O88895 (HDAC3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 3
Short name=HD3
EC=3.5.1.98

Gene names

Name:

Hdac3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	424 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Required to repress transcription of the POU1F1 transcription factor By similarity. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation.
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with HDAC7 and HDAC9. Forms a heterologous complex at least with YY1. Interacts with HDAC10, DAXX 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 and NKAP. Component of the Notch corepressor complex By similarity. Interacts with GLIS2. Interacts with CBFA2T3. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Interacts with and deacetylates MAPK14 By similarity. Interacts with ZMYND15. 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 process	Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	circadian regulation of gene expression Inferred from genetic interaction PubMed 19037247. Source: MGI histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC negative regulation of JNK cascade Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara 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: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Traceable author statement PubMed 12711221. Source: UniProtKB histone deacetylase complex Traceable author statement PubMed 12711221. Source: UniProtKB spindle microtubule Inferred from electronic annotation. Source: Compara transcriptional repressor complex Inferred from electronic annotation. Source: Compara
Molecular_function	NAD-dependent histone deacetylase activity (H3-K14 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K18 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H3-K9 specific) Inferred from electronic annotation. Source: EC NAD-dependent histone deacetylase activity (H4-K16 specific) Inferred from electronic annotation. Source: EC chromatin DNA binding Inferred from direct assay PubMed 18458156. Source: MGI histone deacetylase activity Traceable author statement PubMed 12711221. Source: UniProtKB transcription corepressor activity Inferred from electronic annotation. Source: Compara transcription factor binding Traceable author statement PubMed 12711221. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Nfkbia	Q9Z1E3	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 424	424	Histone deacetylase 3		PRO_0000114697
Regions
	Region	3 – 316	314	Histone deacetylase
Sites
	Active site	135	1	By similarity
Amino acid modifications
	Modified residue	424	1	Phosphoserine By similarity
	Cross-link	44		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Alternative sequence	69 – 259	191	Missing in isoform Short.		VSP_002080

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified November 1, 1998. Version 1. Checksum: B0C3BB2C5CD95E0E	FASTA	424	48,364
	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
	Isoform Short [UniParc]. Checksum: 4052A9AF341E3A66	FASTA	233	26,906
	10 20 30 40 50 60 MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP YQASQHDMCR 70 80 90 100 110 120 FHSEDYIDSL GCDRLGCFNL SIRGHGECVE YVKSFNIPLL VLGGGGYTVR NVARCWTYET 130 140 150 160 170 180 SLLVEEAISE ELPYSEYFEY FAPDFTLHPD VSTRIENQNS RQYLDQIRQT IFENLKMLNH 190 200 210 220 230 APSVQIHDVP ADLLTYDRTD EADAEERGPE ENYSRPEAPN EFYDGDHDND KES

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.
+	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.
IPI	IPI00135456. IPI00228758.
PIR	JC7102.
UniGene	Mm.20521.
3D structure databases
ProteinModelPortal	O88895.
SMR	O88895. Positions 2-370.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-32547N.
IntAct	O88895. 5 interactions.
MINT	MINT-4302141.
PTM databases
PhosphoSite	O88895.
Proteomic databases
PaxDb	O88895.
PRIDE	O88895.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:1343091. Hdac3.
Phylogenomic databases
eggNOG	COG0123.
HOGENOM	HOG000185805.
HOVERGEN	HBG057112.
InParanoid	O88895.
OrthoDB	EOG4MGS79.
Enzyme and pathway databases
Reactome	REACT_127416. Developmental Biology. REACT_27166. Transcriptional Regulation of Adipocyte Differentiation in 3T3-L1 Pre-adipocytes.
Gene expression databases
ArrayExpress	O88895.
Bgee	O88895.
CleanEx	MM_HDAC3.
Genevestigator	O88895.
GermOnline	ENSMUSG00000024454. Mus musculus.
Family and domain databases
Gene3D	3.40.800.20. 1 hit.
InterPro	IPR000286. His_deacetylse. IPR003084. His_deacetylse_1. IPR023801. His_deacetylse_dom. [Graphical view]
PANTHER	PTHR10625. PTHR10625. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037913. His_deacetylse_1. 1 hit.
PRINTS	PR01270. HDASUPER. PR01271. HISDACETLASE.
ProtoNet	Search...
Other
BindingDB	O88895.
ChEMBL	CHEMBL5142.
ChiTaRS	HDAC3. mouse.
SOURCE	Search...

Entry information

Entry name

HDAC3_MOUSE

Accession

Primary (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 3, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program