CDKN2D cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4) [Homo sapiens] - Gene

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Summary

Official Symbol: CDKN2Dprovided by HGNC
Official Full Name: cyclin-dependent kinase inhibitor 2D (p19, inhibits CDK4)provided by HGNC
Primary source: HGNC:1790
See related: Ensembl:ENSG00000129355; HPRD:02957; MIM:600927
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: p19; INK4D; p19-INK4D
Summary: 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. Two alternatively spliced variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 19p13

Sequence :: Chromosome: 19; NC_000019.9 (10677138..10679655, complement)

See CDKN2D in Epigenomics, MapViewer

Chromosome 19 - NC_000019.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

expression of p19INK4D may be an effective predictor of clinical behavior in hepatocellular carcinoma, and therefore, a new prognostic marker
Title: Frequent loss of p19INK4D expression in hepatocellular carcinoma: relationship to tumor differentiation and patient survival.
p19INK4d is transcriptionally regulated by E2F1 through two response elements present in the p19INK4d promoter.
Title: E2F1-mediated upregulation of p19INK4d determines its periodic expression during cell cycle and regulates cellular proliferation.
Results show that overexpression of CDK4, cyclin D1, and Rb proteins, and loss of expression of proteins p16, p27, and p19 were statistically significant in NPC tissues compared with non-cancerous NPE (P<0.05) by real-time RT-PCR and tissue microarray.
Title: Identification of aberrant cell cycle regulation in Epstein-Barr virus-associated nasopharyngeal carcinoma by cDNA microarray and gene set enrichment analysis.
The study shows that mimicking the phosphorylation site of p19INK4d by a glutamate substitution at position 76 dramatically decreases the stability of the native but not an intermediate state.
Title: Conformational switch upon phosphorylation: human CDK inhibitor p19INK4d between the native and partially folded state.
p19(INK4D) knockdown led to a moderate increase (31.7% +/- 5%) in the mean ploidy of megakaryocytes suggesting a role of p19(INK4D) in the endomitotic arrest.
Title: P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1.
Observational study of gene-disease association. (HuGE Navigator)
Title: Cell cycle genes and ovarian cancer susceptibility: a tagSNP analysis.
Data suggest that the graded stability and the facile unfolding of repeats 1 and 2 is a prerequisite for the down-regulation of the inhibitory activity of p19(INK4d) during the cell-cycle.
Title: Folding mechanism of an ankyrin repeat protein: scaffold and active site formation of human CDK inhibitor p19(INK4d).
In addition to its role as cell cycle inhibitor, p19INK4d is involved in maintenance of DNA integrity and, therefore, would contribute to cancer prevention.
Title: Induction of p19INK4d in response to ultraviolet light improves DNA repair and confers resistance to apoptosis in neuroblastoma cells.
p19(INK4d) in addition to p21(WAF1/Cip1) is an important molecular target of HDAC inhibitors inducing growth arrest
Title: Histone deacetylase inhibitors activate INK4d gene through Sp1 site in its promoter.
The human p19(INK4d) gene is under the control of TATA-less promoter and the Sp1 binding site is involved in the transcription.
Title: Molecular cloning and characterization of the human p19(INK4d) gene promoter.

Submit: New GeneRIF Correction See all (13)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
P55273	P11802	CDK4	HPRD	PubMed
P55273	Q00534	CDK6	HPRD	PubMed
P55273	Q9HA65	TBC1D17	HPRD	PubMed
BioGRID:107466	BioGRID:107140	BRCA1	BioGRID	PubMed	Affinity Capture-Western; Biochemical Activity; Reconstituted Complex
BioGRID:107466	BioGRID:107454	CDK4	BioGRID	PubMed	Two-hybrid
BioGRID:107466	BioGRID:107456	CDK6	BioGRID	PubMed	Co-crystal Structure
BioGRID:107466	BioGRID:122849	TBC1D17	BioGRID	PubMed	Two-hybrid
BioGRID:107466	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
cyclin-dependent protein kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
DNA synthesis involved in DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
G1 phase of mitotic cell cycle	TAS Traceable Author Statement more info
G1/S transition of mitotic cell cycle	IDA Inferred from Direct Assay more info	PubMed
anti-apoptosis	IMP Inferred from Mutant Phenotype more info	PubMed
autophagic cell death	IMP Inferred from Mutant Phenotype more info	PubMed
cell cycle arrest	IDA Inferred from Direct Assay more info	PubMed
mitotic cell cycle	TAS Traceable Author Statement more info
negative regulation of cell growth	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
regulation of cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
response to UV	IMP Inferred from Mutant Phenotype more info	PubMed
response to retinoic acid	IMP Inferred from Mutant Phenotype more info	PubMed
response to vitamin D	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	TAS Traceable Author Statement more info
nucleus	IDA Inferred from Direct Assay more info	PubMed

General protein information

Preferred Names: cyclin-dependent kinase 4 inhibitor D

Names: cyclin-dependent kinase 4 inhibitor D; CDK inhibitor p19INK4d; inhibitor of cyclin-dependent kinase 4d; cyclin-dependent kinase 4 inhibitor D p19; cell cycle inhibitor, Nur77 associating protein

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001800.3 → NP_001791.1 cyclin-dependent kinase 4 inhibitor D

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains a different 5' UTR region, and encodes an identical protein, as compared to variant 2.

Source sequence(s)

BC001822, BI462387, U40343

Consensus CDS

CCDS12244.1

UniProtKB/Swiss-Prot

P55273

Related

ENSP00000377224, ENST00000393599

Conserved Domains (2) summary

cd00204
Location:36 – 158
Blast Score: 230

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam12796
Location:50 – 136
Blast Score: 178

Ank_2; Ankyrin repeats (3 copies)
NM_079421.2 → NP_524145.1 cyclin-dependent kinase 4 inhibitor D

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains a different 5' UTR region, and encodes an identical protein, as compared to variant 1.

Source sequence(s)

BC001822, BI669755

Consensus CDS

CCDS12244.1

UniProtKB/Swiss-Prot

P55273

Related

ENSP00000337056, ENST00000335766

Conserved Domains (2) summary

cd00204
Location:36 – 158
Blast Score: 230

ANK; ankyrin repeats; ankyrin repeats mediate protein-protein interactions in very diverse families of proteins. The number of ANK repeats in a protein can range from 2 to over 20 (ankyrins, for example). ANK repeats may occur in combinations with other ...

pfam12796
Location:50 – 136
Blast Score: 178

Ank_2; Ankyrin repeats (3 copies)

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000019.9 Reference GRCh37.p5 Primary Assembly

Range

10677138..10679655, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000151.1 Alternate HuRef

Range

10255057..10257571, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC011475.6 (158947..161464)	None
genomic	AF044171.1	AAD02320.1
genomic	AF061327.1	AAC27450.1
genomic	AF518878.1	AAM54045.1
genomic	CH471106.1	EAW84122.1
		EAW84123.1
mRNA	BC001822.2	AAH01822.1
mRNA	BG719545.1	None
mRNA	BI462387.1	None
mRNA	BI669755.1	None
mRNA	CR542158.1	CAG46955.1
mRNA	U20498.1	AAA85436.1
mRNA	U40343.1	AAB18139.1
mRNA	U49399.1	AAB03772.1
other-genetic	DQ892872.2	ABM83798.1
other-genetic	DQ892951.2	ABM83877.1
other-genetic	DQ896120.2	ABM87119.1