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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

regionally located

adjacent to CDKN2A

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004936 2 - 3878 NP_004927 14 138 - 1997 9230210 unique C terminus NM_078487 2 - 4001 NP_511042 10 78 - 1997 9230210 additional internal region leading to a frame shift

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth         Urinary bladder

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
	ZBTB17 activates the transcription of a number of target genes including the cell cycle inhibitor CDKN2B
	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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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