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FLASH GENE

Symbol

HDAC8

contributors: mct/npt - updated : 08-11-2015

HGNC name	histone deacetylase 8
HGNC id	13315

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_018486 11 - 2064 NP_060956 41.6 377 ubiquitous in brain 2007 1772144 NM_001166448 5 - 2071 NP_001159920 15.6 139 - 2007 1772144 NM_001166418 9 - 1791 NP_001159890 32 286 - 2007 1772144 NM_001166419 8 - 2422 NP_001159891 28.2 256 - 2007 1772144 NM_001166420 4 - 1125 NP_001159892 16 146 - 2007 1772144 NM_001166422 5 - 1033 NP_001159894 17.3 158 - 2007 1772144

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 blood / hematopoietic thymus       highly Cardiovascular heart         Nervous brain       highly Reproductive male system testis     highly Respiratory lung         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cell lineage
cell lines	several tumor cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	nine conserved HDAC bloks important for catalytic function
	a shorter C terminal extension relative to other members of HDAC class I

HOMOLOGY

interspecies

homolog to yeast RpD3

Homologene

FAMILY	histone deacetylase family
	type 1 subfamily

CATEGORY

enzyme , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,chromatin/chromosome
text	localized within the nucleus, but is also found in the cytosol of smooth muscle cells where it associates with the alpha-actin cytoskeleton

basic FUNCTION	regulator of cell proliferation, putative role in cancer development
	associates with the smooth muscle actin cytoskeleton and may regulate the contractile capacity of smooth muscle cells
	has inhibitory effect on forskolin-induced CREB activation
	specifically represses the aberrant expression of homeobox transcription factors such as OTX2 and L1
	may be activated by either or both of metals (Fe(2+) or Zn(2+))depending on cellular concentrations
	required for centrosome cohesion and influenza A virus entry
	play a major role in epigenetic gene silencing during development
	NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes codify for the "cohesin complex" playing a role in chromatid adhesion, DNA repair and gene expression regulation

CELLULAR PROCESS	cell life, proliferation/growth
	nucleotide, chromatin organization, remodeling
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

text	transcriptional corepressor

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule	metal binding, other,
	could bind either or both Fe(2+) or Zn(2+)
	likely potassium is the predominant monovalent cations bound to HDAC8

protein	bound to both CREB1 and PPA1 (recombinant HDAC8 results in decreased CREB1 activation and CREB1 mediated gene transcription in response to forskolin application)
	regulatory mechanism of mutant TP53 transcription via HDAC8
	SOX4 is a direct target gene of FOSL2 and induces expression of HDAC8 in adult T-cell leukemia/lymphoma

cell & other

REGULATION

induced by

ILK2

inhibited by

trichostatin and histone deacetylase inhibitors

ASSOCIATED DISORDERS

corresponding disease(s)

CDLS5 , WTSL1

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in cancer tissues constitutional     --low   caused centrosome splitting, which could also be induced by depleting a centriole-linker protein, rootletin

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   HDAC8 inhibitors may have therapeutic potential for the treatment of myeloproliferative neoplasms (MPNs) cancer     HDAC8-targeting agents might be explored as an adjuvant for tumors carrying a mutant TP53

ANIMAL & CELL MODELS

deletion of Hdac8 in mice leads to perinatal lethality due to skull instability