Target General Infomation
Target ID
T05090
Former ID
TTDI01956
Target Name
Histone deacetylase-3
Gene Name
HDAC3
Synonyms
HD3; Histone deacetylase 3; RPD32; SMAP45; HDAC3
Target Type
Clinical Trial
Disease Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48]
Function
Responsible for 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. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. 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. Probably participates in the regulation of transcription through its binding to the zinc-finger transcription factor YY1; increases YY1 repression activity. Required to repress transcription of the POU1F1 transcription factor.Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:21444723, PubMed:23911289). 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).
BioChemical Class
Carbon-nitrogen hydrolase
UniProt ID
EC Number
EC 3.5.1.98
Sequence
MAKTVAYFYDPDVGNFHYGAGHPMKPHRLALTHSLVLHYGLYKKMIVFKPYQASQHDMCR
FHSEDYIDFLQRVSPTNMQGFTKSLNAFNVGDDCPVFPGLFEFCSRYTGASLQGATQLNN
KICDIAINWAGGLHHAKKFEASGFCYVNDIVIGILELLKYHPRVLYIDIDIHHGDGVQEA
FYLTDRVMTVSFHKYGNYFFPGTGDMYEVGAESGRYYCLNVPLRDGIDDQSYKHLFQPVI
NQVVDFYQPTCIVLQCGADSLGCDRLGCFNLSIRGHGECVEYVKSFNIPLLVLGGGGYTV
RNVARCWTYETSLLVEEAISEELPYSEYFEYFAPDFTLHPDVSTRIENQNSRQYLDQIRQ
TIFENLKMLNHAPSVQIHDVPADLLTYDRTDEADAEERGPEENYSRPEAPNEFYDGDHDN
DKESDVEI
Drugs and Mode of Action
Drug(s) CHR-3996 Drug Info Phase 1 Solid tumours [531893], [543102]
Inhibitor CHR-3996 Drug Info [531893]
droxinostat Drug Info [530619]
RGFP966 Drug Info [532184]
Pathways
KEGG Pathway Thyroid hormone signaling pathway
Alcoholism
Viral carcinogenesis
PANTHER Pathway Wnt signaling pathway
Pathway Interaction Database Signaling events mediated by HDAC Class II
Signaling events mediated by HDAC Class I
Retinoic acid receptors-mediated signaling
Validated targets of C-MYC transcriptional repression
Regulation of retinoblastoma protein
References
Ref 531893A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors. Clin Cancer Res. 2012 May 1;18(9):2687-94.
Ref 543102(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8391).
Ref 530619Selective inhibition of histone deacetylases sensitizes malignant cells to death receptor ligands. Mol Cancer Ther. 2010 Jan;9(1):246-56.
Ref 531893A phase I pharmacokinetic and pharmacodynamic study of CHR-3996, an oral class I selective histone deacetylase inhibitor in refractory solid tumors. Clin Cancer Res. 2012 May 1;18(9):2687-94.
Ref 532184HDAC3-selective inhibitor enhances extinction of cocaine-seeking behavior in a persistent manner. Proc Natl Acad Sci U S A. 2013 Feb 12;110(7):2647-52.

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