Reviewed, UniProtKB/Swiss-Prot Q99P99 (HDAC4_RAT)

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)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1077 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
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. 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 is required for the interaction with 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. Type 2 subfamily.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	Coiled coil
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Biological process	chromatin modification Inferred from electronic annotation. Source: UniProtKB-KW response to drug Inferred from direct assay. Source: RGD transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	histone deacetylase complex Inferred from electronic annotation. Source: InterPro sarcomere Inferred from direct assay. Source: RGD
Molecular function	histone deacetylase activity 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 – 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
Amino acid modifications
	Modified residue	245	1	Phosphoserine; by CaMK4 By similarity
	Modified residue	466	1	Phosphoserine; by CaMK4 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)
	Q99P99-1 [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: 15057822] [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: 16033423] [Abstract] Cited for: INTERACTION WITH BTBD14B.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
UniGene	Rn.23483
3D structure databases
SMR	Q99P99. Positions 650-1026.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99P99.
Proteomic databases
PRIDE	Q99P99.
Genome annotation databases
Ensembl	ENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372; Rattus norvegicus. [Genome view]
Organism-specific databases
RGD	619979. Hdac4.
Phylogenomic databases
HOVERGEN	Q99P99.
Gene expression databases
ArrayExpress	Q99P99.
Genevestigator	Q99P99.
Family and domain databases
InterPro	IPR000286. His_deacetylse. IPR017320. Histone_deAcase_II_euk. [Graphical view]
Gene3D	G3DSA:3.40.800.20. His_deacetylse. 1 hit.
PANTHER	PTHR10625. His_deacetylse. 1 hit.
Pfam	PF00850. Hist_deacetyl. 1 hit. [Graphical view]
PIRSF	PIRSF037911. HDAC_II_euk. 1 hit.
PRINTS	PR01270. HDASUPER.
ProtoNet	Search...

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:	October 13, 2009
This is version 38 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)