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FLASH GENE
Symbol CDKN2B contributors: mct/npt/pgu - updated : 21-06-2017
HGNC name cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4)
HGNC id 1788
Corresponding disease
MNST melanoma-neural system tumor syndrome
Location 9p21.3      Physical location : 22.002.905 - 22.009.312
Synonym name
  • multiple tumor suppressor 2
  • cyclin-dependent kinase 4 inhibitor B
  • p14_CDK inhibitor
  • p15 CDK inhibitor
  • Synonym symbol(s) MTS2, P15, INK4B, TP15, p14-INK4b, p15-INK4b, CDK4I
    DNA
    TYPE functioning gene
    SPECIAL FEATURE opposite orientation
    text
  • tightly linked to CDKN2A
  • overlaps and is transcribed in antisense with respect to CDKN2BAS (Cunnington 2010)
  • STRUCTURE 6.41 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    text structure
  • promoter is a target for the ZNF217 oncogene, the CoREST complex, and DNMT3A
  • MAPPING cloned Y linked N status confirmed
    Physical map
    IFNAP22 9p21 interferon, alpha pseudogene 22 IFNA5 9p22 interferon, alpha 5 KIAA1354 9p22 KIAA1354 protein IFNA6 9p22 interferon, alpha 6 IFNA13 9p22 interferon, alpha 13 IFNA2 9p22 interferon, alpha 2 IFNA8 9p22 interferon, alpha 8 LOC392293 9 similar to Interferon omega-1 precursor (Interferon alpha-II-1) IFNA1 9p22 interferon, alpha 1 LOC392294 9 similar to interferon-alpha IFNT1 9p21.3 interferon tau-1 LOC347217 9p21.3 similar to KH-type splicing regulatory protein (FUSE binding protein 2); KH-type splicing regulatory protein (FUSE-binding protein 2) MTAP 9p22-p21 methylthioadenosine phosphorylase LOC51198 9p21-p22 susceptibility protein NSG-x CDKN2A 9p21.3 cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4) CDKN2B 9p21.3 cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) LOC392295 9 similar to ubiquitin A-52 residue ribosomal protein fusion product 1 DMRTA1 9p21.2 DMRT-like family A1
    regionally located adjacent to CDKN2A
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 3878 14 138 - 1997 9230210
    unique C terminus
    2 - 4001 10 78 - 1997 9230210
    additional internal region leading to a frame shift
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouth    
    Urinarybladder    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, G1, checkpoint, G1S
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • protein P15 with tandemly repeated ankyrin motif
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Cdkn2b
    intraspecies homolog to CDKN2A,highly
    Homologene
    FAMILY
  • CDKN2 cyclin-dependent kinase inhibitor family
  • CATEGORY enzyme , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    basic FUNCTION
  • inhibitor of CDK4/CDK6 dependent phosphorylation of RB1 and so regulator of the G1 progression
  • CDKN2A and CDKN2B play a key role in the control of the G1/S transition of the cell cycle
  • is a cyclin-dependent kinase inhibitor that forms a complex with CDK4 or CDK6 and prevents their activation, resulting in inhibition of cell-cycle progression at the G1/S transition
  • loss of CDKN2B promotes atherosclerosis by increasing the size and complexity of the lipid-laden necrotic core through impaired efferocytosis
  • CELLULAR PROCESS cell cycle, progression
    PHYSIOLOGICAL PROCESS
    text negative regulator
    PATHWAY
    metabolism
    signaling
    a component
  • forming a complex with CDK4, CDK5
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • expression levels of CDKN2A, CDKN2B, and CDKN2BAS are positively correlated
  • is a key regulator of cell proliferation that inhibits cell-cycle progression by blocking the activity of CDK4 and CDK6
  • ZNF217/CoREST complex and specific DNMTs combine likely to generate a hypermethylated state resulting in repression of the CDKN2B gene
  • TDG regulates TGFB1-dependent promoter demethylation and expression of the CDKN2B tumor suppressor gene
  • DLC1 inactivation cooperates with downregulation of CDKN2B and CDKN2A, leading to neoplastic transformation and poor prognosis in cancer
  • SMAD2 overexpression inhibits the proliferation of junctional epithelium (JE) cells by down-regulating MYC and up-regulating CDKN2B and CDKN1B, which resulted in an increase in RB1, leading to cell-cycle arrest
  • control of CD8 T cell proliferation and terminal differentiation by active STAT5B and CDKN2A/CDKN2B
  • ASXL1-mediated HIST2H2AC deubiquitylation and transcriptional activation of CDKN2B expression are linked to its tumor suppressor functions
  • TINCR could bind to STAU1 (staufen1) protein, and influence CDKN2B mRNA stability and expression, thereby affecting the proliferation of gastric cancer (GC)cells
  • cell & other
    REGULATION
    induced by TGF-beta in keratocytes
    ASSOCIATED DISORDERS
    corresponding disease(s) MNST
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    P15 deleted in T or B cell acute lymphoblastic leukemia,follicle center lymphoma (poor prognosis)
    tumoral   deletion    
    in osteosarcomas, Ewing sarcomas and in breast cancer
    tumoral       loss of function
    or deletion in ovarian granulosa cell tumors
    tumoral   deletion    
    by hypermethylation of CpG islands, in acute lymphoblastic leukemia (ALL)
    tumoral   deletion    
    minimal common deleted region removing CDKN2A exon 1 and CDKN2B exon 2 in diffuse large B-cell lymphomas
    constitutional       loss of function
    may not only promote cardiovascular disease through the development of atherosclerosis but may also impair TGFB1 signaling and hypoxic neovessel maturation
    tumoral     --low  
    by hypermethylation may be a poor prognostic marker in childhood ALL
    tumoral germinal mutation      
    will have an impact on familial cancer screening and might prove to influence the management of disseminated disease
    tumoral     --low  
    by promoter methylation may be closely implicated in the pathogenesis of multiple myeloma (MM)
    constitutional     --low  
    and increased smooth muscle cell apoptosis may be one mechanism underlying the 9p21.3 association with aneurysmal disease
    Susceptibility
  • to myocardial infarction
  • to type 2 diabetes
  • to high-grade glioma susceptibility
  • Variant & Polymorphism SNP
  • increasing the risk of myocardial infarction
  • significant contribution of CDKN2A/B gene rs10811661 to type 2 diabetes
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS