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Protein

Histone deacetylase 4

Gene

HDAC4

Organism
Homo sapiens (Human)
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. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.2 Publications

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 bindingi667ZincBy similarity1
Metal bindingi669ZincBy similarity1
Metal bindingi675ZincBy similarity1
Metal bindingi751ZincBy similarity1
Active sitei803By similarity1

GO - Molecular functioni

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

GO - Biological processi

  • B cell activation Source: UniProtKB
  • B cell differentiation Source: UniProtKB
  • cardiac muscle hypertrophy in response to stress Source: BHF-UCL
  • cellular response to mechanical stimulus Source: Ensembl
  • cellular response to parathyroid hormone stimulus Source: Ensembl
  • cellular response to tumor necrosis factor Source: Ensembl
  • chromatin remodeling Source: BHF-UCL
  • histone deacetylation Source: BHF-UCL
  • histone H3 deacetylation Source: BHF-UCL
  • histone H4 deacetylation Source: BHF-UCL
  • inflammatory response Source: UniProtKB
  • negative regulation of cell proliferation Source: Ensembl
  • negative regulation of glycolytic process Source: BHF-UCL
  • negative regulation of myotube differentiation Source: BHF-UCL
  • negative regulation of osteoblast differentiation Source: Ensembl
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • nervous system development Source: UniProtKB
  • osteoblast development Source: Ensembl
  • peptidyl-lysine deacetylation Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of lamellipodium assembly Source: Ensembl
  • positive regulation of neuron apoptotic process Source: Ensembl
  • positive regulation of protein sumoylation Source: UniProtKB
  • positive regulation of reactive oxygen species biosynthetic process Source: Ensembl
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • positive regulation of smooth muscle cell migration Source: Ensembl
  • positive regulation of smooth muscle cell proliferation Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of cardiac muscle contraction by calcium ion signaling Source: Ensembl
  • regulation of gene expression, epigenetic Source: UniProtKB
  • regulation of protein binding Source: BHF-UCL
  • regulation of skeletal muscle fiber development Source: Ensembl
  • response to denervation involved in regulation of muscle adaptation Source: BHF-UCL
  • response to drug Source: Ensembl
  • response to interleukin-1 Source: BHF-UCL
  • skeletal system development Source: Ensembl
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS00927-MONOMER.
BRENDAi3.5.1.98. 2681.
ReactomeiR-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
SIGNORiP56524.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 4 (EC:3.5.1.98)
Short name:
HD4
Gene namesi
Name:HDAC4
Synonyms:KIAA0288
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:14063. 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-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation.

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Brachydactyly-mental retardation syndrome (BDMR)3 Publications
The gene represented in this entry is involved in disease pathogenesis. HDAC4 point mutations and chromosomal microdeletions encompassing this gene have been found in BDMR patients (PubMed:20691407, PubMed:24715439, PubMed:23188045). However, HDAC4 haploinsufficiency is not fully penetrant and multiple genes may contribute to manifestation of the full phenotypic spectrum (PubMed:24715439, PubMed:23188045).3 Publications
Disease descriptionA syndrome resembling the physical anomalies found in Albright hereditary osteodystrophy. Common features are mild facial dysmorphism, congenital heart defects, distinct brachydactyly type E, mental retardation, developmental delay, seizures, autism spectrum disorder, and stocky build. Soft tissue ossification is absent, and there are no abnormalities in parathyroid hormone or calcium metabolism.
See also OMIM:600430

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi246S → A: Reduces phosphorylation and its subsequent nuclear export. 1 Publication1
Mutagenesisi345L → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi346Y → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi347T → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi348S → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi349P → A: May affect interaction with ANKRA2. 2 Publications1
Mutagenesisi349P → G: Decreased interaction with ANKRA2. 1 Publication1
Mutagenesisi350S → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi351L → A or G: Loss of interaction with ANKRA2. 1 Publication1
Mutagenesisi352P → A: Loss of interaction with ANKRA2. 1 Publication1
Mutagenesisi353N → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi354I → A: May affect interaction with ANKRA2. 2 Publications1
Mutagenesisi354I → G: Loss of interaction with ANKRA2. 1 Publication1
Mutagenesisi355T → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi356L → A: No effect on interaction with ANKRA2. 1 Publication1
Mutagenesisi467S → A: Reduces phosphorylation and its subsequent nuclear export. 2 Publications1
Mutagenesisi559K → R: Abolishes sumoylation and reduces the histone deacetylase activity. 1 Publication1
Mutagenesisi632S → A: Reduces phosphorylation and its subsequent nuclear export. 2 Publications1
Mutagenesisi803H → L: Abolishes histone deacetylase activity. 1 Publication1
Mutagenesisi1056V → A: Reduces CaMK-dependent nuclear export. 1 Publication1
Mutagenesisi1062L → A: Reduces CaMK-dependent nuclear export. 1 Publication1

Keywords - Diseasei

Autism spectrum disorder, Mental retardation

Organism-specific databases

DisGeNETi9759.
MalaCardsiHDAC4.
MIMi600430. phenotype.
OpenTargetsiENSG00000068024.
Orphaneti1001. 2q37 microdeletion syndrome.
PharmGKBiPA29229.

Chemistry databases

ChEMBLiCHEMBL3524.
DrugBankiDB06603. Panobinostat.
DB06176. Romidepsin.
GuidetoPHARMACOLOGYi2659.

Polymorphism and mutation databases

BioMutaiHDAC4.
DMDMi259016348.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001146991 – 1084Histone deacetylase 4Add BLAST1084

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei210PhosphoserineBy similarity1
Modified residuei246Phosphoserine; by CaMK4 and SIK11 Publication1
Modified residuei350PhosphoserineCombined sources1 Publication1
Modified residuei467Phosphoserine; by CaMK4 and SIK11 Publication1
Cross-linki559Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)1 Publication
Modified residuei565PhosphoserineBy similarity1
Modified residuei632Phosphoserine; by CaMK4Combined sources1 Publication1
Modified residuei633PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CaMK4 at Ser-246, Ser-467 and Ser-632. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-350, within the PxLPxI/L motif, impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3.2 Publications
Sumoylation on Lys-559 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP56524.
MaxQBiP56524.
PaxDbiP56524.
PeptideAtlasiP56524.
PRIDEiP56524.

PTM databases

iPTMnetiP56524.
PhosphoSitePlusiP56524.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000068024.
CleanExiHS_HDAC4.
ExpressionAtlasiP56524. baseline and differential.
GenevisibleiP56524. HS.

Organism-specific databases

HPAiCAB004431.
HPA048723.

Interactioni

Subunit structurei

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 KDM5B. Interacts with MYOCD (By similarity). Interacts with MORC2. Interacts (via PxLPxI/L motif) with ANKRA2 (via ankyrin repeats). Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2. Interacts with EP300 in the presence of TFAP2C.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ANKRA2Q9H9E13EBI-308629,EBI-10215533
ARP102754EBI-308629,EBI-608057
ATF2P153362EBI-308629,EBI-1170906
BCL6P411823EBI-308629,EBI-765407
BRMS1Q9HCU92EBI-308629,EBI-714781
CCDC136Q96JN2-23EBI-308629,EBI-10171416
CDR2Q018503EBI-308629,EBI-1181367
EFEMP2O959673EBI-308629,EBI-743414
GOLGA2Q083793EBI-308629,EBI-618309
ICP0P083933EBI-308629,EBI-6148881From a different organism.
KRT31Q153233EBI-308629,EBI-948001
KRT38O760153EBI-308629,EBI-1047263
KRT40Q6A1623EBI-308629,EBI-10171697
LDOC1O957513EBI-308629,EBI-740738
MIF4GDA9UHW64EBI-308629,EBI-373498
MTUS2Q5JR593EBI-308629,EBI-742948
PNMA1Q8ND903EBI-308629,EBI-302345
RINT1Q6NUQ13EBI-308629,EBI-726876
RUNX3Q137619EBI-308629,EBI-925990
SFNP319474EBI-308629,EBI-476295
UBE2IP632793EBI-308629,EBI-80168
YWHABP319463EBI-308629,EBI-359815
YWHAEP622584EBI-308629,EBI-356498
YWHAGP619816EBI-308629,EBI-359832
YWHAHQ049174EBI-308629,EBI-306940
YWHAZP631045EBI-308629,EBI-347088

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • histone deacetylase binding Source: BHF-UCL
  • repressing transcription factor binding Source: BHF-UCL
  • RNA polymerase III transcription factor binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi115106. 139 interactors.
DIPiDIP-34565N.
IntActiP56524. 70 interactors.
MINTiMINT-104901.
STRINGi9606.ENSP00000264606.

Chemistry databases

BindingDBiP56524.

Structurei

Secondary structure

11084
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi64 – 112Combined sources49
Helixi115 – 121Combined sources7
Turni122 – 125Combined sources4
Helixi126 – 128Combined sources3
Turni354 – 357Combined sources4
Beta strandi652 – 657Combined sources6
Helixi660 – 662Combined sources3
Beta strandi673 – 675Combined sources3
Helixi681 – 691Combined sources11
Helixi694 – 697Combined sources4
Beta strandi698 – 701Combined sources4
Helixi708 – 711Combined sources4
Turni712 – 714Combined sources3
Helixi717 – 724Combined sources8
Helixi727 – 730Combined sources4
Helixi737 – 745Combined sources9
Beta strandi746 – 748Combined sources3
Beta strandi754 – 756Combined sources3
Helixi762 – 786Combined sources25
Beta strandi789 – 795Combined sources7
Beta strandi813 – 815Combined sources3
Helixi817 – 828Combined sources12
Beta strandi834 – 838Combined sources5
Beta strandi840 – 842Combined sources3
Helixi845 – 851Combined sources7
Beta strandi857 – 864Combined sources8
Helixi866 – 868Combined sources3
Beta strandi870 – 872Combined sources3
Helixi883 – 885Combined sources3
Beta strandi889 – 894Combined sources6
Beta strandi898 – 900Combined sources3
Helixi904 – 913Combined sources10
Helixi915 – 922Combined sources8
Beta strandi925 – 931Combined sources7
Beta strandi936 – 938Combined sources3
Turni940 – 943Combined sources4
Helixi950 – 961Combined sources12
Helixi964 – 966Combined sources3
Beta strandi968 – 972Combined sources5
Helixi978 – 992Combined sources15
Helixi1002 – 1006Combined sources5
Helixi1011 – 1025Combined sources15
Helixi1029 – 1031Combined sources3
Helixi1042 – 1047Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H8NX-ray2.60A/B/C/D62-153[»]
2O94X-ray3.00A/B/C/D62-153[»]
2VQJX-ray2.10A648-1057[»]
2VQMX-ray1.80A648-1057[»]
2VQOX-ray2.15A/B648-1057[»]
2VQQX-ray1.90A/B648-1057[»]
2VQVX-ray3.30A/B648-1057[»]
2VQWX-ray3.00G648-1057[»]
3UXGX-ray1.85B343-359[»]
3UZDX-ray1.86B343-359[»]
3V31X-ray1.57B343-359[»]
4CBTX-ray3.03A/B/C648-1033[»]
4CBYX-ray2.72A/B/C/D648-1033[»]
5A2SX-ray2.65A/B648-1033[»]
ProteinModelPortaliP56524.
SMRiP56524.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56524.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni118 – 313Interaction with MEF2A1 PublicationAdd BLAST196
Regioni655 – 1084Histone deacetylaseAdd BLAST430

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili67 – 177Sequence analysisAdd BLAST111

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi349 – 354PxLPxI/L motif; mediates interaction with ANKRA2 and 14-3-3 proteins1 Publication6
Motifi1051 – 1084Nuclear export signalBy similarityAdd BLAST34

Domaini

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
The PxLPxI/L motif mediates interaction with ankyrin repeats of ANKRA2.1 Publication

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiP56524.
KOiK11406.
OMAiSRQHESH.
OrthoDBiEOG091G0EQO.
PhylomeDBiP56524.
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: P56524-1) [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 QVAPSAVPMD
60 70 80 90 100
LRLDHQFSLP VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL
110 120 130 140 150
SRQHEAQLHE HIKQQQEMLA MKHQQELLEH QRKLERHRQE QELEKQHREQ
160 170 180 190 200
KLQQLKNKEK GKESAVASTE VKMKLQEFVL NKKKALAHRN LNHCISSDPR
210 220 230 240 250
YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP LRKTASEPNL
260 270 280 290 300
KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP
310 320 330 340 350
SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS
360 370 380 390 400
LPNITLGLPA TGPSAGTAGQ QDAERLTLPA LQQRLSLFPG THLTPYLSTS
410 420 430 440 450
PLERDGGAAH SPLLQHMVLL EQPPAQAPLV TGLGALPLHA QSLVGADRVS
460 470 480 490 500
PSIHKLRQHR PLGRTQSAPL PQNAQALQHL VIQQQHQQFL EKHKQQFQQQ
510 520 530 540 550
QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY LDRLPGQKEA
560 570 580 590 600
HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ
610 620 630 640 650
RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP
660 670 680 690 700
RFTTGLVYDT LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC
710 720 730 740 750
IRGRKATLEE LQTVHSEAHT LLYGTNPLNR QKLDSKKLLG SLASVFVRLP
760 770 780 790 800
CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE LVFKVATGEL KNGFAVVRPP
810 820 830 840 850
GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD VHHGNGTQQA
860 870 880 890 900
FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP
910 920 930 940 950
PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA
960 970 980 990 1000
RCFGYLTKQL MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL
1010 1020 1030 1040 1050
PEKVLQQRPN ANAVRSMEKV MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN
1060 1070 1080
EEAETVTAMA SLSVGVKPAE KRPDEEPMEE EPPL
Length:1,084
Mass (Da):119,040
Last modified:September 22, 2009 - v3
Checksum:iBB7FD37652D12398
GO
Isoform 2 (identifier: P56524-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-117: Missing.
     431-431: T → TDWYLS

Note: No experimental confirmation available.
Show »
Length:972
Mass (Da):106,367
Checksum:i86E58F178B37FDC6
GO

Sequence cautioni

The sequence BAA22957 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti373A → T in AAD29046 (PubMed:10220385).Curated1
Sequence conflicti373A → T in BAA22957 (PubMed:9179496).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036042727P → R in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_071965754V → I.1 PublicationCorresponds to variant rs151043798dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0572901 – 117Missing in isoform 2. 1 PublicationAdd BLAST117
Alternative sequenceiVSP_057291431T → TDWYLS in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132607 mRNA. Translation: AAD29046.1.
AB006626 mRNA. Translation: BAA22957.2. Different initiation.
AC017028 Genomic DNA. No translation available.
AC062017 Genomic DNA. No translation available.
KF510800 Genomic DNA. No translation available.
KF510801 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71165.1.
BC039904 mRNA. Translation: AAH39904.1.
CCDSiCCDS2529.1. [P56524-1]
RefSeqiNP_006028.2. NM_006037.3. [P56524-1]
UniGeneiHs.20516.

Genome annotation databases

EnsembliENST00000345617; ENSP00000264606; ENSG00000068024. [P56524-1]
ENST00000543185; ENSP00000440481; ENSG00000068024. [P56524-2]
GeneIDi9759.
KEGGihsa:9759.
UCSCiuc002vyk.4. human. [P56524-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132607 mRNA. Translation: AAD29046.1.
AB006626 mRNA. Translation: BAA22957.2. Different initiation.
AC017028 Genomic DNA. No translation available.
AC062017 Genomic DNA. No translation available.
KF510800 Genomic DNA. No translation available.
KF510801 Genomic DNA. No translation available.
CH471063 Genomic DNA. Translation: EAW71165.1.
BC039904 mRNA. Translation: AAH39904.1.
CCDSiCCDS2529.1. [P56524-1]
RefSeqiNP_006028.2. NM_006037.3. [P56524-1]
UniGeneiHs.20516.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2H8NX-ray2.60A/B/C/D62-153[»]
2O94X-ray3.00A/B/C/D62-153[»]
2VQJX-ray2.10A648-1057[»]
2VQMX-ray1.80A648-1057[»]
2VQOX-ray2.15A/B648-1057[»]
2VQQX-ray1.90A/B648-1057[»]
2VQVX-ray3.30A/B648-1057[»]
2VQWX-ray3.00G648-1057[»]
3UXGX-ray1.85B343-359[»]
3UZDX-ray1.86B343-359[»]
3V31X-ray1.57B343-359[»]
4CBTX-ray3.03A/B/C648-1033[»]
4CBYX-ray2.72A/B/C/D648-1033[»]
5A2SX-ray2.65A/B648-1033[»]
ProteinModelPortaliP56524.
SMRiP56524.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115106. 139 interactors.
DIPiDIP-34565N.
IntActiP56524. 70 interactors.
MINTiMINT-104901.
STRINGi9606.ENSP00000264606.

Chemistry databases

BindingDBiP56524.
ChEMBLiCHEMBL3524.
DrugBankiDB06603. Panobinostat.
DB06176. Romidepsin.
GuidetoPHARMACOLOGYi2659.

PTM databases

iPTMnetiP56524.
PhosphoSitePlusiP56524.

Polymorphism and mutation databases

BioMutaiHDAC4.
DMDMi259016348.

Proteomic databases

EPDiP56524.
MaxQBiP56524.
PaxDbiP56524.
PeptideAtlasiP56524.
PRIDEiP56524.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000345617; ENSP00000264606; ENSG00000068024. [P56524-1]
ENST00000543185; ENSP00000440481; ENSG00000068024. [P56524-2]
GeneIDi9759.
KEGGihsa:9759.
UCSCiuc002vyk.4. human. [P56524-1]

Organism-specific databases

CTDi9759.
DisGeNETi9759.
GeneCardsiHDAC4.
GeneReviewsiHDAC4.
HGNCiHGNC:14063. HDAC4.
HPAiCAB004431.
HPA048723.
MalaCardsiHDAC4.
MIMi600430. phenotype.
605314. gene.
neXtProtiNX_P56524.
OpenTargetsiENSG00000068024.
Orphaneti1001. 2q37 microdeletion syndrome.
PharmGKBiPA29229.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1343. Eukaryota.
COG0123. LUCA.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiP56524.
KOiK11406.
OMAiSRQHESH.
OrthoDBiEOG091G0EQO.
PhylomeDBiP56524.
TreeFamiTF106174.

Enzyme and pathway databases

BioCyciZFISH:HS00927-MONOMER.
BRENDAi3.5.1.98. 2681.
ReactomeiR-HSA-2122947. NOTCH1 Intracellular Domain Regulates Transcription.
R-HSA-2644606. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
R-HSA-2894862. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
SIGNORiP56524.

Miscellaneous databases

ChiTaRSiHDAC4. human.
EvolutionaryTraceiP56524.
GeneWikiiHDAC4.
GenomeRNAii9759.
PROiP56524.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000068024.
CleanExiHS_HDAC4.
ExpressionAtlasiP56524. baseline and differential.
GenevisibleiP56524. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P56524
Secondary accession number(s): E9PGB9
, F5GX36, Q86YH7, Q9UND6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: September 22, 2009
Last modified: November 30, 2016
This is version 177 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.