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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]
HDAC4 (Histone Deacetylase 4) is a Protein Coding gene. Diseases associated with HDAC4 include Chromosome 2Q37 Deletion Syndrome and Brachydactyly. Among its related pathways are Signaling by GPCR and Neural Crest Differentiation. Gene Ontology (GO) annotations related to this gene include sequence-specific DNA binding and transcription factor binding. An important paralog of this gene is HDAC5.
Histone deacetylases (HDACs) are a group of enzymes closely related to sirtuins. They catalyze acetyl group removal from lysine residues in histones and non-histone proteins, causing transcriptional repression. HDACs are usually components of multiprotein complexes.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000976 | contributes_to transcription regulatory region sequence-specific DNA binding | IDA | 18850004 |
GO:0000978 | RNA polymerase II proximal promoter sequence-specific DNA binding | IDA | 24413532 |
GO:0001085 | RNA polymerase II transcription factor binding | IPI | 23867755 |
GO:0003677 | DNA binding | IEA | -- |
GO:0003682 | chromatin binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000118 | histone deacetylase complex | IEA,IDA | 11804585 |
GO:0005634 | nucleus | IEA,IDA | 10869435 |
GO:0005654 | nucleoplasm | TAS | -- |
GO:0005737 | cytoplasm | IEA,IDA | 10869435 |
GO:0005829 | cytosol | IEA,IDA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Signaling by NOTCH1 | ||
2 | Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 |
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3 | HIV Life Cycle |
.45
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4 | Immune response Function of MEF2 in T lymphocytes |
Development Role of HDAC and calcium/calmodulin-dependent kinase (CaMK) in control of skeletal myogenesis
.36
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Immune response Function of MEF2 in T lymphocytes
.36
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5 | MicroRNAs in cardiomyocyte hypertrophy |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000122 | negative regulation of transcription by RNA polymerase II | IEA,IMP | 18850004 |
GO:0001501 | skeletal system development | IEA | -- |
GO:0002076 | osteoblast development | IEA | -- |
GO:0006325 | chromatin organization | IEA | -- |
GO:0006338 | chromatin remodeling | IDA | 18850004 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Belinostat | Approved, Investigational | Pharma | Target, inhibitor | Histone deacetylase (HDAC)inhibitors | 50 | |
Panobinostat | Approved, Investigational | Pharma | Target, inhibitor, Inhibition | Histone deacetylase (HDAC)inhibitors | 145 | |
Romidepsin | Approved, Investigational | Pharma | Target, inhibitor | Histone deacetylase (HDAC)inhibitors | 101 | |
Zinc | Approved, Investigational | Pharma | Target, cofactor | 1687 | ||
zinc acetate | Approved, Investigational | Pharma | Target | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
Valproic acid, sodium salt |
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1069-66-5 |
|
|
Compound | Action | Cas Number |
---|---|---|
Apicidin | Potent histone deacetylase inhibitor | 183506-66-3 |
PCI 34051 | Potent and selective HDAC8 inhibitor | 950762-95-5 |
Valproic acid, sodium salt | Histone deacetylase inhibitor | 1069-66-5 |
Compound | Action | Cas Number |
---|---|---|
AR-42 (OSU-HDAC42) | HDAC inhibitor,novel and potent | 935881-37-1 |
Belinostat (PXD101) | Hydroxamate-type HDAC inhibitor | 414864-00-9 |
BMS-345541(free base) | IKK-1/IKK-2 inhibitor,potent and selective | 445430-58-0 |
HPOB | HDAC6 inhibitor, potent and selective | 1429651-50-2 |
ITF2357 (Givinostat) | HDAC inhibitor | 732302-99-7 |
JNJ-26481585 | Potent HDAC inhibitor | 875320-29-9 |
LAQ824 (NVP-LAQ824,Dacinostat) | HDAC inhibitor,potent and novel | 404951-53-7 |
LMK 235 | HDAC4/HDAC5 inhibitor | 1418033-25-6 |
M344 | HDAC inhibitor,potent and cell-permeable | 251456-60-7 |
MC1568 | Class II HDAC inhibitor,potent and | 852475-26-4 |
Panobinostat (LBH589) | HDAC inhibitor | 404950-80-7 |
Parthenolide | 20554-84-1 | |
Pracinostat (SB939) | Pan-HDAC inhibitor | 929016-96-6 |
Santacruzamate A (CAY10683) | 1477949-42-0 | |
Sodium Phenylbutyrate | Histone deacetylase inhibitor | 1716-12-7 |
Tasquinimod | Antiangiogenic and antineoplastic agent | 254964-60-8 |
TMP269 | HDAC 4/5/7/9 inhibitor | 1314890-29-3 |
Trichostatin A (TSA) | HDAC inhibitor | 58880-19-6 |
Tubacin | HDAC6 inhibitor,potent,selective,reversible,cell-permeable | 1350555-93-9 |
Valproic acid sodium salt (Sodium valproate) | HDAC inhibitor | 1069-66-5 |
Vorinostat (SAHA, MK0683) | HDAC inhibitor | 149647-78-9 |
This gene was present in the common ancestor of eukaryotes.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | HDAC4 30 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | HDAC4 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | HDAC4 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | HDAC4 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Hdac4 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Hdac4 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | HDAC4 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | HDAC4 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | HDAC4 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | hdac4 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | hdac4 30 31 |
|
OneToOne | |
wufc56f08 30 |
|
||||
Fruit Fly (Drosophila melanogaster) |
Insecta | HDAC4 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | hda-4 31 32 |
|
OneToMany | |
F43G6.4 32 |
|
|
|||
Baker's yeast (Saccharomyces cerevisiae) |
Saccharomycetes | HDA1 31 |
|
OneToMany | |
Rice (Oryza sativa) |
Liliopsida | Os.21399 30 |
|
||
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany | |
CSA.5129 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 02 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
813561 | Uncertain Significance: Microcephaly | 239,053,596(-) |
A/G NM_001378414.1(HDAC4):c.3094T>C (p.Tyr1032His) |
MISSENSE | |
871013 | Uncertain Significance: not provided | 239,115,064(-) |
G/A NM_001378414.1(HDAC4):c.1780C>T (p.Leu594Phe) |
MISSENSE | |
871014 | Uncertain Significance: not provided | 239,134,633(-) |
G/A NM_001378414.1(HDAC4):c.989C>T (p.Ala330Val) |
MISSENSE | |
871015 | Uncertain Significance: not provided | 239,236,617(-) |
G/A NM_001378414.1(HDAC4):c.70C>T (p.Arg24Cys) |
MISSENSE | |
930723 | Uncertain Significance: not provided | 239,176,572(-) |
G/A NM_001378414.1(HDAC4):c.340-9C>T |
INTRON |
Disorder | Aliases | PubMed IDs |
---|---|---|
chromosome 2q37 deletion syndrome |
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brachydactyly |
|
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developmental dyspraxia |
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plasma cell neoplasm |
|
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myeloma, multiple |
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