Biology:CDKN2D

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Cyclin-dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene.

The protein encoded by this gene is a member of the INK4 family of cyclin-dependent kinase inhibitors. This protein has been shown to form a stable complex with CDK4 or CDK6, and prevent the activation of the CDK kinases, thus function as a cell growth regulator that controls cell cycle G1 progression. The abundance of the transcript of this gene was found to oscillate in a cell-cycle dependent manner with the lowest expression at mid G1 and a maximal expression during S phase. The negative regulation of the cell cycle involved in this protein was shown to participate in repressing neuronal proliferation, as well as spermatogenesis. The expression of this gene and its protein product (p19) is observed in neurons with neurofibrillary tangles (NFTs) and it is suggested as a marker for senescent neurons. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported.

Note, this protein should not be confused with p19-ARF (mouse) or the human equivalent p14ARF, which are alternative products of the CDKN2A gene.

Further reading

• "Novel INK4 proteins, p19 and p18, are specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6.". Mol. Cell. Biol. 15 (5): 2672–81. 1995. doi:10.1128/MCB.15.5.2672. PMID 7739547. 
• "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4.". Mol. Cell. Biol. 15 (5): 2682–8. 1995. doi:10.1128/MCB.15.5.2682. PMID 7739548. 
• "Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4.". Mol. Biol. Cell 7 (1): 57–70. 1996. doi:10.1091/mbc.7.1.57. PMID 8741839. 
• "Expression and regulation of G1 cell-cycle inhibitors (p16INK4A, p15INK4B, p18INK4C, p19INK4D) in human acute myeloid leukemia and normal myeloid cells.". Leukemia 11 (1): 54–63. 1997. doi:10.1038/sj.leu.2400522. PMID 9001419. 
• "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a.". Nature 395 (6699): 237–43. 1998. doi:10.1038/26155. PMID 9751050. Bibcode: 1998Natur.395..237R. 
• "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d.". Nature 395 (6699): 244–50. 1998. doi:10.1038/26164. PMID 9751051. Bibcode: 1998Natur.395..244B. 
• "Structure of human cyclin-dependent kinase inhibitor p19INK4d: comparison to known ankyrin-repeat-containing structures and implications for the dysfunction of tumor suppressor p16INK4a.". Structure 6 (10): 1279–90. 1998. doi:10.1016/S0969-2126(98)00128-2. PMID 9782052. 
• "Comparison of the effectiveness of adenovirus vectors expressing cyclin kinase inhibitors p16INK4A, p18INK4C, p19INK4D, p21(WAF1/CIP1) and p27KIP1 in inducing cell cycle arrest, apoptosis and inhibition of tumorigenicity.". Oncogene 18 (9): 1663–76. 1999. doi:10.1038/sj.onc.1202466. PMID 10208428. 
• "Mutation testing in melanoma families: INK4A, CDK4 and INK4D.". Br. J. Cancer 80 (1–2): 295–300. 1999. doi:10.1038/sj.bjc.6690354. PMID 10390011. 
• "Postnatal neuronal proliferation in mice lacking Ink4d and Kip1 inhibitors of cyclin-dependent kinases.". Proc. Natl. Acad. Sci. U.S.A. 96 (23): 13462–7. 1999. doi:10.1073/pnas.96.23.13462. PMID 10557343. Bibcode: 1999PNAS...9613462Z. 
• "Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors.". FEBS Lett. 470 (2): 161–6. 2000. doi:10.1016/S0014-5793(00)01307-7. PMID 10734227. 
• "Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis.". Oncogene 19 (36): 4146–50. 2000. doi:10.1038/sj.onc.1203769. PMID 10962575. 
• "Novel expression of cyclin-dependent kinase inhibitors in human B-cell precursors.". Exp. Hematol. 29 (4): 490–8. 2001. doi:10.1016/S0301-472X(01)00619-1. PMID 11301189. 
• "Protein folding and stability of human CDK inhibitor p19(INK4d).". J. Mol. Biol. 315 (3): 447–57. 2002. doi:10.1006/jmbi.2001.5242. PMID 11786024. 
• "Molecular cloning and characterization of the human p19(INK4d) gene promoter.". FEBS Lett. 517 (1–3): 272–6. 2002. doi:10.1016/S0014-5793(02)02647-9. PMID 12062451. 
• "Evidence of a role for the INK4 family of cyclin-dependent kinase inhibitors in ovarian granulosa cell tumors.". Genes Chromosomes Cancer 35 (2): 176–81. 2002. doi:10.1002/gcc.10108. PMID 12203782. 
• "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. 2003. doi:10.1073/pnas.242603899. PMID 12477932. Bibcode: 2002PNAS...9916899M. 
• "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.". Nat. Biotechnol. 21 (5): 566–9. 2004. doi:10.1038/nbt810. PMID 12665801. 
• "Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells.". Br. J. Cancer 88 (8): 1277–80. 2004. doi:10.1038/sj.bjc.6600862. PMID 12698196. 

External links

• CDKN2D human gene location in the UCSC Genome Browser.
• CDKN2D human gene details in the UCSC Genome Browser.
• Overview of all the structural information available in the PDB for UniProt: P55273 (Cyclin-dependent kinase 4 inhibitor D) at the PDBe-KB.