Protein / target
Histone deacetylase 2
Protein at a glance
Biological role
Histone deacetylase activity, hydrolytic mechanism
Primary system
Nervous system
Strongest disease association
neoplasm
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
8 approved · 6 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR (PubMed:12724404). Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development (By similarity). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Component of the SIN3B complex that represses transcription and counteracts the histone acetyltransferase activity of EP300 through the recognition H3K27ac marks by PHF12 and the activity of the histone deacetylase HDAC2 (PubMed:37137925). Also deacetylates non-histone targets: deacetylates TSHZ3, thereby regulating its transcriptional repressor activity (PubMed:19343227). May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation (By similarity). Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A (PubMed:21965678). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation, delactylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:35044827)
Subcellular location
Domains and Gene Ontology detail (76)Hide
Gene Ontology
- Cchromatin
- Cchromosome, telomeric region
- Ccytoplasm
- CESC/E(Z) complex
- Chistone deacetylase complex
- Cnucleoplasm
- Cnucleus
- CNuRD complex
- Cprotein-containing complex
- CSin3-type complex
- Fchromatin binding
- Fenzyme binding
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-termina…
- ·RNA polymerase II-specific DNA-binding transcription factor binding
- ·transcription coregulator binding
- ·circadian regulation of gene expression
Immune signalling
- ·positive regulation of interleukin-1 production
Proteolysis
- ·positive regulation of proteolysis
Metabolic enzyme activity
- ·Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-termina…
Apoptosis & cell death
- ·negative regulation of apoptotic process
Haemostasis
- ·Factors involved in megakaryocyte development and platelet production
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Histone deacetylase 2 inhibitor
Appears in clinical studies involving T-cell non-Hodgkin lymphoma, primary cutaneous T-cell non-Hodgkin lymphoma, primary cutaneous T-cell non-Hodgkin lymphoma, neoplasm
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,412 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 14 total
primary cutaneous T-cell non-Hodgkin lymphoma · ovarian carcinoma · malignant epithelial tumor of ovary
non-small cell lung carcinoma · Hodgkins lymphoma · classic Hodgkin lymphoma
Duchenne muscular dystrophy · Duchenne muscular dystrophy · acquired polycythemia vera
plasma cell myeloma · neoplasm · type 2 diabetes mellitus
plasma cell myeloma
non-small cell lung carcinoma · exocrine pancreatic carcinoma
T-cell non-Hodgkin lymphoma · peripheral T-cell lymphoma, not otherwise specified · neoplasm
T-cell non-Hodgkin lymphoma · peripheral T-cell lymphoma, not otherwise specified · primary cutaneous T-cell non-Hodgkin lymphoma
Duchenne muscular dystrophy · Duchenne muscular dystrophy · acquired polycythemia vera
diffuse large B-cell lymphoma · thyroid cancer · poorly differentiated thyroid gland carcinoma
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.
- New publicationKetogenic Diet Alters the Epigenetic and Immune Landscape of Prostate Cancer to Overcome Resistance to Immune Checkpoint Blockade Therapy.
- New publicationSuberoylanilide Hydroxamic Acid (SAHA) Is a Driver Molecule of Neuroplasticity: Implication for Neurological Diseases.
- New publicationPhase I study of the mTOR inhibitor ridaforolimus and the HDAC inhibitor vorinostat in advanced renal cell carcinoma and other solid tumors.
- New publicationVorinostat in patients with advanced malignant pleural mesothelioma who have progressed on previous chemotherapy (VANTAGE-014): a phase 3, double-blind, randomised, placebo-controlled trial.
- New publicationA phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma.
- New publicationA multicentre phase II study of vorinostat in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma.
- New publicationHIV-1 expression within resting CD4+ T cells after multiple doses of vorinostat.
- New publicationPhase II trial of vorinostat in advanced melanoma.
- New publicationVorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial.
- New publicationAdministration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy.
- New publicationPhase I and pharmacokinetic study of the oral histone deacetylase inhibitor vorinostat in Japanese patients with relapsed or refractory cutaneous T-cell lymphoma.
- New publicationEvaluation of safety, pharmacokinetics, and efficacy of vorinostat, a histone deacetylase inhibitor, in the treatment of gastrointestinal (GI) cancer in a phase I clinical trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.