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Protein

Histone deacetylase 3

Gene

HDAC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 PI3K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress (PubMed:25190803).3 Publications

Catalytic activityi

Hydrolysis of an N6-acetyl-lysine residue of a histone to yield a deacetylated histone.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei135By similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Hydrolase, Repressor
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-1368071 NR1D1 (REV-ERBA) represses gene expression
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1
R-HSA-1989781 PPARA activates gene expression
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214815 HDACs deacetylate histones
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
SABIO-RKiO15379
SignaLinkiO15379
SIGNORiO15379

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 3 (EC:3.5.1.98)
Short name:
HD3
Alternative name(s):
RPD3-2
SMAP45
Gene namesi
Name:HDAC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000171720.9
HGNCiHGNC:4854 HDAC3
MIMi605166 gene
neXtProtiNX_O15379

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi8841
OpenTargetsiENSG00000171720
PharmGKBiPA29228

Chemistry databases

ChEMBLiCHEMBL1829
DrugBankiDB05015 Belinostat
DB05651 MGCD-0103
DB06603 Panobinostat
DB05223 SB939
DB02546 Vorinostat
GuidetoPHARMACOLOGYi2617

Polymorphism and mutation databases

BioMutaiHDAC3

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001146961 – 428Histone deacetylase 3Add BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei424PhosphoserineCombined sources1

Post-translational modificationi

Sumoylated in vitro.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO15379
MaxQBiO15379
PaxDbiO15379
PeptideAtlasiO15379
PRIDEiO15379
ProteomicsDBi48618
48619 [O15379-2]

PTM databases

iPTMnetiO15379
PhosphoSitePlusiO15379

Miscellaneous databases

PMAP-CutDBiO15379

Expressioni

Tissue specificityi

Widely expressed.

Inductioni

Up-regulated by disturbed flow in umbilical vein endothelial cells in vitro (PubMed:25190803).

Gene expression databases

BgeeiENSG00000171720 Expressed in 225 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_HDAC3
ExpressionAtlasiO15379 baseline and differential
GenevisibleiO15379 HS

Organism-specific databases

HPAiCAB005583
HPA052052

Interactioni

Subunit structurei

Interacts with HDAC7 and HDAC9. Forms a heterologous complex at least with YY1. Interacts with DAXX, HDAC10 and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with BTBD14B. Interacts with GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Component of the Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with and deacetylates MAPK14. Interacts with ZMYND15. Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements. Interacts with INSM1 (PubMed:10655483, PubMed:10669754, PubMed:10860984, PubMed:10898795, PubMed:11006275, PubMed:11466315, PubMed:11533236, PubMed:11861901, PubMed:14525983, PubMed:14633989, PubMed:15297880, PubMed:15927959, PubMed:16569215, PubMed:18417529, PubMed:19409814, PubMed:23911289). Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow (PubMed:25190803). Interacts (via C-terminus) with CCAR2 (via N-terminus). Interacts with and deacetylates MEF2D. Interacts with BEND3. Interacts with NKAPL (By similarity). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852).By similarity20 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114368, 222 interactors
CORUMiO15379
DIPiDIP-24253N
IntActiO15379, 83 interactors
MINTiO15379
STRINGi9606.ENSP00000302967

Chemistry databases

BindingDBiO15379

Structurei

Secondary structure

1428
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO15379
SMRiO15379
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni3 – 316Histone deacetylaseAdd BLAST314

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1342 Eukaryota
COG0123 LUCA
GeneTreeiENSGT00910000144047
HOGENOMiHOG000225180
HOVERGENiHBG057112
InParanoidiO15379
KOiK11404
OMAiPRAWTHL
OrthoDBiEOG091G067J
PhylomeDBiO15379
TreeFamiTF352182

Family and domain databases

Gene3Di3.40.800.20, 1 hit
InterProiView protein in InterPro
IPR000286 His_deacetylse
IPR003084 His_deacetylse_1
IPR023801 His_deacetylse_dom
IPR037138 His_deacetylse_dom_sf
IPR023696 Ureohydrolase_dom_sf
PANTHERiPTHR10625 PTHR10625, 1 hit
PfamiView protein in Pfam
PF00850 Hist_deacetyl, 1 hit
PIRSFiPIRSF037913 His_deacetylse_1, 1 hit
PRINTSiPR01270 HDASUPER
PR01271 HISDACETLASE
SUPFAMiSSF52768 SSF52768, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O15379-1) [UniParc]FASTAAdd to basket
Also known as: RPD3-2B

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        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 NQVVDFYQPT
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
Length:428
Mass (Da):48,848
Last modified:July 15, 1998 - v2
Checksum:i94485C1EBDCF5AD0
GO
Isoform 2 (identifier: O15379-2) [UniParc]FASTAAdd to basket
Also known as: RPD3-2A

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: MAKTVAYFYDPDVGN → MIVFKPYQASQHDMCR

Show »
Length:429
Mass (Da):49,111
Checksum:i0B654598513D284B
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ESJ6E7ESJ6_HUMAN
Histone deacetylase 3
HDAC3
218Annotation score:
E7EW19E7EW19_HUMAN
Histone deacetylase 3
HDAC3
53Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti359R → L in AAC52038 (PubMed:9464271).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_033988411N → S. Corresponds to variant dbSNP:rs34901743Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0020791 – 15MAKTV…PDVGN → MIVFKPYQASQHDMCR in isoform 2. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U66914 mRNA Translation: AAC52038.1
U75697 mRNA Translation: AAB88241.1
U75696 mRNA Translation: AAB88240.1
AF005482 mRNA Translation: AAB87752.1
AF039703 mRNA Translation: AAC98927.1
AF059650 Genomic DNA Translation: AAC26509.1
CH471062 Genomic DNA Translation: EAW61915.1
CH471062 Genomic DNA Translation: EAW61916.1
BC000614 mRNA Translation: AAH00614.1
AF053138, AF053137 Genomic DNA Translation: AAC08351.1
AF053139 Genomic DNA Translation: AAC08352.1
CCDSiCCDS4264.1 [O15379-1]
PIRiJC5834
RefSeqiNP_003874.2, NM_003883.3 [O15379-1]
UniGeneiHs.519632

Genome annotation databases

EnsembliENST00000305264; ENSP00000302967; ENSG00000171720 [O15379-1]
GeneIDi8841
KEGGihsa:8841
UCSCiuc003llf.3 human [O15379-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U66914 mRNA Translation: AAC52038.1
U75697 mRNA Translation: AAB88241.1
U75696 mRNA Translation: AAB88240.1
AF005482 mRNA Translation: AAB87752.1
AF039703 mRNA Translation: AAC98927.1
AF059650 Genomic DNA Translation: AAC26509.1
CH471062 Genomic DNA Translation: EAW61915.1
CH471062 Genomic DNA Translation: EAW61916.1
BC000614 mRNA Translation: AAH00614.1
AF053138, AF053137 Genomic DNA Translation: AAC08351.1
AF053139 Genomic DNA Translation: AAC08352.1
CCDSiCCDS4264.1 [O15379-1]
PIRiJC5834
RefSeqiNP_003874.2, NM_003883.3 [O15379-1]
UniGeneiHs.519632

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4A69X-ray2.06A/B1-376[»]
ProteinModelPortaliO15379
SMRiO15379
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114368, 222 interactors
CORUMiO15379
DIPiDIP-24253N
IntActiO15379, 83 interactors
MINTiO15379
STRINGi9606.ENSP00000302967

Chemistry databases

BindingDBiO15379
ChEMBLiCHEMBL1829
DrugBankiDB05015 Belinostat
DB05651 MGCD-0103
DB06603 Panobinostat
DB05223 SB939
DB02546 Vorinostat
GuidetoPHARMACOLOGYi2617

PTM databases

iPTMnetiO15379
PhosphoSitePlusiO15379

Polymorphism and mutation databases

BioMutaiHDAC3

Proteomic databases

EPDiO15379
MaxQBiO15379
PaxDbiO15379
PeptideAtlasiO15379
PRIDEiO15379
ProteomicsDBi48618
48619 [O15379-2]

Protocols and materials databases

DNASUi8841
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000305264; ENSP00000302967; ENSG00000171720 [O15379-1]
GeneIDi8841
KEGGihsa:8841
UCSCiuc003llf.3 human [O15379-1]

Organism-specific databases

CTDi8841
DisGeNETi8841
EuPathDBiHostDB:ENSG00000171720.9
GeneCardsiHDAC3
HGNCiHGNC:4854 HDAC3
HPAiCAB005583
HPA052052
MIMi605166 gene
neXtProtiNX_O15379
OpenTargetsiENSG00000171720
PharmGKBiPA29228
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1342 Eukaryota
COG0123 LUCA
GeneTreeiENSGT00910000144047
HOGENOMiHOG000225180
HOVERGENiHBG057112
InParanoidiO15379
KOiK11404
OMAiPRAWTHL
OrthoDBiEOG091G067J
PhylomeDBiO15379
TreeFamiTF352182

Enzyme and pathway databases

ReactomeiR-HSA-1368071 NR1D1 (REV-ERBA) represses gene expression
R-HSA-193670 p75NTR negatively regulates cell cycle via SC1
R-HSA-1989781 PPARA activates gene expression
R-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2151201 Transcriptional activation of mitochondrial biogenesis
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214815 HDACs deacetylate histones
R-HSA-381340 Transcriptional regulation of white adipocyte differentiation
R-HSA-390471 Association of TriC/CCT with target proteins during biosynthesis
R-HSA-400206 Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
R-HSA-400253 Circadian Clock
R-HSA-5617472 Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
R-HSA-8943724 Regulation of PTEN gene transcription
SABIO-RKiO15379
SignaLinkiO15379
SIGNORiO15379

Miscellaneous databases

ChiTaRSiHDAC3 human
GeneWikiiHDAC3
GenomeRNAii8841
PMAP-CutDBiO15379
PROiPR:O15379
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171720 Expressed in 225 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_HDAC3
ExpressionAtlasiO15379 baseline and differential
GenevisibleiO15379 HS

Family and domain databases

Gene3Di3.40.800.20, 1 hit
InterProiView protein in InterPro
IPR000286 His_deacetylse
IPR003084 His_deacetylse_1
IPR023801 His_deacetylse_dom
IPR037138 His_deacetylse_dom_sf
IPR023696 Ureohydrolase_dom_sf
PANTHERiPTHR10625 PTHR10625, 1 hit
PfamiView protein in Pfam
PF00850 Hist_deacetyl, 1 hit
PIRSFiPIRSF037913 His_deacetylse_1, 1 hit
PRINTSiPR01270 HDASUPER
PR01271 HISDACETLASE
SUPFAMiSSF52768 SSF52768, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiHDAC3_HUMAN
AccessioniPrimary (citable) accession number: O15379
Secondary accession number(s): D3DQE1
, O43268, Q9UEI5, Q9UEV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: November 7, 2018
This is version 201 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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