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Protein

Histone deacetylase 6

Gene

HDAC6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.By similarity3 Publications
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.

Catalytic activityi

Hydrolysis of an N6-acetyl-lysine residue of a histone to yield a deacetylated histone.

Cofactori

Zn2+Note: Binds 3 Zn2+ ions per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei21611
Active sitei61121
Metal bindingi1113Zinc 11
Metal bindingi1115Zinc 11
Metal bindingi1133Zinc 31
Metal bindingi1136Zinc 31
Metal bindingi1145Zinc 21
Metal bindingi1148Zinc 21
Metal bindingi1153Zinc 31
Metal bindingi1160Zinc 31
Metal bindingi1164Zinc 21
Metal bindingi1170Zinc 21
Metal bindingi1183Zinc 11
Metal bindingi1186Zinc 11

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1131 – 1192UBP-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActin-binding, Chromatin regulator, Hydrolase, Repressor
Biological processAutophagy, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.1.98 2681
ReactomeiR-HSA-2122947 NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606 Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862 Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3371511 HSF1 activation
R-HSA-5617833 Cilium Assembly
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-8940973 RUNX2 regulates osteoblast differentiation
SABIO-RKiQ9UBN7
SignaLinkiQ9UBN7
SIGNORiQ9UBN7

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 6 (EC:3.5.1.98)
Short name:
HD6
Gene namesi
Name:HDAC6
Synonyms:KIAA0901
ORF Names:JM21
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000094631.18
HGNCiHGNC:14064 HDAC6
MIMi300272 gene
neXtProtiNX_Q9UBN7

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by chondrodysplasia, severe platyspondyly, hydrocephaly, and facial features with microphthalmia. Bone abnormalities include a distinctive metaphyseal cupping of the metacarpals, metatarsals, and phalanges. Affected females show a milder phenotype with small stature, sometimes associated with body asymmetry and mild mental retardation.
See also OMIM:300863

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi216H → A: Reduces histone deacetylase activity. 1 Publication1
Mutagenesisi611H → A: Reduces histone deacetylase activity. 1 Publication1

Organism-specific databases

DisGeNETi10013
MalaCardsiHDAC6
MIMi300863 phenotype
OpenTargetsiENSG00000094631
Orphaneti163966 X-linked dominant chondrodysplasia, Chassaing-Lacombe type
PharmGKBiPA29231

Chemistry databases

ChEMBLiCHEMBL1865
DrugBankiDB05015 Belinostat
DB06603 Panobinostat
DB06176 Romidepsin
DB05223 SB939
DB02546 Vorinostat
GuidetoPHARMACOLOGYi2618

Polymorphism and mutation databases

BioMutaiHDAC6
DMDMi205371758

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001147031 – 1215Histone deacetylase 6Add BLAST1215

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22PhosphoserineCombined sources1
Modified residuei33Omega-N-methylarginineBy similarity1
Modified residuei1016PhosphothreonineCombined sources1
Modified residuei1021PhosphothreonineCombined sources1
Modified residuei1027PhosphothreonineCombined sources1
Modified residuei1031PhosphothreonineCombined sources1
Modified residuei1034PhosphothreonineCombined sources1
Modified residuei1035PhosphoserineCombined sources1
Modified residuei1040PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by AURKA.1 Publication
Ubiquitinated. Its polyubiquitination however does not lead to its degradation.1 Publication
Sumoylated in vitro.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UBN7
PaxDbiQ9UBN7
PeptideAtlasiQ9UBN7
PRIDEiQ9UBN7
ProteomicsDBi84019

PTM databases

iPTMnetiQ9UBN7
PhosphoSitePlusiQ9UBN7

Expressioni

Gene expression databases

BgeeiENSG00000094631 Expressed in 223 organ(s), highest expression level in adenohypophysis
CleanExiHS_HDAC6
ExpressionAtlasiQ9UBN7 baseline and differential
GenevisibleiQ9UBN7 HS

Organism-specific databases

HPAiCAB004236
HPA003714
HPA026321

Interactioni

Subunit structurei

Interacts with ZMYND15 (By similarity). Interacts with SIRT2 (via both phosphorylated, unphosphorylated, active or inactive forms); the interaction is necessary for the complex to interact with alpha-tubulin. Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions. Interacts with BBIP10, CBFA2T3, CYLD, DDIT3/CHOP, F-actin and HDAC11. Interacts with RIPOR2; this interaction occurs during early myogenic differentiation and prevents HDAC6 to deacetylate tubulin (PubMed:24687993). Interacts with DYSF; this interaction occurs during early myogenic differentiation (PubMed:24687993).By similarity12 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115330, 316 interactors
CORUMiQ9UBN7
DIPiDIP-27544N
IntActiQ9UBN7, 119 interactors
MINTiQ9UBN7
STRINGi9606.ENSP00000334061

Chemistry databases

BindingDBiQ9UBN7

Structurei

Secondary structure

11215
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UBN7
SMRiQ9UBN7
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UBN7

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni87 – 404Histone deacetylase 1Add BLAST318
Regioni482 – 800Histone deacetylase 2Add BLAST319
Regioni1154 – 1156Ubiquitin binding3
Regioni1182 – 1189Ubiquitin binding8

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1131 – 1192UBP-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1343 Eukaryota
COG0123 LUCA
GeneTreeiENSGT00530000062809
HOGENOMiHOG000004769
HOVERGENiHBG051894
InParanoidiQ9UBN7
KOiK11407
OMAiQPHGFCI
OrthoDBiEOG091G0210
PhylomeDBiQ9UBN7
TreeFamiTF106173

Family and domain databases

Gene3Di3.30.40.10, 1 hit
3.40.800.20, 2 hits
InterProiView protein in InterPro
IPR000286 His_deacetylse
IPR023801 His_deacetylse_dom
IPR037138 His_deacetylse_dom_sf
IPR023696 Ureohydrolase_dom_sf
IPR013083 Znf_RING/FYVE/PHD
IPR001607 Znf_UBP
PANTHERiPTHR10625 PTHR10625, 5 hits
PfamiView protein in Pfam
PF00850 Hist_deacetyl, 2 hits
PF02148 zf-UBP, 1 hit
PRINTSiPR01270 HDASUPER
SMARTiView protein in SMART
SM00290 ZnF_UBP, 1 hit
SUPFAMiSSF52768 SSF52768, 2 hits
PROSITEiView protein in PROSITE
PS50271 ZF_UBP, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 17 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q9UBN7-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MTSTGQDSTT TRQRRSRQNP QSPPQDSSVT SKRNIKKGAV PRSIPNLAEV
60 70 80 90 100
KKKGKMKKLG QAMEEDLIVG LQGMDLNLEA EALAGTGLVL DEQLNEFHCL
110 120 130 140 150
WDDSFPEGPE RLHAIKEQLI QEGLLDRCVS FQARFAEKEE LMLVHSLEYI
160 170 180 190 200
DLMETTQYMN EGELRVLADT YDSVYLHPNS YSCACLASGS VLRLVDAVLG
210 220 230 240 250
AEIRNGMAII RPPGHHAQHS LMDGYCMFNH VAVAARYAQQ KHRIRRVLIV
260 270 280 290 300
DWDVHHGQGT QFTFDQDPSV LYFSIHRYEQ GRFWPHLKAS NWSTTGFGQG
310 320 330 340 350
QGYTINVPWN QVGMRDADYI AAFLHVLLPV ALEFQPQLVL VAAGFDALQG
360 370 380 390 400
DPKGEMAATP AGFAQLTHLL MGLAGGKLIL SLEGGYNLRA LAEGVSASLH
410 420 430 440 450
TLLGDPCPML ESPGAPCRSA QASVSCALEA LEPFWEVLVR STETVERDNM
460 470 480 490 500
EEDNVEESEE EGPWEPPVLP ILTWPVLQSR TGLVYDQNMM NHCNLWDSHH
510 520 530 540 550
PEVPQRILRI MCRLEELGLA GRCLTLTPRP ATEAELLTCH SAEYVGHLRA
560 570 580 590 600
TEKMKTRELH RESSNFDSIY ICPSTFACAQ LATGAACRLV EAVLSGEVLN
610 620 630 640 650
GAAVVRPPGH HAEQDAACGF CFFNSVAVAA RHAQTISGHA LRILIVDWDV
660 670 680 690 700
HHGNGTQHMF EDDPSVLYVS LHRYDHGTFF PMGDEGASSQ IGRAAGTGFT
710 720 730 740 750
VNVAWNGPRM GDADYLAAWH RLVLPIAYEF NPELVLVSAG FDAARGDPLG
760 770 780 790 800
GCQVSPEGYA HLTHLLMGLA SGRIILILEG GYNLTSISES MAACTRSLLG
810 820 830 840 850
DPPPLLTLPR PPLSGALASI TETIQVHRRY WRSLRVMKVE DREGPSSSKL
860 870 880 890 900
VTKKAPQPAK PRLAERMTTR EKKVLEAGMG KVTSASFGEE STPGQTNSET
910 920 930 940 950
AVVALTQDQP SEAATGGATL AQTISEAAIG GAMLGQTTSE EAVGGATPDQ
960 970 980 990 1000
TTSEETVGGA ILDQTTSEDA VGGATLGQTT SEEAVGGATL AQTTSEAAME
1010 1020 1030 1040 1050
GATLDQTTSE EAPGGTELIQ TPLASSTDHQ TPPTSPVQGT TPQISPSTLI
1060 1070 1080 1090 1100
GSLRTLELGS ESQGASESQA PGEENLLGEA AGGQDMADSM LMQGSRGLTD
1110 1120 1130 1140 1150
QAIFYAVTPL PWCPHLVAVC PIPAAGLDVT QPCGDCGTIQ ENWVCLSCYQ
1160 1170 1180 1190 1200
VYCGRYINGH MLQHHGNSGH PLVLSYIDLS AWCYYCQAYV HHQALLDVKN
1210
IAHQNKFGED MPHPH
Length:1,215
Mass (Da):131,419
Last modified:September 2, 2008 - v2
Checksum:i6F17731268A33114
GO
Isoform 2 (identifier: Q9UBN7-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:1,063
Mass (Da):114,361
Checksum:iE77E732ACF187AB7
GO

Computationally mapped potential isoform sequencesi

There are 17 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8YDE6A0A2R8YDE6_HUMAN
Histone deacetylase
HDAC6
1,160Annotation score:
A0A2R8YGC5A0A2R8YGC5_HUMAN
Histone deacetylase 6
HDAC6
89Annotation score:
Q9BRX7Q9BRX7_HUMAN
HDAC6 protein
HDAC6
146Annotation score:
A0A2R8Y5Z4A0A2R8Y5Z4_HUMAN
Histone deacetylase 6
HDAC6
91Annotation score:
A6NDI8A6NDI8_HUMAN
Histone deacetylase 6
HDAC6
210Annotation score:
C9J172C9J172_HUMAN
Histone deacetylase 6
HDAC6
142Annotation score:
E7EPS2E7EPS2_HUMAN
Histone deacetylase 6
HDAC6
269Annotation score:
E7EP63E7EP63_HUMAN
Histone deacetylase 6
HDAC6
167Annotation score:
E7ER52E7ER52_HUMAN
Histone deacetylase 6
HDAC6
171Annotation score:
C9JEF4C9JEF4_HUMAN
Histone deacetylase 6
HDAC6
51Annotation score:
There are more potential isoformsShow all

Sequence cautioni

The sequence BAA74924 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046300994T → I2 PublicationsCorresponds to variant dbSNP:rs1127346Ensembl.1
Natural variantiVAR_0689621200N → D1 PublicationCorresponds to variant dbSNP:rs151130423Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0445761 – 152Missing in isoform 2. 1 PublicationAdd BLAST152

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS14306.1 [Q9UBN7-1]
RefSeqiNP_001308155.1, NM_001321226.1 [Q9UBN7-1]
NP_001308156.1, NM_001321227.1 [Q9UBN7-1]
NP_001308157.1, NM_001321228.1 [Q9UBN7-1]
NP_001308158.1, NM_001321229.1 [Q9UBN7-1]
NP_006035.2, NM_006044.3 [Q9UBN7-1]
UniGeneiHs.6764

Genome annotation databases

EnsembliENST00000334136; ENSP00000334061; ENSG00000094631 [Q9UBN7-1]
ENST00000376619; ENSP00000365804; ENSG00000094631 [Q9UBN7-1]
ENST00000426196; ENSP00000402189; ENSG00000094631 [Q9UBN7-1]
ENST00000643374; ENSP00000496046; ENSG00000094631 [Q9UBN7-1]
ENST00000644068; ENSP00000496013; ENSG00000094631 [Q9UBN7-1]
GeneIDi10013
KEGGihsa:10013
UCSCiuc004dks.2 human [Q9UBN7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiHDAC6_HUMAN
AccessioniPrimary (citable) accession number: Q9UBN7
Secondary accession number(s): O94975
, Q6NT75, Q7L3E5, Q96CY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 2, 2008
Last modified: September 12, 2018
This is version 184 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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