Histone deacetylase 1

UniProt Q13547 Organism Homo sapiens Gene HDAC1, RPD3L1 EC 3.5.1.98, 3.5.1.-

Also known as: HDAC1, RPD3L1

Function

Histone deacetylase that catalyzes 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. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. As part of the SIN3B complex is recruited downstream of the constitutively active genes transcriptional start sites through interaction with histones and mitigates histone acetylation and RNA polymerase II progression within transcribed regions contributing to the regulation of transcription. Also functions as a deacetylase for non-histone targets, such as NR1D2, RELA, SP1, SP3, STAT3, ZNF76 and TSHZ3. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity. 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). Involved in CIART-mediated transcriptional repression of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer (By similarity). Required for the transcriptional repression of circadian target genes, such as PER1, mediated by the large PER complex or CRY1 through histone deacetylation (By similarity). In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase and delactylase by mediating decrotonylation ((2E)-butenoyl) and delactylation (lactoyl) of histones, respectively.

Classification

Family (Pfam): PF00850 Hist_deacetyl
InterPro: HDAC_I/II, HDACs, His_deacetylse_dom, His_deacetylse_dom_sf, Ureohydrolase_dom_sf
Functional cluster: Nucleotide & Amino-Acid Biosynthesis Enzymes

Experimental structures · PDB · 11

4BKX X-ray 3.00A
5ICN X-ray 3.30A
6Z2J EM 4.00A
6Z2K EM 4.50A
7AO8 EM 4.50A
7AO9 EM 6.10A
7AOA EM 19.40A
7SME X-ray 2.64A
8VOJ EM 3.77A
8VPQ EM 3.30A
8VRT EM 3.42A

A predicted model is available from AlphaFold.

Gene Ontology · 68

Drugs targeting this protein · 12

ABEXINOSTAT inhibitor
QUISINOSTAT inhibitor
TACEDINALINE inhibitor
MOCETINOSTAT inhibitor
ENTINOSTAT inhibitor
ROMIDEPSIN inhibitor
PANOBINOSTAT LACTATE inhibitor
FIMEPINOSTAT inhibitor
BELINOSTAT inhibitor
CUDC-101 inhibitor
GIVINOSTAT HYDROCHLORIDE inhibitor
VORINOSTAT inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Mesoderm induction early response protein 1 2 shared papers
Histone deacetylase 2 22 shared papers
Histone deacetylase 3 13 shared papers
Paired amphipathic helix protein Sin3a 6 shared papers
Transcription factor Sp3 2 shared papers
Breast cancer metastasis-suppressor 1-like protein 1 shared papers
Histone-binding protein RBBP4 1 shared papers
Homeobox protein TGIF2 1 shared papers
Histone deacetylase 9 2 shared papers
ATP-dependent chromatin remodeler CHD4 6 shared papers
Sentrin-specific protease 1 2 shared papers
Mitotic deacetylase-associated SANT domain protein 1 shared papers

Literature · 95 cited papers

The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase. Epigenetics Chromatin · 2023
ZMYND8 suppresses MAPT213 LncRNA transcription to promote neuronal differentiation. Cell Death Dis. · 2022
Class I histone deacetylases (HDAC1-3) are histone lysine delactylases. Sci. Adv. · 2022
Cross-linking mass spectrometry reveals the structural topology of peripheral NuRD subunits relative to the core complex. FEBS J. · 2021
NP220 mediates silencing of unintegrated retroviral DNA. Nature · 2018
The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish. PLoS Genet. · 2018
A recurrent de novo PACS2 heterozygous missense variant causes neonatal-onset developmental epileptic encephalopathy, facial dysmorphism, and cerebellar dysgenesis. Am. J. Hum. Genet. · 2018
CHD3 and CHD4 form distinct NuRD complexes with different yet overlapping functionality. Nucleic Acids Res. · 2017
Class I histone deacetylases are major histone decrotonylases: evidence for critical and broad function of histone crotonylation in transcription. Cell Res. · 2017
Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
De novo mutations in CHD4, an ATP-dependent chromatin remodeler gene, cause an intellectual disability syndrome with distinctive dysmorphisms. Am. J. Hum. Genet. · 2016
Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin Dynamics. PLoS ONE · 2015
… and 83 more in the literature graph

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