Q9Z2V6 (HDAC5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 5
Short name=HD5
EC=3.5.1.98

Alternative name(s):
Histone deacetylase mHDA1

Gene names

Name:

Hdac5

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	1113 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). 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. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors By similarity.
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with BAHD1 and KDM5B By similarity. Interacts with BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2, AHRR, and a 14-3-3 chaperone protein. Interacts with MYOCD. Interacts with GRK5 By similarity. Interacts with DDIT3/CHOP By similarity. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10
Subcellular location	Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-250 and Ser-488 by AMPK, CaMK1 and SIK1. Ref.8 Ref.11
Domain	The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
Post-translational modification	Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-250 and Ser-488. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import By similarity. Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Ref.8 Ref.10 Ref.11 Ubiquitinated. Polyubiquitination however does not lead to its degradation By similarity.
Sequence similarities	Belongs to the histone deacetylase family. HD type 2 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell differentiation Traceable author statement PubMed 12711221. Source: UniProtKB cellular response to fluid shear stress Inferred from direct assay PubMed 20181743. Source: UniProtKB heart development Inferred from genetic interaction PubMed 15367668. Source: MGI histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC inflammatory response Traceable author statement PubMed 12711221. Source: UniProtKB negative regulation of osteoblast differentiation Inferred from mutant phenotype PubMed 15990875. Source: MGI negative regulation of striated muscle tissue development Traceable author statement PubMed 12711221. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.2. Source: MGI nervous system development Traceable author statement PubMed 12711221. Source: UniProtKB osteoblast development Inferred from mutant phenotype PubMed 15990875. Source: MGI positive regulation of neural precursor cell proliferation Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL positive regulation of stem cell proliferation Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL regulation of myotube differentiation Inferred from direct assay Ref.8. Source: UniProtKB renal tubule morphogenesis Inferred from mutant phenotype PubMed 20181743. Source: UniProtKB response to cocaine Inferred from direct assay PubMed 17988634. Source: MGI
Cellular_component	cytosol Inferred from direct assay PubMed 18198354PubMed 18332106. Source: MGI histone deacetylase complex Traceable author statement PubMed 12711221. Source: UniProtKB nuclear body Inferred from direct assay PubMed 11641275. Source: MGI
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 RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from mutant phenotype PubMed 20181743. Source: UniProtKB core promoter sequence-specific DNA binding Inferred from direct assay PubMed 20181743. Source: UniProtKB histone deacetylase activity Traceable author statement PubMed 12711221. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW transcription corepressor activity Inferred from direct assay Ref.2. Source: MGI transcription factor binding Traceable author statement PubMed 12711221. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1113	1113	Histone deacetylase 5		PRO_0000114702
Regions
	Region	675 – 1019	345	Histone deacetylase
	Motif	1072 – 1113	42	Nuclear export signal By similarity
	Compositional bias	47 – 52	6	Poly-Gly
	Compositional bias	85 – 92	8	Poly-Gln
	Compositional bias	577 – 588	12	Poly-Glu
Sites
	Active site	824	1	By similarity
	Metal binding	687	1	Zinc By similarity
	Metal binding	689	1	Zinc By similarity
	Metal binding	695	1	Zinc By similarity
	Metal binding	772	1	Zinc By similarity
Amino acid modifications
	Modified residue	250	1	Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1 Ref.8 Ref.11
	Modified residue	283	1	Phosphothreonine; by PKC By similarity
	Modified residue	488	1	Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1 Ref.8 Ref.11
	Modified residue	523	1	N6-acetyllysine By similarity
	Modified residue	650	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	250	1	S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-488. Ref.8 Ref.11
	Mutagenesis	488	1	S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-250. Ref.8 Ref.11
	Mutagenesis	824	1	H → A: Abolishes deacetylase activity. Ref.3
	Mutagenesis	884	1	H → F: Disrupts the dot-like nuclear pattern. Ref.3
	Sequence conflict	7	1	S → SA in AAF31418. Ref.2
	Sequence conflict	18	1	G → E in AAF31418. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Z2V6 [UniParc]. Last modified May 1, 2000. Version 2. Checksum: 63071AF45B87815A	FASTA	1,113	120,942
	10 20 30 40 50 60 MNSPNESDGM SGREPSLGIL PRTPLHSIPV AVEVKPVLPG AMPSSMGGGG GGSPSPVELR 70 80 90 100 110 120 GALAGPMDPA LREQQLQQEL LVLKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ 130 140 150 160 170 180 QEMLAAKRQQ ELEQQRQREQ QRQEELEKQR LEQQLLILRN KEKSKESAIA STEVKLRLQE 190 200 210 220 230 240 FLLSKSKEPT PGGLNHSLPQ HPKCWGAHHA SLDQSSPPQS GPPGTPPSYK LPLLGPYDSR 250 260 270 280 290 300 DDFPLRKTAS EPNLKVRSRL KQKVAERRSS PLLRRKDGTV ISTFKKRAVE ITGTGPGVSS 310 320 330 340 350 360 VCNSAPGSGP SSPNSSHSTI AENGFTGSVP NIPTEMIPQH RALPLDSSPN QFSLYTSPSL 370 380 390 400 410 420 PNISLGLQAT VTVTNSHLTA SPKLSTQQEA ERQALQSLRQ GGTLTGKFMS TSSIPGCLLG 430 440 450 460 470 480 VALEGDTSPH GHASLLQHVC SWTGRQQSTL IAVPLHGQSP LVTGERVATS MRTVGKLPRH 490 500 510 520 530 540 RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQMQ LGKILTKTGE LSRQPTTHPE 550 560 570 580 590 600 ETEEELTEQQ EALLGEGALT IPREGSTESE STQEDLEEEE EEEEEEEEDC IQVKDEDGES 610 620 630 640 650 660 GPDEGPDLEE SSAGYKKLFA DAQQLQPLQV YQAPLSLATV PHQALGRTQS SPAAPGSMKS 670 680 690 700 710 720 PTDQPTVVKH LFTTGVVYDT FMLKHQCMCG NTHVHPEHAG RIQSIWSRLQ ETGLLGKCER 730 740 750 760 770 780 IRGRKATLDE IQTVHSEYHT LLYGTSPLNR QKLDSKKLLG PISQKMYAML PCGGIGVDSD 790 800 810 820 830 840 TVWNEMHSSS AVRMAVGCLV ELAFKVAAGE LKNGFAIIRP PGHHAEESTA MGFCFFNSVA 850 860 870 880 890 900 ITAKLLQQKL SVGKVLIVDW DIHHGNGTQQ AFYNDPSVLY ISLHRYDNGN FFPGSGAPEE 910 920 930 940 950 960 VGGGPGVGYN VNVAWTGGVD PPIGDVEYLT AFRTVVMPIA QEFSPDVVLV SAGFDAVEGH 970 980 990 1000 1010 1020 LSPLGGYSVT ARCFGHLTRQ LMTLAGGRVV LALEGGHDLT AICDASEACV SALLSVELQP 1030 1040 1050 1060 1070 1080 LDEAVLQQKP SVNAVATLEK VIEIQSKHWS CVQRFAAGLG CSLREAQTGE KEEAETVSAM 1090 1100 1110 ALLSVGAEQA QAVATQEHSP RPAEEPMEQE PAL

References

[1]	"Identification of a new family of higher eukaryotic histone deacetylases. Coordinate expression of differentiation-dependent chromatin modifiers." Verdel A., Khochbin S. J. Biol. Chem. 274:2440-2445(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J. Tissue: Fetus.
[2]	"Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression." Kao H.-Y., Downes M., Ordentlich P., Evans R.M. Genes Dev. 14:55-66(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH NCOR2. Strain: C57BL/6.
[3]	"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, NUCLEAR EXPORT, MUTAGENESIS OF HIS-824 AND HIS-884.
[4]	"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 CTBP1 AND HDAC9.
[5]	"Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases." Kurtev V., Margueron R., Kroboth K., Ogris E., Cavailles V., Seiser C. J. Biol. Chem. 279:24834-24843(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PHB2.
[6]	"Multiple domains of the receptor-interacting protein 140 contribute to transcription inhibition." Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., Vignon F., Khochbin S., Jalaguier S., Cavailles V. Nucleic Acids Res. 32:1957-1966(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH NRIP1.
[7]	"Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin." Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A., Wang D.Z., Olson E.N. Mol. Cell. Biol. 25:364-376(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MYOCD.
[8]	"SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes." Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T., Shelton G.D., Montminy M. Nat. Med. 13:597-603(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-250 AND SER-488, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-250 AND SER-488.
[9]	"Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5." Oshima M., Mimura J., Yamamoto M., Fujii-Kuriyama Y. Biochem. Biophys. Res. Commun. 364:276-282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH AHRR.
[10]	"Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes." Martini J.S., Raake P., Vinge L.E., DeGeorge B.R. Jr., Chuprun J.K., Harris D.M., Gao E., Eckhart A.D., Pitcher J.A., Koch W.J. Proc. Natl. Acad. Sci. U.S.A. 105:12457-12462(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GRK5, PHOSPHORYLATION.
[11]	"AMP-activated protein kinase regulates beta-catenin transcription via histone deacetylase 5." Zhao J.X., Yue W.F., Zhu M.J., Du M. J. Biol. Chem. 286:16426-16434(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-250 AND SER-488, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-250 AND SER-488.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF006602 mRNA. Translation: AAD09834.2. AF207748 mRNA. Translation: AAF31418.1.
IPI	IPI00816951.
UniGene	Mm.22665.
3D structure databases
ProteinModelPortal	Q9Z2V6.
SMR	Q9Z2V6. Positions 68-132, 672-1072.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40855N.
IntAct	Q9Z2V6. 1 interaction.
PTM databases
PhosphoSite	Q9Z2V6.
Proteomic databases
PaxDb	Q9Z2V6.
PRIDE	Q9Z2V6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
MGI	MGI:1333784. Hdac5.
Phylogenomic databases
eggNOG	COG0123.
HOVERGEN	HBG057100.
OrthoDB	EOG4DR9BQ.
Gene expression databases
CleanEx	MM_HDAC5.
Genevestigator	Q9Z2V6.
GermOnline	ENSMUSG00000008855. Mus musculus.
Family and domain databases
Gene3D	3.40.800.20. 1 hit.
InterPro	IPR000286. His_deacetylse. IPR023801. His_deacetylse_dom. IPR024643. Hist_deacetylase_Gln_rich_N. IPR017320. Histone_deAcase_II_euk. [Graphical view]
PANTHER	PTHR10625. PTHR10625. 1 hit.
Pfam	PF12203. HDAC4_Gln. 1 hit. PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037911. HDAC_II_euk. 1 hit.
PRINTS	PR01270. HDASUPER.
ProtoNet	Search...
Other
BindingDB	Q9Z2V6.
ChEMBL	CHEMBL2768.
ChiTaRS	HDAC5. mouse.
SOURCE	Search...

Entry information

Entry name

HDAC5_MOUSE

Accession

Primary (citable) accession number: Q9Z2V6
Secondary accession number(s): Q9JL73

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	April 3, 2013
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program