Reviewed, UniProtKB/Swiss-Prot Q9UQL6 (HDAC5_HUMAN)

Names and origin

Protein names

Recommended name:
    Histone deacetylase 5
      Short name=HD5
    EC=3.5.1.98
Alternative name(s):
    Antigen NY-CO-9

Gene names

Name:	HDAC5
Synonyms:	KIAA0600

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1122 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.
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with AHRR By similarity. Interacts with BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with KDM5B.
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-259 and Ser-498 by CaMK. Ref.8
Tissue specificity	Ubiquitous.
Domain	The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm By similarity.
Post-translational modification	Phosphorylated by CaMK at Ser-259 and Ser-498. The phosphorylation is required for the export to the cytoplasm. Ref.8 Ref.9 Ubiquitinated. Polyubiquitination however does not lead to its degradation. Ref.11
Sequence similarities	Belongs to the histone deacetylase family. Type 2 subfamily.
Sequence caution	The sequence AAC18040.1 differs from that shown. Reason: Frameshift at position 1085.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	B cell differentiation Traceable author statement. Source: UniProtKB chromatin remodeling Ref.1 Traceable author statement. Source: ProtInc chromatin silencing Traceable author statement. Source: ProtInc inflammatory response Traceable author statement. Source: UniProtKB negative regulation of striated muscle 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
Molecular function	histone deacetylase activity Ref.1 Traceable author statement. Source: UniProtKB specific transcriptional repressor activity Traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRMS1	Q9HCU9	2	EBI-715576,EBI-714781
HDAC3	O15379	1	EBI-715576,EBI-607682
HIST1H4A	P62805	1	EBI-715576,EBI-302023

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9UQL6-1)

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 2 (identifier: Q9UQL6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     684-768: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1122	1122	Histone deacetylase 5		PRO_0000114701
Regions
	Region	684 – 1028	345	Histone deacetylase
	Motif	1081 – 1122	42	Nuclear export signal
	Compositional bias	47 – 52	6	Poly-Gly
	Compositional bias	85 – 92	8	Poly-Gln
	Compositional bias	596 – 599	4	Poly-Glu
	Compositional bias	1099 – 1104	6	Poly-Ala
Sites
	Active site	833	1	By similarity
Amino acid modifications
	Modified residue	259	1	Phosphoserine; by CaMK Ref.9
	Modified residue	498	1	Phosphoserine; by CaMK Ref.9
Natural variations
	Alternative sequence	684 – 768	85	Missing in isoform 2.		VSP_002081
	Natural variant	137	1	R → Q: dbSNP rs438096.		VAR_055903
	Natural variant	565	1	G → A: dbSNP rs33916560.		VAR_055904
Experimental info
	Mutagenesis	259	1	S → A: Reduces CaMK-dependent phosphorylation and the subsequent nuclear export. Abolishes nuclear export; when associated with A-498. Ref.8
	Mutagenesis	279	1	S → A: No effect. Ref.8
	Mutagenesis	498	1	S → A: Reduces CaMK-dependent phosphorylation and the subsequent nuclear export. Abolishes nuclear export; when associated with A-259. Ref.8
	Mutagenesis	661	1	S → A: No effect. Ref.8
	Mutagenesis	713	1	S → A: No effect. Ref.8
	Mutagenesis	1086	1	V → A: Reduces CaMK-dependent nuclear export. Ref.10
	Mutagenesis	1092	1	L → A: Reduces CaMK-dependent nuclear export. Ref.10
	Sequence conflict	593	1	E → D in BAA25526. Ref.2
	Sequence conflict	671	1	S → N Ref.5
	Sequence conflict	684	1	G → S Ref.5
	Sequence conflict	1026	1	E → K Ref.5
	Sequence conflict	1074	1	E → G Ref.5
	Sequence conflict	1093	1	S → L Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: CF4BBB8B9A288FEC	FASTA	1,122	121,992
	10 20 30 40 50 60 MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR 70 80 90 100 110 120 GALVGSVDPT LREQQLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ 130 140 150 160 170 180 QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS 190 200 210 220 230 240 TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL 250 260 270 280 290 300 PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI 310 320 330 340 350 360 TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSPNQ 370 380 390 400 410 420 FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST 430 440 450 460 470 480 SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS 490 500 510 520 530 540 MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE 550 560 570 580 590 600 LPRQPTTHPE ETEEELTEQQ EVLLGEGALT MPREGSTESE STQEDLEEED EEEDGEEEED 610 620 630 640 650 660 CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ 670 680 690 700 710 720 SSPAAPGGMK SPPDQPVKHL FTTGVVYDTF MLKHQCMCGN THVHPEHAGR IQSIWSRLQE 730 740 750 760 770 780 TGLLSKCERI RGRKATLDEI QTVHSEYHTL LYGTSPLNRQ KLDSKKLLGP ISQKMYAVLP 790 800 810 820 830 840 CGGIGVDSDT VWNEMHSSSA VRMAVGCLLE LAFKVAAGEL KNGFAIIRPP GHHAEESTAM 850 860 870 880 890 900 GFCFFNSVAI TAKLLQQKLN VGKVLIVDWD IHHGNGTQQA FYNDPSVLYI SLHRYDNGNF 910 920 930 940 950 960 FPGSGAPEEV GGGPGVGYNV NVAWTGGVDP PIGDVEYLTA FRTVVMPIAH EFSPDVVLVS 970 980 990 1000 1010 1020 AGFDAVEGHL SPLGGYSVTA RCFGHLTRQL MTLAGGRVVL ALEGGHDLTA ICDASEACVS 1030 1040 1050 1060 1070 1080 ALLSVELQPL DEAVLQQKPN INAVATLEKV IEIQSKHWSC VQKFAAGLGR SLREAQAGET 1090 1100 1110 1120 EEAETVSAMA LLSVGAEQAQ AAAAREHSPR PAEEPMEQEP AL
	Isoform 2. Checksum: 5EC4148BF869A479	FASTA	1,037	112,205
	10 20 30 40 50 60 MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR 70 80 90 100 110 120 GALVGSVDPT LREQQLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ 130 140 150 160 170 180 QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS 190 200 210 220 230 240 TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL 250 260 270 280 290 300 PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI 310 320 330 340 350 360 TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSPNQ 370 380 390 400 410 420 FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST 430 440 450 460 470 480 SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS 490 500 510 520 530 540 MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE 550 560 570 580 590 600 LPRQPTTHPE ETEEELTEQQ EVLLGEGALT MPREGSTESE STQEDLEEED EEEDGEEEED 610 620 630 640 650 660 CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ 670 680 690 700 710 720 SSPAAPGGMK SPPDQPVKHL FTTGPISQKM YAVLPCGGIG VDSDTVWNEM HSSSAVRMAV 730 740 750 760 770 780 GCLLELAFKV AAGELKNGFA IIRPPGHHAE ESTAMGFCFF NSVAITAKLL QQKLNVGKVL 790 800 810 820 830 840 IVDWDIHHGN GTQQAFYNDP SVLYISLHRY DNGNFFPGSG APEEVGGGPG VGYNVNVAWT 850 860 870 880 890 900 GGVDPPIGDV EYLTAFRTVV MPIAHEFSPD VVLVSAGFDA VEGHLSPLGG YSVTARCFGH 910 920 930 940 950 960 LTRQLMTLAG GRVVLALEGG HDLTAICDAS EACVSALLSV ELQPLDEAVL QQKPNINAVA 970 980 990 1000 1010 1020 TLEKVIEIQS KHWSCVQKFA AGLGRSLREA QAGETEEAET VSAMALLSVG AEQAQAAAAR 1030 EHSPRPAEEP MEQEPAL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Three proteins define a class of human histone deacetylases related to yeast Hda1p." Grozinger C.M., Hassig C.A., Schreiber S.L. Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999) [PubMed: 10220385] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed: 12168954] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Eye and Testis.
[5]	"Characterization of human colon cancer antigens recognized by autologous antibodies." Scanlan M.J., Chen Y.-T., Williamson B., Gure A.O., Stockert E., Gordan J.D., Tuereci O., Sahin U., Pfreundschuh M., Old L.J. Int. J. Cancer 76:652-658(1998) [PubMed: 9610721] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 189-1122 (ISOFORM 1). Tissue: Colon carcinoma.
[6]	"Chromosomal organization and localization of the human histone deacetylase 5 gene (HDAC5)." Mahlknecht U., Schnittger S., Ottmann O.G., Schoch C., Mosebach M., Hiddemann W., Hoelzer D. Biochim. Biophys. Acta 1493:342-348(2000) [PubMed: 11018260] [Abstract] Cited for: GENE ORGANIZATION.
[7]	"BCoR, a novel corepressor involved in BCL-6 repression." Huynh K.D., Fischle W., Verdin E., Bardwell V.J. Genes Dev. 14:1810-1823(2000) [PubMed: 10898795] [Abstract] Cited for: INTERACTION WITH BCOR.
[8]	"Signal-dependent nuclear export of a histone deacetylase regulates muscle differentiation." McKinsey T.A., Zhang C.-L., Lu J., Olson E.N. Nature 408:106-111(2000) [PubMed: 11081517] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-259; SER-279; SER-498; SER-661 AND SER-713.
[9]	"Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5." McKinsey T.A., Zhang C.-L., Olson E.N. Proc. Natl. Acad. Sci. U.S.A. 97:14400-14405(2000) [PubMed: 11114197] [Abstract] Cited for: INTERACTION WITH 14-3-3, PHOSPHORYLATION AT SER-259 AND SER-498.
[10]	"Identification of a signal-responsive nuclear export sequence in class II histone deacetylases." McKinsey T.A., Zhang C.-L., Olson E.N. Mol. Cell. Biol. 21:6312-6321(2001) [PubMed: 11509672] [Abstract] Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF VAL-1086 AND LEU-1092.
[11]	"Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes." Hook S.S., Orian A., Cowley S.M., Eisenman R.N. Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002) [PubMed: 12354939] [Abstract] Cited for: UBIQUITINATION.
[12]	"Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases." Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., Freemont P., Taylor-Papadimitriou J. Int. J. Cancer 121:265-275(2007) [PubMed: 17373667] [Abstract] Cited for: INTERACTION WITH KDM5B.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF132608 mRNA. Translation: AAD29047.1. AB011172 mRNA. Translation: BAA25526.2. Different initiation. BC013140 mRNA. Translation: AAH13140.1. Different termination. BC051824 mRNA. Translation: AAH51824.1. AF039691 mRNA. Translation: AAC18040.1. Frameshift. BK000028 Genomic DNA. Translation: DAA00017.1.
IPI	IPI00217801. IPI00328289.
RefSeq	NP_001015053.1. NP_005465.2.
UniGene	Hs.438782
3D structure databases
SMR	Q9UQL6. Positions 681-1063.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UQL6. 6 interactions.
PTM databases
PhosphoSite	Q9UQL6.
Proteomic databases
PRIDE	Q9UQL6.
Genome annotation databases
Ensembl	ENSG00000108840. Homo sapiens. [Contig view]
GeneID	10014.
KEGG	hsa:10014.
Organism-specific databases
GeneCards	GC17M039509.
H-InvDB	HIX0013862.
HGNC	HGNC:14068. HDAC5.
HPA	CAB019400.
MIM	605315. gene.
PharmGKB	PA29230.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9UQL6.
HOVERGEN	Q9UQL6.
Enzyme and pathway databases
Pathway_Interaction_DB	hdac_classi_pathway. Signaling events mediated by HDAC Class I. hdac_classii_pathway. Signaling events mediated by HDAC Class II.
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9UQL6.
Bgee	Q9UQL6.
CleanEx	HS_HDAC5.
GermOnline	ENSG00000108840. Homo sapiens.
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
NextBio	37831.
SOURCE	Search...

Entry information

Entry name

HDAC5_HUMAN

Accession

Primary (citable) accession number: Q9UQL6
Secondary accession number(s): O60340, O60528, Q96DY4

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	May 1, 2000
Last modified:	June 16, 2009
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)