DegronMD - O15379(HDAC3)

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:21030595, PubMed:21444723, PubMed:25301942, PubMed:28497810, PubMed:28167758). 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 ARNTL/BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1 (By similarity). The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By similarity). Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (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 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). {ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21444723, 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:34608293}. View more >>

GO - Biological processes (BP): View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A333G	TCGA-12-0829	GBM	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.25
p.A333G	DO11166	GBM	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.25
p.E347D	TCGA-A5-A0GP	UCEC	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.E347D	DO41109	UCEC	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.E330K	TCGA-AP-A0LM	UCEC	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.E330K	TCGA-EO-A3AV	UCEC	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.E330K	DO43306	UCEC	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.E330K	DO52412	UCEC	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.A333V	TCGA-BR-4184	STAD	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.25
p.A333V	DO38328	STAD	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.25
p.L338F	TCGA-E2-A155	BRCA	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation altering degron motif	0.6981
p.L338F	DO1707	BRCA	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation altering degron motif	0.6981
p.S351L	TCGA-VN-A88I	PRAD	TCGA	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.0556
p.S351L	DO49854	PRAD	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.0556
p.P340T	DO228948	LICA	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation altering degron motif	0.5919
p.E347K	DO222837	MELA	ICGC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.1667
p.R345C	SIDM01108	Non-Small Cell Lung Carcinoma	GDSC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.2222
p.R345C	ACH-000309	Lung Cancer	CCLE	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.2222
p.R345C	SK-LU-1	lung	COSMIC	FTLHPD	LIG_APCC_ABBA_1	336:341	Mutation rewiring degron network	0.2222

DegronMD: protein-targeted degradation, mutation and drug response to degrons

HDAC3

UniProt ID: O15379

Entrez ID: 8841

Protein name: Histone deacetylase 3 (HD3) (EC 3.5.1.98) (Protein deacetylase HDAC3) (EC 3.5.1.-) (Protein deacylase HDAC3) (EC 3.5.1.-) (RPD3-2) (SMAP45)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for HDAC3 in