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CDKN2B cyclin dependent kinase inhibitor 2B [ Homo sapiens (human) ]

Gene ID: 1030, updated on 15-Apr-2019

Summary

Official Symbol
CDKN2Bprovided by HGNC
Official Full Name
cyclin dependent kinase inhibitor 2Bprovided by HGNC
Primary source
HGNC:HGNC:1788
See related
Ensembl:ENSG00000147883 MIM:600431
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]
Expression
Broad expression in colon (RPKM 20.3), small intestine (RPKM 17.6) and 17 other tissues See more
Orthologs

Genomic context

See CDKN2B in Genome Data Viewer
Location:
9p21.3
Exon count:
2
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 9 NC_000009.12 (22002903..22009313, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (22002902..22009312, complement)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene tubulin beta 8 class VIII pseudogene 1 Neighboring gene methylthioadenosine phosphorylase Neighboring gene CDKN2A divergent transcript Neighboring gene CDKN2B antisense RNA 1 Neighboring gene cyclin dependent kinase inhibitor 2A Neighboring gene ubiquitin A-52 residue ribosomal protein fusion product 1 pseudogene 6 Neighboring gene DMRT like family A1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
1000 Genomes-based imputation identifies novel and refined associations for the Wellcome Trust Case Control Consortium phase 1 Data.
NHGRI GWA Catalog
A common variant on chromosome 9p21 affects the risk of myocardial infarction.
NHGRI GWA Catalog
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
NHGRI GWA Catalog
A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans.
NHGRI GWA Catalog
A genome-wide association study in the Japanese population confirms 9p21 and 14q23 as susceptibility loci for primary open angle glaucoma.
NHGRI GWA Catalog
A genome-wide association study of nasopharyngeal carcinoma identifies three new susceptibility loci.
NHGRI GWA Catalog
A genome-wide association study of optic disc parameters.
NHGRI GWA Catalog
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.
NHGRI GWA Catalog
Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data.
NHGRI GWA Catalog
Association between chromosome 9p21 variants and the ankle-brachial index identified by a meta-analysis of 21 genome-wide association studies.
NHGRI GWA Catalog
Chromosome 7p11.2 (EGFR) variation influences glioma risk.
NHGRI GWA Catalog
Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.
NHGRI GWA Catalog
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
NHGRI GWA Catalog
Genome-wide association meta-analysis identifies new endometriosis risk loci.
NHGRI GWA Catalog
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
NHGRI GWA Catalog
Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
NHGRI GWA Catalog
Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction.
NHGRI GWA Catalog
Genome-wide association study identifies five new breast cancer susceptibility loci.
NHGRI GWA Catalog
Genome-wide association study identifies five susceptibility loci for glioma.
NHGRI GWA Catalog
Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia.
NHGRI GWA Catalog
Genome-wide association study identifies three novel loci for type 2 diabetes.
NHGRI GWA Catalog
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
NHGRI GWA Catalog
Genome-wide association study of coronary and aortic calcification implicates risk loci for coronary artery disease and myocardial infarction.
NHGRI GWA Catalog
Genome-wide association study of coronary artery disease in the Japanese.
NHGRI GWA Catalog
Genome-wide association study of intracranial aneurysm identifies three new risk loci.
NHGRI GWA Catalog
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.
NHGRI GWA Catalog
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
NHGRI GWA Catalog
Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma.
NHGRI GWA Catalog
Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies.
NHGRI GWA Catalog
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
NHGRI GWA Catalog
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
NHGRI GWA Catalog
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
NHGRI GWA Catalog
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
NHGRI GWA Catalog
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
NHGRI GWA Catalog
Susceptibility loci for intracranial aneurysm in European and Japanese populations.
NHGRI GWA Catalog
Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
NHGRI GWA Catalog
Two-marker association tests yield new disease associations for coronary artery disease and hypertension.
NHGRI GWA Catalog

Pathways from BioSystems

  • Cell Cycle, organism-specific biosystem (from REACTOME)
    Cell Cycle, organism-specific biosystem
    Cell Cycle
  • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
    Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
  • Cell cycle, organism-specific biosystem (from KEGG)
    Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • Cell cycle, conserved biosystem (from KEGG)
    Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • Cellular Senescence, organism-specific biosystem (from REACTOME)
    Cellular Senescence, organism-specific biosystemCellular senescence involves irreversible growth arrest accompanied by phenotypic changes such as enlarged morphology, reorganization of chromatin through formation of senescence-associated heterochr...
  • Cellular responses to stress, organism-specific biosystem (from REACTOME)
    Cellular responses to stress, organism-specific biosystemCells are subject to external molecular and physical stresses such as foreign molecules that perturb metabolic or signaling processes, and changes in temperature or pH. The ability of cells and tissu...
  • Cyclin D associated events in G1, organism-specific biosystem (from REACTOME)
    Cyclin D associated events in G1, organism-specific biosystemThree D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and...
  • FoxO signaling pathway, organism-specific biosystem (from KEGG)
    FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
  • G1 Phase, organism-specific biosystem (from REACTOME)
    G1 Phase, organism-specific biosystemEarly cell cycle progression in G1 is under the control of the D-type cyclins together with Cdk4 and Cdk6. An important target for these CDKs is the Retinoblastoma (Rb) protein, which when phosphoryl...
  • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
    G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • HTLV-I infection, organism-specific biosystem (from KEGG)
    HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • HTLV-I infection, conserved biosystem (from KEGG)
    HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
  • Integrated Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Cancer Pathway, organism-specific biosystem
    Integrated Cancer Pathway
  • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
  • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
    Mitotic G1-G1/S phases, organism-specific biosystem
    Mitotic G1-G1/S phases
  • Oncogene Induced Senescence, organism-specific biosystem (from REACTOME)
    Oncogene Induced Senescence, organism-specific biosystemOncogene-induced senescence is triggered by high level of RAS/RAF/MAPK signaling that can be caused, for example, by oncogenic mutations in RAS or RAF proteins, or by oncogenic mutations in growth fa...
  • Oxidative Stress Induced Senescence, organism-specific biosystem (from REACTOME)
    Oxidative Stress Induced Senescence, organism-specific biosystemOxidative stress, caused by increased concentration of reactive oxygen species (ROS) in the cell, can happen as a consequence of mitochondrial dysfunction induced by the oncogenic RAS (Moiseeva et al...
  • Pathways in cancer, organism-specific biosystem (from KEGG)
    Pathways in cancer, organism-specific biosystem
    Pathways in cancer
  • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
    Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
    Regulation of nuclear SMAD2/3 signaling
  • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystem (from REACTOME)
    SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription, organism-specific biosystemAfter phosphorylated SMAD2 and/or SMAD3 form a heterotrimer with SMAD4, SMAD2/3:SMAD4 complex translocates to the nucleus (Xu et al. 2000, Kurisaki et al. 2001, Xiao et al. 2003). In the nucleus, lin...
  • Senescence-Associated Secretory Phenotype (SASP), organism-specific biosystem (from REACTOME)
    Senescence-Associated Secretory Phenotype (SASP), organism-specific biosystemThe culture medium of senescent cells in enriched in secreted proteins when compared with the culture medium of quiescent i.e. presenescent cells and these secreted proteins constitute the so-called ...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
    Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
  • Signaling by TGF-beta Receptor Complex, organism-specific biosystem (from REACTOME)
    Signaling by TGF-beta Receptor Complex, organism-specific biosystemThe TGF-beta/BMP pathway incorporates several signaling pathways that share most, but not all, components of a central signal transduction engine. The general signaling scheme is rather simple: upon ...
  • Small cell lung cancer, organism-specific biosystem (from KEGG)
    Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • Small cell lung cancer, conserved biosystem (from KEGG)
    Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
  • TGF-beta signaling pathway, organism-specific biosystem (from KEGG)
    TGF-beta signaling pathway, organism-specific biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
  • TGF-beta signaling pathway, conserved biosystem (from KEGG)
    TGF-beta signaling pathway, conserved biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
  • Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystem (from REACTOME)
    Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer, organism-specific biosystemIn the nucleus, SMAD2/3:SMAD4 heterotrimer complex acts as a transcriptional regulator. The activity of SMAD2/3 complex is regulated both positively and negatively by association with other transcrip...
  • Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
    Validated targets of C-MYC transcriptional repression, organism-specific biosystem
    Validated targets of C-MYC transcriptional repression
  • Viral carcinogenesis, organism-specific biosystem (from KEGG)
    Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
  • Viral carcinogenesis, conserved biosystem (from KEGG)
    Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Process Evidence Code Pubs
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 
cellular senescence IMP
Inferred from Mutant Phenotype
more info
PubMed 
megakaryocyte differentiation IEP
Inferred from Expression Pattern
more info
PubMed 
mitotic cell cycle checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of G1/S transition of mitotic cell cycle TAS
Traceable Author Statement
more info
 
negative regulation of cell proliferation IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of cyclin-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
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 transcription by RNA polymerase II TAS
Traceable Author Statement
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 serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
spleen development 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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
cyclin-dependent kinase 4 inhibitor B
Names
CDK inhibitory protein
CDK4B inhibitor
MTS-2
cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
cyclin-dependent kinases 4 and 6 binding protein
multiple tumor suppressor 2
p14-INK4b
p14_CDK inhibitor
p14_INK4B
p15 CDK inhibitor
p15-INK4b
p15_INK4B

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

  1. NG_023297.1 RefSeqGene

    Range
    5001..11411
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    See identical proteins and their annotated locations for NP_004927.2

    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
    UniProtKB/TrEMBL
    K7PPU3
    Related
    ENSP00000276925.6, ENST00000276925.7
    Conserved Domains (2) summary
    cd00204
    Location:21132
    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 ...
    sd00045
    Location:4676
    ANK; ANK repeat [structural motif]
  2. NM_078487.2NP_511042.1  cyclin-dependent kinase 4 inhibitor B isoform 2

    See identical proteins and their annotated locations for NP_511042.1

    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/Swiss-Prot
    P42772
    Related
    ENSP00000369487.4, ENST00000380142.4
    Conserved Domains (1) summary
    cl02529
    Location:2154
    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: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p12 Primary Assembly

    Range
    22002903..22009313 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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