CDKN2B cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) [Homo sapiens] - Gene

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Summary

Official Symbol: CDKN2Bprovided by HGNC
Official Full Name: cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)provided by HGNC
Primary source: HGNC:1788
Locus tag: RP11-149I2.1
See related: Ensembl:ENSG00000147883; HPRD:02696; MIM:600431; Vega:OTTHUMG00000019691
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: P15; MTS2; TP15; CDK4I; INK4B; p15INK4b
Summary: This gene lies adjacent to the tumor suppressor gene CDKN2A in a region that is frequently mutated and deleted in a wide variety of tumors. This gene encodes a cyclin-dependent kinase inhibitor, which forms a complex with CDK4 or CDK6, and prevents the activation of the CDK kinases, thus the encoded protein functions as a cell growth regulator that controls cell cycle G1 progression. The expression of this gene was found to be dramatically induced by TGF beta, which suggested its role in the TGF beta induced growth inhibition. Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 9p21

Sequence :: Chromosome: 9; NC_000009.11 (22002902..22009312, complement)

See CDKN2B in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 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?

findings indicate that the inactivation of the CDKN2A/B locus is a frequent event in Ph+ acute lymphoblastic leukemia; deletions are frequently acquired at leukemia progression and are a poor prognostic marker
Title: CDKN2A/B alterations impair prognosis in adult BCR-ABL1-positive acute lymphoblastic leukemia patients.
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.
Six SNP(rs7754840 in CDKAL1, rs391300 in SRR, rs2383208 in CDKN2A/2B, rs4402960 in IGF2BP2, rs10830963 in MTNR1B, rs4607517 in GCK)risk alleles of type 2 diabetes were associated with GDM in pregnant Chinese women.
Title: Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population.
2 genes of loss, CDKN2B and PTCH1, are associated with poor overall survival in patients with squamous cell carcinoma of the lung and may be useful as prognostic markers
Title: Association of copy number loss of CDKN2B and PTCH1 with poor overall survival in patients with pulmonary squamous cell carcinoma.
cases with inactivation of all p14(ARF), p15(INK4b), and p16(INK4a) genes showed the worst prognosis in a combined prognostic assessment
Title: Prognostic significance of p14ARF, p15INK4b, and p16INK4a inactivation in malignant peripheral nerve sheath tumors.
rs4977756, a genetic variant of CDKN2B and CDKN2A, was one of 3 genetic variants implicated in a pool of US epidemiologic studies of glioma risk
Title: Joint associations between genetic variants and reproductive factors in glioma risk among women.
DNA sequence analysis of the breakpoints and junctions of CDKN2A and CDKN2B gene deletions in diffuse large B-cell lymphomas
Title: Molecular characterization of 9p21 deletions shows a minimal common deleted region removing CDKN2A exon 1 and CDKN2B exon 2 in diffuse large B-cell lymphomas.
Data show that deletion of CDKN2A and CDKN2B as well as the sequences just upstream and downstream were confirmed in SCC.
Title: DNA copy number profile discriminates between esophageal adenocarcinoma and squamous cell carcinoma and represents an independent prognostic parameter in esophageal adenocarcinoma.
Phenylhexyl isothiocyanate treatment results in the demethylation of CPG island in p15 gene, inducing re-expression of p15 in Molt-4 cells.
Title: [Phenylhexyl isothiocyanate induces gene p15 re-expression by regulating histone methylation and DNA demethylation in Molt-4 cells].
Single nucleotide polymorphisms in CDKN2B is associated with Philadelphia positive acute lymphoblastic leukemia.
Title: A polymorphism in the chromosome 9p21 ANRIL locus is associated to Philadelphia positive acute lymphoblastic leukemia.

Submit: New GeneRIF Correction See all (124)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

A common variant on chromosome 9p21 affects the risk of myocardial infarction.

A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.

A genome-wide association study of optic disc parameters.

A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data.

Chromosome 7p11.2 (EGFR) variation influences glioma risk.

Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.

Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.

Genome-wide association study identifies five new breast cancer susceptibility loci.

Genome-wide association study identifies five susceptibility loci for glioma.

Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.

Genome-wide association study of intracranial aneurysm identifies three new risk loci.

Genome-wide association study of type 2 diabetes in a sample from Mexico City and a meta-analysis of a Mexican-American sample from Starr County, Texas.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

Susceptibility loci for intracranial aneurysm in European and Japanese populations.

Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

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Products	Interactant	Other Gene	Source	Pubs	Description
NC_000009.9		PIAS2	BIND	PubMed	Miz1 interacts with p-p15Ink4b.
P42772	O15145	ARPC3	HPRD	PubMed
P42772	Coiled-coil domain containing 90B	CCDC90B	HPRD	PubMed
P42772	P11802	CDK4	HPRD	PubMed
P42772	P49336	CDK8	HPRD	PubMed
P42772	O95163	IKBKAP	HPRD	PubMed
P42772	Q9P2H0	KIAA1377	HPRD	PubMed
P42772	P43364	MAGEA11	HPRD	PubMed
P42772	Q13105	ZBTB17	HPRD	PubMed
BioGRID:107464	BioGRID:115401	ARPC3	BioGRID	PubMed	Two-hybrid
BioGRID:107464	BioGRID:121923	CCDC90B	BioGRID	PubMed	Two-hybrid
BioGRID:107464	BioGRID:107454	CDK4	BioGRID	PubMed	Two-hybrid
BioGRID:107464	BioGRID:114090	IKBKAP	BioGRID	PubMed	Two-hybrid
BioGRID:107464	BioGRID:121617	KIAA1377	BioGRID	PubMed	Two-hybrid
BioGRID:107464	BioGRID:110284	MAGEA11	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
cyclin-dependent protein kinase inhibitor activity	IDA Inferred from Direct Assay more info	PubMed
cyclin-dependent protein kinase inhibitor activity	NAS Non-traceable Author Statement more info	PubMed
kinase activity	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction 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
G2/M transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
cell cycle arrest	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to extracellular stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to nutrient	IMP Inferred from Mutant Phenotype more info	PubMed
megakaryocyte differentiation	IEP Inferred from Expression Pattern more info	PubMed
mitotic cell cycle	TAS Traceable Author Statement more info
mitotic cell cycle G1/S transition checkpoint	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of epithelial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of phosphorylation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of epithelial cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of transforming growth factor beta receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cyclin-dependent protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
response to cytokine stimulus	IEA Inferred from Electronic Annotation more info
response to organic cyclic compound	IEA Inferred from Electronic Annotation more info

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 B

Names: cyclin-dependent kinase 4 inhibitor B; MTS-2; p14-INK4b; p14_INK4B; p15-INK4b; p15_INK4B; CDK4B inhibitor; p14_CDK inhibitor; p15 CDK inhibitor; CDK inhibitory protein; multiple tumor suppressor 2; cyclin-dependent kinases 4 and 6 binding 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.

Genomic

NG_023297.1 RefSeqGene

Range

5001..11411

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_004936.3 → NP_004927.2 cyclin-dependent kinase 4 inhibitor B isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

AF488731, BC014469, BC018984, BI560960

Consensus CDS

CCDS6512.1

UniProtKB/Swiss-Prot

P42772

Related

ENSP00000276925, OTTHUMP00000021154, ENST00000276925, OTTHUMT00000051932

Conserved Domains (2) summary

cd00204
Location:18 – 132
Blast Score: 190

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:18 – 110
Blast Score: 135

Ank_2; Ankyrin repeats (3 copies)
NM_078487.2 → NP_511042.1 cyclin-dependent kinase 4 inhibitor B isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses a different splice site, which leads to a translation frame shift, when compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct C-terminus when compared to isoform 1.

Source sequence(s)

AF004819, AF488731, BC014469, BC018984, BI560960

Consensus CDS

CCDS6513.1

UniProtKB/TrEMBL

O15125

UniProtKB/Swiss-Prot

P42772

Related

ENSP00000369487, OTTHUMP00000021155, ENST00000380142, OTTHUMT00000051933

Conserved Domains (1) summary

cd00204
Location:18 – 54
Blast Score: 88

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 ...

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_000009.11 Reference GRCh37.p5 Primary Assembly

Range

22002902..22009312, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

21966171..21972582, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AF058758.1	AAF28397.1
genomic	AF513858.1	AAM44859.1
genomic	AJ844637.1	CAH59951.1
genomic	AL449423.14	CAH70602.1
		CAH70603.1
genomic	CH471071.2	EAW58596.1
		EAW58597.1
genomic	S69805.1	AAD14049.1
genomic	S75756.1	AAD14186.1
mRNA	AF004819.1	AAB69989.1
mRNA	AF488409.1	None
mRNA	AF488410.1	AAO49471.1
mRNA	AF488731.1	None
mRNA	BC014469.1	AAH14469.1
mRNA	BC018984.2	None
mRNA	BI560960.1	None
mRNA	CR536529.1	CAG38766.1
mRNA	L36844.1	AAA50282.1
mRNA	U17075.1	AAC50075.1
other-genetic	AM392641.1	CAL37519.1
other-genetic	AM392962.1	CAL37840.1
other-genetic	AM393264.1	CAL38142.1
other-genetic	AM393391.1	CAL38269.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
AAB32712.1	GenPept
O15125	GenPept	UniProtKB/TrEMBL:O15125
P42772.1	GenPept	UniProtKB/Swiss-Prot:P42772
Q5ZEY8	GenPept	UniProtKB/TrEMBL:Q5ZEY8
Q86WJ4	GenPept	UniProtKB/TrEMBL:Q86WJ4
Q8NIA6	GenPept	UniProtKB/TrEMBL:Q8NIA6
Q9UM95	GenPept	UniProtKB/TrEMBL:Q9UM95