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Protein

Histone deacetylase 4

Gene

Hdac4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi664ZincBy similarity1
Metal bindingi666ZincBy similarity1
Metal bindingi672ZincBy similarity1
Metal bindingi743ZincBy similarity1
Active sitei795By similarity1

GO - Molecular functioni

  • activating transcription factor binding Source: MGI
  • chromatin binding Source: MGI
  • core promoter binding Source: MGI
  • DNA binding Source: MGI
  • histone deacetylase activity Source: MGI
  • histone deacetylase binding Source: MGI
  • NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
  • potassium ion binding Source: MGI
  • protein deacetylase activity Source: MGI
  • protein kinase binding Source: UniProtKB
  • repressing transcription factor binding Source: MGI
  • RNA polymerase III transcription factor binding Source: MGI
  • sequence-specific DNA binding Source: Ensembl
  • transcription corepressor activity Source: MGI
  • transcription factor binding Source: UniProtKB
  • zinc ion binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 4 (EC:3.5.1.98)
Short name:
HD4
Gene namesi
Name:Hdac4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:3036234. Hdac4.

Subcellular locationi

  • 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-465 and Ser-629 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation (By similarity).By similarity

GO - Cellular componenti

  • A band Source: MGI
  • actomyosin Source: MGI
  • cytoplasm Source: BHF-UCL
  • cytosol Source: MGI
  • histone deacetylase complex Source: MGI
  • neuromuscular junction Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: BHF-UCL
  • protein complex Source: Ensembl
  • sarcomere Source: MGI
  • transcriptional repressor complex Source: MGI
  • Z disc Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002810331 – 1076Histone deacetylase 4Add BLAST1076

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei209PhosphoserineCombined sources1
Modified residuei245Phosphoserine; by CaMK4 and SIK11 Publication1
Modified residuei349PhosphoserineBy similarity1
Modified residuei465Phosphoserine; by CaMK4 and SIK1Combined sources1 Publication1
Cross-linki556Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei562PhosphoserineCombined sources1
Modified residuei629Phosphoserine; by CaMK4By similarity1
Modified residuei630PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by CaMK4 at Ser-245, Ser-465 and Ser-629. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 (By similarity).By similarity
Sumoylation on Lys-556 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ6NZM9.
PaxDbiQ6NZM9.
PeptideAtlasiQ6NZM9.
PRIDEiQ6NZM9.

PTM databases

iPTMnetiQ6NZM9.
PhosphoSitePlusiQ6NZM9.

Expressioni

Gene expression databases

BgeeiENSMUSG00000026313.
CleanExiMM_HDAC4.
ExpressionAtlasiQ6NZM9. baseline and differential.
GenevisibleiQ6NZM9. MM.

Interactioni

Subunit structurei

Interacts with HDAC7. Homodimer. 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 BTBD14B. Interacts with KDM5B. Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2 (By similarity). Interacts with EP300 in the presence of TFAP2C (By similarity). Interacts with AHRR. Interacts with MYOCD.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Runx2Q087753EBI-646397,EBI-903354

GO - Molecular functioni

Protein-protein interaction databases

BioGridi229009. 14 interactors.
DIPiDIP-36317N.
IntActiQ6NZM9. 6 interactors.
MINTiMINT-5183788.
STRINGi10090.ENSMUSP00000008995.

Structurei

3D structure databases

ProteinModelPortaliQ6NZM9.
SMRiQ6NZM9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni117 – 312Interaction with MEF2ABy similarityAdd BLAST196
Regioni652 – 1076Histone deacetylaseBy similarityAdd BLAST425

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili66 – 169Sequence analysisAdd BLAST104

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi348 – 353PxLPxI/L motif; mediates interaction with ANKRA2 and 14-3-3 proteinsBy similarity6
Motifi1043 – 1076Nuclear export signalBy similarityAdd BLAST34

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi464 – 499Gln-richAdd BLAST36
Compositional biasi561 – 568Poly-Glu8

Domaini

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.By similarity
The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.By similarity

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiQ6NZM9.
KOiK11406.
OMAiSRQHESH.
OrthoDBiEOG091G0EQO.
PhylomeDBiQ6NZM9.
TreeFamiTF106174.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR033660. HDAC4.
IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PTHR10625:SF100. PTHR10625:SF100. 1 hit.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6NZM9-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPTAVPMD
60 70 80 90 100
LRLDHQFSLP LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS
110 120 130 140 150
RQHEAQLHEH IKQQQEMLAM KHQQELLEHQ RKLERHRQEQ ELEKQHREQK
160 170 180 190 200
LQQLKNKEKG KESAVASTEV KMKLQEFVLN KKKALAHRNL NHCISSDPRY
210 220 230 240 250
WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL RKTASEPNLK
260 270 280 290 300
LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
310 320 330 340 350
SPNSSSGNVS TENGIAPTVP SAPAETSLAH RLVTREGSVA PLPLYTSPSL
360 370 380 390 400
PNITLGLPAT GPAAGAAGQQ DAERLALPAL QQRILFPGTH LTPYLSTSPL
410 420 430 440 450
ERDGAAAHNP LLQHMVLLEQ PPTQTPLVTG LGALPLHSQS LVGADRVSPS
460 470 480 490 500
IHKLRQHRPL GRTQSAPLPQ NAQALQHLVI QQQHQQFLEK HKQQFQQQQL
510 520 530 540 550
HLSKIISKPS EPPRQPESHP EETEEELREH QALLDEPYLD RLPGQKEPSL
560 570 580 590 600
AGVQVKQEPI ESEEEEAEAT RETEPGQRPA TEQELLFRQQ ALLLEQQRIH
610 620 630 640 650
QLRNYQASME AAGIPVSFGS HRPLSRAQSS PASATFPMSV QEPPTKPRFT
660 670 680 690 700
TGLVYDTLML KHQCTCGNTN SHPEHAGRIQ SIWSRLQETG LRGKCECIRG
710 720 730 740 750
RKATLEELQT VHSEAHTLLY GTNPLNRQKL DSSLTSVFVR LPCGGVGVDS
760 770 780 790 800
DTIWNEVHSS GAARLAVGCV VELVFKVATG ELKNGFAVVR PPGHHAEEST
810 820 830 840 850
PMGFCYFNSV AVAAKLLQQR LNVSKILIVD WDVHHGNGTQ QAFYNDPNVL
860 870 880 890 900
YMSLHRYDDG NFFPGSGAPD EVGTGPGVGF NVNMAFTGGL EPPMGDAEYL
910 920 930 940 950
AAFRTVVMPI ANEFAPDVVL VSSGFDAVEG HPTPLGGYNL SAKCFGYLTK
960 970 980 990 1000
QLMGLAGGRL VLALEGGHDL TAICDASEAC VSALLGNELE PLPEKVLHQR
1010 1020 1030 1040 1050
PNANAVHSME KVMDIHSKYW RCLQRLSSTV GHSLIEAQKC EKEEAETVTA
1060 1070
MASLSVGVKP AEKRSEEEPM EEEPPL
Length:1,076
Mass (Da):118,562
Last modified:July 5, 2004 - v1
Checksum:iA3CCC3CCCBB903A0
GO
Isoform 2 (identifier: Q6NZM9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-171: Missing.
     732-732: S → SKKLLG

Note: No experimental confirmation available.
Show »
Length:910
Mass (Da):99,124
Checksum:i80C1A8CA5567EE19
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti569A → S in BAE33147 (PubMed:16141072).Curated1
Sequence conflicti904R → K in BAE33147 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0239521 – 171Missing in isoform 2. 1 PublicationAdd BLAST171
Alternative sequenceiVSP_023953732S → SKKLLG in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK029933 mRNA. Translation: BAE43272.1.
AK155250 mRNA. Translation: BAE33147.1.
AK162369 mRNA. Translation: BAE36877.1.
BC066052 mRNA. Translation: AAH66052.1.
CCDSiCCDS48324.1. [Q6NZM9-1]
RefSeqiNP_997108.1. NM_207225.2. [Q6NZM9-1]
XP_017174977.1. XM_017319488.1. [Q6NZM9-1]
UniGeneiMm.318567.

Genome annotation databases

EnsembliENSMUST00000008995; ENSMUSP00000008995; ENSMUSG00000026313. [Q6NZM9-1]
ENSMUST00000097644; ENSMUSP00000095249; ENSMUSG00000026313. [Q6NZM9-1]
GeneIDi208727.
KEGGimmu:208727.
UCSCiuc007cbe.2. mouse. [Q6NZM9-2]
uc007cbf.2. mouse. [Q6NZM9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK029933 mRNA. Translation: BAE43272.1.
AK155250 mRNA. Translation: BAE33147.1.
AK162369 mRNA. Translation: BAE36877.1.
BC066052 mRNA. Translation: AAH66052.1.
CCDSiCCDS48324.1. [Q6NZM9-1]
RefSeqiNP_997108.1. NM_207225.2. [Q6NZM9-1]
XP_017174977.1. XM_017319488.1. [Q6NZM9-1]
UniGeneiMm.318567.

3D structure databases

ProteinModelPortaliQ6NZM9.
SMRiQ6NZM9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi229009. 14 interactors.
DIPiDIP-36317N.
IntActiQ6NZM9. 6 interactors.
MINTiMINT-5183788.
STRINGi10090.ENSMUSP00000008995.

PTM databases

iPTMnetiQ6NZM9.
PhosphoSitePlusiQ6NZM9.

Proteomic databases

EPDiQ6NZM9.
PaxDbiQ6NZM9.
PeptideAtlasiQ6NZM9.
PRIDEiQ6NZM9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000008995; ENSMUSP00000008995; ENSMUSG00000026313. [Q6NZM9-1]
ENSMUST00000097644; ENSMUSP00000095249; ENSMUSG00000026313. [Q6NZM9-1]
GeneIDi208727.
KEGGimmu:208727.
UCSCiuc007cbe.2. mouse. [Q6NZM9-2]
uc007cbf.2. mouse. [Q6NZM9-1]

Organism-specific databases

CTDi9759.
MGIiMGI:3036234. Hdac4.

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiQ6NZM9.
KOiK11406.
OMAiSRQHESH.
OrthoDBiEOG091G0EQO.
PhylomeDBiQ6NZM9.
TreeFamiTF106174.

Miscellaneous databases

ChiTaRSiHdac4. mouse.
PROiQ6NZM9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000026313.
CleanExiMM_HDAC4.
ExpressionAtlasiQ6NZM9. baseline and differential.
GenevisibleiQ6NZM9. MM.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR033660. HDAC4.
IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PTHR10625:SF100. PTHR10625:SF100. 1 hit.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.
ProtoNetiSearch...

Entry informationi

Entry nameiHDAC4_MOUSE
AccessioniPrimary (citable) accession number: Q6NZM9
Secondary accession number(s): Q3TRZ9, Q3U2J3, Q3V3Y4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: July 5, 2004
Last modified: November 30, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.