Hdac3
entrez
15183
canonical
uniprot
O88895
canonical
ensembl
ENSMUSG00000024454
resolver
ensp
ENSMUSP00000037981
resolver
genesymbol
Hdac3
resolver
uniprot
O88896
resolver
uniprot
Q3UM33
resolver
uniprot
Q9JM08
resolver
uniprot_entry
HDAC3_MOUSE
resolver
uniprot_entry
Q9JM08_MOUSE
resolver
uniprot_sec
O88896
resolver
uniprot_sec
Q3UM33
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:0000250|UniProtKB:O15379}.
uniprot
proteins
amino_acid_sequence
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCRFHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNNKICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEAFYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVISQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTVRNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQTIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDNDKESDVEI
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:23911289, PubMed:30279482). 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). 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 (PubMed:19204783). 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 (By similarity). Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner (PubMed:26776516). 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 (PubMed:26776516). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver (PubMed:19037247). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3 (By similarity). Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (By similarity). 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:30279482). Catalyzes decrotonylation of MAPRE1/EB1 (By similarity). Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR) (By similarity). {ECO:0000250|UniProtKB:O15379, ECO:0000269|PubMed:19037247, ECO:0000269|PubMed:19204783, ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:26776516, ECO:0000269|PubMed:30279482}.
uniprot
proteins
mass_dalton
48821
uniprot
proteins
mutagenesis
MUTAGEN 134..136; /note="HHA->QAS: Deacetylase-dead mutant. No effect on its interaction with BMAL1, CRY1 and FBXL3 or its ability to regulate the circadian clock."; /evidence="ECO:0000269|PubMed:26776516"; MUTAGEN 424; /note="S->A: Deacetylase-dead mutant. No effect on its interaction with BMAL1, CRY1 and FBXL3 or its ability to regulate the circadian clock."; /evidence="ECO:0000269|PubMed:26776516
uniprot
proteins
post_translational_modification
PTM: Sumoylated in vitro. {ECO:0000269|PubMed:19204783}.; PTM: Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation. {ECO:0000250|UniProtKB:O15379}.
uniprot
proteins
protein_family
HD type 1 subfamily
uniprot
proteins
protein_family
Histone deacetylase family
uniprot
proteins
pubmed
10491319
uniprot
proteins
pubmed
10984530
uniprot
proteins
pubmed
11022042
uniprot
proteins
pubmed
11533236
uniprot
proteins
pubmed
12130660
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15711539
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16326862
uniprot
proteins
pubmed
16537907
uniprot
proteins
pubmed
19037247
uniprot
proteins
pubmed
19204783
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20675388
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
23911289
uniprot
proteins
pubmed
25875095
uniprot
proteins
pubmed
26776516
uniprot
proteins
pubmed
30279482
uniprot
proteins
pubmed
30455454
uniprot
proteins
sequence_length
428
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26776516}. Chromosome {ECO:0000250|UniProtKB:O15379}. Cytoplasm {ECO:0000269|PubMed:26776516}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:O15379}. Note=Colocalizes with XBP1 and AKT1 in the cytoplasm. Predominantly expressed in the nucleus in the presence of CCAR2. {ECO:0000250|UniProtKB:O15379}.
uniprot
proteins