CDC6

CDC6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CCH, 2CCI, 4I5L, 4I5N
Identifiers
Aliases	CDC6, CDC18L, HsCDC18, Hscell division cycle 6
External IDs	MGI: 1345150 HomoloGene: 68172 GeneCards: CDC6
Gene ontology Molecular function • nucleotide binding • kinase binding • protein binding • ATP binding Cellular component • cytoplasm • cytosol • Golgi apparatus • spindle pole • nucleoplasm • spindle midzone • nucleus Biological process • regulation of cyclin-dependent protein serine/threonine kinase activity • mitotic nuclear division • cellular response to vasopressin • positive regulation of fibroblast proliferation • G1/S transition of mitotic cell cycle • negative regulation of DNA replication • regulation of transcription involved in G1/S transition of mitotic cell cycle • cell division • positive regulation of cytokinesis • DNA replication checkpoint • DNA replication • cellular response to angiotensin • DNA replication initiation • traversing start control point of mitotic cell cycle • positive regulation of chromosome segregation • positive regulation of cyclin-dependent protein serine/threonine kinase activity • regulation of mitotic metaphase/anaphase transition • cell cycle • negative regulation of cell proliferation Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	990	23834
Ensembl	ENSG00000094804	ENSMUSG00000017499
UniProt	Q99741	O89033
RefSeq (mRNA)	NM_001254	NM_001025779 NM_011799
RefSeq (protein)	NP_001245.1	NP_001020950.1 NP_035929.1
Location (UCSC)	Chr 17: 40.29 – 40.3 Mb	Chr 11: 98.91 – 98.92 Mb
PubMed search	[1]	[2]
Wikidata

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Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.^[3][4]

The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Cdc6, a protein essential for the initiation of DNA replication. This protein functions as a regulator at the early steps of DNA replication. It localizes in the cell nucleus during cell cycle phase G1, but translocates to the cytoplasm at the start of S phase. The subcellular translocation of this protein during the cell cycle is regulated through its phosphorylation by cyclin-dependent kinases. Transcription of this protein was reported to be regulated in response to mitogenic signals through a transcriptional control mechanism involving E2F proteins.^[5]

Interactions

CDC6 has been shown to interact with ORC1L,^[4][6] ORC2L,^[6][7] Cyclin A2,^[4][8] PPP2R3B,^[9] MCM3,^[7][10] PPP2R3A,^[11] MCM7^[6][10] and PSKH1.^[8]

See also

• Cdc6 homolog in Saccharomyces cerevisiae

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Williams RS, Shohet RV, Stillman B (February 1997). "A human protein related to yeast Cdc6p". Proc Natl Acad Sci U S A. 94 (1): 142–7. doi:10.1073/pnas.94.1.142. PMC 19260. PMID 8990175.
4. Saha P, Chen J, Thome KC, Lawlis SJ, Hou ZH, Hendricks M, Parvin JD, Dutta A (May 1998). "Human CDC6/Cdc18 Associates with Orc1 and Cyclin-cdk and Is Selectively Eliminated from the Nucleus at the Onset of S Phase". Mol Cell Biol. 18 (5): 2758–67. doi:10.1128/mcb.18.5.2758. PMC 110655. PMID 9566895.
5. "Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae)".
6. Kneissl, Margot; Pütter Vera; Szalay Aladar A; Grummt Friedrich (March 2003). "Interaction and assembly of murine pre-replicative complex proteins in yeast and mouse cells". J. Mol. Biol. England. 327 (1): 111–28. doi:10.1016/S0022-2836(03)00079-2. ISSN 0022-2836. PMID 12614612.
7. 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. UNITED STATES. 20 (22): 8602–12. doi:10.1128/MCB.20.22.8602-8612.2000. ISSN 0270-7306. PMC 102165. PMID 11046155.
8. Petersen, B O; Lukas J; Sørensen C S; Bartek J; Helin K (January 1999). "Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization". EMBO J. ENGLAND. 18 (2): 396–410. doi:10.1093/emboj/18.2.396. ISSN 0261-4189. PMC 1171134. PMID 9889196.
9. Yan, Z; Fedorov S A; Mumby M C; Williams R S (February 2000). "PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells". Mol. Cell. Biol. UNITED STATES. 20 (3): 1021–9. doi:10.1128/MCB.20.3.1021-1029.2000. ISSN 0270-7306. PMC 85219. PMID 10629059.
10. 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. UNITED STATES. 274 (36): 25927–32. doi:10.1074/jbc.274.36.25927. ISSN 0021-9258. PMID 10464337.
11. Davis, Anthony J; Yan Zhen; Martinez Bobbie; Mumby Marc C (June 2008). "Protein Phosphatase 2A Is Targeted to Cell Division Control Protein 6 by a Calcium-binding Regulatory Subunit". J. Biol. Chem. United States. 283 (23): 16104–14. doi:10.1074/jbc.M710313200. ISSN 0021-9258. PMC 2414307. PMID 18397887.

Further reading

• Yan Z, DeGregori J, Shohet R, et al. (1998). "Cdc6 is regulated by E2F and is essential for DNA replication in mammalian cells". Proc. Natl. Acad. Sci. U.S.A. 95 (7): 3603–8. doi:10.1073/pnas.95.7.3603. PMC 19882. PMID 9520412.
• Hateboer G, Wobst A, Petersen BO, et al. (1998). "Cell Cycle-Regulated Expression of Mammalian CDC6 Is Dependent on E2F". Mol. Cell. Biol. 18 (11): 6679–97. PMC 109252. PMID 9774682.
• Ohtani K, Tsujimoto A, Ikeda M, Nakamura M (1998). "Regulation of cell growth-dependent expression of mammalian CDC6 gene by the cell cycle transcription factor E2F". Oncogene. 17 (14): 1777–85. doi:10.1038/sj.onc.1202105. PMID 9778043.
• Stoeber K, Mills AD, Kubota Y, et al. (1999). "Cdc6 protein causes premature entry into S phase in a mammalian cell-free system". EMBO J. 17 (24): 7219–29. doi:10.1093/emboj/17.24.7219. PMC 1171068. PMID 9857179.
• Petersen BO, Lukas J, Sørensen CS, et al. (1999). "Phosphorylation of mammalian CDC6 by cyclin A/CDK2 regulates its subcellular localization". EMBO J. 18 (2): 396–410. doi:10.1093/emboj/18.2.396. PMC 1171134. PMID 9889196.
• van Hannen EJ, Zwart G, van Agterveld MP, et al. (1999). "Changes in Bacterial and Eukaryotic Community Structure after Mass Lysis of Filamentous Cyanobacteria Associated with Viruses". Appl. Environ. Microbiol. 65 (2): 795–801. PMC 91097. PMID 9925618.
• Takei Y, Yamamoto K, Tsujimoto G (1999). "Identification of the sequence responsible for the nuclear localization of human Cdc6". FEBS Lett. 447 (2–3): 292–6. doi:10.1016/S0014-5793(99)00306-3. PMID 10214964.
• Jiang W, Wells NJ, Hunter T (1999). "Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6". Proc. Natl. Acad. Sci. U.S.A. 96 (11): 6193–8. doi:10.1073/pnas.96.11.6193. PMC 26858. PMID 10339564.
• Fujita M, Yamada C, Goto H, et al. (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.
• Yan Z, Fedorov SA, Mumby MC, Williams RS (2000). "PR48, a Novel Regulatory Subunit of Protein Phosphatase 2A, Interacts with Cdc6 and Modulates DNA Replication in Human Cells". Mol. Cell. Biol. 20 (3): 1021–9. doi:10.1128/MCB.20.3.1021-1029.2000. PMC 85219. PMID 10629059.
• Takahashi Y, Rayman JB, Dynlacht BD (2000). "Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression". Genes Dev. 14 (7): 804–16. doi:10.1101/gad.14.7.804. PMC 316494. PMID 10766737.
• Takayama M, Taira T, Iguchi-Ariga SM, Ariga H (2000). "CDC6 interacts with c-Myc to inhibit E-box-dependent transcription by abrogating c-Myc/Max complex". FEBS Lett. 477 (1–2): 43–8. doi:10.1016/S0014-5793(00)01756-7. PMID 10899308.
• Petersen BO, Wagener C, Marinoni F, et al. (2000). "Cell cycle– and cell growth–regulated proteolysis of mammalian CDC6 is dependent on APC–CDH1". Genes Dev. 14 (18): 2330–43. doi:10.1101/gad.832500. PMC 316932. PMID 10995389.
• Méndez J, Stillman B (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.
• Delmolino LM, Saha P, Dutta A (2001). "Multiple mechanisms regulate subcellular localization of human CDC6". J. Biol. Chem. 276 (29): 26947–54. doi:10.1074/jbc.M101870200. PMID 11346650.
• Fujita M, Ishimi Y, Nakamura H, et al. (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.
• Biermann E, Baack M, Kreitz S, Knippers R (2002). "Synthesis and turn-over of the replicative Cdc6 protein during the HeLa cell cycle". Eur. J. Biochem. 269 (3): 1040–6. doi:10.1046/j.0014-2956.2001.02746.x. PMID 11846807.
• Robles LD, Frost AR, Davila M, et al. (2002). "Down-regulation of Cdc6, a cell cycle regulatory gene, in prostate cancer". J. Biol. Chem. 277 (28): 25431–8. doi:10.1074/jbc.M201199200. PMID 12006585.