Cyclin D2

Cyclin D2
Identifiers
Symbols	CCND2 ; KIAK0002; MPPH3
External IDs	OMIM: 123833 MGI: 88314 HomoloGene: 37525 ChEMBL: 3613 GeneCards: CCND2 Gene
Gene ontology Molecular function • protein binding • protein kinase binding Cellular component • cyclin-dependent protein kinase holoenzyme complex • chromatin • nucleus • nucleoplasm • nucleolus • cytosol • nuclear membrane Biological process • positive regulation of protein phosphorylation • cell cycle • positive regulation of cyclin-dependent protein serine/threonine kinase activity • cell division Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	894	12444
Ensembl	ENSG00000118971	ENSMUSG00000000184
UniProt	P30279	P30280
RefSeq (mRNA)	NM_001759	NM_009829
RefSeq (protein)	NP_001750	NP_033959
Location (UCSC)	Chr 12: 4.27 – 4.31 Mb	Chr 6: 127.13 – 127.15 Mb
PubMed search

G1/S-specific cyclin-D2 is a protein that in humans is encoded by the CCND2 gene.^[1]

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 cyclin-dependent 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. Knockout studies of the homologous gene in mouse suggest the essential roles of this gene in ovarian granulosa and germ cell proliferation. High level expression of this gene was observed in ovarian and testicular tumors.^[2]

Clinical significance

Mutations in CCND2 are associated to megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome .^[3]

References

1. Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT (Jul 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.
2. "Entrez Gene: CCND2 cyclin D2".
3. Mirzaa GM, Parry DA, Fry AE, Giamanco KA, Schwartzentruber J, Vanstone M, Logan CV, Roberts N, Johnson CA, Singh S, Kholmanskikh SS, Adams C, Hodge RD, Hevner RF, Bonthron DT, Braun KP, Faivre L, Rivière JB, St-Onge J, Gripp KW, Mancini GM, Pang K, Sweeney E, van Esch H, Verbeek N, Wieczorek D, Steinraths M, Majewski J, Boycott KM, Pilz DT, Ross ME, Dobyns WB, Sheridan EG (May 2014). "De novo CCND2 mutations leading to stabilization of cyclin D2 cause megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome". Nature Genetics 46 (5): 510–5. doi:10.1038/ng.2948. PMC 4004933. PMID 24705253.

Further reading

• Xiong Y, Menninger J, Beach D, Ward DC (Jul 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.
• Hirai H, Roussel MF, Kato JY, Ashmun RA, Sherr CJ (May 1995). "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6". Molecular and Cellular Biology 15 (5): 2672–81. PMC 230497. PMID 7739547.
• Meyerson M, Harlow E (Mar 1994). "Identification of G1 kinase activity for cdk6, a novel cyclin D partner". Molecular and Cellular Biology 14 (3): 2077–86. PMC 358568. PMID 8114739.
• Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM (May 1993). "Functional interactions of the retinoblastoma protein with mammalian D-type cyclins". Cell 73 (3): 487–97. doi:10.1016/0092-8674(93)90136-E. PMID 8343202.
• Palmero I, Holder A, Sinclair AJ, Dickson C, Peters G (Apr 1993). "Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines". Oncogene 8 (4): 1049–54. PMID 8455931.
• Brooks AR, Shiffman D, Chan CS, Brooks EE, Milner PG (Apr 1996). "Functional analysis of the human cyclin D2 and cyclin D3 promoters". The Journal of Biological Chemistry 271 (15): 9090–9. doi:10.1074/jbc.271.15.9090. PMID 8621559.
• Hirai H, Sherr CJ (Nov 1996). "Interaction of D-type cyclins with a novel myb-like transcription factor, DMP1". Molecular and Cellular Biology 16 (11): 6457–67. PMC 231647. PMID 8887674.
• Sicinski P, Donaher JL, Geng Y, Parker SB, Gardner H, Park MY, Robker RL, Richards JS, McGinnis LK, Biggers JD, Eppig JJ, Bronson RT, Elledge SJ, Weinberg RA (Dec 1996). "Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis". Nature 384 (6608): 470–4. doi:10.1038/384470a0. PMID 8945475.
• Kitagawa M, Higashi H, Jung HK, Suzuki-Takahashi I, Ikeda M, Tamai K, Kato J, Segawa K, Yoshida E, Nishimura S, Taya Y (Dec 1996). "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2". The EMBO Journal 15 (24): 7060–9. PMC 452531. PMID 9003781.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Guidato S, McLoughlin DM, Grierson AJ, Miller CC (Jan 1998). "Cyclin D2 interacts with cdk-5 and modulates cellular cdk-5/p35 activity". Journal of Neurochemistry 70 (1): 335–40. doi:10.1046/j.1471-4159.1998.70010335.x. PMID 9422379.
• Gómez Lahoz E, Liegeois NJ, Zhang P, Engelman JA, Horner J, Silverman A, Burde R, Roussel MF, Sherr CJ, Elledge SJ, DePinho RA (Jan 1999). "Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: cooperative interactions in vivo". Molecular and Cellular Biology 19 (1): 353–63. PMC 83893. PMID 9858559.
• Bartkova J, Rajpert-de Meyts E, Skakkebaek NE, Bartek J (Apr 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): 573–81. doi:10.1002/(SICI)1096-9896(199904)187:5<573::AID-PATH289>3.0.CO;2-H. PMID 10398124.
• Bouchard C, Thieke K, Maier A, Saffrich R, Hanley-Hyde J, Ansorge W, Reed S, Sicinski P, Bartek J, Eilers M (Oct 1999). "Direct induction of cyclin D2 by Myc contributes to cell cycle progression and sequestration of p27". The EMBO Journal 18 (19): 5321–33. doi:10.1093/emboj/18.19.5321. PMC 1171602. PMID 10508165.
• Sansal I, Dupont E, Toru D, Evrard C, Rouget P (Oct 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.
• Choi D, Lee EY, Yoon S, Hwang S, Yoon BK, Lee JH (Nov 2000). "Clinical correlation of cyclin D2 mRNA expression in human luteinized granulosa cells". Journal of Assisted Reproduction and Genetics 17 (10): 574–9. doi:10.1023/A:1026470825514. PMC 3455455. PMID 11209538.
• Tanguay DA, Colarusso TP, Doughty C, Pavlovic-Ewers S, Rothstein TL, Chiles TC (Apr 2001). "Cutting edge: differential signaling requirements for activation of assembled cyclin D3-cdk4 complexes in B-1 and B-2 lymphocyte subsets". Journal of Immunology 166 (7): 4273–7. doi:10.4049/jimmunol.166.7.4273. PMID 11254678.
• Choi D, Yoon S, Lee E, Hwang S, Yoon B, Lee J (Feb 2001). "The expression of pseudogene cyclin D2 mRNA in the human ovary may be a novel marker for decreased ovarian function associated with the aging process". Journal of Assisted Reproduction and Genetics 18 (2): 110–3. doi:10.1023/A:1026538826392. PMC 3455561. PMID 11285977.