MCM2

MCM2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4UUZ, 5BNV, 5BNX, 5BO0, 5C3I, 5JA4
Identifiers
Aliases	MCM2, BM28, CCNL1, CDCL1, D3S3194, MITOTIN, cdc19, minichromosome maintenance complex component 2, DFNA70
External IDs	OMIM: 116945 MGI: 105380 HomoloGene: 3325 GeneCards: MCM2
Gene ontology Molecular function • DNA binding • nucleotide binding • helicase activity • histone binding • metal ion binding • DNA helicase activity • protein binding • enzyme binding • DNA replication origin binding • hydrolase activity • ATP binding Cellular component • cytoplasm • microtubule cytoskeleton • nucleoplasm • nuclear origin of replication recognition complex • chromatin • MCM complex • nuclear chromosome, telomeric region • nucleus Biological process • cellular response to interleukin-4 • nucleosome assembly • G1/S transition of mitotic cell cycle • DNA replication • DNA replication initiation • cell cycle • DNA unwinding involved in DNA replication • DNA duplex unwinding Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4171	17216
Ensembl	ENSG00000073111	ENSMUSG00000002870
UniProt	P49736	P97310
RefSeq (mRNA)	NM_004526	NM_008564
RefSeq (protein)	NP_004517.2	NP_032590.2
Location (UCSC)	Chr 3: 127.6 – 127.62 Mb	Chr 6: 88.88 – 88.9 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

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DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene.^[3][4]

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 forms a complex with MCM4, 6, and 7, and has been shown to regulate the helicase activity of the complex. This protein is phosphorylated, and thus regulated by, protein kinases CDC2 and CDC7.^[5]

Interactions

MCM2 has been shown to interact with:

• AKAP8,^[6]
• Cell division cycle 7-related protein kinase,^[7]
• MCM3,^[7]
• MCM4,^{[7][8][9][10]}
• MCM5,^[7][11]
• MCM6,^{[7][8][9][12][13]}
• MCM7,^{[7][8][9][13][14]}
• ORC1L,^[7]
• ORC2L,^[7]
• ORC4L,^[7]
• ORC5L,^[7] and
• Replication protein A1.^[7]

See also

• Mini Chromosome Maintenance

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Todorov IT, Lavigne J, Sakr F, Kaneva R, Foisy S, Bibor-Hardy V (Jul 1991). "Nuclear matrix protein mitotin messenger RNA is expressed at constant levels during the cell cycle". Biochem Biophys Res Commun. 177 (1): 395–400. doi:10.1016/0006-291X(91)91996-P. PMID 1710453.
4. Mincheva A, Todorov I, Werner D, Fink TM, Lichter P (Jan 1994). "The human gene for nuclear protein BM28 (CDCL1), a new member of the early S-phase family of proteins, maps to chromosome band 3q21". Cytogenet Cell Genet. 65 (4): 276–7. doi:10.1159/000133647. PMID 8258304.
5. "Entrez Gene: MCM2 MCM2 minichromosome maintenance deficient 2, mitotin (S. cerevisiae)".
6. Eide T, Taskén KA, Carlson C, Williams G, Jahnsen T, Taskén K, Collas P (Jul 2003). "Protein kinase A-anchoring protein AKAP95 interacts with MCM2, a regulator of DNA replication". J. Biol. Chem. 278 (29): 26750–6. doi:10.1074/jbc.M300765200. PMID 12740381.
7. Kneissl M, Pütter V, Szalay AA, Grummt F (Mar 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.
8. 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.
9. You Z, Komamura Y, Ishimi Y (Dec 1999). "Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity". Mol. Cell. Biol. 19 (12): 8003–15. PMC 84885. PMID 10567526.
10. Ishimi Y, Ichinose S, Omori A, Sato K, Kimura H (Sep 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.
11. DaFonseca CJ, Shu F, Zhang JJ (Mar 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.
12. Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
13. You Z, Ishimi Y, Masai H, Hanaoka F (Nov 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.
14. Fujita M, Kiyono T, Hayashi Y, Ishibashi M (Apr 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

• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S (1995). "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1.". DNA Res. 1 (1): 27–35. doi:10.1093/dnares/1.1.27. PMID 7584026.
• Nomura N, Miyajima N, Sazuka T, Tanaka A, Kawarabayasi Y, Sato S, Nagase T, Seki N, Ishikawa K, Tabata S (1995). "Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1 (supplement).". DNA Res. 1 (1): 47–56. doi:10.1093/dnares/1.1.47. PMID 7584028.
• Nakatsuru S, Sudo K, Nakamura Y (1995). "Isolation and mapping of a human gene (MCM2) encoding a product homologous to yeast proteins involved in DNA replication.". Cytogenet. Cell Genet. 68 (3–4): 226–30. doi:10.1159/000133918. PMID 7842741.
• Todorov IT, Pepperkok R, Philipova RN, Kearsey SE, Ansorge W, Werner D (1994). "A human nuclear protein with sequence homology to a family of early S phase proteins is required for entry into S phase and for cell division". J. Cell. Sci. 107 (1): 253–65. PMID 8175912.
• 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.
• 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.
• Jiang W, McDonald D, Hope TJ, Hunter T (1999). "Mammalian Cdc7-Dbf4 protein kinase complex is essential for initiation of DNA replication". EMBO J. 18 (20): 5703–13. doi:10.1093/emboj/18.20.5703. PMC 1171637. PMID 10523313.
• 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. 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.
• Masai H, Matsui E, You Z, Ishimi Y, Tamai K, Arai K (2000). "Human Cdc7-related kinase complex. In vitro phosphorylation of MCM by concerted actions of Cdks and Cdc7 and that of a criticial threonine residue of Cdc7 bY Cdks". J. Biol. Chem. 275 (37): 29042–52. doi:10.1074/jbc.M002713200. PMID 10846177.
• 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 G(2) phase". Nucleic Acids Res. 28 (23): 4769–77. doi:10.1093/nar/28.23.4769. PMC 115166. PMID 11095689.
• Burke TW, Cook JG, Asano M, Nevins JR (2001). "Replication factors MCM2 and ORC1 interact with the histone acetyltransferase HBO1". J. Biol. Chem. 276 (18): 15397–408. doi:10.1074/jbc.M011556200. PMID 11278932.
• Tan DF, Huberman JA, Hyland A, Loewen GM, Brooks JS, Beck AF, Todorov IT, Bepler G (2002). "MCM2--a promising marker for premalignant lesions of the lung: a cohort study". BMC Cancer. 1: 6. doi:10.1186/1471-2407-1-6. PMC 35283. PMID 11472637.
• Ishimi Y, Komamura-Kohno Y, Arai K, Masai H (2001). "Biochemical activities associated with mouse Mcm2 protein". J. Biol. Chem. 276 (46): 42744–52. doi:10.1074/jbc.M106861200. PMID 11568184.
• Wohlschlegel JA, Dhar SK, Prokhorova TA, Dutta A, Walter JC (2002). "Xenopus Mcm10 binds to origins of DNA replication after Mcm2-7 and stimulates origin binding of Cdc45". Mol. Cell. 9 (2): 233–40. doi:10.1016/S1097-2765(02)00456-2. PMID 11864598.
• Kodani I, Shomori K, Osaki M, Kuratate I, Ryoke K, Ito H (2002). "Expression of minichromosome maintenance 2 (MCM2), Ki-67, and cell-cycle-related molecules, and apoptosis in the normal-dysplasia-carcinoma sequence of the oral mucosa". Pathobiology. 69 (3): 150–8. doi:10.1159/000048770. PMID 11872961.
• Edwards MC, Tutter AV, Cvetic C, Gilbert CH, Prokhorova TA, Walter JC (2002). "MCM2-7 complexes bind chromatin in a distributed pattern surrounding the origin recognition complex in Xenopus egg extracts". J. Biol. Chem. 277 (36): 33049–57. doi:10.1074/jbc.M204438200. PMID 12087101.
• Osaki M, Osaki M, Yamashita H, Shomori K, Yoshida H, Ito H (2003). "Expression of minichromosome maintenance-2 in human malignant fibrous histiocytomas: Correlations with Ki-67 and P53 expression, and apoptosis". Int. J. Mol. Med. 10 (2): 161–8. doi:10.3892/ijmm.10.2.161. PMID 12119552.