HDAC3
entrez
8841
canonical
uniprot
O15379
canonical
ensembl
ENSG00000171720
resolver
ensp
ENSP00000302967
resolver
genesymbol
HDAC3
resolver
hgnc
HGNC:4854
resolver
uniprot
D3DQE1
resolver
uniprot
O43268
resolver
uniprot
Q9UEI5
resolver
uniprot
Q9UEV0
resolver
uniprot_entry
HDAC3_HUMAN
resolver
uniprot_sec
D3DQE1
resolver
uniprot_sec
O43268
resolver
uniprot_sec
Q9UEI5
resolver
uniprot_sec
Q9UEV0
resolver
activity_regulation
ACTIVITY REGULATION: 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. {ECO:0000269|PubMed:22230954}.
uniprot
proteins
amino_acid_sequence
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCRFHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVINQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDNDKESDVEI
uniprot
proteins
ec_number
3.5.1.-
uniprot
proteins
ec_number
3.5.1.98
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:22230954, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942, ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892, ECO:0000269|PubMed:34545082, ECO:0000269|PubMed:34608293, ECO:0000269|PubMed:35044827, ECO:0000269|PubMed:38961290}.
uniprot
proteins
mass_dalton
48848
uniprot
proteins
mutagenesis
MUTAGEN 17..25; /note="HYGAGHPMK->CYAAGHPMI: Abolished interaction with NCOR2 and activation of the histone deacetylase activity."; /evidence="ECO:0000269|PubMed:22230954"; MUTAGEN 130..132; /note="AGG->VRPP: Impaired protein deacetylase activity without affecting the protein decrotonylase activity."; /evidence="ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:34608293"; MUTAGEN 264..265; /note="DR->PM: Abolished interaction with NCOR2 and activation of the histone deacetylase activity."; /evidence="ECO:0000269|PubMed:22230954"; MUTAGEN 265; /note="R->P: Abolished interaction with NCOR2 and activation of the histone deacetylase activity."; /evidence="ECO:0000269|PubMed:22230954"; MUTAGEN 298; /note="Y->F: Strongly decreased protein deacetylase activity."; /evidence="ECO:0000269|PubMed:25301942
uniprot
proteins
post_translational_modification
PTM: Sumoylated in vitro. {ECO:0000269|PubMed:12032081}.; PTM: Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation. {ECO:0000269|PubMed:32404892}.
uniprot
proteins
protein_family
HD type 1 subfamily
uniprot
proteins
protein_family
Histone deacetylase family
uniprot
proteins
pubmed
10051405
uniprot
proteins
pubmed
10655483
uniprot
proteins
pubmed
10669754
uniprot
proteins
pubmed
10809664
uniprot
proteins
pubmed
10860984
uniprot
proteins
pubmed
10898795
uniprot
proteins
pubmed
10944117
uniprot
proteins
pubmed
11006275
uniprot
proteins
pubmed
11466315
uniprot
proteins
pubmed
11533236
uniprot
proteins
pubmed
11861901
uniprot
proteins
pubmed
11931768
uniprot
proteins
pubmed
12032081
uniprot
proteins
pubmed
12628926
uniprot
proteins
pubmed
14525983
uniprot
proteins
pubmed
14633989
uniprot
proteins
pubmed
15297880
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15572445
uniprot
proteins
pubmed
15653507
uniprot
proteins
pubmed
15927959
uniprot
proteins
pubmed
16569215
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
18279852
uniprot
proteins
pubmed
18417529
uniprot
proteins
pubmed
19409814
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21030595
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21444723
uniprot
proteins
pubmed
21914818
uniprot
proteins
pubmed
22230954
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23911289
uniprot
proteins
pubmed
25190803
uniprot
proteins
pubmed
25301942
uniprot
proteins
pubmed
28167758
uniprot
proteins
pubmed
28497810
uniprot
proteins
pubmed
29192674
uniprot
proteins
pubmed
32404892
uniprot
proteins
pubmed
34545082
uniprot
proteins
pubmed
34608293
uniprot
proteins
pubmed
35044827
uniprot
proteins
pubmed
38961290
uniprot
proteins
pubmed
9346952
uniprot
proteins
pubmed
9464271
uniprot
proteins
pubmed
9501169
uniprot
proteins
sequence_length
428
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21030595}. Chromosome {ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18417529}. Cytoplasm {ECO:0000269|PubMed:25190803}. Cytoplasm, cytosol {ECO:0000269|PubMed:21030595}. Note=Colocalizes with XBP1 and AKT1 in the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus in the presence of CCAR2 (PubMed:21030595). {ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:25190803}.
uniprot
proteins