CDC6

Cell division cycle 6
Rendering of 2CCH​
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2CCH​, 2CCI​, 4I5L​, 4I5N​
Identifiers
Symbols	CDC6 ; CDC18L; HsCDC18; HsCDC6
External IDs	OMIM: 602627 MGI: 1345150 HomoloGene: 68172 GeneCards: CDC6 Gene
Gene ontology Molecular function • nucleotide binding • protein binding • ATP binding • kinase binding Cellular component • spindle pole • nucleus • nucleoplasm • cytoplasm • Golgi apparatus • cytosol • spindle midzone Biological process • DNA replication checkpoint • regulation of cyclin-dependent protein serine/threonine kinase activity • G1/S transition of mitotic cell cycle • regulation of transcription involved in G1/S transition of mitotic cell cycle • mitotic cell cycle • DNA replication • DNA replication initiation • mitotic nuclear division • traversing start control point of mitotic cell cycle • negative regulation of DNA replication • negative regulation of cell proliferation • regulation of mitotic metaphase/anaphase transition • positive regulation of cytokinesis • cell division • positive regulation of chromosome segregation 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
RefSeq (protein)	NP_001245	NP_001020950
Location (UCSC)	Chr 17: 40.29 – 40.3 Mb	Chr 11: 98.91 – 98.92 Mb
PubMed search

Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene.^[1][2]

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.^[3]

Interactions

CDC6 has been shown to interact with ORC1L,^[2][4] ORC2L,^[4][5] Cyclin A2,^[2][6] PPP2R3B,^[7] MCM3,^[5][8] PPP2R3A,^[9] MCM7^[4][8] and PSKH1.^[6]

See also

• Cdc6 homolog in Saccharomyces cerevisiae

References

1. 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.
2. 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. PMC 110655. PMID 9566895.
3. "Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae)".
4. 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.
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. (UNITED STATES) 20 (22): 8602–12. doi:10.1128/MCB.20.22.8602-8612.2000. ISSN 0270-7306. PMC 102165. PMID 11046155.
6. 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.
7. 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.
8. 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.
9. 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.