HDAC1

Oncogene
Histone deacetylase 1 UniProt accession Q13547

Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (PubMed:16762839, PubMed:17704056, PubMed:28497810). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:16762839, PubMed:17704056). Histone deacetylases act via the formation of large multiprotein complexes (PubMed:16762839, PubMed:17704056).

Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). 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 (PubMed:21041482). Also functions as a deacetylase for non-histone targets, such as NR1D2, RELA, SP1, SP3, STAT3, ZNF76 and TSHZ3 (PubMed:12837748, PubMed:16285960, PubMed:16337145, PubMed:16478997, PubMed:17996965, PubMed:19343227).

Deacetylates SP proteins, SP1 and SP3, and regulates their function (PubMed:12837748, PubMed:16478997). Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons (PubMed:19081374). Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation (PubMed:19081374).

Deacetylates TSHZ3 and regulates its transcriptional repressor activity (PubMed:19343227). Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B (PubMed:17000776). Deacetylates NR1D2 and abrogates the effect of KAT5-mediated relieving of NR1D2 transcription repression activity (PubMed:17996965).

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 (PubMed:28497810, PubMed:35044827)

Source: UniProt

Part of the core histone deacetylase (HDAC) complex composed of HDAC1, HDAC2, RBBP4 and RBBP7, the core complex associates with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex (PubMed:12493763, PubMed:12724404, PubMed:19061646). Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:11102443, PubMed:16428440, PubMed:28977666, PubMed:33283408). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:16428440, PubMed:28977666, PubMed:33283408).

Component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and PHF21A/BHC80 (PubMed:12493763). The BHC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I (PubMed:12493763). Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2 (PubMed:12724404).

Component of the SIN3B complex, which includes SIN3B, HDAC1, PHF12 and MORF4L1 (PubMed:21041482). Found in a trimeric complex with APBB1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (PubMed:19343227). Forms a complex comprising APPL1, RUVBL2, APPL2, CTNNB1 and HDAC2 (PubMed:19433865).

Component of a RCOR/GFI/KDM1A/HDAC complex (By similarity). Part of a complex composed of TRIM28, HDAC1, HDAC2 and EHMT2 (PubMed:17704056). Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2 (PubMed:19061646).

The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A (By similarity). Associates with the 9-1-1 complex; interacts with HUS1 (PubMed:10846170). Found in a complex with DNMT3A and HDAC7 (By similarity).

Found in a complex with YY1, SIN3A and GON4L (By similarity). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (PubMed:25653165). Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1 (By similarity).

Interacts with GFI1; the interaction is direct (By similarity). Interacts directly with GFI1B (By similarity). Interacts with TSHZ3 (via N-terminus); the interaction is direct (PubMed:19343227).

Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (PubMed:14633989). Interacts with BANP (PubMed:16166625). Interacts with BAZ2A/TIP5 (By similarity).

Interacts with BCL6 (PubMed:15454082). Interacts with BCOR (PubMed:10898795). Interacts with BHLHE40/DEC1 (PubMed:21829689).

Interacts with BRCC3; this interaction is enhanced in the presence of PWWP2B (By similarity). Interacts with BRMS1 (PubMed:17000776). Interacts with BRMS1L (PubMed:15451426).

Interacts with C10orf90/FATS (via its N-terminal); the interaction prevents binding of HDAC1 to CDKN1A/p21 and facilitates the acetylation and stabilization of CDKN1A/p21 (By similarity). Interacts with CBFA2T3 (PubMed:11533236). Interacts with CCAR2 (PubMed:21030595).

Interacts with CDK2AP1 (PubMed:20523938). Interacts with CHD3 (PubMed:28977666). Interacts with CHD4 (PubMed:25593309, PubMed:27616479, PubMed:28977666, PubMed:36064715).

Interacts with CHFR (PubMed:19182791). Interacts with CIART (By similarity). Interacts with CDKN1A/p21 (By similarity).

Interacts with CDK5 complexed to CDK5R1 (p25) (By similarity). Interacts with CRY1 (By similarity). Interacts with DAXX (PubMed:10669754).

Interacts with DDIT3/CHOP (PubMed:17872950). Interacts with DDX5 (PubMed:17369852). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852).

Interacts with DNMT1 (By similarity). Interacts with DNTTIP1 (PubMed:25653165). Interacts with E4F1 (PubMed:12730668).

Interacts with EP300 (PubMed:16762839). Interacts with ERCC6 (PubMed:26030138). Interacts with GATAD2A (PubMed:33283408).

Interacts with HCFC1 (PubMed:12670868). Interacts with HDAC9 (PubMed:10487760, PubMed:10655483). Interacts with HUS1 (PubMed:10846170).

Interacts with INSM1 (PubMed:16569215). Interacts with KDM4A (PubMed:15927959). Interacts with KDM5A; this interaction impairs histone deacetylation (By similarity).

Interacts with KDM5B (PubMed:17373667). Interacts with KLF1 (By similarity). Interacts with MBD3L2 (PubMed:15701600).

Interacts with MIER1 (PubMed:12482978). Interacts with NFE4 (PubMed:15273251). Interacts with NR4A2/NURR1 (By similarity).

Interacts with NR1D2 (via C-terminus) (PubMed:17996965). Interacts with NRIP1 (PubMed:11006275). Interacts with NSD2 (By similarity).

Interacts with PACS2 (PubMed:29656858). Interacts with PHB2 (By similarity). Interacts with PPHLN1 (PubMed:17963697).

Interacts with PRDM6 (By similarity). Interacts with PRDM16 (PubMed:19049980). Interacts with PWWP2A in a MTA1-dependent manner (By similarity).

Interacts with PWWP2B (By similarity). Interacts with RB1 (PubMed:19081374). Interacts with RERE (By similarity).

Interacts with SANBR (via the BTB domain) (By similarity). Interacts with SAMSN1 (By similarity). Interacts with SAP30L (PubMed:16820529).

Interacts with SETDB1 (By similarity). Interacts with SIN3A (By similarity). Interacts with SMAD3 (PubMed:19049980).

Interacts with SMAD4; positively regulated by ZBTB7A (PubMed:25514493). Interacts with SMARCAD1 (PubMed:21549307). Interacts with SMARCA4/BRG1 (PubMed:19081374).

Interacts with SMYD2 (By similarity). Interacts with SMYD4 (via MYND-type zinc finger) (PubMed:30110327). Interacts with SP1; the interaction deacetylates SP1 and regulates its transcriptional activity (PubMed:16478997).

Interacts with SP3; the interaction deacetylates SP3 and regulates its transcriptional activity (PubMed:12837748, PubMed:17548428). In vitro, C(18) ceramides increase this interaction and the subsequent SP3 deacetylation and SP3-mediated repression of the TERT promoter (PubMed:12837748, PubMed:17548428). Interacts with SPEN/MINT (PubMed:11331609).

Interacts with SPHK2 (PubMed:19729656). Interacts with SUV39H1 (By similarity). Interacts with TGIF (PubMed:11427533).

Interacts with TGIF2 (PubMed:11427533). Interacts with TRAF6 (PubMed:18093978). Interacts with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits its acetylation (PubMed:17704056).

Interacts with TSC22D3 isoform 1; this interaction affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 transcriptional activity (By similarity). Interacts with UHRF1 (PubMed:15361834). Interacts with UHRF2 (PubMed:15361834).

Interacts with ZBTB7A (PubMed:25514493). Interacts with ZMYND8 (PubMed:25593309, PubMed:36064715). Interacts with ZMYND15 (By similarity).

Interacts with ZNF431 (By similarity). Interacts with ZNF516; this interaction is enhanced in the presence of PWWP2B (By similarity). Interacts with ZNF541 (By similarity).

Interacts with ZNF638 (PubMed:30487602). Interacts with ZNHIT1 (By similarity). Interacts with the non-histone region of MACROH2A1 (By similarity).

Identified in a complex with HDAC2, KCTD19, DNTTIP1 and ZNF541 (By similarity). Interacts with VRK1 (PubMed:37179361)

(Microbial infection) Interacts with SV40 large T antigen

Source: UniProt
Nucleus
Source: UniProt

Ubiquitous, with higher levels in heart, pancreas and testis, and lower levels in kidney and brain

Source: UniProt
  • Transcription of E2F targets under negative control by DREAM complex
  • Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
  • G0 and Early G1
  • p75NTR negatively regulates cell cycle via SC1
  • Formation of the beta-catenin:TCF transactivating complex
  • NOTCH1 Intracellular Domain Regulates Transcription
  • Downregulation of SMAD2/3:SMAD4 transcriptional activity
  • SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription
  • Constitutive Signaling by NOTCH1 PEST Domain Mutants
  • Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
  • HDACs deacetylate histones
  • Notch-HLH transcription pathway
  • Deactivation of the beta-catenin transactivating complex
  • ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
  • NoRC negatively regulates rRNA expression
  • SUMOylation of chromatin organization proteins
  • Repression of WNT target genes
  • Regulation of TP53 Activity through Acetylation
  • G1/S-Specific Transcription
  • RNA Polymerase I Transcription Initiation
  • RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
  • Regulation of PTEN gene transcription
  • Estrogen-dependent gene expression
  • Loss of MECP2 binding ability to 5mC-DNA
  • Regulation of MECP2 expression and activity
  • MECP2 regulates neuronal receptors and channels
  • MECP2 regulates transcription of neuronal ligands
  • FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
  • Potential therapeutics for SARS
  • STAT3 nuclear events downstream of ALK signaling
  • Nuclear events stimulated by ALK signaling in cancer
  • Negative Regulation of CDH1 Gene Transcription
  • Regulation of MITF-M-dependent genes involved in apoptosis
  • Regulation of MITF-M-dependent genes involved in cell cycle and proliferation
  • Factors involved in megakaryocyte development and platelet production
  • Regulation of endogenous retroelements by KRAB-ZFP proteins
  • Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
  • Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
  • Transcriptional and post-translational regulation of MITF-M expression and activity
Source: Reactome via UniProt

Mutations

Cancer Type Mutation Percentage
Central Nervous System Astrocytoma Grade Iv 0.19%
Lung Adenocarcinoma 0.35%
Lung Small Cell Carcinoma 0.59%
Lung Squamous Cell Carcinoma 0.54%
Oesophagus Squamous Cell Carcinoma 0.12%
Pancreas Ductal Carcinoma 0.41%

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to HDAC1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

No clinical trials information available.