Q9Z2V5 (HDAC6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Histone deacetylase mHDA2

Gene names

Name:

Hdac6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1149 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.5 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. Ref.5
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 By similarity.
Subunit structure	Interacts with HDAC11 and SIRT2. Interacts with F-actin 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 CBFA2T3. Interacts with ZMYND15. Interacts with DDIT3/CHOP By similarity. Ref.3 Ref.5 Ref.6
Subcellular location	Nucleus. Cytoplasm. Note: It is mainly cytoplasmic, where it is associated with microtubules. Ref.5
Tissue specificity	Detected in keratinocytes (at protein level). Ref.5
Post-translational modification	Phosphorylated by AURKA By similarity. Ubiquitinated. Its polyubiquitination however does not lead to its degradation By similarity. Sumoylated in vitro By similarity.
Sequence similarities	Belongs to the histone deacetylase family. HD type 2 subfamily. Contains 1 UBP-type zinc finger.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Repeat Zinc-finger
Ligand	Actin-binding Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Hsp90 deacetylation Inferred from mutant phenotype PubMed 17785525. Source: MGI aggresome assembly Inferred from genetic interaction PubMed 16810319. Source: MGI cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara cellular response to misfolded protein Inferred from mutant phenotype PubMed 17785525. Source: MGI histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC lysosome localization Inferred from electronic annotation. Source: Compara macroautophagy Inferred from electronic annotation. Source: Compara misfolded or incompletely synthesized protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of microtubule depolymerization Inferred from direct assay PubMed 12486003. Source: MGI negative regulation of proteolysis Inferred from electronic annotation. Source: Compara peptidyl-lysine deacetylation Inferred from electronic annotation. Source: Compara polyubiquitinated misfolded protein transport Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of chaperone-mediated protein complex assembly Inferred from electronic annotation. Source: Compara positive regulation of epithelial cell migration Inferred from electronic annotation. Source: Compara positive regulation of receptor biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of signal transduction Inferred from electronic annotation. Source: Compara protein complex disassembly Inferred from genetic interaction PubMed 17785525. Source: MGI protein polyubiquitination Inferred from direct assay PubMed 11689694. Source: MGI regulation of establishment of protein localization Inferred from mutant phenotype PubMed 22792322. Source: MGI regulation of receptor activity Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to growth factor stimulus Inferred from electronic annotation. Source: Compara response to toxin Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway Inferred from mutant phenotype PubMed 17785525. Source: MGI
Cellular_component	aggresome Inferred from electronic annotation. Source: Compara caveola Inferred from electronic annotation. Source: Compara cell leading edge Inferred from electronic annotation. Source: Compara cytoplasmic microtubule Inferred from direct assay PubMed 12606581. Source: MGI cytosol Inferred from direct assay Ref.5. Source: UniProtKB dynein complex Inferred from electronic annotation. Source: Compara histone deacetylase complex Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay Ref.5. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara
Molecular_function	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 beta-tubulin binding Inferred from direct assay PubMed 12606581. Source: MGI histone deacetylase activity Inferred from direct assay PubMed 11689694Ref.1. Source: MGI microtubule binding Inferred from direct assay Ref.5. Source: UniProtKB tubulin deacetylase activity Inferred from direct assay Ref.5. Source: UniProtKB ubiquitin binding Inferred from direct assay PubMed 16810319. Source: MGI zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1149	1149	Histone deacetylase 6		PRO_0000114704
Regions
	Zinc finger	1065 – 1126	62	UBP-type
	Region	87 – 403	317	Histone deacetylase 1
	Region	481 – 799	319	Histone deacetylase 2
	Region	1088 – 1090	3	Ubiquitin binding By similarity
	Region	1116 – 1123	8	Ubiquitin binding By similarity
	Compositional bias	455 – 460	6	Poly-Glu
Sites
	Active site	215	1	1 By similarity
	Active site	610	1	2 By similarity
	Metal binding	1047	1	Zinc 1 By similarity
	Metal binding	1049	1	Zinc 1 By similarity
	Metal binding	1067	1	Zinc 3 By similarity
	Metal binding	1070	1	Zinc 3 By similarity
	Metal binding	1079	1	Zinc 2 By similarity
	Metal binding	1082	1	Zinc 2 By similarity
	Metal binding	1087	1	Zinc 3 By similarity
	Metal binding	1094	1	Zinc 3 By similarity
	Metal binding	1098	1	Zinc 2 By similarity
	Metal binding	1104	1	Zinc 2 By similarity
	Metal binding	1117	1	Zinc 1 By similarity
	Metal binding	1120	1	Zinc 1 By similarity
Amino acid modifications
	Modified residue	15	1	Phosphoserine Ref.4
Experimental info
	Sequence conflict	133	1	R → W in AAD09835. Ref.1
	Sequence conflict	394	1	V → I in AAD09835. Ref.1
	Sequence conflict	421	1	T → I in AAD09835. Ref.1
	Sequence conflict	532	1	D → G in AAD09835. Ref.1
	Sequence conflict	836	1	M → S in AAD09835. Ref.1
	Sequence conflict	851	1	I → V in AAD09835. Ref.1
	Sequence conflict	1126 – 1127	2	HE → QD in AAD09835. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9Z2V5 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: D5F73BA3F79AF520	FASTA	1,149	125,787
	10 20 30 40 50 60 MTSTGQDSST RQRKSRHNPQ SPLQESSATL KRGGKKCAVP HSSPNLAEVK KKGKMKKLSQ 70 80 90 100 110 120 PAEEDLVVGL QGLDLNPETR VPVGTGLVFD EQLNDFHCLW DDSFPESPER LHAIREQLIL 130 140 150 160 170 180 EGLLGRCVSF QARFAEKEEL MLVHSLEYID LMETTQYMNE GELRVLAETY DSVYLHPNSY 190 200 210 220 230 240 SCACLATGSV LRLVDALMGA EIRNGMAVIR PPGHHAQHNL MDGYCMFNHL AVAARYAQKK 250 260 270 280 290 300 HRIQRVLIVD WDVHHGQGTQ FIFDQDPSVL YFSIHRYEHG RFWPHLKASN WSTIGFGQGQ 310 320 330 340 350 360 GYTINVPWNQ TGMRDADYIA AFLHILLPVA SEFQPQLVLV AAGFDALHGD PKGEMAATPA 370 380 390 400 410 420 GFAHLTHLLM GLAGGKLILS LEGGYNLRAL AKGVSASLHT LLGDPCPMLE SCVVPCASAQ 430 440 450 460 470 480 TSIYCTLEAL EPFWEVLERS VETQEEDEVE EAVLEEEEEE GGWEATALPM DTWPLLQNRT 490 500 510 520 530 540 GLVYDEKMMS HCNLWDNHHP ETPQRILRIM CHLEEVGLAA RCLILPARPA LDSELLTCHS 550 560 570 580 590 600 AEYVEHLRTT EKMKTRDLHR EGANFDSIYI CPSTFACAKL ATGAACRLVE AVLSGEVLNG 610 620 630 640 650 660 IAVVRPPGHH AEPNAACGFC FFNSVAVAAR HAQIIAGRAL RILIVDWDVH HGNGTQHIFE 670 680 690 700 710 720 DDPSVLYVSL HRYDRGTFFP MGDEGASSQV GRDAGIGFTV NVPWNGPRMG DADYLAAWHR 730 740 750 760 770 780 LVLPIAYEFN PELVLISAGF DAAQGDPLGG CQVTPEGYAH LTHLLMGLAG GRIILILEGG 790 800 810 820 830 840 YNLASISESM AACTHSLLGD PPPQLTLLRP PQSGALVSIS EVIQVHRKYW RSLRLMKMED 850 860 870 880 890 900 KEECSSSRLV IKKLPPTASP VSAKEMTTPK GKVPEESVRK TIAALPGKES TLGQAKSKMA 910 920 930 940 950 960 KAVLAQGQSS EQAAKGTTLD LATSKETVGG ATTDLWASAA APENFPNQTT SVEALGETEP 970 980 990 1000 1010 1020 TPPASHTNKQ TTGASPLQGV TAQQSLQLGV LSTLELSREA EEAHDSEEGL LGEAAGGQDM 1030 1040 1050 1060 1070 1080 NSLMLTQGFG DFNTQDVFYA VTPLSWCPHL MAVCPIPAAG LDVSQPCKTC GTVQENWVCL 1090 1100 1110 1120 1130 1140 TCYQVYCSRY VNAHMVCHHE ASEHPLVLSC VDLSTWCYVC QAYVHHEDLQ DVKNAAHQNK FGEDMPHSH

References

	« Hide 'large scale' referencesShow 'large scale' 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6J. Tissue: Fetus.
[2]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[3]	"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.
[4]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, MASS SPECTROMETRY. Tissue: Melanoma.
[5]	"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: FUNCTION, INTERACTION WITH CYLD AND MICROTUBULES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[6]	"Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor essential for spermiogenesis and male fertility." Yan W., Si Y., Slaymaker S., Li J., Zheng H., Young D.L., Aslanian A., Saunders L., Verdin E., Charo I.F. J. Biol. Chem. 285:31418-31426(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ZMYND15.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF006603 mRNA. Translation: AAD09835.2. AL670169 Genomic DNA. Translation: CAM17240.1.
IPI	IPI00323705.
PIR	T13964.
RefSeq	NP_001123888.1. NM_001130416.1. NP_034543.3. NM_010413.3.
UniGene	Mm.29854.
3D structure databases
ProteinModelPortal	Q9Z2V5.
SMR	Q9Z2V5. Positions 85-455, 480-830, 1043-1144.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Z2V5. 5 interactions.
MINT	MINT-220628.
PTM databases
PhosphoSite	Q9Z2V5.
Proteomic databases
PaxDb	Q9Z2V5.
PRIDE	Q9Z2V5.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000033501; ENSMUSP00000033501; ENSMUSG00000031161. ENSMUST00000115642; ENSMUSP00000111306; ENSMUSG00000031161.
GeneID	15185.
KEGG	mmu:15185.
Organism-specific databases
CTD	10013.
MGI	MGI:1333752. Hdac6.
Phylogenomic databases
eggNOG	COG0123.
GeneTree	ENSGT00530000062809.
HOGENOM	HOG000004769.
HOVERGEN	HBG051894.
KO	K11407.
OrthoDB	EOG40P464.
Gene expression databases
ArrayExpress	Q9Z2V5.
Bgee	Q9Z2V5.
CleanEx	MM_HDAC6.
Genevestigator	Q9Z2V5.
GermOnline	ENSMUSG00000031161. Mus musculus.
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	Q9Z2V5.
ChEMBL	CHEMBL2878.
NextBio	287707.
SOURCE	Search...

Entry information

Entry name

HDAC6_MOUSE

Accession

Primary (citable) accession number: Q9Z2V5
Secondary accession number(s): B1AUA6

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	July 27, 2011
Last modified:	May 1, 2013
This is version 108 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program