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HDAC4

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 II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. [provided by RefSeq, Jul 2008]
Full Name
Histone Deacetylase 4
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. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Deacetylates HSPA1A and HSPA1B at 'Lys-77' leading to their preferential binding to co-chaperone STUB1 (PubMed:27708256).
Biological Process
B cell activation Source: UniProtKB
B cell differentiation Source: UniProtKB
Cardiac muscle hypertrophy in response to stress Source: BHF-UCL
Chromatin remodeling Source: BHF-UCL
Histone deacetylation Source: BHF-UCL
Histone H3 deacetylation Source: BHF-UCL
Histone H4 deacetylation Source: BHF-UCL
Inflammatory response Source: UniProtKB
Negative regulation of DNA-binding transcription factor activity Source: BHF-UCL
Negative regulation of glycolytic process Source: BHF-UCL
Negative regulation of myotube differentiation Source: BHF-UCL
Negative regulation of transcription, DNA-templated Source: BHF-UCL
Negative regulation of transcription by RNA polymerase II Source: BHF-UCL
Nervous system development Source: UniProtKB
Peptidyl-lysine deacetylation Source: BHF-UCL
Positive regulation of cell population proliferation Source: BHF-UCL
Positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
Positive regulation of protein sumoylation Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: BHF-UCL
Positive regulation of transcription by RNA polymerase II Source: BHF-UCL
Protein deacetylation Source: UniProtKB
Regulation of gene expression, epigenetic Source: UniProtKB
Regulation of protein binding Source: BHF-UCL
Response to denervation involved in regulation of muscle adaptation Source: BHF-UCL
Response to interleukin-1 Source: BHF-UCL
Cellular Location
Nucleus; Cytoplasm. Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation. Interaction with SIK3 leads to HDAC4 retention in the cytoplasm (By similarity).
Involvement in disease
Brachydactyly-mental retardation syndrome (BDMR):
The gene represented in this entry is involved in disease pathogenesis. HDAC4 point mutations and chromosomal microdeletions encompassing this gene have been found in BDMR patients (PubMed:20691407, PubMed:24715439, PubMed:23188045). However, HDAC4 haploinsufficiency is not fully penetrant and multiple genes may contribute to manifestation of the full phenotypic spectrum (PubMed:24715439, PubMed:23188045). A syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.
PTM
Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-350, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3.
Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.

Anti-HDAC4 antibodies

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Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse, Rat, Monkey
Clone: CBFYH-0872
Application*: WB, IP
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: CBFYH-0871
Application*: E, IF, P, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: CBFYH-0870
Application*: IC, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBFYH-0868
Application*: WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: CBFYH-0866
Application*: E, IC, IP, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBFYH-0865
Application*: E, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Mouse, Rat, Human
Clone: CBFYH-3038
Application*: WB, IP, E, IC, CI
Target: HDAC4
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: D15C3
Application*: WB, IP
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human
Clone: CBFYH-3037
Application*: WB, IP
Target: HDAC4
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Rat
Clone: 14H4L10
Application*: WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2b, κ
Specificity: Human
Clone: 14A9C47
Application*: WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CAP889
Application*: ICC, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CAP888
Application*: ICC, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CAP887
Application*: ELISA, ICC, WB
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse, Rat
Clone: CB405A
Application*: ELISA, WB, ICC
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: 7B2
Application*: WB
Target: HDAC4
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: D8T3Q
Application*: WB, IP
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a, κ
Specificity: Human
Clone: 2B11
Application*: WB, E
Target: HDAC4
Host: Mouse
Antibody Isotype: IgG2a
Specificity: Human, Mouse, Rat, Monkey
Clone: 4A3-H7-C6
Application*: WB, IP
More Infomation
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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