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Protein

Histone deacetylase 6

Gene

Hdac6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.By similarity2 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 (By similarity).By similarity

Catalytic activityi

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Cofactori

Zn2+By similarityNote: Binds 3 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei2151By similarity1
Active sitei6102By similarity1
Metal bindingi1047Zinc 1By similarity1
Metal bindingi1049Zinc 1By similarity1
Metal bindingi1067Zinc 3By similarity1
Metal bindingi1070Zinc 3By similarity1
Metal bindingi1079Zinc 2By similarity1
Metal bindingi1082Zinc 2By similarity1
Metal bindingi1087Zinc 3By similarity1
Metal bindingi1094Zinc 3By similarity1
Metal bindingi1098Zinc 2By similarity1
Metal bindingi1104Zinc 2By similarity1
Metal bindingi1117Zinc 1By similarity1
Metal bindingi1120Zinc 1By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1065 – 1126UBP-typePROSITE-ProRule annotationAdd BLAST62

GO - Molecular functioni

GO - Biological processi

  • aggresome assembly Source: MGI
  • cellular response to hydrogen peroxide Source: MGI
  • cellular response to misfolded protein Source: MGI
  • cellular response to topologically incorrect protein Source: MGI
  • collateral sprouting Source: MGI
  • dendritic spine morphogenesis Source: MGI
  • histone deacetylation Source: MGI
  • Hsp90 deacetylation Source: MGI
  • intracellular protein transport Source: MGI
  • lysosome localization Source: MGI
  • macroautophagy Source: MGI
  • misfolded or incompletely synthesized protein catabolic process Source: MGI
  • mitochondrion localization Source: ParkinsonsUK-UCL
  • mitophagy in response to mitochondrial depolarization Source: ParkinsonsUK-UCL
  • negative regulation of microtubule depolymerization Source: MGI
  • negative regulation of protein complex disassembly Source: MGI
  • negative regulation of proteolysis Source: MGI
  • peptidyl-lysine deacetylation Source: MGI
  • polyubiquitinated misfolded protein transport Source: MGI
  • positive regulation of chaperone-mediated protein complex assembly Source: MGI
  • positive regulation of epithelial cell migration Source: MGI
  • positive regulation of hydrogen peroxide-mediated programmed cell death Source: MGI
  • positive regulation of receptor biosynthetic process Source: MGI
  • positive regulation of signal transduction Source: MGI
  • protein complex disassembly Source: MGI
  • protein deacetylation Source: MGI
  • protein polyubiquitination Source: MGI
  • regulation of establishment of protein localization Source: MGI
  • regulation of fat cell differentiation Source: MGI
  • regulation of gene expression, epigenetic Source: MGI
  • regulation of protein stability Source: MGI
  • regulation of receptor activity Source: MGI
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to growth factor Source: MGI
  • response to misfolded protein Source: MGI
  • response to organic substance Source: MGI
  • response to toxic substance Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • tubulin deacetylation Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: MGI
  • ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Actin-binding, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.5.1.98. 3474.
ReactomeiR-MMU-3371511. HSF1 activation.
R-MMU-5617833. Assembly of the primary cilium.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 6 (EC:3.5.1.98)
Short name:
HD6
Alternative name(s):
Histone deacetylase mHDA2
Gene namesi
Name:Hdac6
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1333752. Hdac6.

Subcellular locationi

GO - Cellular componenti

  • aggresome Source: MGI
  • axon Source: UniProtKB
  • caveola Source: MGI
  • cell body Source: MGI
  • cell leading edge Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: UniProtKB
  • dendrite Source: UniProtKB
  • dynein complex Source: Ensembl
  • histone deacetylase complex Source: MGI
  • inclusion body Source: MGI
  • microtubule Source: MGI
  • microtubule associated complex Source: MGI
  • neuron projection Source: MGI
  • nucleus Source: UniProtKB
  • perikaryon Source: UniProtKB
  • perinuclear region of cytoplasm Source: MGI
  • protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2878.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001147041 – 1149Histone deacetylase 6Add BLAST1149

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei21PhosphoserineCombined sources1
Modified residuei32Omega-N-methylarginineCombined sources1
Modified residuei43PhosphoserineCombined sources1
Modified residuei958PhosphothreonineBy similarity1
Modified residuei961PhosphothreonineBy similarity1
Modified residuei967PhosphothreonineBy similarity1
Modified residuei971PhosphothreonineBy similarity1
Modified residuei975PhosphoserineBy similarity1
Modified residuei1148PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by AURKA.By similarity
Ubiquitinated. Its polyubiquitination however does not lead to its degradation (By similarity).By similarity
Sumoylated in vitro.By similarity

Keywords - PTMi

Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9Z2V5.
MaxQBiQ9Z2V5.
PaxDbiQ9Z2V5.
PeptideAtlasiQ9Z2V5.
PRIDEiQ9Z2V5.

PTM databases

iPTMnetiQ9Z2V5.
PhosphoSitePlusiQ9Z2V5.

Expressioni

Tissue specificityi

Expressed in neurons of the cortex. Expressed in Purkinje cells. Detected in keratinocytes (at protein level).2 Publications

Gene expression databases

BgeeiENSMUSG00000031161.
CleanExiMM_HDAC6.
ExpressionAtlasiQ9Z2V5. baseline and differential.
GenevisibleiQ9Z2V5. MM.

Interactioni

Subunit structurei

Interacts with BBIP10, DDIT3/CHOP, F-actin and HDAC11. 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 (By similarity). Interacts with CBFA2T3, CYLD and ZMYND15. Interacts with FAM65B (By similarity).By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ADRBK1P211462EBI-1009256,EBI-1036401From a different organism.
CyldQ80TQ23EBI-1009256,EBI-943859

GO - Molecular functioni

Protein-protein interaction databases

BioGridi200263. 41 interactors.
DIPiDIP-36461N.
IntActiQ9Z2V5. 33 interactors.
MINTiMINT-220628.
STRINGi10090.ENSMUSP00000033501.

Chemistry databases

BindingDBiQ9Z2V5.

Structurei

3D structure databases

ProteinModelPortaliQ9Z2V5.
SMRiQ9Z2V5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni87 – 403Histone deacetylase 1Add BLAST317
Regioni481 – 799Histone deacetylase 2Add BLAST319
Regioni1088 – 1090Ubiquitin bindingBy similarity3
Regioni1116 – 1123Ubiquitin bindingBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi455 – 460Poly-Glu6

Sequence similaritiesi

Contains 1 UBP-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1065 – 1126UBP-typePROSITE-ProRule annotationAdd BLAST62

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000004769.
HOVERGENiHBG051894.
InParanoidiQ9Z2V5.
KOiK11407.
OMAiRYINAHM.
OrthoDBiEOG091G0210.
TreeFamiTF106173.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.40.800.20. 2 hits.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 3 hits.
PfamiPF00850. Hist_deacetyl. 2 hits.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PRINTSiPR01270. HDASUPER.
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS50271. ZF_UBP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9Z2V5-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTSTGQDSST RQRKSRHNPQ SPLQESSATL KRGGKKCAVP HSSPNLAEVK
60 70 80 90 100
KKGKMKKLSQ PAEEDLVVGL QGLDLNPETR VPVGTGLVFD EQLNDFHCLW
110 120 130 140 150
DDSFPESPER LHAIREQLIL EGLLGRCVSF QARFAEKEEL MLVHSLEYID
160 170 180 190 200
LMETTQYMNE GELRVLAETY DSVYLHPNSY SCACLATGSV LRLVDALMGA
210 220 230 240 250
EIRNGMAVIR PPGHHAQHNL MDGYCMFNHL AVAARYAQKK HRIQRVLIVD
260 270 280 290 300
WDVHHGQGTQ FIFDQDPSVL YFSIHRYEHG RFWPHLKASN WSTIGFGQGQ
310 320 330 340 350
GYTINVPWNQ TGMRDADYIA AFLHILLPVA SEFQPQLVLV AAGFDALHGD
360 370 380 390 400
PKGEMAATPA GFAHLTHLLM GLAGGKLILS LEGGYNLRAL AKGVSASLHT
410 420 430 440 450
LLGDPCPMLE SCVVPCASAQ TSIYCTLEAL EPFWEVLERS VETQEEDEVE
460 470 480 490 500
EAVLEEEEEE GGWEATALPM DTWPLLQNRT GLVYDEKMMS HCNLWDNHHP
510 520 530 540 550
ETPQRILRIM CHLEEVGLAA RCLILPARPA LDSELLTCHS AEYVEHLRTT
560 570 580 590 600
EKMKTRDLHR EGANFDSIYI CPSTFACAKL ATGAACRLVE AVLSGEVLNG
610 620 630 640 650
IAVVRPPGHH AEPNAACGFC FFNSVAVAAR HAQIIAGRAL RILIVDWDVH
660 670 680 690 700
HGNGTQHIFE DDPSVLYVSL HRYDRGTFFP MGDEGASSQV GRDAGIGFTV
710 720 730 740 750
NVPWNGPRMG DADYLAAWHR LVLPIAYEFN PELVLISAGF DAAQGDPLGG
760 770 780 790 800
CQVTPEGYAH LTHLLMGLAG GRIILILEGG YNLASISESM AACTHSLLGD
810 820 830 840 850
PPPQLTLLRP PQSGALVSIS EVIQVHRKYW RSLRLMKMED KEECSSSRLV
860 870 880 890 900
IKKLPPTASP VSAKEMTTPK GKVPEESVRK TIAALPGKES TLGQAKSKMA
910 920 930 940 950
KAVLAQGQSS EQAAKGTTLD LATSKETVGG ATTDLWASAA APENFPNQTT
960 970 980 990 1000
SVEALGETEP TPPASHTNKQ TTGASPLQGV TAQQSLQLGV LSTLELSREA
1010 1020 1030 1040 1050
EEAHDSEEGL LGEAAGGQDM NSLMLTQGFG DFNTQDVFYA VTPLSWCPHL
1060 1070 1080 1090 1100
MAVCPIPAAG LDVSQPCKTC GTVQENWVCL TCYQVYCSRY VNAHMVCHHE
1110 1120 1130 1140
ASEHPLVLSC VDLSTWCYVC QAYVHHEDLQ DVKNAAHQNK FGEDMPHSH
Length:1,149
Mass (Da):125,787
Last modified:July 27, 2011 - v3
Checksum:iD5F73BA3F79AF520
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti133R → W in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti394V → I in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti421T → I in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti532D → G in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti836M → S in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti851I → V in AAD09835 (PubMed:9891014).Curated1
Sequence conflicti1126 – 1127HE → QD in AAD09835 (PubMed:9891014).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006603 mRNA. Translation: AAD09835.2.
AL670169 Genomic DNA. Translation: CAM17240.1.
CCDSiCCDS40845.1.
PIRiT13964.
RefSeqiNP_001123888.1. NM_001130416.1.
NP_034543.3. NM_010413.3.
XP_006527630.1. XM_006527567.2.
XP_017173877.1. XM_017318388.1.
XP_017173878.1. XM_017318389.1.
UniGeneiMm.29854.

Genome annotation databases

EnsembliENSMUST00000033501; ENSMUSP00000033501; ENSMUSG00000031161.
ENSMUST00000115642; ENSMUSP00000111306; ENSMUSG00000031161.
GeneIDi15185.
KEGGimmu:15185.
UCSCiuc009snh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF006603 mRNA. Translation: AAD09835.2.
AL670169 Genomic DNA. Translation: CAM17240.1.
CCDSiCCDS40845.1.
PIRiT13964.
RefSeqiNP_001123888.1. NM_001130416.1.
NP_034543.3. NM_010413.3.
XP_006527630.1. XM_006527567.2.
XP_017173877.1. XM_017318388.1.
XP_017173878.1. XM_017318389.1.
UniGeneiMm.29854.

3D structure databases

ProteinModelPortaliQ9Z2V5.
SMRiQ9Z2V5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200263. 41 interactors.
DIPiDIP-36461N.
IntActiQ9Z2V5. 33 interactors.
MINTiMINT-220628.
STRINGi10090.ENSMUSP00000033501.

Chemistry databases

BindingDBiQ9Z2V5.
ChEMBLiCHEMBL2878.

PTM databases

iPTMnetiQ9Z2V5.
PhosphoSitePlusiQ9Z2V5.

Proteomic databases

EPDiQ9Z2V5.
MaxQBiQ9Z2V5.
PaxDbiQ9Z2V5.
PeptideAtlasiQ9Z2V5.
PRIDEiQ9Z2V5.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000033501; ENSMUSP00000033501; ENSMUSG00000031161.
ENSMUST00000115642; ENSMUSP00000111306; ENSMUSG00000031161.
GeneIDi15185.
KEGGimmu:15185.
UCSCiuc009snh.2. mouse.

Organism-specific databases

CTDi10013.
MGIiMGI:1333752. Hdac6.

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000004769.
HOVERGENiHBG051894.
InParanoidiQ9Z2V5.
KOiK11407.
OMAiRYINAHM.
OrthoDBiEOG091G0210.
TreeFamiTF106173.

Enzyme and pathway databases

BRENDAi3.5.1.98. 3474.
ReactomeiR-MMU-3371511. HSF1 activation.
R-MMU-5617833. Assembly of the primary cilium.

Miscellaneous databases

PROiQ9Z2V5.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031161.
CleanExiMM_HDAC6.
ExpressionAtlasiQ9Z2V5. baseline and differential.
GenevisibleiQ9Z2V5. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
3.40.800.20. 2 hits.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 3 hits.
PfamiPF00850. Hist_deacetyl. 2 hits.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PRINTSiPR01270. HDASUPER.
SMARTiSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEiPS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHDAC6_MOUSE
AccessioniPrimary (citable) accession number: Q9Z2V5
Secondary accession number(s): B1AUA6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 145 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.