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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi667 – 6671ZincBy similarity
Metal bindingi669 – 6691ZincBy similarity
Metal bindingi675 – 6751ZincBy similarity
Metal bindingi751 – 7511ZincBy similarity
Active sitei803 – 8031By similarity

GO - Molecular functioni

  • activating transcription factor binding Source: BHF-UCL
  • 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
  • NAD-dependent histone deacetylase activity (H3-K18 specific) Source: UniProtKB-EC
  • NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB-EC
  • NAD-dependent histone deacetylase activity (H4-K16 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
  • 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 protein sumoylation Source: UniProtKB
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • 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

BRENDAi3.5.1.98. 2681.
ReactomeiREACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.

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
ProteomesiUP000005640 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
  • 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)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

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)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi246 – 2461S → A: Reduces phosphorylation and its subsequent nuclear export. 1 Publication
Mutagenesisi467 – 4671S → A: Reduces phosphorylation and its subsequent nuclear export. 2 Publications
Mutagenesisi559 – 5591K → R: Abolishes sumoylation and reduces the histone deacetylase activity. 1 Publication
Mutagenesisi632 – 6321S → A: Reduces phosphorylation and its subsequent nuclear export. 2 Publications
Mutagenesisi803 – 8031H → L: Abolishes histone deacetylase activity. 1 Publication
Mutagenesisi1056 – 10561V → A: Reduces CaMK-dependent nuclear export. 1 Publication
Mutagenesisi1062 – 10621L → A: Reduces CaMK-dependent nuclear export. 1 Publication

Keywords - Diseasei

Autism spectrum disorder, Mental retardation

Organism-specific databases

MIMi600430. phenotype.
Orphaneti1001. 2q37 microdeletion syndrome.
PharmGKBiPA29229.

Polymorphism and mutation databases

BioMutaiHDAC4.
DMDMi259016348.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10841084Histone deacetylase 4PRO_0000114699Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei246 – 2461Phosphoserine; by CaMK4 and SIK11 Publication
Modified residuei350 – 3501Phosphoserine2 Publications
Modified residuei467 – 4671Phosphoserine; by CaMK4 and SIK11 Publication
Cross-linki559 – 559Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei632 – 6321Phosphoserine; by CaMK43 Publications
Modified residuei633 – 6331Phosphoserine1 Publication

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 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

MaxQBiP56524.
PaxDbiP56524.
PRIDEiP56524.

PTM databases

PhosphoSiteiP56524.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiP56524.
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 with ANKRA2. Interacts with EP300 in the presence of TFAP2C.By similarity7 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
YWHAHQ049173EBI-308629,EBI-306940
YWHAZP631045EBI-308629,EBI-347088

Protein-protein interaction databases

BioGridi115106. 202 interactions.
DIPiDIP-34565N.
IntActiP56524. 43 interactions.
MINTiMINT-104901.
STRINGi9606.ENSP00000264606.

Structurei

Secondary structure

1
1084
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi64 – 11249Combined sources
Helixi115 – 1217Combined sources
Turni122 – 1254Combined sources
Helixi126 – 1283Combined sources
Turni354 – 3574Combined sources
Beta strandi652 – 6576Combined sources
Helixi660 – 6623Combined sources
Beta strandi673 – 6753Combined sources
Helixi681 – 69111Combined sources
Helixi694 – 6974Combined sources
Beta strandi698 – 7014Combined sources
Helixi708 – 7114Combined sources
Turni712 – 7143Combined sources
Helixi717 – 7248Combined sources
Helixi727 – 7304Combined sources
Helixi737 – 7459Combined sources
Beta strandi746 – 7483Combined sources
Beta strandi754 – 7563Combined sources
Helixi762 – 78625Combined sources
Beta strandi789 – 7957Combined sources
Beta strandi813 – 8153Combined sources
Helixi817 – 82812Combined sources
Beta strandi834 – 8385Combined sources
Beta strandi840 – 8423Combined sources
Helixi845 – 8517Combined sources
Beta strandi857 – 8648Combined sources
Helixi866 – 8683Combined sources
Beta strandi870 – 8723Combined sources
Helixi883 – 8853Combined sources
Beta strandi889 – 8946Combined sources
Beta strandi898 – 9003Combined sources
Helixi904 – 91310Combined sources
Helixi915 – 9228Combined sources
Beta strandi925 – 9317Combined sources
Beta strandi936 – 9383Combined sources
Turni940 – 9434Combined sources
Helixi950 – 96112Combined sources
Helixi964 – 9663Combined sources
Beta strandi968 – 9725Combined sources
Helixi978 – 99215Combined sources
Helixi1002 – 10065Combined sources
Helixi1011 – 102515Combined sources
Helixi1029 – 10313Combined sources
Helixi1042 – 10476Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP56524.
SMRiP56524. Positions 62-129, 650-1051.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP56524.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni118 – 313196Interaction with MEF2AAdd
BLAST
Regioni655 – 1084430Histone deacetylaseAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili67 – 177111Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1051 – 108434Nuclear export signalBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0123.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiP56524.
KOiK11406.
OMAiDHQFSMP.
OrthoDBiEOG7RFTH5.
PhylomeDBiP56524.
TreeFamiTF106174.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR019154. Arb2_domain.
IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PfamiPF09757. Arb2. 1 hit.
PF12203. 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 BAA22957.2 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti373 – 3731A → T in AAD29046 (PubMed:10220385).Curated
Sequence conflicti373 – 3731A → T in BAA22957 (PubMed:9179496).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti727 – 7271P → R in a breast cancer sample; somatic mutation. 1 Publication
VAR_036042
Natural varianti754 – 7541V → I.1 Publication
VAR_071965

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 117117Missing in isoform 2. 1 PublicationVSP_057290Add
BLAST
Alternative sequencei431 – 4311T → TDWYLS in isoform 2. 1 PublicationVSP_057291

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
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[»]
ProteinModelPortaliP56524.
SMRiP56524. Positions 62-129, 650-1051.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115106. 202 interactions.
DIPiDIP-34565N.
IntActiP56524. 43 interactions.
MINTiMINT-104901.
STRINGi9606.ENSP00000264606.

Chemistry

BindingDBiP56524.
ChEMBLiCHEMBL3524.
GuidetoPHARMACOLOGYi2659.

PTM databases

PhosphoSiteiP56524.

Polymorphism and mutation databases

BioMutaiHDAC4.
DMDMi259016348.

Proteomic databases

MaxQBiP56524.
PaxDbiP56524.
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.
GeneCardsiGC02M239969.
GeneReviewsiHDAC4.
HGNCiHGNC:14063. HDAC4.
HPAiCAB004431.
HPA048723.
MIMi600430. phenotype.
605314. gene.
neXtProtiNX_P56524.
Orphaneti1001. 2q37 microdeletion syndrome.
PharmGKBiPA29229.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0123.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiP56524.
KOiK11406.
OMAiDHQFSMP.
OrthoDBiEOG7RFTH5.
PhylomeDBiP56524.
TreeFamiTF106174.

Enzyme and pathway databases

BRENDAi3.5.1.98. 2681.
ReactomeiREACT_118780. NOTCH1 Intracellular Domain Regulates Transcription.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.

Miscellaneous databases

ChiTaRSiHDAC4. human.
EvolutionaryTraceiP56524.
GeneWikiiHDAC4.
GenomeRNAii9759.
NextBioi35507317.
PROiP56524.
SOURCEiSearch...

Gene expression databases

BgeeiP56524.
CleanExiHS_HDAC4.
ExpressionAtlasiP56524. baseline and differential.
GenevisibleiP56524. HS.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR019154. Arb2_domain.
IPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PfamiPF09757. Arb2. 1 hit.
PF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Leukemia.
  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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    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. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Testis.
  7. "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] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH MEF2A.
  8. "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] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH MEF2C AND MEF2D, MUTAGENESIS OF HIS-803.
  9. Cited for: PHOSPHORYLATION AT SER-246; SER-467 AND SER-632, MUTAGENESIS OF SER-246; SER-467 AND SER-632.
  10. "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] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-467 AND SER-632.
  11. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEAR EXPORT SIGNAL, MUTAGENESIS OF VAL-1056 AND LEU-1062.
  12. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NR2C1.
  13. Cited for: HOMODIMERIZATION, SUMOYLATION AT LYS-559, MUTAGENESIS OF LYS-559.
  14. "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] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KDM5B.
  15. "Nuclear calcium/calmodulin-dependent protein kinase IIdelta preferentially transmits signals to histone deacetylase 4 in cardiac cells."
    Little G.H., Bai Y., Williams T., Poizat C.
    J. Biol. Chem. 282:7219-7231(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION BY CAMK2D.
  16. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632 AND SER-633, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  17. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  18. "Haploinsufficiency of HDAC4 causes brachydactyly mental retardation syndrome, with brachydactyly type E, developmental delays, and behavioral problems."
    Williams S.R., Aldred M.A., Der Kaloustian V.M., Halal F., Gowans G., McLeod D.R., Zondag S., Toriello H.V., Magenis R.E., Elsea S.H.
    Am. J. Hum. Genet. 87:219-228(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN BDMR.
  19. "Involvement of histone deacetylation in MORC2-mediated down-regulation of carbonic anhydrase IX."
    Shao Y., Li Y., Zhang J., Liu D., Liu F., Zhao Y., Shen T., Li F.
    Nucleic Acids Res. 38:2813-2824(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MORC2.
  20. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  22. "Differential regulation of estrogen receptor alpha expression in breast cancer cells by metastasis-associated protein 1."
    Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y., Kim Y.N., Seong J.K., Lee M.O.
    Cancer Res. 74:1484-1494(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH EP300.
  23. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-632, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  24. Cited for: X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 343-359 IN COMPLEX WITH ANKRA2, PHOSPHORYLATION AT SER-350.
  25. Cited for: VARIANT [LARGE SCALE ANALYSIS] ARG-727.
  26. "20 ans apres: a second mutation in MAOA identified by targeted high-throughput sequencing in a family with altered behavior and cognition."
    Piton A., Poquet H., Redin C., Masurel A., Lauer J., Muller J., Thevenon J., Herenger Y., Chancenotte S., Bonnet M., Pinoit J.M., Huet F., Thauvin-Robinet C., Jaeger A.S., Le Gras S., Jost B., Gerard B., Peoc'h K.
    , Launay J.M., Faivre L., Mandel J.L.
    Eur. J. Hum. Genet. 22:776-783(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ILE-754.

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: June 24, 2015
This is version 162 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

External Data

Dasty 3

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 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.