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; OMA:CCND3 - orthologs
Gene location (Human)
Chr.	Chromosome 6 (human)
End	42,050,357 bp
Gene location (Mouse)
Chr.	Chromosome 17 (mouse)
End	47,910,616 bp
RNA expression pattern
	Top expressed in
	granulocyte; ; thymus; ; blood; ; spleen; ; lymph node; ; mononuclear cell; ; monocyte; ; right adrenal cortex; ; right lung; ; bone marrow;
	Top expressed in
	granulocyte; ; thymus; ; fetal liver hematopoietic progenitor cell; ; tibiofemoral joint; ; yolk sac; ; efferent ductule; ; human fetus; ; dermis; ; adrenal gland; ; atrium;
	More reference expression data
	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
	896
	12445
	ENSG00000112576
	ENSMUSG00000034165
	P30281
	P30282
NM_001136017; NM_001136125; NM_001136126; NM_001287427; NM_001287434;
	NM_001760
	NM_001081635; NM_001081636; NM_007632
NP_001129489; NP_001129597; NP_001129598; NP_001274356; NP_001274363;
	NP_001751
	NP_001075104; NP_001075105; NP_031658
	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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000112576 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000034165 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT (July 1992). "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes". Genomics. 13 (3): 565–574. doi:10.1016/0888-7543(92)90126-D. PMID 1386335.
^ "Entrez Gene: CCND3 cyclin D3".
^ Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. (Cancer Genome Atlas Network) (October 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.
^ ^a ^b Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I (March 2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". The Biochemical Journal. 378 (Pt 2): 673–679. doi:10.1042/BJ20031765. PMC 1223988. PMID 14641107.
^ Zhang S, Cai M, Zhang S, Xu S, Chen S, Chen X, et al. (September 2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". The Journal of Biological Chemistry. 277 (38): 35314–35322. doi:10.1074/jbc.M202179200. PMID 12082095.
^ ^a ^b Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
^ ^a ^b ^c Lin J, Jinno S, Okayama H (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–2009. doi:10.1038/sj.onc.1204375. PMID 11360184.
^ ^a ^b Zhang Q, Wang X, Wolgemuth DJ (June 1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–2800. doi:10.1210/endo.140.6.6756. PMID 10342870.
^ ^a ^b Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, et al. (February 2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". The Journal of Biological Chemistry. 278 (8): 6355–6362. doi:10.1074/jbc.M210697200. PMID 12482873.
^ Meyerson M, Harlow E (March 1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Molecular and Cellular Biology. 14 (3): 2077–2086. doi:10.1128/MCB.14.3.2077. PMC 358568. PMID 8114739.
^ Shen X, Yang Y, Liu W, Sun M, Jiang J, Zong H, et al. (August 2004). "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3". FEBS Letters. 573 (1–3): 139–146. Bibcode:2004FEBSL.573..139S. doi:10.1016/j.febslet.2004.07.071. PMID 15327989. S2CID 16005938.

Motokura T, Keyomarsi K, Kronenberg HM, Arnold A (October 1992). "Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene". The Journal of Biological Chemistry. 267 (28): 20412–20415. doi:10.1016/S0021-9258(19)88717-3. PMID 1383201.
Xiong Y, Menninger J, Beach D, Ward DC (July 1992). "Molecular cloning and chromosomal mapping of CCND genes encoding human D-type cyclins". Genomics. 13 (3): 575–584. 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". Cytogenetics and Cell Genetics. 61 (1): 5–7. doi:10.1159/000133359. PMID 1387066.
Matsuoka S, Yamaguchi M, Matsukage A (April 1994). "D-type cyclin-binding regions of proliferating cell nuclear antigen". The Journal of Biological Chemistry. 269 (15): 11030–11036. doi:10.1016/S0021-9258(19)78087-9. PMID 7908906.
Meyerson M, Harlow E (March 1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Molecular and Cellular Biology. 14 (3): 2077–2086. doi:10.1128/MCB.14.3.2077. PMC 358568. PMID 8114739.
Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA (May 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 (April 1996). "Functional analysis of the human cyclin D2 and cyclin D3 promoters". The Journal of Biological Chemistry. 271 (15): 9090–9099. doi:10.1074/jbc.271.15.9090. PMID 8621559.
Tiefenbrun N, Melamed D, Levy N, Resnitzky D, Hoffman I, Reed SI, et al. (July 1996). "Alpha interferon suppresses the cyclin D3 and cdc25A genes, leading to a reversible G0-like arrest". Molecular and Cellular Biology. 16 (7): 3934–3944. doi:10.1128/MCB.16.7.3934. PMC 231390. PMID 8668211.
Hirai H, Sherr CJ (November 1996). "Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1". Molecular and Cellular Biology. 16 (11): 6457–6467. 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, et al. (June 1998). "Cyclin D3 expression in normal, reactive and neoplastic tissues". The Journal of Pathology. 185 (2): 159–166. 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, et al. (January 1999). "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular Biology. 19 (1): 353–363. doi:10.1128/mcb.19.1.353. PMC 83893. PMID 9858559.
Gabrielli BG, Sarcevic B, Sinnamon J, Walker G, Castellano M, Wang XQ, et al. (May 1999). "A cyclin D-Cdk4 activity required for G2 phase cell cycle progression is inhibited in ultraviolet radiation-induced G2 phase delay". The Journal of Biological Chemistry. 274 (20): 13961–13969. doi:10.1074/jbc.274.20.13961. PMID 10318807.
Zhang Q, Wang X, Wolgemuth DJ (June 1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–2800. doi:10.1210/endo.140.6.6756. PMID 10342870.
Bartkova J, Rajpert-de Meyts E, Skakkebaek NE, Bartek J (April 1999). "D-type cyclins in adult human testis and testicular cancer: relation to cell type, proliferation, differentiation, and malignancy". The Journal of Pathology. 187 (5): 573–581. 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, et al. (August 2000). "Evidence for a telomere-independent "clock" limiting RAS oncogene-driven proliferation of human thyroid epithelial cells". Molecular and Cellular Biology. 20 (15): 5690–5699. doi:10.1128/MCB.20.15.5690-5699.2000. PMC 86042. PMID 10891505.
Sansal I, Dupont E, Toru D, Evrard C, Rouget P (October 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): 5000–5009. doi:10.1038/sj.onc.1203843. PMID 11042687.
Fink JR, LeBien TW (April 2001). "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors". Experimental Hematology. 29 (4): 490–498. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189.
Lin J, Jinno S, Okayama H (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–2009. doi:10.1038/sj.onc.1204375. PMID 11360184.
Bartkova J, Thullberg M, Slezak P, Jaramillo E, Rubio C, Thomassen LH, et al. (June 2001). "Aberrant expression of G1-phase cell cycle regulators in flat and exophytic adenomas of the human colon". Gastroenterology. 120 (7): 1680–1688. doi:10.1053/gast.2001.24880. PMID 11375949.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000112576 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[pmid1386335-5] Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT (July 1992). "Genomic organization, chromosomal localization, and independent expression of human cyclin D genes". Genomics. 13 (3): 565–574. doi:10.1016/0888-7543(92)90126-D. PMID 1386335.

[6] "Entrez Gene: CCND3 cyclin D3".

[nature11412-7] Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. (Cancer Genome Atlas Network) (October 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.

[pmid14641107-8] Arsenijevic T, Degraef C, Dumont JE, Roger PP, Pirson I (March 2004). "A novel partner for D-type cyclins: protein kinase A-anchoring protein AKAP95". The Biochemical Journal. 378 (Pt 2): 673–679. doi:10.1042/BJ20031765. PMC 1223988. PMID 14641107.

[pmid12082095-9] Zhang S, Cai M, Zhang S, Xu S, Chen S, Chen X, et al. (September 2002). "Interaction of p58(PITSLRE), a G2/M-specific protein kinase, with cyclin D3". The Journal of Biological Chemistry. 277 (38): 35314–35322. doi:10.1074/jbc.M202179200. PMID 12082095.

[pmid16189514-10] Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.

[pmid11360184-11] Lin J, Jinno S, Okayama H (April 2001). "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence". Oncogene. 20 (16): 2000–2009. doi:10.1038/sj.onc.1204375. PMID 11360184.

[pmid10342870-12] Zhang Q, Wang X, Wolgemuth DJ (June 1999). "Developmentally regulated expression of cyclin D3 and its potential in vivo interacting proteins during murine gametogenesis". Endocrinology. 140 (6): 2790–2800. doi:10.1210/endo.140.6.6756. PMID 10342870.

[pmid12482873-13] Despouy G, Bastie JN, Deshaies S, Balitrand N, Mazharian A, Rochette-Egly C, et al. (February 2003). "Cyclin D3 is a cofactor of retinoic acid receptors, modulating their activity in the presence of cellular retinoic acid-binding protein II". The Journal of Biological Chemistry. 278 (8): 6355–6362. doi:10.1074/jbc.M210697200. PMID 12482873.

[pmid8114739-14] Meyerson M, Harlow E (March 1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Molecular and Cellular Biology. 14 (3): 2077–2086. doi:10.1128/MCB.14.3.2077. PMC 358568. PMID 8114739.

[pmid15327989-15] Shen X, Yang Y, Liu W, Sun M, Jiang J, Zong H, et al. (August 2004). "Identification of the p28 subunit of eukaryotic initiation factor 3(eIF3k) as a new interaction partner of cyclin D3". FEBS Letters. 573 (1–3): 139–146. Bibcode:2004FEBSL.573..139S. doi:10.1016/j.febslet.2004.07.071. PMID 15327989. S2CID 16005938.

[1]

Cyclin D3

Function

Clinical significance

Interactions

See also

References

Further reading