Browse HDAC3

Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus Cytoplasm Cytoplasm, cytosol Note=Colocalizes with XBP1 and AKT1 in the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus in the presence of CCAR2.
Domain PF00850 Histone deacetylase domain
Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:21444723, PubMed:23911289). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803).

> Gene Ontology
 
Biological Process GO:0000226 microtubule cytoskeleton organization
GO:0001933 negative regulation of protein phosphorylation
GO:0006476 protein deacetylation
GO:0006606 protein import into nucleus
GO:0006913 nucleocytoplasmic transport
GO:0007051 spindle organization
GO:0007254 JNK cascade
GO:0007623 circadian rhythm
GO:0016570 histone modification
GO:0016575 histone deacetylation
GO:0017038 protein import
GO:0031098 stress-activated protein kinase signaling cascade
GO:0031647 regulation of protein stability
GO:0031929 TOR signaling
GO:0032006 regulation of TOR signaling
GO:0032008 positive regulation of TOR signaling
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032872 regulation of stress-activated MAPK cascade
GO:0032873 negative regulation of stress-activated MAPK cascade
GO:0033157 regulation of intracellular protein transport
GO:0034405 response to fluid shear stress
GO:0034504 protein localization to nucleus
GO:0035601 protein deacylation
GO:0042306 regulation of protein import into nucleus
GO:0042307 positive regulation of protein import into nucleus
GO:0042326 negative regulation of phosphorylation
GO:0042990 regulation of transcription factor import into nucleus
GO:0042991 transcription factor import into nucleus
GO:0042993 positive regulation of transcription factor import into nucleus
GO:0043409 negative regulation of MAPK cascade
GO:0044744 protein targeting to nucleus
GO:0046328 regulation of JNK cascade
GO:0046329 negative regulation of JNK cascade
GO:0046822 regulation of nucleocytoplasmic transport
GO:0046824 positive regulation of nucleocytoplasmic transport
GO:0048511 rhythmic process
GO:0051169 nuclear transport
GO:0051170 nuclear import
GO:0051222 positive regulation of protein transport
GO:0051225 spindle assembly
GO:0051403 stress-activated MAPK cascade
GO:0070302 regulation of stress-activated protein kinase signaling cascade
GO:0070303 negative regulation of stress-activated protein kinase signaling cascade
GO:0070932 histone H3 deacetylation
GO:0071498 cellular response to fluid shear stress
GO:0090316 positive regulation of intracellular protein transport
GO:0098732 macromolecule deacylation
GO:1900180 regulation of protein localization to nucleus
GO:1900182 positive regulation of protein localization to nucleus
GO:1902532 negative regulation of intracellular signal transduction
GO:1902593 single-organism nuclear import
GO:1903533 regulation of protein targeting
GO:1903829 positive regulation of cellular protein localization
GO:1904589 regulation of protein import
GO:1904591 positive regulation of protein import
GO:1904951 positive regulation of establishment of protein localization
Molecular Function GO:0003682 chromatin binding
GO:0003714 transcription corepressor activity
GO:0004407 histone deacetylase activity
GO:0008134 transcription factor binding
GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds
GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
GO:0017136 NAD-dependent histone deacetylase activity
GO:0019213 deacetylase activity
GO:0030332 cyclin binding
GO:0031078 histone deacetylase activity (H3-K14 specific)
GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0033558 protein deacetylase activity
GO:0034979 NAD-dependent protein deacetylase activity
GO:0042826 histone deacetylase binding
GO:0051059 NF-kappaB binding
Cellular Component GO:0000118 histone deacetylase complex
GO:0005819 spindle
GO:0005874 microtubule
GO:0005876 spindle microtubule
GO:0017053 transcriptional repressor complex
> KEGG and Reactome Pathway
 
KEGG hsa04919 Thyroid hormone signaling pathway
Reactome R-HSA-5619507: Activation of HOX genes during differentiation
R-HSA-5617472: Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-390471: Association of TriC/CCT with target proteins during biosynthesis
R-HSA-1368108: BMAL1
R-HSA-390466: Chaperonin-mediated protein folding
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-400253: Circadian Clock
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-535734: Fatty acid, triacylglycerol, and ketone body metabolism
R-HSA-3214815: HDACs deacetylate histones
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-392499: Metabolism of proteins
R-HSA-1592230: Mitochondrial biogenesis
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-1368071: NR1D1 (REV-ERBA) represses gene expression
R-HSA-1852241: Organelle biogenesis and maintenance
R-HSA-1989781: PPARA activates gene expression
R-HSA-391251: Protein folding
R-HSA-1368082: RORA activates gene expression
R-HSA-400206: Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
R-HSA-166520: Signalling by NGF
R-HSA-2151201: Transcriptional activation of mitochondrial biogenesis
R-HSA-381340: Transcriptional regulation of white adipocyte differentiation
R-HSA-193704: p75 NTR receptor-mediated signalling
R-HSA-193670: p75NTR negatively regulates cell cycle via SC1
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HDAC3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between HDAC3 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
27733359LymphomaInhibit immunityHDAC3 loss-of-function rescued repression of these enhancers and corresponding genes, including MHC class II, and more profoundly suppressed CREBBP-mutant lymphomas in vitro and in vivo.
19430493Ovarian carcinomaInhibit immunity (NK cell function)Furthermore, by small interfering RNA-mediated knockdown and overexpression of HDAC1-3, we showed that HDAC3 is a repressor of ULBPs expression in epithelial cancer cells. Remarkably, TSA treatment caused the complete release of HDAC3 from the ULBP1-3 promoters.
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of HDAC3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of HDAC3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1530.358
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1210.957
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.180.91
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.0720.786
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1980.906
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.4150.849
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0420.909
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0950.952
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.0070.997
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.1030.954
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.2220.934
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.070.205
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HDAC3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.41.460.177
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.41.75.70.231
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HDAC3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HDAC3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HDAC3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HDAC3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HDAC3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HDAC3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHDAC3
Namehistone deacetylase 3
Aliases HD3; RPD3-2; SMAP45
Chromosomal Location5q31.1-q31.2
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HDAC3 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting HDAC3.
ID Name Drug Type Targets #Targets
DB02546VorinostatSmall MoleculeHDAC1, HDAC2, HDAC3, HDAC6, HDAC85
DB05015BelinostatSmall MoleculeHDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......11
DB05223PracinostatSmall MoleculeHDAC1, HDAC2, HDAC3, HDAC64
DB06603PanobinostatSmall MoleculeHDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......11
DB11830MocetinostatSmall MoleculeHDAC1, HDAC2, HDAC33