MCM2

"MCM-2" redirects here. For the warship, see USS Defender (MCM-2).

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 location (Human) Chr. Chromosome 3 (human) [1] Band 3q21.3 Start 127,598,410 bp [1] End 127,622,436 bp [1]
Gene location (Mouse) Chr. Chromosome 6 (mouse) [2] Band 6|6 D1 Start 88,860,456 bp [2] End 88,875,762 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in oocyte secondary oocyte embryo ganglionic eminence cancellous bone bone marrow cells appendix stromal cell of endometrium hair follicle placenta Top expressed in maxillary prominence somite primitive streak Paneth cell yolk sac abdominal wall thymus ureter endocardial cushion secondary oocyte More reference expression data BioGPS More reference expression data
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 single-stranded DNA binding single-stranded DNA helicase activity 3'-5' DNA helicase activity Cellular component cytoplasm microtubule cytoskeleton nucleoplasm nuclear origin of replication recognition complex chromatin MCM complex nucleus cytosol nucleolus Biological process cellular response to interleukin-4 nucleosome assembly G1 phase DNA replication DNA replication initiation DNA unwinding involved in DNA replication apoptotic process cell cycle cochlea development G1/S transition of mitotic cell cycle negative regulation of DNA helicase activity double-strand break repair via break-induced replication pre-replicative complex assembly involved in nuclear cell cycle DNA replication mitotic DNA replication initiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4171 17216 Ensembl ENSG00000073111 ENSMUSG00000002870 UniProt P49736 P97310 RefSeq (mRNA) NM_004526 NM_008564 RefSeq (protein) NP_004517 NP_032590 Location (UCSC) Chr 3: 127.6 – 127.62 Mb Chr 6: 88.86 – 88.88 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

DNA replication licensing factor MCM2 is a protein that in humans is encoded by the MCM2 gene. ^{[5] [6]}

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. ^[7]

Interactions

MCM2 has been shown to interact with:

• AKAP8, ^[8]
• Cell division cycle 7-related protein kinase, ^[9]
• MCM3, ^[9]
• MCM4, ^{[9] [10] [11] [12]}
• MCM5, ^{[9] [13]}
• MCM6, ^{[9] [10] [11] [14] [15]}
• MCM7, ^{[9] [10] [11] [15] [16]}
• ORC1L, ^[9]
• ORC2L, ^[9]
• ORC4L, ^[9]
• ORC5L, ^[9] and
• Replication protein A1. ^[9]

See also

• Mini Chromosome Maintenance

References

1. GRCh38: Ensembl release 89: ENSG00000073111 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000002870 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: MCM2 MCM2 minichromosome maintenance deficient 2, mitotin (S. cerevisiae)".
8. 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.
9. 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.
10. 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.
11. 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. doi:10.1128/MCB.19.12.8003. PMC   84885 . PMID   10567526.
12. 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.
13. 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. Bibcode:2001PNAS...98.3034D. doi: 10.1073/pnas.061487598 . PMC   30602 . PMID   11248027.
14. 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. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
15. 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.
16. 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. doi:10.1242/jcs.107.1.253. 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. 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.
• 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 critical 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. S2CID   11047685.
• 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.