CDKN2C cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4) [Homo sapiens] - Gene

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Summary

Official Symbol: CDKN2Cprovided by HGNC
Official Full Name: cyclin-dependent kinase inhibitor 2C (p18, inhibits CDK4)provided by HGNC
Primary source: HGNC:1789
Locus tag: RP11-278J17.2
See related: Ensembl:ENSG00000123080; HPRD:04534; MIM:603369; Vega:OTTHUMG00000008046
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: p18; INK4C; p18-INK4C
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 interact 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. Ectopic expression of this gene was shown to suppress the growth of human cells in a manner that appears to correlate with the presence of a wild-type RB1 function. Studies in the knockout mice suggested the roles of this gene in regulating spermatogenesis, as well as in suppressing tumorigenesis. Two alternatively spliced transcript variants of this gene, which encode an identical protein, have been reported. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 1p32

Sequence :: Chromosome: 1; NC_000001.10 (51434367..51440309)

See CDKN2C in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 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 p15, p18 and p27 was not generally related to the MEN1 gene mutational status of the investigated 18 pancreatic endocrine tumours.
Title: Evaluation of CDKN2C/p18, CDKN1B/p27 and CDKN2B/p15 mRNA expression, and CpG methylation status in sporadic and MEN1-associated pancreatic endocrine tumours.
propose that the contrasting behavior of the two very similar INK4 proteins could reflect their respective roles in senescence versus differentiation
Title: Contrasting behavior of the p18INK4c and p16INK4a tumor suppressors in both replicative and oncogene-induced senescence.
results demonstrate for the first time that N-Myc is a downstream target of RET2A signaling, and propose that induction of N-Myc by RET2A is a key step leading to lower p18 levels during MEN2A tumorigenesis
Title: N-Myc is a downstream target of RET signaling and is required for transcriptional regulation of p18(Ink4c) by the transforming mutant RET(C634R).
review presents the recent advances in MEN-4 and other multiple endocrine neoplasias and summarises the current knowledge of how P27KIP1 and p18-INK4C may be implicated in endocrine neoplasia [review]
Title: MEN-4 and other multiple endocrine neoplasias due to cyclin-dependent kinase inhibitors (p27(Kip1) and p18(INK4C)) mutations.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Single nucleotide polymorphisms of matrix metalloproteinase 9 (MMP9) and tumor protein 73 (TP73) interact with Epstein-Barr virus in chronic lymphocytic leukemia: results from the European case-control study EpiLymph.
Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
Title: MicroRNA-related genetic variations as predictors for risk of second primary tumor and/or recurrence in patients with early-stage head and neck cancer.
Results identified a molecular basis for CDK inhibitors to exert an antitumor effect in p18-deficient cancers and support the clinical use of CDK inhibitors.
Title: Expression levels of p18INK4C modify the cellular efficacy of cyclin-dependent kinase inhibitors via regulation of Mcl-1 expression in tumor cell lines.
p18(INK4C) is a downstream target of GATA3, constrains luminal progenitor cell expansion, and suppresses luminal tumorigenesis in the mammary gland
Title: CDK inhibitor p18(INK4c) is a downstream target of GATA3 and restrains mammary luminal progenitor cell proliferation and tumorigenesis.
The down-regulation of p18(INK4C) expression may contribute to the tumorigenesis of pituitary adenomas.
Title: Expression of p18(INK4C) is down-regulated in human pituitary adenomas.
Purpose was to investigate genetic alterations of CDKN2C gene in 38 pituitary adenomas. The absence of CDKN2C protein was correlated with LOH of the CDKN2C locus on chromosome 1 and with methylation of the CDKN2C promoter.
Title: Frequent loss of the CDKN2C (p18INK4c) gene product in pituitary adenomas.

Submit: New GeneRIF Correction See all (25)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

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Products	Interactant	Other Gene	Source	Pubs	Description
P42773	P51693	APLP1	HPRD	PubMed
P42773	Coiled-coil domain containing 90B	CCDC90B	HPRD	PubMed
P42773	P11802	CDK4	HPRD	PubMed
P42773	Q00534	CDK6	HPRD	PubMed
P42773	Q8N726	CDKN2A	HPRD	PubMed
P42773	Q7L5N1	COPS6	HPRD	PubMed
P42773	Q14919	DRAP1	HPRD	PubMed
P42773	O60383	GDF9	HPRD	PubMed
P42773	Q5T3J3	LRIF1	HPRD	PubMed
P42773	P55769	NHP2L1	HPRD	PubMed
P42773	Hypothetical protein DKFZp564O0523	RBM48	HPRD	PubMed
P42773	Q04724	TLE1	HPRD	PubMed
P42773	P04637	TP53	HPRD	PubMed
P42773	Q13432	UNC119	HPRD	PubMed
BioGRID:107465	BioGRID:106830	APLP1	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:121923	CCDC90B	BioGRID	PubMed	Two-hybrid
	NP_000066.1	CDK4	BIND	PubMed	An unspecified isoform of p18 interacts with cdk4. This interaction was modeled on a demonstrated interaction between human p18 and cdk4 from an unspecified species.
BioGRID:107465	BioGRID:107454	CDK4	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex; Two-hybrid
	NP_001250.1	CDK6	BIND	PubMed	An unspecified isoform of p18 interacts with cdk6. This interaction was modeled on a demonstrated interaction between human p18 and cdk6 from an unspecified species.
BioGRID:107465	BioGRID:107456	CDK6	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western; Co-crystal Structure; Reconstituted Complex; Two-hybrid
BioGRID:107465	BioGRID:116176	COPS6	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:115838	DRAP1	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:108930	GDF9	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:120905	LRIF1	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:110874	NHP2L1	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:120171	QPCTL	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107465	BioGRID:123855	RBM48	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:112943	TLE1	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:113010	TP53	BioGRID	PubMed	Two-hybrid
BioGRID:107465	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:107465	BioGRID:114548	UNC119	BioGRID	PubMed	Two-hybrid

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
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
cell cycle arrest	IDA Inferred from Direct Assay more info	PubMed
induction of apoptosis	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 phosphorylation	IDA Inferred from Direct Assay more info	PubMed
oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
regulation of cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay 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 C

Names: cyclin-dependent kinase 4 inhibitor C; p18-INK6; CDK6 inhibitor p18; cyclin-dependent inhibitor; cyclin-dependent kinase 6 inhibitor p18

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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_001262.2 → NP_001253.1 cyclin-dependent kinase 4 inhibitor C

Status: REVIEWED

Description

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

Source sequence(s)

AF041248

Consensus CDS

CCDS555.1

UniProtKB/Swiss-Prot

P42773

UniProtKB/TrEMBL

Q6ICV4

Related

ENSP00000379452, ENST00000396148

Conserved Domains (3) summary

cd00204
Location:37 – 156
Blast Score: 231

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:74 – 161
Blast Score: 163

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:38 – 90
Blast Score: 84

Ank_4; Ankyrin repeats (many copies)
NM_078626.2 → NP_523240.1 cyclin-dependent kinase 4 inhibitor C

Status: REVIEWED

Description

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

Source sequence(s)

BE783451, BE831176, U17074

Consensus CDS

CCDS555.1

UniProtKB/Swiss-Prot

P42773

UniProtKB/TrEMBL

Q6ICV4

Related

ENSP00000360826, OTTHUMP00000009730, ENST00000371761, OTTHUMT00000022057

Conserved Domains (3) summary

cd00204
Location:37 – 156
Blast Score: 231

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:74 – 161
Blast Score: 163

Ank_2; Ankyrin repeats (3 copies)

pfam13637
Location:38 – 90
Blast Score: 84

Ank_4; Ankyrin repeats (many 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_000001.10 Reference GRCh37.p5 Primary Assembly

Range

51434367..51440309

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

49551948..49557890

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF041249.1	AAC39783.1
genomic	AF041250.1	AAC39783.1
genomic	AF058759.1	AAF28398.1
genomic	AL359977.16	CAH70191.1
genomic	AL590455.20	CAH71955.1
genomic	AY094608.1	AAM11873.1
genomic	CH471059.2	EAX06833.1
		EAX06834.1
		EAX06835.1
		EAX06836.1
genomic	HI558639.1	CBX47327.1
mRNA	AF041248.1	AAC39782.1
mRNA	AK021794.1	None
mRNA	AK091170.1	BAG52297.1
mRNA	BC000598.1	AAH00598.1
mRNA	BC005041.1	AAH05041.1
mRNA	BC016173.1	AAH16173.1
mRNA	BC017036.1	None
mRNA	BE783451.1	None
mRNA	BE831176.1	None
mRNA	CR450289.1	CAG29285.1
mRNA	U17074.1	AAC50074.1
other-genetic	DQ891516.2	ABM82442.1
other-genetic	DQ894707.2	ABM85633.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P42773.1	GenPept	UniProtKB/Swiss-Prot:P42773
Q6ICV4	GenPept	UniProtKB/TrEMBL:Q6ICV4
Q9P1T2	GenPept	UniProtKB/TrEMBL:Q9P1T2