Q9UBN7 (HDAC6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 6
Short name=HD6
EC=3.5.1.98

Gene names

Name:	HDAC6
Synonyms:	KIAA0901
ORF Names:	JM21

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1215 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 By similarity. Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Ref.12 Ref.16 In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy. Ref.12 Ref.16
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Cofactor	Binds 3 zinc ions per subunit.
Subunit structure	Interacts with CBFA2T3, HDAC11 and SIRT2. Interacts with F-actin. Interacts with BBIP10. Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions. Interacts with CYLD. Interacts with ZMYND15 By similarity. Interacts with DDIT3/CHOP. Ref.8 Ref.9 Ref.13 Ref.15 Ref.17 Ref.18 Ref.20
Subcellular location	Nucleus. Cytoplasm. Note: It is mainly cytoplasmic, where it is associated with microtubules.
Post-translational modification	Phosphorylated by AURKA. Ref.14 Ubiquitinated. Its polyubiquitination however does not lead to its degradation. Ref.11 Sumoylated in vitro. Ref.10
Sequence similarities	Belongs to the histone deacetylase family. HD type 2 subfamily. Contains 1 UBP-type zinc finger.
Sequence caution	The sequence BAA74924.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Autophagy Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Zinc-finger
Ligand	Actin-binding Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Hsp90 deacetylation Inferred from mutant phenotype PubMed 19158084. Source: BHF-UCL aggresome assembly Inferred from mutant phenotype PubMed 14675537. Source: BHF-UCL cellular response to hydrogen peroxide Inferred from mutant phenotype PubMed 18606987. Source: BHF-UCL cellular response to misfolded protein Inferred from electronic annotation. Source: Compara cellular response to topologically incorrect protein Inferred from mutant phenotype PubMed 16192271. Source: BHF-UCL histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC lysosome localization Inferred from mutant phenotype PubMed 16192271. Source: BHF-UCL macroautophagy Inferred from mutant phenotype PubMed 16192271. Source: BHF-UCL misfolded or incompletely synthesized protein catabolic process Inferred from mutant phenotype PubMed 14675537. Source: BHF-UCL negative regulation of hydrogen peroxide metabolic process Inferred by curator PubMed 18606987. Source: BHF-UCL negative regulation of microtubule depolymerization Inferred from electronic annotation. Source: Compara negative regulation of oxidoreductase activity Inferred by curator PubMed 18606987. Source: BHF-UCL negative regulation of protein complex disassembly Inferred from mutant phenotype PubMed 15916966. Source: BHF-UCL negative regulation of proteolysis Inferred from mutant phenotype PubMed 18356165. Source: BHF-UCL negative regulation of transcription, DNA-dependent Inferred from sequence or structural similarity PubMed 11861901. Source: UniProtKB peptidyl-lysine deacetylation Inferred from mutant phenotype PubMed 18356165PubMed 18606987. Source: BHF-UCL polyubiquitinated misfolded protein transport Inferred from mutant phenotype PubMed 14675537. Source: BHF-UCL positive regulation of apoptotic process Inferred from mutant phenotype PubMed 18606987. Source: BHF-UCL positive regulation of chaperone-mediated protein complex assembly Inferred from mutant phenotype PubMed 19158084. Source: BHF-UCL positive regulation of epithelial cell migration Inferred from mutant phenotype Ref.12. Source: BHF-UCL positive regulation of receptor biosynthetic process Inferred from mutant phenotype PubMed 15916966PubMed 18316616. Source: BHF-UCL positive regulation of signal transduction Inferred from mutant phenotype PubMed 19158084. Source: BHF-UCL protein complex disassembly Inferred from electronic annotation. Source: Compara protein polyubiquitination Inferred from electronic annotation. Source: Compara regulation of androgen receptor signaling pathway Traceable author statement PubMed 18852123. Source: BHF-UCL regulation of microtubule-based movement Inferred by curator PubMed 19228685. Source: BHF-UCL regulation of receptor activity Inferred from mutant phenotype PubMed 19158084. Source: BHF-UCL response to growth factor stimulus Inferred from mutant phenotype PubMed 18356165. Source: BHF-UCL response to misfolded protein Inferred from mutant phenotype PubMed 14675537. Source: BHF-UCL response to toxin Inferred from mutant phenotype PubMed 19158084. Source: BHF-UCL transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Inferred from electronic annotation. Source: Compara
Cellular_component	aggresome Inferred from direct assay PubMed 14675537. Source: BHF-UCL caveola Inferred from direct assay PubMed 18356165. Source: BHF-UCL cell leading edge Inferred from direct assay Ref.12. Source: BHF-UCL cytoplasmic microtubule Inferred from electronic annotation. Source: Compara cytosol Inferred from sequence or structural similarity. Source: UniProtKB histone deacetylase complex Inferred from direct assay Ref.9. Source: UniProtKB microtubule Inferred from direct assay Ref.13. Source: UniProtKB microtubule associated complex Inferred from direct assay PubMed 19228685. Source: BHF-UCL perinuclear region of cytoplasm Inferred from direct assay Ref.12. Source: BHF-UCL
Molecular_function	Hsp90 protein binding Inferred from direct assay PubMed 15916966. Source: BHF-UCL 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 alpha-tubulin binding Inferred from direct assay PubMed 19228685. Source: BHF-UCL dynein complex binding Inferred from direct assay PubMed 14675537. Source: BHF-UCL enzyme binding Inferred from sequence or structural similarity PubMed 11861901. Source: UniProtKB histone deacetylase activity Inferred from direct assay Ref.1. Source: BHF-UCL microtubule binding Inferred from sequence or structural similarity. Source: UniProtKB polyubiquitin binding Inferred from direct assay PubMed 14675537. Source: BHF-UCL tau protein binding Inferred from direct assay PubMed 18636984. Source: BHF-UCL tubulin deacetylase activity Inferred from direct assay Ref.13. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ATP13A2	Q9NQ11	2	EBI-301697,EBI-6308763
BRMS1	Q9HCU9	2	EBI-301697,EBI-714781
Cdc20	Q62623	2	EBI-301697,EBI-2256532	From a different organism.
EGFR	P00533	8	EBI-301697,EBI-297353
tax	P03409	4	EBI-301697,EBI-5236464	From a different organism.

Alternative products

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

Isoform 1 (identifier: Q9UBN7-1)

Also known as: HDAC6p131;

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: Q9UBN7-2)

Also known as: HDAC6p114;

The sequence of this isoform differs from the canonical sequence as follows:
     1-152: Missing.

Note: Required for TGF-beta1-activated gene expression associated with epithelial-mesenchymal transition (EMT) in A549 cells.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1215

1215

Histone deacetylase 6

PRO_0000114703

Regions

Zinc finger

1131 – 1192

62

UBP-type

Region

87 – 404

318

Histone deacetylase 1

Region

482 – 800

319

Histone deacetylase 2

Region

1154 – 1156

3

Ubiquitin binding

Region

1182 – 1189

8

Ubiquitin binding

Sites

Active site

216

1

1

Active site

611

1

2

Metal binding

1113

1

Zinc 1

Metal binding

1115

1

Zinc 1

Metal binding

1133

1

Zinc 3

Metal binding

1136

1

Zinc 3

Metal binding

1145

1

Zinc 2

Metal binding

1148

1

Zinc 2

Metal binding

1153

1

Zinc 3

Metal binding

1160

1

Zinc 3

Metal binding

1164

1

Zinc 2

Metal binding

1170

1

Zinc 2

Metal binding

1183

1

Zinc 1

Metal binding

1186

1

Zinc 1

Amino acid modifications

Modified residue

16

1

Phosphoserine By similarity

Natural variations

Alternative sequence

1 – 152

152

Missing in isoform 2.

VSP_044576

Natural variant

994

1

T → I. Ref.1 Ref.4
Corresponds to variant rs1127346 [ dbSNP | Ensembl ].

VAR_046300

Natural variant

1200

1

N → D. Ref.7
Corresponds to variant rs151130423 [ dbSNP | Ensembl ].

VAR_068962

Experimental info

Mutagenesis

216

1

H → A: Reduces histone deacetylase activity. Ref.11

Mutagenesis

611

1

H → A: Reduces histone deacetylase activity. Ref.11

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

1215

Helix Strand Turn

Details...

Helix

1116 – 1118

3

Turn

1134 – 1136

3

Beta strand

1140 – 1145

6

Turn

1146 – 1148

3

Beta strand

1151 – 1153

3

Turn

1155 – 1158

4

Helix

1160 – 1168

9

Beta strand

1172 – 1175

4

Turn

1176 – 1178

3

Beta strand

1181 – 1183

3

Turn

1184 – 1187

4

Beta strand

1188 – 1190

3

Helix

1193 – 1195

3

Helix

1196 – 1207

12

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (HDAC6p131) [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 6F17731268A33114	FASTA	1,215	131,419
	10 20 30 40 50 60 MTSTGQDSTT TRQRRSRQNP QSPPQDSSVT SKRNIKKGAV PRSIPNLAEV KKKGKMKKLG 70 80 90 100 110 120 QAMEEDLIVG LQGMDLNLEA EALAGTGLVL DEQLNEFHCL WDDSFPEGPE RLHAIKEQLI 130 140 150 160 170 180 QEGLLDRCVS FQARFAEKEE LMLVHSLEYI DLMETTQYMN EGELRVLADT YDSVYLHPNS 190 200 210 220 230 240 YSCACLASGS VLRLVDAVLG AEIRNGMAII RPPGHHAQHS LMDGYCMFNH VAVAARYAQQ 250 260 270 280 290 300 KHRIRRVLIV DWDVHHGQGT QFTFDQDPSV LYFSIHRYEQ GRFWPHLKAS NWSTTGFGQG 310 320 330 340 350 360 QGYTINVPWN QVGMRDADYI AAFLHVLLPV ALEFQPQLVL VAAGFDALQG DPKGEMAATP 370 380 390 400 410 420 AGFAQLTHLL MGLAGGKLIL SLEGGYNLRA LAEGVSASLH TLLGDPCPML ESPGAPCRSA 430 440 450 460 470 480 QASVSCALEA LEPFWEVLVR STETVERDNM EEDNVEESEE EGPWEPPVLP ILTWPVLQSR 490 500 510 520 530 540 TGLVYDQNMM NHCNLWDSHH PEVPQRILRI MCRLEELGLA GRCLTLTPRP ATEAELLTCH 550 560 570 580 590 600 SAEYVGHLRA TEKMKTRELH RESSNFDSIY ICPSTFACAQ LATGAACRLV EAVLSGEVLN 610 620 630 640 650 660 GAAVVRPPGH HAEQDAACGF CFFNSVAVAA RHAQTISGHA LRILIVDWDV HHGNGTQHMF 670 680 690 700 710 720 EDDPSVLYVS LHRYDHGTFF PMGDEGASSQ IGRAAGTGFT VNVAWNGPRM GDADYLAAWH 730 740 750 760 770 780 RLVLPIAYEF NPELVLVSAG FDAARGDPLG GCQVSPEGYA HLTHLLMGLA SGRIILILEG 790 800 810 820 830 840 GYNLTSISES MAACTRSLLG DPPPLLTLPR PPLSGALASI TETIQVHRRY WRSLRVMKVE 850 860 870 880 890 900 DREGPSSSKL VTKKAPQPAK PRLAERMTTR EKKVLEAGMG KVTSASFGEE STPGQTNSET 910 920 930 940 950 960 AVVALTQDQP SEAATGGATL AQTISEAAIG GAMLGQTTSE EAVGGATPDQ TTSEETVGGA 970 980 990 1000 1010 1020 ILDQTTSEDA VGGATLGQTT SEEAVGGATL AQTTSEAAME GATLDQTTSE EAPGGTELIQ 1030 1040 1050 1060 1070 1080 TPLASSTDHQ TPPTSPVQGT TPQISPSTLI GSLRTLELGS ESQGASESQA PGEENLLGEA 1090 1100 1110 1120 1130 1140 AGGQDMADSM LMQGSRGLTD QAIFYAVTPL PWCPHLVAVC PIPAAGLDVT QPCGDCGTIQ 1150 1160 1170 1180 1190 1200 ENWVCLSCYQ VYCGRYINGH MLQHHGNSGH PLVLSYIDLS AWCYYCQAYV HHQALLDVKN 1210 IAHQNKFGED MPHPH
	Isoform 2 (HDAC6p114) [UniParc]. Checksum: E77E732ACF187AB7	FASTA	1,063	114,361
	10 20 30 40 50 60 METTQYMNEG ELRVLADTYD SVYLHPNSYS CACLASGSVL RLVDAVLGAE IRNGMAIIRP 70 80 90 100 110 120 PGHHAQHSLM DGYCMFNHVA VAARYAQQKH RIRRVLIVDW DVHHGQGTQF TFDQDPSVLY 130 140 150 160 170 180 FSIHRYEQGR FWPHLKASNW STTGFGQGQG YTINVPWNQV GMRDADYIAA FLHVLLPVAL 190 200 210 220 230 240 EFQPQLVLVA AGFDALQGDP KGEMAATPAG FAQLTHLLMG LAGGKLILSL EGGYNLRALA 250 260 270 280 290 300 EGVSASLHTL LGDPCPMLES PGAPCRSAQA SVSCALEALE PFWEVLVRST ETVERDNMEE 310 320 330 340 350 360 DNVEESEEEG PWEPPVLPIL TWPVLQSRTG LVYDQNMMNH CNLWDSHHPE VPQRILRIMC 370 380 390 400 410 420 RLEELGLAGR CLTLTPRPAT EAELLTCHSA EYVGHLRATE KMKTRELHRE SSNFDSIYIC 430 440 450 460 470 480 PSTFACAQLA TGAACRLVEA VLSGEVLNGA AVVRPPGHHA EQDAACGFCF FNSVAVAARH 490 500 510 520 530 540 AQTISGHALR ILIVDWDVHH GNGTQHMFED DPSVLYVSLH RYDHGTFFPM GDEGASSQIG 550 560 570 580 590 600 RAAGTGFTVN VAWNGPRMGD ADYLAAWHRL VLPIAYEFNP ELVLVSAGFD AARGDPLGGC 610 620 630 640 650 660 QVSPEGYAHL THLLMGLASG RIILILEGGY NLTSISESMA ACTRSLLGDP PPLLTLPRPP 670 680 690 700 710 720 LSGALASITE TIQVHRRYWR SLRVMKVEDR EGPSSSKLVT KKAPQPAKPR LAERMTTREK 730 740 750 760 770 780 KVLEAGMGKV TSASFGEEST PGQTNSETAV VALTQDQPSE AATGGATLAQ TISEAAIGGA 790 800 810 820 830 840 MLGQTTSEEA VGGATPDQTT SEETVGGAIL DQTTSEDAVG GATLGQTTSE EAVGGATLAQ 850 860 870 880 890 900 TTSEAAMEGA TLDQTTSEEA PGGTELIQTP LASSTDHQTP PTSPVQGTTP QISPSTLIGS 910 920 930 940 950 960 LRTLELGSES QGASESQAPG EENLLGEAAG GQDMADSMLM QGSRGLTDQA IFYAVTPLPW 970 980 990 1000 1010 1020 CPHLVAVCPI PAAGLDVTQP CGDCGTIQEN WVCLSCYQVY CGRYINGHML QHHGNSGHPL 1030 1040 1050 1060 VLSYIDLSAW CYYCQAYVHH QALLDVKNIA HQNKFGEDMP HPH

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT ILE-994.
[2]	"Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	Ohara O., Suyama M., Kikuno R., Nagase T., Ishikawa K. Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"Transcription map in Xp11.23." Strom T.M., Gutwillinger N., Nyakatura G., Hellebrand H., Drescher B., Rosenthal A., Meindl A. Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-994. Tissue: Brain.
[5]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ASP-1200. Tissue: Ovary and Placenta.
[8]	"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.
[9]	"Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family." Gao L., Cueto M.A., Asselbergs F., Atadja P. J. Biol. Chem. 277:25748-25755(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HDAC11.
[10]	"The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase." Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A. EMBO J. 21:2682-2691(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUMOYLATION.
[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] [Europe PMC] [Abstract] Cited for: UBIQUITINATION, MUTAGENESIS OF HIS-216 AND HIS-611.
[12]	"HDAC6 is a microtubule-associated deacetylase." Hubbert C., Guardiola A., Shao R., Kawaguchi Y., Ito A., Nixon A., Yoshida M., Wang X.-F., Yao T.-P. Nature 417:455-458(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[13]	"The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase." North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E. Mol. Cell 11:437-444(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SIRT2.
[14]	"HEF1-dependent Aurora A activation induces disassembly of the primary cilium." Pugacheva E.N., Jablonski S.A., Hartman T.R., Henske E.P., Golemis E.A. Cell 129:1351-1363(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION BY AURKA.
[15]	"Critical and functional regulation of CHOP (C/EBP homologous protein) through the N-terminal portion." Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H. J. Biol. Chem. 282:35687-35694(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DDIT3.
[16]	"Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to aggresomes via binding to HDAC6." Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D., Chin L.S. J. Cell Biol. 178:1025-1038(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[17]	"A BBSome subunit links ciliogenesis, microtubule stability and acetylation." Loktev A.V., Zhang Q., Beck J.S., Searby C.C., Scheetz T.E., Bazan F., Slusarski D.C., Sheffield V.C., Jackson P.K., Nachury M.V. Dev. Cell 15:854-865(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BBIP10.
[18]	"The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition." Kalveram B., Schmidtke G., Groettrup M. J. Cell Sci. 121:4079-4088(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH UBD.
[19]	"Requirement of a novel splicing variant of human histone deacetylase 6 for TGF-beta1-mediated gene activation." Zhuang Y., Nguyen H.T., Lasky J.A., Cao S., Li C., Hu J., Guo X., Burow M.E., Shan B. Biochem. Biophys. Res. Commun. 392:608-613(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2).
[20]	"CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin." Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R. EMBO J. 29:131-144(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CYLD.
[21]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]	"Crystal structure of human HDAC6 zinc finger domain." Structural genomics consortium (SGC) Submitted (FEB-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH ZINC IONS.
[23]	"Crystal structure of human HDAC6 zinc finger domain and ubiquitin C-terminal peptide RLRGG." Structural genomics consortium (SGC) Submitted (APR-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH ZINC IONS AND UBIQUITIN C-TERMINAL PEPTIDE RLRGG.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF132609 mRNA. Translation: AAD29048.1.
AB020708 mRNA. Translation: BAA74924.2. Different initiation.
AJ011972 mRNA. Translation: CAA09893.1.
AF196971 Genomic DNA. No translation available.
CH471224 Genomic DNA. Translation: EAW50748.1.
BC013737 mRNA. Translation: AAH13737.1.
BC069243 mRNA. Translation: AAH69243.1.

IPI

IPI00005711.
IPI00940882.

RefSeq

NP_006035.2. NM_006044.2.

UniGene

Hs.6764.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C5K	X-ray	1.55	A	1109-1215	[»]
3GV4	X-ray	1.72	A	1109-1215	[»]
3PHD	X-ray	3.00	A/B/C/D	1109-1215	[»]

ProteinModelPortal

Q9UBN7.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-27544N.

IntAct

Q9UBN7. 20 interactions.

MINT

MINT-238367.

STRING

9606.ENSP00000334061.

PTM databases

PhosphoSite

Q9UBN7.

Polymorphism databases

DMDM

205371758.

Proteomic databases

PaxDb

Q9UBN7.

PRIDE

Q9UBN7.

Protocols and materials databases

DNASU

10013.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000334136; ENSP00000334061; ENSG00000094631.
ENST00000376619; ENSP00000365804; ENSG00000094631.
ENST00000595349; ENSP00000470544; ENSG00000269101.
ENST00000597097; ENSP00000471818; ENSG00000269101.

GeneID

10013.

KEGG

hsa:10013.

UCSC

uc004dks.1. human.

Organism-specific databases

CTD

10013.

GeneCards

GC0XP048659.

H-InvDB

HIX0016783.

HGNC

HGNC:14064. HDAC6.

HPA

CAB004236.
HPA003714.
HPA026321.

MIM

300272. gene.

neXtProt

NX_Q9UBN7.

Orphanet

163966. X-linked dominant chondrodysplasia, Chassaing-Lacombe type.

PharmGKB

PA29231.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0123.

HOGENOM

HOG000004769.

HOVERGEN

HBG051894.

InParanoid

Q9UBN7.

KO

K11407.

OrthoDB

EOG40P464.

PhylomeDB

Q9UBN7.

Enzyme and pathway databases

BRENDA

3.5.1.98. 2681.

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_111102. Signal Transduction.

SABIO-RK

Q9UBN7.

Gene expression databases

ArrayExpress

Q9UBN7.

Bgee

Q9UBN7.

CleanEx

HS_HDAC6.

Genevestigator

Q9UBN7.

GermOnline

ENSG00000094631. Homo sapiens.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.
3.40.800.20. 2 hits.

InterPro

IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]

PANTHER

PTHR10625. PTHR10625. 1 hit.

Pfam

PF00850. Hist_deacetyl. 2 hits.
PF02148. zf-UBP. 1 hit.
[Graphical view]

PRINTS

PR01270. HDASUPER.

SMART

SM00290. ZnF_UBP. 1 hit.
[Graphical view]

PROSITE

PS50271. ZF_UBP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9UBN7.

ChEMBL

CHEMBL1865.

ChiTaRS

HDAC6. human.

DrugBank

DB02546. Vorinostat.

EvolutionaryTrace

Q9UBN7.

GenomeRNAi

10013.

NextBio

37827.

SOURCE

Search...

Entry information

Entry name

HDAC6_HUMAN

Accession

Primary (citable) accession number: Q9UBN7
Secondary accession number(s): O94975 , Q6NT75, Q7L3E5, Q96CY0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	September 2, 2008
Last modified:	May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.