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, MGORS5
External IDs	OMIM: 602627 MGI: 1345150 HomoloGene: 68172 GeneCards: CDC6
Gene location (Human) Chr. Chromosome 17 (human) [1] Band 17q21.2 Start 40,287,879 bp [1] End 40,304,657 bp [1]
Gene location (Mouse) Chr. Chromosome 11 (mouse) [2] Band 11|11 D Start 98,798,627 bp [2] End 98,814,766 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence secondary oocyte rectum stromal cell of endometrium bone marrow cells appendix lymph node islet of Langerhans spleen smooth muscle tissue Top expressed in primitive streak abdominal wall morula otic placode endocardial cushion somite maxillary prominence Paneth cell ureter hand More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding kinase binding protein binding ATP binding DNA replication origin binding Cellular component spindle pole spindle midzone nucleus cytoplasm nucleolus nucleoplasm cytosol Biological process regulation of cyclin-dependent protein serine/threonine kinase activity cellular response to vasopressin positive regulation of fibroblast proliferation 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 signaling 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 population proliferation mitotic cell cycle G1/S transition of mitotic cell cycle mitotic DNA replication checkpoint signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 990 23834 Ensembl ENSG00000094804 ENSMUSG00000017499 UniProt Q99741 O89033 RefSeq (mRNA) NM_001254 NM_001025779 NM_011799 NM_001362735 RefSeq (protein) NP_001245 NP_001020950 NP_035929 NP_001349664 Location (UCSC) Chr 17: 40.29 – 40.3 Mb Chr 11: 98.8 – 98.81 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Cell division control protein 6 homolog is a protein that in humans is encoded by the CDC6 gene. ^{[5] [6]}

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. ^[7]

Interactions

CDC6 has been shown to interact with ORC1L, ^{[6] [8]} ORC2L, ^{[8] [9]} Cyclin A2, ^{[6] [10]} PPP2R3B, ^[11] MCM3, ^{[9] [12]} PPP2R3A, ^[13] MCM7 ^{[8] [12]} and PSKH1. ^[10]

See also

• Cdc6, the family of orthologs in eukaryotes

References

1. GRCh38: Ensembl release 89: ENSG00000094804 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000017499 - 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. 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. Bibcode:1997PNAS...94..142S. doi: 10.1073/pnas.94.1.142 . PMC   19260 . PMID   8990175.
6. 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.
7. "Entrez Gene: CDC6 cell division cycle 6 homolog (S. cerevisiae)".
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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. Bibcode:1998PNAS...95.3603Y. 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. doi:10.1128/mcb.18.11.6679. 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. Bibcode:1999ApEnM..65..795V. doi:10.1128/AEM.65.2.795-801.1999. 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. S2CID   39852055.
• 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. Bibcode:1999PNAS...96.6193J. 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. S2CID   12965556.
• 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.

External links

• Human CDC6 genome location and CDC6 gene details page in the UCSC Genome Browser .