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.[7] Two alternatively spliced variants of this gene, which encode an identical protein, have been reported.[6]
Note, this protein should not be confused with p19-ARF (mouse) or the human equivalent p14ARF, which are alternative products of the CDKN2A gene.
Referencesedit
^ abcGRCh38: Ensembl release 89: ENSG00000129355 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000096472 - 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.
^Okuda T, Hirai H, Valentine VA, Shurtleff SA, Kidd VJ, Lahti JM, Sherr CJ, Downing JR (Mar 1996). "Molecular cloning, expression pattern, and chromosomal localization of human CDKN2D/INK4d, an inhibitor of cyclin D-dependent kinases". Genomics. 29 (3): 623–30. doi:10.1006/geno.1995.9957. PMID 8575754.
^Dehkordi, Shiva Kazempour; Walker, Jamie; Sah, Eric; Bennett, Emma; Atrian, Farzaneh; Frost, Bess; Woost, Benjamin; Bennett, Rachel E.; Orr, Timothy C.; Zhou, Yingyue; Andhey, Prabhakar S.; Colonna, Marco; Sudmant, Peter H.; Xu, Peng; Wang, Minghui; Zhang, Bin; Zare, Habil; Orr, Miranda E. (December 2021). "Profiling senescent cells in human brains reveals neurons with CDKN2D/p19 and tau neuropathology". Nature Aging. 1 (12): 1107–1116. doi:10.1038/s43587-021-00142-3. PMC9075501. PMID 35531351. S2CID 245059153.
Further readingedit
Hirai H, Roussel MF, Kato JY, et al. (1995). "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. doi:10.1128/MCB.15.5.2672. PMC230497. PMID 7739547.
Chan FK, Zhang J, Cheng L, et al. (1995). "Identification of human and mouse p19, a novel CDK4 and CDK6 inhibitor with homology to p16ink4". Mol. Cell. Biol. 15 (5): 2682–8. doi:10.1128/MCB.15.5.2682. PMC230498. PMID 7739548.
Guan KL, Jenkins CW, Li Y, et al. (1996). "Isolation and characterization of p19INK4d, a p16-related inhibitor specific to CDK6 and CDK4". Mol. Biol. Cell. 7 (1): 57–70. doi:10.1091/mbc.7.1.57. PMC278612. PMID 8741839.
Schwaller J, Pabst T, Koeffler HP, et al. (1997). "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. doi:10.1038/sj.leu.2400522. PMID 9001419.
Russo AA, Tong L, Lee JO, et al. (1998). "Structural basis for inhibition of the cyclin-dependent kinase Cdk6 by the tumour suppressor p16INK4a". Nature. 395 (6699): 237–43. Bibcode:1998Natur.395..237R. doi:10.1038/26155. PMID 9751050. S2CID 204997058.
Brotherton DH, Dhanaraj V, Wick S, et al. (1998). "Crystal structure of the complex of the cyclin D-dependent kinase Cdk6 bound to the cell-cycle inhibitor p19INK4d". Nature. 395 (6699): 244–50. Bibcode:1998Natur.395..244B. doi:10.1038/26164. PMID 9751051. S2CID 13337394.
Baumgartner R, Fernandez-Catalan C, Winoto A, et al. (1998). "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. doi:10.1016/S0969-2126(98)00128-2. PMID 9782052.
Schreiber M, Muller WJ, Singh G, Graham FL (1999). "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. doi:10.1038/sj.onc.1202466. PMID 10208428.
Newton Bishop JA, Harland M, Bennett DC, et al. (1999). "Mutation testing in melanoma families: INK4A, CDK4 and INK4D". Br. J. Cancer. 80 (1–2): 295–300. doi:10.1038/sj.bjc.6690354. PMC2363010. PMID 10390011.
Zindy F, Cunningham JJ, Sherr CJ, et al. (1999). "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. Bibcode:1999PNAS...9613462Z. doi:10.1073/pnas.96.23.13462. PMC23970. PMID 10557343.
Thullberg M, Bartkova J, Khan S, et al. (2000). "Distinct versus redundant properties among members of the INK4 family of cyclin-dependent kinase inhibitors". FEBS Lett. 470 (2): 161–6. doi:10.1016/S0014-5793(00)01307-7. PMID 10734227. S2CID 45439595.
Bartkova J, Thullberg M, Rajpert-De Meyts E, et al. (2000). "Lack of p19INK4d in human testicular germ-cell tumours contrasts with high expression during normal spermatogenesis". Oncogene. 19 (36): 4146–50. doi:10.1038/sj.onc.1203769. PMID 10962575.
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.
Zeeb M, Rösner H, Zeslawski W, et al. (2002). "Protein folding and stability of human CDK inhibitor p19(INK4d)". J. Mol. Biol. 315 (3): 447–57. doi:10.1006/jmbi.2001.5242. PMID 11786024.
Matsuzaki Y, Miyazawa K, Yokota T, et al. (2002). "Molecular cloning and characterization of the human p19(INK4d) gene promoter". FEBS Lett. 517 (1–3): 272–6. doi:10.1016/S0014-5793(02)02647-9. PMID 12062451. S2CID 82054693.
Arcellana-Panlilio MY, Egeler RM, Ujack E, et al. (2002). "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. doi:10.1002/gcc.10108. PMID 12203782. S2CID 27477191.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC139241. PMID 12477932.
Gevaert K, Goethals M, Martens L, et al. (2004). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nat. Biotechnol. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801. S2CID 23783563.
Komata T, Kanzawa T, Takeuchi H, et al. (2004). "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. doi:10.1038/sj.bjc.6600862. PMC2747579. PMID 12698196.
cdkn2d, cyclin, dependent, kinase, inhibitor, enzyme, that, humans, encoded, gene, available, structurespdbortholog, search, pdbe, rcsblist, codes1bd8, 1bi8identifiersaliases, ink4d, ink4d, cyclin, dependent, kinase, inhibitor, cyclin, dependent, kinase, inhib. Cyclin dependent kinase 4 inhibitor D is an enzyme that in humans is encoded by the CDKN2D gene 5 6 CDKN2DAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes1BD8 1BI8IdentifiersAliasesCDKN2D INK4D p19 p19 INK4D cyclin dependent kinase inhibitor 2D cyclin dependent kinase inhibitor 2DExternal IDsOMIM 600927 MGI 105387 HomoloGene 36081 GeneCards CDKN2DGene location Human Chr Chromosome 19 human 1 Band19p13 2Start10 566 460 bp 1 End10 569 059 bp 1 Gene location Mouse Chr Chromosome 9 mouse 2 Band9 9 A3Start21 199 706 bp 2 End21 202 703 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed inmonocytecingulate gyrusprefrontal cortexamygdalanucleus accumbensdorsolateral prefrontal cortexcaudate nucleusbloodBrodmann area 9putamenTop expressed inatriumthymusmedial ganglionic eminencesacculeendocardial cushioncingulate gyrusatrioventricular valvedorsomedial hypothalamic nucleusmammillary bodyventromedial nucleusMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein binding cyclin dependent protein serine threonine kinase inhibitor activity protein kinase bindingCellular componentcytoplasm nucleoplasm nucleus cytosol cyclin D2 CDK4 complexBiological processDNA synthesis involved in DNA repair regulation of cyclin dependent protein serine threonine kinase activity negative regulation of cysteine type endopeptidase activity involved in apoptotic process response to vitamin D response to retinoic acid negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage negative regulation of cell growth cell cycle negative regulation of phosphorylation response to UV autophagic cell death negative regulation of cell population proliferation sensory perception of sound negative regulation of cell cycle G1 S phase transition G1 S transition of mitotic cell cycle negative regulation of cyclin dependent protein serine threonine kinase activity negative regulation of G1 S transition of mitotic cell cycleSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez103212581EnsemblENSG00000129355ENSMUSG00000096472UniProtP55273Q60773RefSeq mRNA NM 079421NM 001800NM 009878RefSeq protein NP 001791NP 524145NP 034008Location UCSC Chr 19 10 57 10 57 MbChr 9 21 2 21 2 MbPubMed search 3 4 WikidataView Edit HumanView Edit MouseThe 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 7 Two alternatively spliced variants of this gene which encode an identical protein have been reported 6 Note this protein should not be confused with p19 ARF mouse or the human equivalent p14ARF which are alternative products of the CDKN2A gene References edit a b c GRCh38 Ensembl release 89 ENSG00000129355 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000096472 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 Okuda T Hirai H Valentine VA Shurtleff SA Kidd VJ Lahti JM Sherr CJ Downing JR Mar 1996 Molecular cloning expression pattern and chromosomal localization of human CDKN2D INK4d an inhibitor of cyclin D dependent kinases Genomics 29 3 623 30 doi 10 1006 geno 1995 9957 PMID 8575754 a b Entrez Gene CDKN2D cyclin dependent kinase inhibitor 2D p19 inhibits CDK4 Dehkordi Shiva Kazempour Walker Jamie Sah Eric Bennett Emma Atrian Farzaneh Frost Bess Woost Benjamin Bennett Rachel E Orr Timothy C Zhou Yingyue Andhey Prabhakar S Colonna Marco Sudmant Peter H Xu Peng Wang Minghui Zhang Bin Zare Habil Orr Miranda E December 2021 Profiling senescent cells in human brains reveals neurons with CDKN2D p19 and tau neuropathology Nature Aging 1 12 1107 1116 doi 10 1038 s43587 021 00142 3 PMC 9075501 PMID 35531351 S2CID 245059153 Further reading editHirai H Roussel MF Kato JY et al 1995 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 doi 10 1128 MCB 15 5 2672 PMC 230497 PMID 7739547 Chan FK Zhang J Cheng L et al 1995 Identification of human and mouse p19 a novel CDK4 and CDK6 inhibitor with homology to p16ink4 Mol Cell Biol 15 5 2682 8 doi 10 1128 MCB 15 5 2682 PMC 230498 PMID 7739548 Guan KL Jenkins CW Li Y et al 1996 Isolation and characterization of p19INK4d a p16 related inhibitor specific to CDK6 and CDK4 Mol Biol Cell 7 1 57 70 doi 10 1091 mbc 7 1 57 PMC 278612 PMID 8741839 Schwaller J Pabst T Koeffler HP et al 1997 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 doi 10 1038 sj leu 2400522 PMID 9001419 Russo AA Tong L Lee JO et al 1998 Structural basis for inhibition of the cyclin dependent kinase Cdk6 by the tumour suppressor p16INK4a Nature 395 6699 237 43 Bibcode 1998Natur 395 237R doi 10 1038 26155 PMID 9751050 S2CID 204997058 Brotherton DH Dhanaraj V Wick S et al 1998 Crystal structure of the complex of the cyclin D dependent kinase Cdk6 bound to the cell cycle inhibitor p19INK4d Nature 395 6699 244 50 Bibcode 1998Natur 395 244B doi 10 1038 26164 PMID 9751051 S2CID 13337394 Baumgartner R Fernandez Catalan C Winoto A et al 1998 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 doi 10 1016 S0969 2126 98 00128 2 PMID 9782052 Schreiber M Muller WJ Singh G Graham FL 1999 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 doi 10 1038 sj onc 1202466 PMID 10208428 Newton Bishop JA Harland M Bennett DC et al 1999 Mutation testing in melanoma families INK4A CDK4 and INK4D Br J Cancer 80 1 2 295 300 doi 10 1038 sj bjc 6690354 PMC 2363010 PMID 10390011 Zindy F Cunningham JJ Sherr CJ et al 1999 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 Bibcode 1999PNAS 9613462Z doi 10 1073 pnas 96 23 13462 PMC 23970 PMID 10557343 Thullberg M Bartkova J Khan S et al 2000 Distinct versus redundant properties among members of the INK4 family of cyclin dependent kinase inhibitors FEBS Lett 470 2 161 6 doi 10 1016 S0014 5793 00 01307 7 PMID 10734227 S2CID 45439595 Bartkova J Thullberg M Rajpert De Meyts E et al 2000 Lack of p19INK4d in human testicular germ cell tumours contrasts with high expression during normal spermatogenesis Oncogene 19 36 4146 50 doi 10 1038 sj onc 1203769 PMID 10962575 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 Zeeb M Rosner H Zeslawski W et al 2002 Protein folding and stability of human CDK inhibitor p19 INK4d J Mol Biol 315 3 447 57 doi 10 1006 jmbi 2001 5242 PMID 11786024 Matsuzaki Y Miyazawa K Yokota T et al 2002 Molecular cloning and characterization of the human p19 INK4d gene promoter FEBS Lett 517 1 3 272 6 doi 10 1016 S0014 5793 02 02647 9 PMID 12062451 S2CID 82054693 Arcellana Panlilio MY Egeler RM Ujack E et al 2002 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 doi 10 1002 gcc 10108 PMID 12203782 S2CID 27477191 Strausberg RL Feingold EA Grouse LH et al 2003 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 Bibcode 2002PNAS 9916899M doi 10 1073 pnas 242603899 PMC 139241 PMID 12477932 Gevaert K Goethals M Martens L et al 2004 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N terminal peptides Nat Biotechnol 21 5 566 9 doi 10 1038 nbt810 PMID 12665801 S2CID 23783563 Komata T Kanzawa T Takeuchi H et al 2004 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 doi 10 1038 sj bjc 6600862 PMC 2747579 PMID 12698196 External links editCDKN2D 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 nbsp This article on a gene on human chromosome 19 is a stub You can help Wikipedia by expanding it vte Retrieved from https en wikipedia org w index php title CDKN2D amp oldid 1157721744, wikipedia, wiki, book, books, library,
