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O88895 (HDAC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 3

Short name=HD3
EC=3.5.1.98
Gene names
Name:Hdac3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length424 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.11

Catalytic activity

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Subunit structure

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. Interact with SMRT/NCOR2 and BCL6 on DNA enhancer elements. Interacts with INSM1. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Nucleus By similarity Ref.9.

Post-translational modification

Sumoylated in vitro. Ref.9

Sequence similarities

Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin modification

Traceable author statement PubMed 12711221. Source: UniProtKB

circadian regulation of gene expression

Inferred from genetic interaction PubMed 19037247. Source: MGI

histone deacetylation

Inferred from mutant phenotype PubMed 15832170. Source: MGI

negative regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of mitotic cell cycle

Inferred from direct assay PubMed 10542131. Source: MGI

regulation of multicellular organism growth

Inferred from genetic interaction PubMed 19037247. Source: MGI

spindle assembly

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Traceable author statement PubMed 12711221. Source: UniProtKB

histone deacetylase complex

Traceable author statement PubMed 12711221. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Traceable author statement PubMed 12711221. Source: UniProtKB

spindle microtubule

Inferred from electronic annotation. Source: Ensembl

transcriptional repressor complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay PubMed 14980219PubMed 15681609. Source: MGI

NAD-dependent histone deacetylase activity (H3-K14 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K18 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

chromatin DNA binding

Inferred from direct assay PubMed 18458156. Source: MGI

chromatin binding

Inferred from direct assay PubMed 15832170. Source: MGI

histone deacetylase activity

Traceable author statement PubMed 12711221. Source: UniProtKB

transcription corepressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

transcription factor binding

Traceable author statement PubMed 12711221. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

NfkbiaQ9Z1E32EBI-302263,EBI-644427

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: O88895-1)

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.
Isoform Short (identifier: O88895-2)

The sequence of this isoform differs from the canonical sequence as follows:
     69-259: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 424424Histone deacetylase 3
PRO_0000114697

Regions

Region3 – 316314Histone deacetylase

Sites

Active site1351 By similarity

Amino acid modifications

Modified residue4241Phosphoserine By similarity
Cross-link44Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence69 – 259191Missing in isoform Short.
VSP_002080

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: B0C3BB2C5CD95E0E

FASTA42448,364
        10         20         30         40         50         60 
MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP YQASQHDMCR 

        70         80         90        100        110        120 
FHSEDYIDFL QRVSPTNMQG FTKSLNAFNV GDDCPVFPGL FEFCSRYTGA SLQGATQLNN 

       130        140        150        160        170        180 
KICDIAINWA GGLHHAKKFE ASGFCYVNDI VIGILELLKY HPRVLYIDID IHHGDGVQEA 

       190        200        210        220        230        240 
FYLTDRVMTV SFHKYGNYFF PGTGDMYEVG AESGRYYCLN VPLRDGIDDQ SYKHLFQPVI 

       250        260        270        280        290        300 
SQVVDFYQPT CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV 

       310        320        330        340        350        360 
RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN SRQYLDQIRQ 

       370        380        390        400        410        420 
TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP EENYSRPEAP NEFYDGDHDN 


DKES 

« Hide

Isoform Short [UniParc].

Checksum: 4052A9AF341E3A66
Show »

FASTA23326,906

References

[1]"Cloning and characterization of the murine histone deacetylase (HDAC3)."
Mahlknecht U., Hoelzer D., Bucala R., Verdin E.
Biochem. Biophys. Res. Commun. 263:482-490(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
Strain: C3H and C57BL/6J.
[2]"Identification of a nuclear domain with deacetylase activity."
Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.
Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC7.
[3]"Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor."
Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.
J. Biol. Chem. 276:35-39(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC9.
[4]"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain."
Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W.
Mol. Cell. Biol. 21:6470-6483(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[5]"Tissue-specific regulation of retinal and pituitary precursor cell proliferation."
Li X., Perissi V., Liu F., Rose D.W., Rosenfeld M.G.
Science 297:1180-1183(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DACH1.
[6]"Histone deacetylase 9 couples neuronal activity to muscle chromatin acetylation and gene expression."
Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., Schaeffer L.
Nat. Neurosci. 8:313-321(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC9.
[7]"Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses transcription through interaction with C-terminal binding protein 1 (CtBP1)."
Kim S.-C., Kim Y.-S., Jetten A.M.
Nucleic Acids Res. 33:6805-6815(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GLIS2.
[8]"PRISM/PRDM6, a transcriptional repressor that promotes the proliferative gene program in smooth muscle cells."
Davis C.A., Haberland M., Arnold M.A., Sutherland L.B., McDonald O.G., Richardson J.A., Childs G., Harris S., Owens G.K., Olson E.N.
Mol. Cell. Biol. 26:2626-2636(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PRDM6.
[9]"HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a novel deacetylase activity-independent function of HDAC3."
Gupta P., Ho P.C., Ha S.G., Lin Y.W., Wei L.N.
PLoS ONE 4:E4363-E4363(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION, INTERACTION WITH HDAC3, SUBCELLULAR LOCATION.
[10]"Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor essential for spermiogenesis and male fertility."
Yan W., Si Y., Slaymaker S., Li J., Zheng H., Young D.L., Aslanian A., Saunders L., Verdin E., Charo I.F.
J. Biol. Chem. 285:31418-31426(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZMYND15.
[11]"A hybrid mechanism of action for BCL6 in B cells defined by formation of functionally distinct complexes at enhancers and promoters."
Hatzi K., Jiang Y., Huang C., Garrett-Bakelman F., Gearhart M.D., Giannopoulou E.G., Zumbo P., Kirouac K., Bhaskara S., Polo J.M., Kormaksson M., Mackerell A.D. Jr., Xue F., Mason C.E., Hiebert S.W., Prive G.G., Cerchietti L., Bardwell V.J., Elemento O., Melnick A.
Cell Rep. 4:578-588(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DEACETYLATION OF H3K27.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF074881 mRNA. Translation: AAC36305.1.
AF074882 mRNA. Translation: AAC36306.1.
AF079310, AF079309 Genomic DNA. Translation: AAC67258.1.
PIRJC7102.
UniGeneMm.20521.

3D structure databases

ProteinModelPortalO88895.
SMRO88895. Positions 2-370.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-32547N.
IntActO88895. 8 interactions.
MINTMINT-4302141.

Chemistry

BindingDBO88895.

PTM databases

PhosphoSiteO88895.

Proteomic databases

PaxDbO88895.
PRIDEO88895.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1343091. Hdac3.

Phylogenomic databases

eggNOGCOG0123.
HOGENOMHOG000185805.
HOVERGENHBG057112.
InParanoidO88895.

Enzyme and pathway databases

ReactomeREACT_188576. Developmental Biology.
REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.

Gene expression databases

ArrayExpressO88895.
BgeeO88895.
CleanExMM_HDAC3.
GenevestigatorO88895.

Family and domain databases

Gene3D3.40.800.20. 1 hit.
InterProIPR000286. His_deacetylse.
IPR003084. His_deacetylse_1.
IPR023801. His_deacetylse_dom.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037913. His_deacetylse_1. 1 hit.
PRINTSPR01270. HDASUPER.
PR01271. HISDACETLASE.
ProtoNetSearch...

Other

ChiTaRSHDAC3. mouse.
PROO88895.
SOURCESearch...

Entry information

Entry nameHDAC3_MOUSE
AccessionPrimary (citable) accession number: O88895
Secondary accession number(s): O88896
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: April 16, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot