Skip Header

 
Contribute Send feedback

Reviewed, UniProtKB/Swiss-Prot P56524 (HDAC4_HUMAN)

Last modified November 25, 2008. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Hide | Top

Names and origin

Protein namesRecommended name:
    Histone deacetylase 4
      Short name=HD4
    EC=3.5.1.98
Gene names
Name: HDAC4
Synonyms: KIAA0288
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Hide | Top

Protein attributes

Sequence length1084 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

Hide | Top

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.

Catalytic activity

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

Subunit structure

Interacts with HDAC7 By similarity. Homodimer. Homodimerization via its N-terminal domain. Interacts with MEF2C, AHRR, and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with BTBD14B By similarity. Interacts with JARID1B.

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-246, Ser-467 and Ser-632 by CaMK4. The nuclear localization probably depends on sumoylation.

Tissue specificity

Ubiquitous.

Domain

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.

Post-translational modification

Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues is required for the interaction with 14-3-3.

Sumoylation on Lys-559 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.

Hide | Top

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10841084Histone deacetylase 4
PRO_0000114699

Regions

Region118 – 313196Interaction with MEF2A
Region655 – 1084430Histone deacetylase
Coiled coil67 – 177111 Potential
Motif1051 – 108434Nuclear export signal By similarity

Sites

Active site8031 By similarity

Amino acid modifications

Modified residue2461Phosphoserine; by CaMK4
Modified residue4671Phosphoserine; by CaMK4
Modified residue5651Phosphoserine
Modified residue6321Phosphoserine; by CaMK4
Modified residue6331Phosphoserine
Cross-link559Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)

Natural variations

Natural variant7271P → R in a breast cancer sample; somatic mutation.
VAR_036042

Experimental info

Mutagenesis2461S → A: Reduces phosphorylation and its subsequent nuclear export
Mutagenesis4671S → A: Reduces phosphorylation and its subsequent nuclear export
Mutagenesis5591K → R: Abolishes sumoylation and reduces the histone deacetylase activity
Mutagenesis6321S → A: Reduces phosphorylation and its subsequent nuclear export
Mutagenesis8031H → L: Abolishes histone deacetylase activity
Mutagenesis10561V → A: Reduces CaMK-dependent nuclear export
Mutagenesis10621L → A: Reduces CaMK-dependent nuclear export

Secondary structure

1 ............................................................................... 1084
Helix Strand Turn

Details...

Hide | Top

Sequences

Sequence LengthMass (Da)Tools
P56524-1 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: DF5F30DA9C4295FD

FASTA1,084119,070
        10         20         30         40         50         60 
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPSAVPMD LRLDHQFSLP 

        70         80         90        100        110        120 
VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL SRQHEAQLHE HIKQQQEMLA 

       130        140        150        160        170        180 
MKHQQELLEH QRKLERHRQE QELEKQHREQ KLQQLKNKEK GKESAVASTE VKMKLQEFVL 

       190        200        210        220        230        240 
NKKKALAHRN LNHCISSDPR YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP 

       250        260        270        280        290        300 
LRKTASEPNL KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP 

       310        320        330        340        350        360 
SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS LPNITLGLPA 

       370        380        390        400        410        420 
TGPSAGTAGQ QDTERLTLPA LQQRLSLFPG THLTPYLSTS PLERDGGAAH SPLLQHMVLL 

       430        440        450        460        470        480 
EQPPAQAPLV TGLGALPLHA QSLVGADRVS PSIHKLRQHR PLGRTQSAPL PQNAQALQHL 

       490        500        510        520        530        540 
VIQQQHQQFL EKHKQQFQQQ QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY 

       550        560        570        580        590        600 
LDRLPGQKEA HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ 

       610        620        630        640        650        660 
RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP RFTTGLVYDT 

       670        680        690        700        710        720 
LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC IRGRKATLEE LQTVHSEAHT 

       730        740        750        760        770        780 
LLYGTNPLNR QKLDSKKLLG SLASVFVRLP CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE 

       790        800        810        820        830        840 
LVFKVATGEL KNGFAVVRPP GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD 

       850        860        870        880        890        900 
VHHGNGTQQA FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP 

       910        920        930        940        950        960 
PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA RCFGYLTKQL 

       970        980        990       1000       1010       1020 
MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL PEKVLQQRPN ANAVRSMEKV 

      1030       1040       1050       1060       1070       1080 
MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN EEAETVTAMA SLSVGVKPAE KRPDEEPMEE 


EPPL

« Hide

Hide | Top

References

« Hide 'large scale' references
[1]"Three proteins define a class of human histone deacetylases related to yeast Hda1p."
Grozinger C.M., Hassig C.A., Schreiber S.L.
Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999) [PubMed: 10220385] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Construction and characterization of human brain cDNA libraries suitable for analysis of cDNA clones encoding relatively large proteins."
Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Nomura N.
DNA Res. 4:53-59(1997) [PubMed: 9179496] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]Ohara O., Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Nomura N.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION TO N-TERMINUS.
[4]"HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional corepressor."
Wang A.H., Bertos N.R., Vezmar M., Pelletier N., Crosato M., Heng H.H., Th'ng J., Han J., Yang X.-J.
Mol. Cell. Biol. 19:7816-7827(1999) [PubMed: 10523670] [Abstract]
Cited for: CHARACTERIZATION, INTERACTION WITH MEF2C AND MEF2D, MUTAGENESIS OF HIS-803.
[5]"HDAC4 deacetylase associates with and represses the MEF2 transcription factor."
Miska E.A., Karlsson C., Langley E., Nielsen S.J., Pines J., Kouzarides T.
EMBO J. 18:5099-5107(1999) [PubMed: 10487761] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MEF2A.
[6]"Regulation of histone deacetylase 4 by binding of 14-3-3 proteins."
Wang A.H., Kruhlak M.J., Wu J., Bertos N.R., Vezmar M., Posner B.I., Bazett-Jones D.P., Yang X.-J.
Mol. Cell. Biol. 20:6904-6912(2000) [PubMed: 10958686] [Abstract]
Cited for: PHOSPHORYLATION AT SER-246; SER-467 AND SER-632, MUTAGENESIS OF SER-246; SER-467 AND SER-632.
[7]"Identification of a signal-responsive nuclear export sequence in class II histone deacetylases."
McKinsey T.A., Zhang C.-L., Olson E.N.
Mol. Cell. Biol. 21:6312-6321(2001) [PubMed: 11509672] [Abstract]
Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF VAL-1056 AND LEU-1062.
[8]"The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking."
Zhao X., Ito A., Kane C.D., Liao T.-S., Bolger T.A., Lemrow S.M., Means A.R., Yao T.-P.
J. Biol. Chem. 276:35042-35048(2001) [PubMed: 11470791] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-467 AND SER-632.
[9]"The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases."
Franco P.J., Farooqui M., Seto E., Wei L.-N.
Mol. Endocrinol. 15:1318-1328(2001) [PubMed: 11463856] [Abstract]
Cited for: INTERACTION WITH NR2C1.
[10]"The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase."
Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.
EMBO J. 21:2682-2691(2002) [PubMed: 12032081] [Abstract]
Cited for: HOMODIMERIZATION, SUMOYLATION AT LYS-559, MUTAGENESIS OF LYS-559.
[11]"Breast cancer associated transcriptional repressor PLU-1/JARID1B interacts directly with histone deacetylases."
Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., Freemont P., Taylor-Papadimitriou J.
Int. J. Cancer 121:265-275(2007) [PubMed: 17373667] [Abstract]
Cited for: INTERACTION WITH JARID1B.
[12]"A quantitative atlas of mitotic phosphorylation."