UniProtKB - O88895 (HDAC3_MOUSE)
Histone deacetylase 3
Hdac3
Functioni
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 (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 PI3K/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 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 (PubMed:26776516).
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 (PubMed:19037247).
Also functions as deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and RARA (By similarity).
Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding (By similarity).
In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (By similarity).
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:30279482).
Catalyzes decrotonylation of MAPRE1/EB1 (By similarity).
By similarity5 PublicationsCatalytic activityi
- EC:3.5.1.982 PublicationsThis reaction proceeds in the forward2 Publications direction.
- This reaction proceeds in the forwardBy similarity direction.
- This reaction proceeds in the forward1 Publication direction.
- H2O + N6-(2-hydroxyisobutanoyl)-L-lysyl-[protein] = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein]By similarityThis reaction proceeds in the forwardBy similarity direction.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 135 | By similarity | 1 |
GO - Molecular functioni
- chromatin binding Source: MGI
- chromatin DNA binding Source: MGI
- cyclin binding Source: MGI
- deacetylase activity Source: MGI
- DNA binding Source: MGI
- DNA-binding transcription factor binding Source: UniProtKB
- enzyme binding Source: MGI
- GTPase binding Source: MGI
- histone deacetylase activity Source: UniProtKB
- histone deacetylase binding Source: MGI
- histone decrotonylase activity Source: UniProtKB
- NF-kappaB binding Source: MGI
- protein deacetylase activity Source: MGI
- transcription corepressor activity Source: UniProtKB
- transcription corepressor binding Source: MGI
GO - Biological processi
- cellular response to fluid shear stress Source: UniProtKB
- chromatin organization Source: UniProtKB
- circadian regulation of gene expression Source: UniProtKB
- cornified envelope assembly Source: MGI
- epidermis development Source: MGI
- establishment of skin barrier Source: MGI
- gene expression Source: MGI
- histone deacetylation Source: MGI
- histone H4 deacetylation Source: MGI
- histone H4-K12 deacetylation Source: MGI
- in utero embryonic development Source: MGI
- negative regulation of cardiac muscle cell differentiation Source: MGI
- negative regulation of DNA-binding transcription factor activity Source: MGI
- negative regulation of interleukin-1 production Source: MGI
- negative regulation of JNK cascade Source: MGI
- negative regulation of protein export from nucleus Source: MGI
- negative regulation of transcription, DNA-templated Source: MGI
- negative regulation of transcription by RNA polymerase II Source: MGI
- negative regulation of tumor necrosis factor production Source: MGI
- positive regulation of cold-induced thermogenesis Source: YuBioLab
- positive regulation of neuron apoptotic process Source: MGI
- positive regulation of protein import into nucleus Source: UniProtKB
- positive regulation of protein phosphorylation Source: UniProtKB
- positive regulation of protein ubiquitination Source: UniProtKB
- positive regulation of TOR signaling Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- positive regulation of type B pancreatic cell apoptotic process Source: MGI
- protein deacetylation Source: MGI
- regulation of circadian rhythm Source: UniProtKB
- regulation of mitotic cell cycle Source: MGI
- regulation of multicellular organism growth Source: MGI
- regulation of protein stability Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- spindle assembly Source: MGI
Keywordsi
Molecular function | Chromatin regulator, Hydrolase, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
BRENDAi | 3.5.1.98, 3474 |
Reactomei | R-MMU-3214815, HDACs deacetylate histones R-MMU-350054, Notch-HLH transcription pathway R-MMU-400206, Regulation of lipid metabolism by PPARalpha R-MMU-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux R-MMU-9701898, STAT3 nuclear events downstream of ALK signaling R-MMU-9707564, Cytoprotection by HMOX1 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:1343091, Hdac3 |
VEuPathDBi | HostDB:ENSMUSG00000024454 |
Subcellular locationi
Cytoskeleton
- mitotic spindle Source: MGI
Cytosol
- cytosol Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: MGI
Nucleus
- histone deacetylase complex Source: MGI
- nucleoplasm Source: MGI
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: MGI
Other locations
- chromatin Source: MGI
- cytoplasm Source: UniProtKB
- transcription repressor complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 134 – 136 | HHA → QAS: Deacetylase-dead mutant. No effect on its interaction with ARNTL/BMAL1, CRY1 and FBXL3 or its ability to regulate the circadian clock. 1 Publication | 3 | |
Mutagenesisi | 424 | S → A: Deacetylase-dead mutant. No effect on its interaction with ARNTL/BMAL1, CRY1 and FBXL3 or its ability to regulate the circadian clock. 1 Publication | 1 |
Chemistry databases
ChEMBLi | CHEMBL5142 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000114697 | 1 – 428 | Histone deacetylase 3Add BLAST | 428 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 424 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O88895 |
MaxQBi | O88895 |
PaxDbi | O88895 |
PeptideAtlasi | O88895 |
PRIDEi | O88895 |
ProteomicsDBi | 269819 [O88895-1] 269820 [O88895-2] 334754 |
PTM databases
iPTMneti | O88895 |
PhosphoSitePlusi | O88895 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000024454, Expressed in spermatocyte and 313 other tissues |
Interactioni
Subunit structurei
Interacts with HDAC7 and HDAC9 (PubMed:10984530, PubMed:11022042, PubMed:15711539).
Interacts with DAXX, KDM4A, HDAC10 and DACH1 (PubMed:12130660).
Found in a complex with NCOR1 and NCOR2 (By similarity).
Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (By similarity).
Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY (PubMed:16537907).
Interacts with BTBD14B (By similarity).
Interacts with GLIS2 (PubMed:16326862).
Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation (PubMed:19204783).
Component of the Notch corepressor complex (By similarity).
Interacts with CBFA2T3 and NKAP (PubMed:11533236).
Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1 (By similarity).
Interacts with ZMYND15 (PubMed:20675388).
Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements (By similarity).
Interacts with INSM1 (By similarity).
Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (By similarity).
Interacts (via C-terminus) with CCAR2 (via N-terminus) (By similarity).
Interacts with and deacetylates MEF2D (By similarity).
Interacts with BEND3 (By similarity).
Interacts with NKAPL (PubMed:25875095).
Interacts with DHX36; this interaction occurs in a RNA-dependent manner (By similarity).
Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3 (PubMed:26776516).
Interacts with FBXL3 and ARNTL/BMAL1 (PubMed:26776516).
Interacts with NCOR1 (PubMed:19037247).
Interacts with RARA (By similarity).
Interacts with SETD5 (PubMed:30455454).
By similarity13 PublicationsBinary interactionsi
O88895
With | #Exp. | IntAct |
---|---|---|
Mecp2 [Q9Z2D6] | 5 | EBI-302263,EBI-1188816 |
Nfkbia [Q9Z1E3] | 2 | EBI-302263,EBI-644427 |
Nr2e1 [Q64104] | 2 | EBI-302263,EBI-15658561 |
Smarca4 [Q3TKT4] | 2 | EBI-302263,EBI-1210244 |
GO - Molecular functioni
- cyclin binding Source: MGI
- DNA-binding transcription factor binding Source: UniProtKB
- enzyme binding Source: MGI
- GTPase binding Source: MGI
- histone deacetylase binding Source: MGI
- NF-kappaB binding Source: MGI
- transcription corepressor binding Source: MGI
Protein-protein interaction databases
CORUMi | O88895 |
DIPi | DIP-32547N |
IntActi | O88895, 21 interactors |
MINTi | O88895 |
STRINGi | 10090.ENSMUSP00000037981 |
Chemistry databases
BindingDBi | O88895 |
Miscellaneous databases
RNActi | O88895, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 3 – 316 | Histone deacetylaseAdd BLAST | 314 | |
Regioni | 387 – 424 | DisorderedSequence analysisAdd BLAST | 38 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 387 – 405 | Basic and acidic residuesSequence analysisAdd BLAST | 19 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1342, Eukaryota |
GeneTreei | ENSGT00940000160487 |
HOGENOMi | CLU_007727_7_6_1 |
InParanoidi | O88895 |
OMAi | GWLRAFH |
OrthoDBi | 732770at2759 |
TreeFami | TF352182 |
Family and domain databases
Gene3Di | 3.40.800.20, 1 hit |
InterProi | View protein in InterPro IPR000286, His_deacetylse IPR003084, His_deacetylse_1 IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR023696, Ureohydrolase_dom_sf |
Pfami | View protein in Pfam PF00850, Hist_deacetyl, 1 hit |
PIRSFi | PIRSF037913, His_deacetylse_1, 1 hit |
PRINTSi | PR01270, HDASUPER PR01271, HISDACETLASE |
SUPFAMi | SSF52768, SSF52768, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP
60 70 80 90 100
YQASQHDMCR FHSEDYIDFL QRVSPTNMQG FTKSLNAFNV GDDCPVFPGL
110 120 130 140 150
FEFCSRYTGA SLQGATQLNN KICDIAINWA GGLHHAKKFE ASGFCYVNDI
160 170 180 190 200
VIGILELLKY HPRVLYIDID IHHGDGVQEA FYLTDRVMTV SFHKYGNYFF
210 220 230 240 250
PGTGDMYEVG AESGRYYCLN VPLRDGIDDQ SYKHLFQPVI SQVVDFYQPT
260 270 280 290 300
CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV
310 320 330 340 350
RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN
360 370 380 390 400
SRQYLDQIRQ TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP
410 420
EENYSRPEAP NEFYDGDHDN DKESDVEI
The sequence of this isoform differs from the canonical sequence as follows:
69-259: Missing.
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketH6UK62 | H6UK62_MOUSE | HDAC3 splicing HDAC3delta | Hdac3 | 120 | Annotation score: | ||
A0A494B9Q7 | A0A494B9Q7_MOUSE | Histone deacetylase 3 | Hdac3 | 75 | Annotation score: |
Sequence cautioni
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_002080 | 69 – 259 | Missing in isoform Short. 1 PublicationAdd BLAST | 191 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF074881 mRNA Translation: AAC36305.1 Sequence problems. AF074882 mRNA Translation: AAC36306.1 Sequence problems. AF079310, AF079309 Genomic DNA Translation: AAC67258.1 Sequence problems. AK145158 mRNA Translation: BAE26265.1 AC129315 Genomic DNA No translation available. BC139300 mRNA Translation: AAI39301.1 BC139301 mRNA Translation: AAI39302.1 |
PIRi | JC7102 |
RefSeqi | NP_034541.2, NM_010411.2 |
Genome annotation databases
Ensembli | ENSMUST00000043498; ENSMUSP00000037981; ENSMUSG00000024454 [O88895-1] |
GeneIDi | 15183 |
KEGGi | mmu:15183 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF074881 mRNA Translation: AAC36305.1 Sequence problems. AF074882 mRNA Translation: AAC36306.1 Sequence problems. AF079310, AF079309 Genomic DNA Translation: AAC67258.1 Sequence problems. AK145158 mRNA Translation: BAE26265.1 AC129315 Genomic DNA No translation available. BC139300 mRNA Translation: AAI39301.1 BC139301 mRNA Translation: AAI39302.1 |
PIRi | JC7102 |
RefSeqi | NP_034541.2, NM_010411.2 |
3D structure databases
AlphaFoldDBi | O88895 |
SMRi | O88895 |
ModBasei | Search... |
Protein-protein interaction databases
CORUMi | O88895 |
DIPi | DIP-32547N |
IntActi | O88895, 21 interactors |
MINTi | O88895 |
STRINGi | 10090.ENSMUSP00000037981 |
Chemistry databases
BindingDBi | O88895 |
ChEMBLi | CHEMBL5142 |
PTM databases
iPTMneti | O88895 |
PhosphoSitePlusi | O88895 |
Proteomic databases
EPDi | O88895 |
MaxQBi | O88895 |
PaxDbi | O88895 |
PeptideAtlasi | O88895 |
PRIDEi | O88895 |
ProteomicsDBi | 269819 [O88895-1] 269820 [O88895-2] 334754 |
Protocols and materials databases
Antibodypediai | 3568, 958 antibodies from 48 providers |
DNASUi | 15183 |
Genome annotation databases
Ensembli | ENSMUST00000043498; ENSMUSP00000037981; ENSMUSG00000024454 [O88895-1] |
GeneIDi | 15183 |
KEGGi | mmu:15183 |
Organism-specific databases
CTDi | 8841 |
MGIi | MGI:1343091, Hdac3 |
VEuPathDBi | HostDB:ENSMUSG00000024454 |
Phylogenomic databases
eggNOGi | KOG1342, Eukaryota |
GeneTreei | ENSGT00940000160487 |
HOGENOMi | CLU_007727_7_6_1 |
InParanoidi | O88895 |
OMAi | GWLRAFH |
OrthoDBi | 732770at2759 |
TreeFami | TF352182 |
Enzyme and pathway databases
BRENDAi | 3.5.1.98, 3474 |
Reactomei | R-MMU-3214815, HDACs deacetylate histones R-MMU-350054, Notch-HLH transcription pathway R-MMU-400206, Regulation of lipid metabolism by PPARalpha R-MMU-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux R-MMU-9701898, STAT3 nuclear events downstream of ALK signaling R-MMU-9707564, Cytoprotection by HMOX1 |
Miscellaneous databases
BioGRID-ORCSi | 15183, 28 hits in 82 CRISPR screens |
ChiTaRSi | Hdac3, mouse |
PROi | PR:O88895 |
RNActi | O88895, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000024454, Expressed in spermatocyte and 313 other tissues |
Family and domain databases
Gene3Di | 3.40.800.20, 1 hit |
InterProi | View protein in InterPro IPR000286, His_deacetylse IPR003084, His_deacetylse_1 IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR023696, Ureohydrolase_dom_sf |
Pfami | View protein in Pfam PF00850, Hist_deacetyl, 1 hit |
PIRSFi | PIRSF037913, His_deacetylse_1, 1 hit |
PRINTSi | PR01270, HDASUPER PR01271, HISDACETLASE |
SUPFAMi | SSF52768, SSF52768, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HDAC3_MOUSE | |
Accessioni | O88895Primary (citable) accession number: O88895 Secondary accession number(s): O88896, Q3UM33 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | February 23, 2022 | |
Last modified: | May 25, 2022 | |
This is version 178 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families