Browse HDAC6

Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
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. Perikaryon Cell projection, dendrite Cell projection, axon Note=It is mainly cytoplasmic, where it is associated with microtubules.
Domain PF00850 Histone deacetylase domain
PF02148 Zn-finger in ubiquitin-hydrolases and other protein
Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). 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 (By similarity). Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. ; FUNCTION: In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.

> Gene Ontology
 
Biological Process GO:0000209 protein polyubiquitination
GO:0000226 microtubule cytoskeleton organization
GO:0000302 response to reactive oxygen species
GO:0000422 mitophagy
GO:0000423 macromitophagy
GO:0001667 ameboidal-type cell migration
GO:0006476 protein deacetylation
GO:0006515 misfolded or incompletely synthesized protein catabolic process
GO:0006914 autophagy
GO:0006979 response to oxidative stress
GO:0007018 microtubule-based movement
GO:0007019 microtubule depolymerization
GO:0007026 negative regulation of microtubule depolymerization
GO:0007409 axonogenesis
GO:0009636 response to toxic substance
GO:0009755 hormone-mediated signaling pathway
GO:0010035 response to inorganic substance
GO:0010310 regulation of hydrogen peroxide metabolic process
GO:0010421 hydrogen peroxide-mediated programmed cell death
GO:0010469 regulation of receptor activity
GO:0010506 regulation of autophagy
GO:0010631 epithelial cell migration
GO:0010632 regulation of epithelial cell migration
GO:0010634 positive regulation of epithelial cell migration
GO:0010639 negative regulation of organelle organization
GO:0010727 negative regulation of hydrogen peroxide metabolic process
GO:0010821 regulation of mitochondrion organization
GO:0010869 regulation of receptor biosynthetic process
GO:0010870 positive regulation of receptor biosynthetic process
GO:0016049 cell growth
GO:0016236 macroautophagy
GO:0016358 dendrite development
GO:0016570 histone modification
GO:0016575 histone deacetylation
GO:0018205 peptidyl-lysine modification
GO:0030335 positive regulation of cell migration
GO:0030518 intracellular steroid hormone receptor signaling pathway
GO:0030521 androgen receptor signaling pathway
GO:0030522 intracellular receptor signaling pathway
GO:0031109 microtubule polymerization or depolymerization
GO:0031110 regulation of microtubule polymerization or depolymerization
GO:0031111 negative regulation of microtubule polymerization or depolymerization
GO:0031114 regulation of microtubule depolymerization
GO:0031334 positive regulation of protein complex assembly
GO:0031647 regulation of protein stability
GO:0032418 lysosome localization
GO:0032800 receptor biosynthetic process
GO:0032886 regulation of microtubule-based process
GO:0032984 macromolecular complex disassembly
GO:0033143 regulation of intracellular steroid hormone receptor signaling pathway
GO:0034599 cellular response to oxidative stress
GO:0034614 cellular response to reactive oxygen species
GO:0034983 peptidyl-lysine deacetylation
GO:0035601 protein deacylation
GO:0035966 response to topologically incorrect protein
GO:0035967 cellular response to topologically incorrect protein
GO:0036473 cell death in response to oxidative stress
GO:0036474 cell death in response to hydrogen peroxide
GO:0040017 positive regulation of locomotion
GO:0040029 regulation of gene expression, epigenetic
GO:0042542 response to hydrogen peroxide
GO:0042743 hydrogen peroxide metabolic process
GO:0043112 receptor metabolic process
GO:0043162 ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
GO:0043241 protein complex disassembly
GO:0043242 negative regulation of protein complex disassembly
GO:0043244 regulation of protein complex disassembly
GO:0043254 regulation of protein complex assembly
GO:0043401 steroid hormone mediated signaling pathway
GO:0043624 cellular protein complex disassembly
GO:0044089 positive regulation of cellular component biogenesis
GO:0045444 fat cell differentiation
GO:0045598 regulation of fat cell differentiation
GO:0045861 negative regulation of proteolysis
GO:0048545 response to steroid hormone
GO:0048588 developmental cell growth
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0048668 collateral sprouting
GO:0048813 dendrite morphogenesis
GO:0051131 chaperone-mediated protein complex assembly
GO:0051261 protein depolymerization
GO:0051272 positive regulation of cellular component movement
GO:0051341 regulation of oxidoreductase activity
GO:0051354 negative regulation of oxidoreductase activity
GO:0051493 regulation of cytoskeleton organization
GO:0051494 negative regulation of cytoskeleton organization
GO:0051640 organelle localization
GO:0051646 mitochondrion localization
GO:0051788 response to misfolded protein
GO:0060560 developmental growth involved in morphogenesis
GO:0060632 regulation of microtubule-based movement
GO:0060765 regulation of androgen receptor signaling pathway
GO:0060996 dendritic spine development
GO:0060997 dendritic spine morphogenesis
GO:0061564 axon development
GO:0061726 mitochondrion disassembly
GO:0070301 cellular response to hydrogen peroxide
GO:0070507 regulation of microtubule cytoskeleton organization
GO:0070841 inclusion body assembly
GO:0070842 aggresome assembly
GO:0070843 misfolded protein transport
GO:0070844 polyubiquitinated protein transport
GO:0070845 polyubiquitinated misfolded protein transport
GO:0070846 Hsp90 deacetylation
GO:0070932 histone H3 deacetylation
GO:0071218 cellular response to misfolded protein
GO:0071383 cellular response to steroid hormone stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0072593 reactive oxygen species metabolic process
GO:0090034 regulation of chaperone-mediated protein complex assembly
GO:0090035 positive regulation of chaperone-mediated protein complex assembly
GO:0090042 tubulin deacetylation
GO:0090130 tissue migration
GO:0090132 epithelium migration
GO:0097061 dendritic spine organization
GO:0097468 programmed cell death in response to reactive oxygen species
GO:0098732 macromolecule deacylation
GO:0098779 mitophagy in response to mitochondrial depolarization
GO:0098780 response to mitochondrial depolarisation
GO:1900407 regulation of cellular response to oxidative stress
GO:1900409 positive regulation of cellular response to oxidative stress
GO:1901031 regulation of response to reactive oxygen species
GO:1901033 positive regulation of response to reactive oxygen species
GO:1901298 regulation of hydrogen peroxide-mediated programmed cell death
GO:1901300 positive regulation of hydrogen peroxide-mediated programmed cell death
GO:1901879 regulation of protein depolymerization
GO:1901880 negative regulation of protein depolymerization
GO:1902882 regulation of response to oxidative stress
GO:1902884 positive regulation of response to oxidative stress
GO:1903008 organelle disassembly
GO:1903146 regulation of mitophagy
GO:1903201 regulation of oxidative stress-induced cell death
GO:1903205 regulation of hydrogen peroxide-induced cell death
GO:1903209 positive regulation of oxidative stress-induced cell death
GO:1905206 positive regulation of hydrogen peroxide-induced cell death
GO:2000147 positive regulation of cell motility
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000378 negative regulation of reactive oxygen species metabolic process
Molecular Function GO:0001047 core promoter binding
GO:0003779 actin binding
GO:0004407 histone deacetylase activity
GO:0008013 beta-catenin binding
GO:0008017 microtubule binding
GO:0015631 tubulin 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:0031072 heat shock protein binding
GO:0031078 histone deacetylase activity (H3-K14 specific)
GO:0031593 polyubiquitin binding
GO:0031625 ubiquitin protein ligase binding
GO:0032041 NAD-dependent histone deacetylase activity (H3-K14 specific)
GO:0032182 ubiquitin-like protein binding
GO:0033558 protein deacetylase activity
GO:0034979 NAD-dependent protein deacetylase activity
GO:0042826 histone deacetylase binding
GO:0042903 tubulin deacetylase activity
GO:0043014 alpha-tubulin binding
GO:0043130 ubiquitin binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0048156 tau protein binding
GO:0048487 beta-tubulin binding
GO:0051787 misfolded protein binding
GO:0051879 Hsp90 protein binding
GO:0070840 dynein complex binding
Cellular Component GO:0000118 histone deacetylase complex
GO:0005770 late endosome
GO:0005771 multivesicular body
GO:0005874 microtubule
GO:0005875 microtubule associated complex
GO:0005881 cytoplasmic microtubule
GO:0005901 caveola
GO:0016234 inclusion body
GO:0016235 aggresome
GO:0030286 dynein complex
GO:0030424 axon
GO:0030425 dendrite
GO:0031252 cell leading edge
GO:0043025 neuronal cell body
GO:0043204 perikaryon
GO:0044297 cell body
GO:0044853 plasma membrane raft
GO:0045121 membrane raft
GO:0098589 membrane region
GO:0098857 membrane microdomain
> KEGG and Reactome Pathway
 
KEGG -
Reactome R-HSA-3371556: Cellular response to heat stress
R-HSA-2262752: Cellular responses to stress
R-HSA-5617833: Cilium Assembly
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-3371511: HSF1 activation
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-1852241: Organelle biogenesis and maintenance
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
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between HDAC6 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 HDAC6 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28408401Non-small Cell Lung CarcinomaInhibit immunity (T cell function)By evaluating human peripheral blood and NSCLC tumors, we show that the selective HDAC6 inhibitor ricolinostat promotes phenotypic changes that support enhanced T-cell activation and improved function of antigen-presenting cells.
29487385MelanomaInhibit immunity; immunotherapy targetHistone deacetylase (HDAC) inhibitor ACY241 enhances anti-tumor activities of antigen-specific central memory cytotoxic T lymphocytes against multiple myeloma and solid tumors. Here we show ACY241 significantly reduces the frequency of CD138+MM cells, CD4+CD25+FoxP3+regulatory T cells, and HLA-DRLow/-CD11b+CD33+myeloid-derived suppressor cells; and decreases expression of PD1/PD-L1 on CD8+T cells and of immune checkpoints in bone marrow cells from myeloma patients. ACY241 increased B7 (CD80, CD86) and MHC (Class I, Class II) expression on tumor and dendritic cells. ACY241 induces co-stimulatory (CD28, 41BB, CD40L, OX40) and activation (CD38) molecule expression in a dose- and time-dependent manner, and anti-tumor activities, evidenced by increased perforin/CD107a expression, IFN-γ/IL-2/TNF-α production, and antigen-specific central memory CTL.
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
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 HDAC6 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
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
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 HDAC6 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1660.429
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2580.877
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.1040.928
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4560.294
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.260.908
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.7120.818
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1350.679
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.2870.85
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0430.98
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.4480.799
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 281.1690.647
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0370.498
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of HDAC6 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) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 103100101
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)211714.3014.30.238
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)131115.4015.40.482
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) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
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
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of HDAC6. 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
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of HDAC6. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by HDAC6.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of HDAC6. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of HDAC6 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between HDAC6 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolHDAC6
Namehistone deacetylase 6
Aliases KIAA0901; JM21; FLJ16239; PPP1R90; protein phosphatase 1, regulatory subunit 90; CPBHM
Chromosomal LocationXp11.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting HDAC6 collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting HDAC6.
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
DB06176RomidepsinSmall MoleculeABCC1, HDAC1, HDAC2, HDAC4, HDAC65
DB06603PanobinostatSmall MoleculeHDAC1, HDAC10, HDAC11, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7, H ......11