Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:O15379 HDAC3
| Class:Id | ReferenceGeneProduct:401336 |
|---|---|
| _chainChangeLog | chain:1-428 added on Sat February 7 2015 |
| _displayName | UniProt:O15379 HDAC3 |
| _timestamp | 2026-02-20 22:22:13 |
| chain | chain:1-428 |
| checksum | 94485C1EBDCF5AD0 |
| comment | FUNCTION Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates (PubMed:21030595, PubMed:21444723, PubMed:23911289, PubMed:25301942, PubMed:28167758, PubMed:28497810, PubMed:32404892, PubMed:22230954). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (PubMed:23911289). Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity (PubMed:23911289, PubMed:22230954). Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression (PubMed:23911289). Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (By similarity). During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758). In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl), 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) and isonicotinyl acyl groups from lysine residues, leading to protein decrotonylation, delactylation, de-2-hydroxyisobutyrylation and deisonicotinylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293, PubMed:34545082, PubMed:35044827). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (PubMed:38961290).CATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetateCATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[protein] + H2O = L-lysyl-[protein] + acetateCATALYTIC ACTIVITY N(6)-(2E)-butenoyl-L-lysyl-[protein] + H2O = (2E)-2-butenoate + L-lysyl-[protein]CATALYTIC ACTIVITY N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + H2O = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein]CATALYTIC ACTIVITY N(6)-[(S)-lactoyl]-L-lysyl-[protein] + H2O = (S)-lactate + L-lysyl-[protein]CATALYTIC ACTIVITY N(6)-isonicotinyl-L-lysyl-[protein] + H2O = isonicotinate + L-lysyl-[protein]COFACTOR Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) promotes the histone deacetylase activity by acting as an intermolecular glue between HDAC3 and NCOR2, thereby promoting its association with the N-Cor complex, a prerequisite for the histone deacetylase activity.SUBUNIT Interacts with HDAC7 and HDAC9 (PubMed:10655483, PubMed:11466315). Interacts with DAXX, KDM4A, HDAC10 and DACH1 (PubMed:10669754, PubMed:11861901, PubMed:14525983, PubMed:15927959). Found in a complex with NCOR1 and NCOR2 (PubMed:10860984, PubMed:22230954). Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:11931768). Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY (PubMed:10898795, PubMed:11006275, PubMed:15297880). Interacts with BTBD14B (By similarity). Interacts with GLIS2 (By similarity). Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation (By similarity). Component of the Notch corepressor complex (PubMed:19409814). Interacts with CBFA2T3 and NKAP (PubMed:11533236, PubMed:19409814). Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (PubMed:14633989). Interacts with ZMYND15 (By similarity). Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements (PubMed:23911289). Interacts with INSM1 (PubMed:16569215, PubMed:18417529). Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (PubMed:25190803). Interacts (via C-terminus) with CCAR2 (via N-terminus) (PubMed:21030595). Interacts with and deacetylates MEF2D (PubMed:21030595). Interacts with BEND3 (PubMed:21914818). Interacts with NKAPL (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3 (By similarity). Interacts with FBXL3 and BMAL1 (By similarity). Interacts with NCOR1 (By similarity). Interacts with RARA (PubMed:28167758). Interacts with SETD5 (By similarity).SUBUNIT (Microbial infection) Interacts with human cytomegalovirus (HHV-5) immediate early protein IE1; this interaction decreases histone acetylation and allows transcriptional activation by the virus.INTERACTION Colocalizes with XBP1 and AKT1 in the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus in the presence of CCAR2 (PubMed:21030595).ALTERNATIVE PRODUCTS Widely expressed.INDUCTION Up-regulated by disturbed flow in umbilical vein endothelial cells in vitro (PubMed:25190803).PTM Sumoylated in vitro.PTM Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation.SIMILARITY Belongs to the histone deacetylase family. HD type 1 subfamily. |
| created | [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 |
| description | recommendedName: Histone deacetylase 3 shortName: HD3 ecNumber evidence="33 45"3.5.1.98 alternativeName: Protein deacetylase HDAC3 ecNumber evidence="19 31 43 44"3.5.1.- alternativeName: fullName evidence="42"Protein deacylase HDAC3 ecNumber evidence="33 34 36 37 38 46"3.5.1.- alternativeName: RPD3-2 alternativeName: SMAP45 |
| geneName | HDAC3 |
| identifier | O15379 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Biological rhythms Chromatin regulator Chromosome Cytoplasm Host-virus interaction Hydrolase Nucleus Phosphoprotein Proteomics identification Reference proteome Repressor Transcription Transcription regulation Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | HDAC3 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8988987] ENSEMBL:ENSG00000171720 HDAC3 [Homo sapiens] |
| secondaryIdentifier | HDAC3_HUMAN D3DQE1 O43268 Q9UEI5 Q9UEV0 |
| sequenceLength | 428 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:56412] UniProt:O15379-1 HDAC3 [Homo sapiens] [ReferenceIsoform:148323] UniProt:O15379-2 HDAC3 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:442464] HDAC3 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6813777] Unfolded HDAC3 [cytosol] [Homo sapiens] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:O15379 HDAC3 (401336)
