Histone deacetylase 3

Details

Name
Histone deacetylase 3
Kind
protein
Synonyms
  • 3.5.1.98
  • HD3
  • Protein deacetylase HDAC3
  • Protein deacylase HDAC3
  • RPD3-2
  • SMAP45
Gene Name
HDAC3
UniProtKB Entry
O15379Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0004649|Histone deacetylase 3
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCR
FHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNN
KICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEA
FYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVI
NQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTV
RNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQ
TIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDN
DKESDVEI
Number of residues
428
Molecular Weight
48847.385
Theoretical pI
4.79
GO Classification
Functions
DNA-binding transcription factor binding / histone decrotonylase activity / protein de-2-hydroxyisobutyrylase activity / protein decrotonylase activity / protein lysine deacetylase activity / transcription corepressor binding
Processes
cornified envelope assembly / DNA repair-dependent chromatin remodeling / epigenetic regulation of gene expression / establishment of mitotic spindle orientation / establishment of skin barrier / in utero embryonic development / negative regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / positive regulation of cold-induced thermogenesis / positive regulation of protein import into nucleus / positive regulation of protein ubiquitination / positive regulation of transcription by RNA polymerase II / regulation of circadian rhythm / transcription by RNA polymerase II
Components
mitotic spindle / transcription repressor complex
General 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). 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 (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 (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) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674, PubMed:34608293). Catalyzes decrotonylation of MAPRE1/EB1 (PubMed:34608293)
Specific Function
chromatin binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0021323|Histone deacetylase 3 (HDAC3)
ATGGCCAAGACCGTGGCCTATTTCTACGACCCCGACGTGGGCAACTTCCACTACGGAGCT
GGACACCCTATGAAGCCCCATCGCCTGGCATTGACCCATAGCCTGGTCCTGCATTACGGT
CTCTATAAGAAGATGATCGTCTTCAAGCCATACCAGGCCTCCCAACATGACATGTGCCGC
TTCCACTCCGAGGACTACATTGACTTCCTGCAGAGAGTCAGCCCCACCAATATGCAAGGC
TTCACCAAGAGTCTTAATGCCTTCAACGTAGGCGATGACTGCCCAGTGTTTCCCGGGCTC
TTTGAGTTCTGCTCGCGTTACACAGGCGCATCTCTGCAAGGAGCAACCCAGCTGAACAAC
AAGATCTGTGATATTGCCATTAACTGGGCTGGTGGTCTGCACCATGCCAAGAAGTTTGAG
GCCTCTGGCTTCTGCTATGTCAACGACATTGTGATTGGCATCCTGGAGCTGCTCAAGTAC
CACCCTCGGGTGCTCTACATTGACATTGACATCCACCATGGTGACGGGGTTCAAGAAGCT
TTCTACCTCACTGACCGGGTCATGACGGTGTCCTTCCACAAATACGGAAATTACTTCTTC
CCTGGCACAGGTGACATGTATGAAGTCGGGGCAGAGAGTGGCCGCTACTACTGTCTGAAC
GTGCCCCTGCGGGATGGCATTGATGACCAGAGTTACAAGCACCTTTTCCAGCCGGTTATC
AACCAGGTAGTGGACTTCTACCAACCCACGTGCATTGTGCTCCAGTGTGGAGCTGACTCT
CTGGGCTGTGATCGATTGGGCTGCTTTAACCTCAGCATCCGAGGGCATGGGGAATGCGTT
GAATATGTCAAGAGCTTCAATATCCCTCTACTCGTGCTGGGTGGTGGTGGTTATACTGTC
CGAAATGTTGCCCGCTGCTGGACATATGAGACATCGCTGCTGGTAGAAGAGGCCATTAGT
GAGGAGCTTCCCTATAGTGAATACTTCGAGTACTTTGCCCCAGACTTCACACTTCATCCA
GATGTCAGCACCCGCATCGAGAATCAGAACTCACGCCAGTATCTGGACCAGATCCGCCAG
ACAATCTTTGAAAACCTGAAGATGCTGAACCATGCACCTAGTGTCCAGATTCATGACGTG
CCTGCAGACCTCCTGACCTATGACAGGACTGATGAGGCTGATGCAGAGGAGAGGGGTCCT
GAGGAGAACTATAGCAGGCCAGAGGCACCCAATGAGTTCTATGATGGAGACCATGACAAT
GACAAGGAAAGCGATGTGGAGATTTAA
Chromosome Location
5
Locus
5q31.3
External Identifiers
ResourceLink
UniProtKB IDO15379
UniProtKB Entry NameHDAC3_HUMAN
GenBank Protein ID2326173
GenBank Gene IDU66914
GeneCard IDHDAC3
GenAtlas IDHDAC3
HGNC IDHGNC:4854
PDB ID(s)4A69
KEGG IDhsa:8841
IUPHAR/Guide To Pharmacology ID2617
NCBI Gene ID8841
General References
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Vorinostatapproved, investigationalyestargetinhibitorDetails
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MocetinostatinvestigationalunknowntargetDetails
MartinostatinvestigationalyestargetinhibitorDetails