HDAC8

Protein identityUniProt · HPA

UniProt accession

Q9BY41

Gene

HDAC8

Ensembl

ENSG00000147099

Chromosome

X

Canonical length

377 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins

OverviewNCBI Gene

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

377 residues, UniProt reviewed canonical sequence.

>Q9BY41|HDAC8
     1  MEEPEEPADS GQSLVPVYIY SPEYVSMCDS LAKIPKRASM VHSLIEAYAL HKQMRIVKPK
    61  VASMEEMATF HTDAYLQHLQ KVSQEGDDDH PDSIEYGLGY DCPATEGIFD YAAAIGGATI
   121  TAAQCLIDGM CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFE RILYVDLDLH
   181  HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDVSDVGLG KGRYYSVNVP IQDGIQDEKY
   241  YQICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY ILQWQLATLI
   301  LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH
   361  RIQQILNYIK GNLKHVV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HDAC8 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

22 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HDAC8.

Disease | AllUniProt

Conditions HDAC8 is implicated in, by any mechanism.

• Cornelia de Lange syndrome 5 (CDLS5) MIM:300882

Disease | GeneticClinVar

96 pathogenic / likely-pathogenic of 450 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Cornelia de Lange syndrome 5
• Inborn genetic diseases
• Thyroid cancer, nonmedullary, 1
• Intellectual disability
• Cornelia de Lange syndrome 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.3

gnomAD pLI

0.98

gnomAD missense Z

2.82

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• chromatin organization
• heterochromatin formation
• mitotic sister chromatid cohesion
• negative regulation of protein ubiquitination
• negative regulation of transcription by RNA polymerase II
• regulation of protein stability
• regulation of telomere maintenance

Molecular functions

• DNA-binding transcription factor binding
• histone deacetylase activity
• histone deacetylase activity, hydrolytic mechanism
• histone decrotonylase activity
• Hsp70 protein binding
• Hsp90 protein binding
• metal ion binding
• protein lysine deacetylase activity

Cellular components

• cytoplasm
• histone deacetylase complex
• nuclear chromosome
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Histone deacetylase HDAC
• Class I/II Histone deacetylase HDAC
• Ureohydrolase domain superfamily
• Histone deacetylase domain
• Histone deacetylase domain superfamily
• Histone deacetylase domain

KeywordsUniProt

• Chromatin regulator
• Chromosome
• Cytoplasm
• Hydrolase
• Intellectual disability
• Metal-binding
• Nucleus
• Obesity
• Phosphoprotein
• Repressor
• Transcription
• Transcription regulation

InteractionsUniProt · HPA

Protein binding partners of HDAC8 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CBFA2T3
• PEPB2-MYH11
• RUNX1