Cyclin D3

CCND3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3G33
Identifiers
Aliases	CCND3 , cyclin D3
External IDs	OMIM: 123834 MGI: 88315 HomoloGene: 20419 GeneCards: CCND3
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p21.1 Start 41,934,934 bp [1] End 42,050,357 bp [1]
Gene location (Mouse) Chr. Chromosome 17 (mouse) [2] Band 17 C|17 23.37 cM Start 47,815,976 bp [2] End 47,910,616 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in thymus blood spleen lymph node monocyte right lung bone marrow upper lobe of left lung Left adrenal gland cancellous bone Top expressed in thymus yolk sac dermis adrenal gland atrium spleen belly cord abdominal wall maxillary prominence internal carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function cyclin-dependent protein serine/threonine kinase activity protein binding protein kinase binding protein kinase activity cyclin-dependent protein serine/threonine kinase regulator activity Cellular component nucleoplasm cyclin-dependent protein kinase holoenzyme complex membrane nucleus cytoplasm Biological process T cell proliferation cell cycle positive regulation of protein phosphorylation signal transduction positive regulation of cyclin-dependent protein serine/threonine kinase activity regulation of cell cycle cell division negative regulation of transcription by RNA polymerase II regulation of cell population proliferation regulation of insulin receptor signaling pathway regulation of cyclin-dependent protein serine/threonine kinase activity mitotic cell cycle protein phosphorylation regulation of mitotic nuclear division positive regulation of cell population proliferation positive regulation of cell cycle positive regulation of G1/S transition of mitotic cell cycle Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 896 12445 Ensembl ENSG00000112576 ENSMUSG00000034165 UniProt P30281 P30282 RefSeq (mRNA) NM_001136017 NM_001136125 NM_001136126 NM_001287427 NM_001287434 NM_001760 NM_001081635 NM_001081636 NM_007632 RefSeq (protein) NP_001129489 NP_001129597 NP_001129598 NP_001274356 NP_001274363 NP_001751 NP_001075104 NP_001075105 NP_031658 Location (UCSC) Chr 6: 41.93 – 42.05 Mb Chr 17: 47.82 – 47.91 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

G1/S-specific cyclin-D3 is a protein that in humans is encoded by the CCND3 gene. ^[5]

Function

The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. Cyclins function as regulators of CDK kinases. Different cyclins exhibit distinct expression and degradation patterns which contribute to the temporal coordination of each mitotic event. This cyclin forms a complex with and functions as a regulatory subunit of CDK4 or CDK6, whose activity is required for cell cycle G1/S transition. This protein has been shown to interact with and be involved in the phosphorylation of tumor suppressor protein Rb. The CDK4 activity associated with this cyclin was reported to be necessary for cell cycle progression through G2 phase into mitosis after UV radiation. ^[6]

Clinical significance

Mutations in CCND3 are implicated in cases of breast cancer. ^[7]

Interactions

Cyclin D3 has been shown to interact with:

• AKAP8, ^[8]
• CDC2L1, ^[9]
• CDKN1B, ^{[10] [11] [12]}
• CRABP2, ^[13]
• Cyclin-dependent kinase 4, ^{[8] [10] [11] [12]}
• Cyclin-dependent kinase 6, ^{[11] [14]}
• EIF3K, ^[15] and
• Retinoic acid receptor alpha. ^[13]

See also

• Cyclin
• Cyclin D

References

1. GRCh38: Ensembl release 89: ENSG00000112576 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034165 - 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. Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT (August 1992). "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes". Genomics. 13 (3): 565–74. doi:10.1016/0888-7543(92)90126-D. PMID   1386335.
6. "Entrez Gene: CCND3 cyclin D3".
7. Koboldt, Daniel C.; Fulton, Robert S.; McLellan, Michael D.; Schmidt, Heather; Kalicki-Veizer, Joelle; McMichael, Joshua F.; Fulton, Lucinda L.; Dooling, David J.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Ally, Adrian; Balasundaram, Miruna; Butterfield, Yaron S. N.; Carlsen, Rebecca; Carter, Candace; Chu, Andy; Chuah, Eric; Chun, Hye-Jung E.; Coope, Robin J. N.; Dhalla, Noreen; Guin, Ranabir; Hirst, Carrie; Hirst, Martin; Holt, Robert A.; Lee, Darlene; Li, Haiyan I.; Mayo, Michael; Moore, Richard A.; et al. (2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. Bibcode:2012Natur.490...61T. doi:10.1038/nature11412. PMC   3465532 . PMID   23000897.
8. Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I (2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". Biochem. J. 378 (Pt 2): 673–9. doi:10.1042/BJ20031765. PMC   1223988 . PMID   14641107.
9. Zhang S, Cai M, Zhang S, Xu S, Chen S, Chen X, Chen C, Gu J (2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". J. Biol. Chem. 277 (38): 35314–22. doi: 10.1074/jbc.M202179200 . PMID   12082095.
10. 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 (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.
11. Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–9. doi: 10.1038/sj.onc.1204375 . PMID   11360184.
12. Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–800. doi: 10.1210/endo.140.6.6756 . PMID   10342870.
13. Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, Chomienne C, Delva L (2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". J. Biol. Chem. 278 (8): 6355–62. doi: 10.1074/jbc.M210697200 . PMID   12482873.
14. Meyerson M, Harlow E (1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Mol. Cell. Biol. 14 (3): 2077–86. doi:10.1128/MCB.14.3.2077. PMC   358568 . PMID   8114739.
15. Shen X, Yang Y, Liu W, Sun M, Jiang J, Zong H, Gu J (2004). "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3". FEBS Lett. 573 (1–3): 139–46. doi: 10.1016/j.febslet.2004.07.071 . PMID   15327989. S2CID   16005938.

Further reading

• Motokura T, Keyomarsi K, Kronenberg HM, Arnold A (1992). "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene". J. Biol. Chem. 267 (28): 20412–5. doi: 10.1016/S0021-9258(19)88717-3 . PMID   1383201.
• Xiong Y, Menninger J, Beach D, Ward DC (1992). "Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins". Genomics. 13 (3): 575–84. doi:10.1016/0888-7543(92)90127-E. PMID   1386336.
• Motokura T, Yi HF, Kronenberg HM, McBride OW, Arnold A (1992). "Assignment of the human cyclin D3 gene (CCND3) to chromosome 6p----q13". Cytogenet. Cell Genet. 61 (1): 5–7. doi:10.1159/000133359. PMID   1387066.
• Matsuoka S, Yamaguchi M, Matsukage A (1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". J. Biol. Chem. 269 (15): 11030–6. doi: 10.1016/S0021-9258(19)78087-9 . PMID   7908906.
• Meyerson M, Harlow E (1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Mol. Cell. Biol. 14 (3): 2077–86. doi:10.1128/MCB.14.3.2077. PMC   358568 . PMID   8114739.
• Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA (1993). "Physical interaction of the retinoblastoma protein with human D cyclins". Cell. 73 (3): 499–511. doi:10.1016/0092-8674(93)90137-F. PMID   8490963. S2CID   24708871.
• Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (1996). "Functional analysis of the human cyclin D2 and cyclin D3 promoters". J. Biol. Chem. 271 (15): 9090–9. doi: 10.1074/jbc.271.15.9090 . PMID   8621559.
• Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed SI, Kimchi A (1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Mol. Cell. Biol. 16 (7): 3934–44. doi:10.1128/MCB.16.7.3934. PMC   231390 . PMID   8668211.
• Hirai H, Sherr CJ (1996). "Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1". Mol. Cell. Biol. 16 (11): 6457–67. doi:10.1128/MCB.16.11.6457. PMC   231647 . PMID   8887674.
• Doglioni C, Chiarelli C, Macrí E, Dei Tos AP, Meggiolaro E, Dalla Palma P, Barbareschi M (1998). "Cyclin D3 expression in normal, reactive and neoplastic tissues". J. Pathol. 185 (2): 159–66. doi:10.1002/(SICI)1096-9896(199806)185:2<159::AID-PATH73>3.0.CO;2-0. PMID   9713342. S2CID   38572590.
• Gómez Lahoz E, Liegeois NJ, Zhang P, Engelman JA, Horner J, Silverman A, Burde R, Roussel MF, Sherr CJ, Elledge SJ, DePinho RA (1999). "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Mol. Cell. Biol. 19 (1): 353–63. doi:10.1128/mcb.19.1.353. PMC   83893 . PMID   9858559.
• Gabrielli BG, Sarcevic B, Sinnamon J, Walker G, Castellano M, Wang XQ, Ellem KA (1999). "A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay". J. Biol. Chem. 274 (20): 13961–9. doi: 10.1074/jbc.274.20.13961 . PMID   10318807.
• Zhang Q, Wang X, Wolgemuth DJ (1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–800. doi: 10.1210/endo.140.6.6756 . PMID   10342870.
• Bartkova J, Rajpert-de Meyts E, Skakkebaek NE, Bartek J (1999). "D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy". J. Pathol. 187 (5): 573–81. doi:10.1002/(SICI)1096-9896(199904)187:5<573::AID-PATH289>3.0.CO;2-H. PMID   10398124. S2CID   9474072.
• Jones CJ, Kipling D, Morris M, Hepburn P, Skinner J, Bounacer A, Wyllie FS, Ivan M, Bartek J, Wynford-Thomas D, Bond JA (2000). "Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells". Mol. Cell. Biol. 20 (15): 5690–9. doi:10.1128/MCB.20.15.5690-5699.2000. PMC   86042 . PMID   10891505.
• Sansal I, Dupont E, Toru D, Evrard C, Rouget P (2000). "NPDC-1, a regulator of neural cell proliferation and differentiation, interacts with E2F-1, reduces its binding to DNA and modulates its transcriptional activity". Oncogene. 19 (43): 5000–9. doi: 10.1038/sj.onc.1203843 . PMID   11042687.
• Fink JR, LeBien TW (2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Exp. Hematol. 29 (4): 490–8. doi: 10.1016/S0301-472X(01)00619-1 . PMID   11301189.
• Lin J, Jinno S, Okayama H (2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–9. doi: 10.1038/sj.onc.1204375 . PMID   11360184.
• Bartkova J, Thullberg M, Slezak P, Jaramillo E, Rubio C, Thomassen LH, Bartek J (2001). "Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon". Gastroenterology. 120 (7): 1680–8. doi:10.1053/gast.2001.24880. PMID   11375949.