Q99P99 (HDAC4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone deacetylase 4
Short name=HD4
EC=3.5.1.98

Gene names

Name:

Hdac4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [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 › Rattus

Protein attributes

Sequence length	1077 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. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D By similarity.
Catalytic activity	Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.
Subunit structure	Interacts with HDAC7. Homodimer By similarity. Homodimerization via its N-terminal domain. Interacts with MEF2C and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with KDM5B and AHRR By similarity. Interacts with BTBD14B. Interacts with MYOCD. Interacts with ANKRA2 By similarity. Ref.3
Subcellular location	Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-245, Ser-466 and Ser-630 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation By similarity.
Domain	The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm By similarity.
Post-translational modification	Phosphorylated by CaMK4 at Ser-245, Ser-466 and Ser-630. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349 impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 By similarity. Sumoylation on Lys-557 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.
Sequence similarities	Belongs to the histone deacetylase family. HD type 2 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
Ligand	Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chromatin remodeling Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of glycolysis Inferred from electronic annotation. Source: Compara negative regulation of myotube differentiation Inferred from electronic annotation. Source: Compara negative regulation of osteoblast differentiation Inferred from electronic annotation. Source: Compara negative regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara negative regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara osteoblast development Inferred from electronic annotation. Source: Compara peptidyl-lysine deacetylation Inferred from electronic annotation. Source: Compara positive regulation of cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein sumoylation Inferred from electronic annotation. Source: Compara positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara regulation of cardiac muscle contraction by calcium ion signaling Inferred from electronic annotation. Source: Compara regulation of protein binding Inferred from electronic annotation. Source: Compara response to denervation involved in regulation of muscle adaptation Inferred from electronic annotation. Source: Compara response to drug Inferred from direct assay PubMed 16767219. Source: RGD response to interleukin-1 Inferred from electronic annotation. Source: Compara skeletal system development Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	A band Inferred from direct assay PubMed 18250163. Source: MGI Z disc Inferred from direct assay PubMed 18250163. Source: MGI actomyosin Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay PubMed 22360269. Source: RGD histone deacetylase complex Inferred from electronic annotation. Source: Compara neuromuscular junction Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 16767219PubMed 22360269. Source: RGD protein complex Inferred from direct assay PubMed 22360269. Source: RGD transcriptional repressor complex 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 core promoter binding Inferred from direct assay PubMed 21586557. Source: RGD histone deacetylase activity Inferred from mutant phenotype PubMed 21586557. Source: RGD potassium ion binding Inferred from electronic annotation. Source: Compara sequence-specific DNA binding Inferred from electronic annotation. Source: Compara transcription corepressor activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1077	1077	Histone deacetylase 4		PRO_0000281034
Regions
	Region	117 – 312	196	Interaction with MEF2A By similarity
	Region	653 – 1077	425	Histone deacetylase By similarity
	Coiled coil	66 – 169	104	Potential
	Motif	1044 – 1077	34	Nuclear export signal By similarity
	Compositional bias	465 – 500	36	Gln-rich
	Compositional bias	562 – 569	8	Poly-Glu
Sites
	Active site	796	1	By similarity
	Metal binding	665	1	Zinc By similarity
	Metal binding	667	1	Zinc By similarity
	Metal binding	673	1	Zinc By similarity
	Metal binding	744	1	Zinc By similarity
Amino acid modifications
	Modified residue	245	1	Phosphoserine; by CaMK4 and SIK1 By similarity
	Modified residue	349	1	Phosphoserine By similarity
	Modified residue	466	1	Phosphoserine; by CaMK4 and SIK1 By similarity
	Modified residue	563	1	Phosphoserine By similarity
	Modified residue	630	1	Phosphoserine; by CaMK4 By similarity
	Modified residue	631	1	Phosphoserine By similarity
	Cross-link	557		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q99P99 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 88127299D9962DBA	FASTA	1,077	118,652
	10 20 30 40 50 60 MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD LRLDHQFSLP 70 80 90 100 110 120 LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM 130 140 150 160 170 180 KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN 190 200 210 220 230 240 KKKALAHRNL NHCMSSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL 250 260 270 280 290 300 RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS 310 320 330 340 350 360 SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT 370 380 390 400 410 420 GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP LERDGGAAHN PLLQHMVLLE 430 440 450 460 470 480 QPPTQTPLVT GLGALPLHTQ SLVGADRVSP SIHKLRQHRP LGRTQSAPLP QNAQALQHLV 490 500 510 520 530 540 IQQQHQQFLE KHKQQFQQQQ LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL 550 560 570 580 590 600 DRLPGQKEPS LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI 610 620 630 640 650 660 HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF TTGLVYDTLM 670 680 690 700 710 720 LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR GRKATLEELQ TVHSEAHTLL 730 740 750 760 770 780 YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD SDTIWNEVHS SGAARLAVGC VVELVFKVAT 790 800 810 820 830 840 GELKNGFAVV RPPGHHAEES TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT 850 860 870 880 890 900 QQAFYNDPNV LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY 910 920 930 940 950 960 LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT KQLMGLAGGR 970 980 990 1000 1010 1020 IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ RPNANAVHSM EKVMGIHSEY 1030 1040 1050 1060 1070 WRCLQRLSPT VGHSLIEAQK CENEEAETVT AMASLSVGVK PAEKRSEEEP MEEEPPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Genome sequence of the Brown Norway rat yields insights into mammalian evolution." Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S. Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Brown Norway.
[2]	"Expression pattern of rat histone deacetylases." Wilquet V., Chavez M., Korbers R., Geerts A. Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 55-208. Strain: Wistar. Tissue: Testis.
[3]	"The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal-like cultures." Korutla L., Wang P.J., Mackler S.A. J. Neurochem. 94:786-793(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BTBD14B.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AABR03067902 Genomic DNA. No translation available. AABR03068091 Genomic DNA. No translation available. AABR03070452 Genomic DNA. No translation available. AF321132 mRNA. Translation: AAK11185.1.
IPI	IPI00367142.
RefSeq	NP_445901.1. NM_053449.1.
UniGene	Rn.23483.
3D structure databases
ProteinModelPortal	Q99P99.
SMR	Q99P99. Positions 62-128, 648-1044.
ModBase	Search...
PTM databases
PhosphoSite	Q99P99.
Proteomic databases
PaxDb	Q99P99.
PRIDE	Q99P99.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372.
GeneID	363287.
KEGG	rno:363287.
UCSC	RGD:619979. rat.
Organism-specific databases
CTD	9759.
RGD	619979. Hdac4.
Phylogenomic databases
eggNOG	COG0123.
GeneTree	ENSGT00530000062809.
HOGENOM	HOG000232065.
HOVERGEN	HBG057100.
InParanoid	Q99P99.
KO	K11406.
OrthoDB	EOG44MXRC.
Gene expression databases
Genevestigator	Q99P99.
Family and domain databases
Gene3D	3.40.800.20. 1 hit.
InterPro	IPR000286. His_deacetylse. IPR023801. His_deacetylse_dom. IPR024643. Hist_deacetylase_Gln_rich_N. IPR017320. Histone_deAcase_II_euk. [Graphical view]
PANTHER	PTHR10625. PTHR10625. 1 hit.
Pfam	PF12203. HDAC4_Gln. 1 hit. PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037911. HDAC_II_euk. 1 hit.
PRINTS	PR01270. HDASUPER.
ProtoNet	Search...
Other
BindingDB	Q99P99.
ChEMBL	CHEMBL2874.
NextBio	683134.

Entry information

Entry name

HDAC4_RAT

Accession

Primary (citable) accession number: Q99P99

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 20, 2007
Last sequence update:	March 20, 2007
Last modified:	May 1, 2013
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program