell. Biol. 19 (9): 6154–63. PMC 84545. PMID 10454562.
• Fujita M, Yamada C, Goto H, Yokoyama N, Kuzushima K, Inagaki M, Tsurumi T (1999). "Cell cycle regulation of human CDC6 protein. Intracellular localization, interaction with the human mcm complex, and CDC2 kinase-mediated hyperphosphorylation". J. Biol. Chem. 274 (36): 25927–32. doi:10.1074/jbc.274.36.25927. PMID 10464337.
• Kuwahara K, Yoshida M, Kondo E, Sakata A, Watanabe Y, Abe E, Kouno Y, Tomiyasu S, Fujimura S, Tokuhisa T, Kimura H, Ezaki T, Sakaguchi N (2000). "A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication". Blood 95 (7): 2321–8. PMID 10733502.
• Hofmann Y, Becker J, Wright F, Avner ED, Mrug M, Guay-Woodford LM, Somlo S, Zerres K, Germino GG, Onuchic LF (2000). "Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease". Eur. J. Hum. Genet. 8 (3): 163–6. doi:10.1038/sj.ejhg.5200426. PMID 10780780.
• Abe E, Kuwahara K, Yoshida M, Suzuki M, Terasaki H, Matsuo Y, Takahashi EI, Sakaguchi N (2000). "Structure, expression, and chromosomal localization of the human gene encoding a germinal center-associated nuclear protein (GANP) that associates with MCM3 involved in the initiation of DNA replication". Gene 255 (2): 219–27. doi:10.1016/S0378-1119(00)00336-X. PMID 11024281.