Q8VH37 (HDAC8_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 8
Short name=HD8
EC=3.5.1.98

Gene names

Name:

Hdac8

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	377 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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility By similarity.
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Cofactor	Binds 1 divalent metal cation per subunit.
Enzyme regulation	Its activity is inhibited by trichostatin A (TSA) and butyrate, 2 well known histone deacetylase inhibitors. histone deacetylase inhibitor By similarity.
Subunit structure	Interacts with CBFA2T3. Interacts with phosphorylated SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated degradation. Associates with alpha-SMA (smooth muscle alpha-actin) By similarity. Ref.5
Subcellular location	Nucleus By similarity. Cytoplasm By similarity.
Post-translational modification	Phosphorylated by PKA on serine 39. Phosphorylation reduces deacetylase activity observed preferentially on histones H3 and H4 By similarity.
Sequence similarities	Belongs to the histone deacetylase family. HD type 1 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	Metal-binding
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	histone H3 deacetylation Inferred from electronic annotation. Source: GOC histone H4 deacetylation Inferred from electronic annotation. Source: GOC regulation of cohesin localization to chromatin Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW sister chromatid cohesion Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Traceable author statement PubMed 12711221. Source: UniProtKB histone deacetylase complex Traceable author statement PubMed 12711221. Source: UniProtKB
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 histone deacetylase activity Traceable author statement PubMed 12711221. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW transcription factor binding Traceable author statement PubMed 12711221. Source: UniProtKB
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q8VH37-1)

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: Q8VH37-2)

The sequence of this isoform differs from the canonical sequence as follows:
     246-253: SVLKEVYQ → RACFTRTP
     254-377: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 377	377	Histone deacetylase 8		PRO_0000114709
Regions
	Region	14 – 324	311	Histone deacetylase
Sites
	Active site	143	1	Proton acceptor By similarity
	Metal binding	178	1	Divalent metal cation By similarity
	Metal binding	180	1	Divalent metal cation By similarity
	Metal binding	267	1	Divalent metal cation By similarity
	Binding site	101	1	Substrate By similarity
	Binding site	151	1	Substrate; via carbonyl oxygen By similarity
	Binding site	306	1	Substrate By similarity
Amino acid modifications
	Modified residue	39	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	246 – 253	8	SVLKEVYQ → RACFTRTP in isoform 2.		VSP_007178
	Alternative sequence	254 – 377	124	Missing in isoform 2.		VSP_007179
Experimental info
	Sequence conflict	88	1	E → D in AAL47569. Ref.3
	Sequence conflict	118	1	G → A in AAL47569. Ref.3
	Sequence conflict	130	1	K → M in AAL47569. Ref.3
	Sequence conflict	170	1	D → E in AAL47569. Ref.3
	Sequence conflict	187	1	D → V in AAL47569. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 11, 2003. Version 2. Checksum: EEBD7B2517B235CD	FASTA	377	41,772
	10 20 30 40 50 60 MEMPEEPANS GHSLPPVYIY SPEYVSICDS LVKVPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDEDH PDSIEYGLGY DCPATEGIFD YAAAIGGGTI 130 140 150 160 170 180 TAAQCLIDGK CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFD RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDMSDVGLG KGRYYSVNVP IQDGIQDEKY 250 260 270 280 290 300 YHICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY VLQWQLATLI 310 320 330 340 350 360 LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH 370 RIQQILNYIK GNLKHVV
	Isoform 2 [UniParc]. Checksum: 982E94F21829B340	FASTA	253	28,122
	10 20 30 40 50 60 MEMPEEPANS GHSLPPVYIY SPEYVSICDS LVKVPKRASM VHSLIEAYAL HKQMRIVKPK 70 80 90 100 110 120 VASMEEMATF HTDAYLQHLQ KVSQEGDEDH PDSIEYGLGY DCPATEGIFD YAAAIGGGTI 130 140 150 160 170 180 TAAQCLIDGK CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFD RILYVDLDLH 190 200 210 220 230 240 HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDMSDVGLG KGRYYSVNVP IQDGIQDEKY 250 YHICERACFT RTP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Brain, Embryo and Thymus.
[2]	"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] (ISOFORM 1). Tissue: Pituitary.
[3]	"Selective regulation of class I and II histone deacetylase expression in cultured neural cells." Ajamian F., Suuronen T., Salminen A. Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 58-206.
[4]	Lubec G., Kang S.U. Submitted (APR-2007) to UniProtKB Cited for: PROTEIN SEQUENCE OF 195-223, MASS SPECTROMETRY. Strain: C57BL/6. Tissue: Brain.
[5]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK011332 mRNA. Translation: BAB27550.1. AK131998 mRNA. Translation: BAE20928.1. BC061257 mRNA. Translation: AAH61257.1. AK034511 mRNA. Translation: BAC28737.1. AK041965 mRNA. Translation: BAC31116.1. AY066003 mRNA. Translation: AAL47569.1.
IPI	IPI00132657. IPI00264257.
RefSeq	NP_081658.1. NM_027382.3.
UniGene	Mm.328128.
3D structure databases
ProteinModelPortal	Q8VH37.
SMR	Q8VH37. Positions 14-377.
ModBase	Search...
PTM databases
PhosphoSite	Q8VH37.
Proteomic databases
PaxDb	Q8VH37.
PRIDE	Q8VH37.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000087916; ENSMUSP00000085226; ENSMUSG00000067567.
GeneID	70315.
KEGG	mmu:70315.
UCSC	uc009tyq.1. mouse.
Organism-specific databases
CTD	55869.
MGI	MGI:1917565. Hdac8.
Phylogenomic databases
eggNOG	COG0123.
GeneTree	ENSGT00530000062889.
HOGENOM	HOG000225180.
HOVERGEN	HBG057112.
InParanoid	Q8VH37.
KO	K11405.
OrthoDB	EOG405S1D.
Gene expression databases
ArrayExpress	Q8VH37.
Bgee	Q8VH37.
CleanEx	MM_HDAC8.
Genevestigator	Q8VH37.
Family and domain databases
Gene3D	3.40.800.20. 1 hit.
InterPro	IPR000286. His_deacetylse. IPR003084. His_deacetylse_1. IPR023801. His_deacetylse_dom. [Graphical view]
PANTHER	PTHR10625. PTHR10625. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037913. His_deacetylse_1. 1 hit.
PRINTS	PR01270. HDASUPER. PR01271. HISDACETLASE.
ProtoNet	Search...
Other
BindingDB	Q8VH37.
ChEMBL	CHEMBL2347.
NextBio	331374.
SOURCE	Search...

Entry information

Entry name

HDAC8_MOUSE

Accession

Primary (citable) accession number: Q8VH37
Secondary accession number(s): Q3V270, Q9D0K6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 11, 2003
Last sequence update:	April 11, 2003
Last modified:	April 3, 2013
This is version 96 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program