Reviewed, UniProtKB/Swiss-Prot Q9Z2V6 (HDAC5_MOUSE)

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)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	1113 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 KDM5B By similarity. Interacts with BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2, AHRR, and a 14-3-3 chaperone protein.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. 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 CaMK By similarity.
Domain	The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
Post-translational modification	Phosphorylated by CaMK at Ser-250 and Ser-488. The phosphorylation is required for the export to the cytoplasm By similarity. Ubiquitinated. Polyubiquitination however does not lead to its degradation By similarity.
Sequence similarities	Belongs to the histone deacetylase family. Type 2 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	B cell differentiation Traceable author statement. Source: UniProtKB chromatin modification Traceable author statement. Source: UniProtKB heart development Inferred from genetic interaction. Source: MGI inflammatory response Traceable author statement. Source: UniProtKB negative regulation of striated muscle development Traceable author statement. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Ref.2 Inferred from direct assay. Source: MGI nervous system development Traceable author statement. Source: UniProtKB transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Traceable author statement. Source: UniProtKB histone deacetylase complex Traceable author statement. Source: UniProtKB nuclear body Inferred from direct assay. Source: MGI
Molecular function	histone deacetylase activity Traceable author statement. Source: UniProtKB specific transcriptional repressor activity Traceable author statement. Source: UniProtKB transcription corepressor activity Ref.2 Inferred from direct assay. Source: MGI
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
Amino acid modifications
	Modified residue	250	1	Phosphoserine; by CaMK By similarity
	Modified residue	488	1	Phosphoserine; by CaMK By similarity
Experimental info
	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)
	Q9Z2V6-1 [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: 9891014] [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: 10640276] [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: 10984530] [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: 11022042] [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: 15140878] [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: 15060175] [Abstract] Cited for: INTERACTION WITH NRIP1.
[7]	"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: 17949687] [Abstract] Cited for: INTERACTION WITH AHRR.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF006602 mRNA. Translation: AAD09834.2. AF207748 mRNA. Translation: AAF31418.1.
IPI	IPI00816951.
UniGene	Mm.22665
3D structure databases
SMR	Q9Z2V6. Positions 672-1054.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z2V6. 1 interaction.
PTM databases
PhosphoSite	Q9Z2V6.
Genome annotation databases
Ensembl	ENSMUSG00000008855. Mus musculus. [Contig view]
Organism-specific databases
MGI	MGI:1333784. Hdac5.
Phylogenomic databases
HOVERGEN	Q9Z2V6.
Gene expression databases
ArrayExpress	Q9Z2V6.
Bgee	Q9Z2V6.
CleanEx	MM_HDAC5.
GermOnline	ENSMUSG00000008855. Mus musculus.
Family and domain databases
InterPro	IPR000286. His_deacetylse. IPR017320. Histone_deAcase_II_euk. [Graphical view]
Gene3D	G3DSA:3.40.800.20. His_deacetylse. 1 hit.
PANTHER	PTHR10625. His_deacetylse. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037911. HDAC_II_euk. 1 hit.
PRINTS	PR01270. HDASUPER.
ProtoNet	Search...
Other Resources
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:	June 16, 2009
This is version 76 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)