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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

  • chromatin binding Source: UniProtKB
  • cyclin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone deacetylase activity Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
  • NF-kappaB binding Source: UniProtKB
  • protein deacetylase activity Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • cellular response to fluid shear stress Source: UniProtKB
  • chromatin organization Source: UniProtKB
  • circadian rhythm Source: Reactome
  • negative regulation of apoptotic process Source: ProtInc
  • negative regulation of JNK cascade Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • positive regulation of protein import into nucleus Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of TOR signaling Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • protein deacetylation Source: UniProtKB
  • regulation of lipid metabolic process Source: Reactome
  • regulation of protein stability Source: UniProtKB
  • spindle assembly Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW

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
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).By similarity19 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cyclin binding Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone deacetylase binding Source: UniProtKB
  • NF-kappaB binding Source: UniProtKB
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114368, 221 interactors
CORUMiO15379
DIPiDIP-24253N
IntActiO15379, 85 interactors
MINTiO15379
STRINGi9606.ENSP00000302967

Chemistry databases

BindingDBiO15379

Structurei

Secondary structure

1428
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 8Combined sources4
Turni11 – 14Combined sources4
Helixi27 – 38Combined sources12
Helixi41 – 44Combined sources4
Beta strandi45 – 48Combined sources4
Helixi55 – 58Combined sources4
Turni59 – 61Combined sources3
Helixi64 – 72Combined sources9
Turni75 – 77Combined sources3
Helixi78 – 81Combined sources4
Helixi82 – 88Combined sources7
Beta strandi91 – 94Combined sources4
Helixi100 – 119Combined sources20
Beta strandi124 – 128Combined sources5
Beta strandi145 – 147Combined sources3
Helixi149 – 157Combined sources9
Turni158 – 160Combined sources3
Beta strandi164 – 168Combined sources5
Beta strandi170 – 172Combined sources3
Helixi175 – 180Combined sources6
Turni181 – 183Combined sources3
Beta strandi185 – 194Combined sources10
Helixi212 – 214Combined sources3
Beta strandi217 – 223Combined sources7
Helixi229 – 247Combined sources19
Beta strandi250 – 255Combined sources6
Helixi258 – 260Combined sources3
Helixi273 – 284Combined sources12
Beta strandi290 – 293Combined sources4
Helixi300 – 314Combined sources15
Helixi329 – 332Combined sources4
Turni333 – 335Combined sources3
Beta strandi337 – 339Combined sources3
Helixi352 – 367Combined sources16

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

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

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

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: July 18, 2018
This is version 198 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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  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. SIMILARITY comments
    Index of protein domains and families

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