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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:HDAC4

Protein Summary

check button Gene summary
Gene name: HDAC4
ASpdb.0 ID: 9759
Gene
Gene symbol

HDAC4

Gene ID

9759

Gene namehistone deacetylase 4
SynonymsAHO3|BDMR|HA6116|HD4|HDAC-4|HDAC-A|HDACA|NEDCHF|NEDCHID
Cytomap

2q37.3

Type of geneprotein-coding
Descriptionhistone deacetylase 4histone deacetylase A
Modification date20240403
UniProtAcc

P56524


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneHDAC4

GO:0000118

histone deacetylase complex

11804585

GeneHDAC4

GO:0000122

negative regulation of transcription by RNA polymerase II

16236793

GeneHDAC4

GO:0000122

negative regulation of transcription by RNA polymerase II

10869435

GeneHDAC4

GO:0000785

chromatin

31127039

GeneHDAC4

GO:0000976

transcription cis-regulatory region binding

18850004

GeneHDAC4

GO:0000978

RNA polymerase II cis-regulatory region sequence-specific DNA binding

24413532

GeneHDAC4

GO:0004407

histone deacetylase activity

10220385|10869435|12590135

GeneHDAC4

GO:0005634

nucleus

10869435|19281832|23867755|26019235

GeneHDAC4

GO:0005654

nucleoplasm

-

GeneHDAC4

GO:0005737

cytoplasm

10869435|19281832

GeneHDAC4

GO:0005829

cytosol

-

GeneHDAC4

GO:0006338

chromatin remodeling

18850004

GeneHDAC4

GO:0006476

protein deacetylation

27708256

GeneHDAC4

GO:0008270

zinc ion binding

18614528

GeneHDAC4

GO:0016607

nuclear speck

-

GeneHDAC4

GO:0017053

transcription repressor complex

11804585

GeneHDAC4

GO:0030955

potassium ion binding

18614528

GeneHDAC4

GO:0033235

positive regulation of protein sumoylation

17696781

GeneHDAC4

GO:0033558

protein lysine deacetylase activity

18614528

GeneHDAC4

GO:0034983

peptidyl-lysine deacetylation

18614528

GeneHDAC4

GO:0042393

histone binding

19276356

GeneHDAC4

GO:0045814

negative regulation of gene expression, epigenetic

10869435

GeneHDAC4

GO:0060090

molecular adaptor activity

31127039

GeneHDAC4

GO:0060337

type I interferon-mediated signaling pathway

31127039



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
P56524-1P56524-1_2vqm_A.pdb2VQMX-ray1.8A6501051

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
P56524HDAC4P56524-1P56524-210849721117Deletionnonenone00
P56524HDAC4P56524-1P56524-21084972431431SubstitutionTTDWYLS314319

check buttonMultiple sequence alignment of our canonical and alternatively spliced HDAC4

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HDAC4
UniProt-idENSGENSTENSP
P56524-1ENSG00000068024.18ENST00000345617.7ENSP00000264606.3

UniProt-idNM IDNP ID
P56524-1NM_006037.3NP_006028.2

check buttonAmino acid sequences of our canonical and alternatively spliced HDAC4
accession_idProtein sequence
P56524-1MSSQSHPDGLSGRDQPVELLNPARVNHMPSTVDVATALPLQVAPSAVPMDLRLDHQFSLPVAEPALREQQLQQELLALKQKQQIQRQILI
AEFQRQHEQLSRQHEAQLHEHIKQQQEMLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVL
NKKKALAHRNLNHCISSDPRYWYGKTQHSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLR
RKDGPVVTALKKRPLDVTDSACSSAPGSGPSSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPA
TGPSAGTAGQQDAERLTLPALQQRLSLFPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLLEQPPAQAPLVTGLGALPLHAQSLVGADRVS
PSIHKLRQHRPLGRTQSAPLPQNAQALQHLVIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPY
LDRLPGQKEAHAQAGVQVKQEPIESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQASMEAAGIPVSFGGHRPLSRA
QSSPASATFPVSVQEPPTKPRFTTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHT
LLYGTNPLNRQKLDSKKLLGSLASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPM
GFCYFNSVAVAAKLLQQRLSVSKILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDP
PMGDAEYLAAFRTVVMPIASEFAPDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVS
ALLGNELDPLPEKVLQQRPNANAVRSMEKVMEIHSKYWRCLQRTTSTAGRSLIEAQTCENEEAETVTAMASLSVGVKPAEKRPDEEPMEE
P56524-2MLAMKHQQELLEHQRKLERHRQEQELEKQHREQKLQQLKNKEKGKESAVASTEVKMKLQEFVLNKKKALAHRNLNHCISSDPRYWYGKTQ
HSSLDQSSPPQSGVSTSYNHPVLGMYDAKDDFPLRKTASEPNLKLRSRLKQKVAERRSSPLLRRKDGPVVTALKKRPLDVTDSACSSAPG
SGPSSPNNSSGSVSAENGIAPAVPSIPAETSLAHRLVAREGSAAPLPLYTSPSLPNITLGLPATGPSAGTAGQQDAERLTLPALQQRLSL
FPGTHLTPYLSTSPLERDGGAAHSPLLQHMVLLEQPPAQAPLVTDWYLSGLGALPLHAQSLVGADRVSPSIHKLRQHRPLGRTQSAPLPQ
NAQALQHLVIQQQHQQFLEKHKQQFQQQQLQMNKIIPKPSEPARQPESHPEETEEELREHQALLDEPYLDRLPGQKEAHAQAGVQVKQEP
IESDEEEAEPPREVEPGQRQPSEQELLFRQQALLLEQQRIHQLRNYQASMEAAGIPVSFGGHRPLSRAQSSPASATFPVSVQEPPTKPRF
TTGLVYDTLMLKHQCTCGSSSSHPEHAGRIQSIWSRLQETGLRGKCECIRGRKATLEELQTVHSEAHTLLYGTNPLNRQKLDSKKLLGSL
ASVFVRLPCGGVGVDSDTIWNEVHSAGAARLAVGCVVELVFKVATGELKNGFAVVRPPGHHAEESTPMGFCYFNSVAVAAKLLQQRLSVS
KILIVDWDVHHGNGTQQAFYSDPSVLYMSLHRYDDGNFFPGSGAPDEVGTGPGVGFNVNMAFTGGLDPPMGDAEYLAAFRTVVMPIASEF
APDVVLVSSGFDAVEGHPTPLGGYNLSARCFGYLTKQLMGLAGGRIVLALEGGHDLTAICDASEACVSALLGNELDPLPEKVLQQRPNAN

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
HDAC4 (go to UniProt):P56524

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
P56524Coiled coil67177Ontology_term=ECO:0000255;evidence=ECO:0000255Type=Deletion;Start=1;End=117


Gene Isoform Structures and Expression Levels for HDAC4

check buttonGene structures of our canonical and alternative spliced genes of HDAC4
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of HDAC4

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of P56524-1
3D view using mol* of P56524-2


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of P56524-1
all structure
pLDDT distribution across the protein length of P56524-2
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of P56524-1
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
P56524-11.032281.085741.2230.6330.6690.8630.760.7880.9651.427104,106,107,108,110,111,114,115,118,349,350,351,48
3,485,486,487,488,489,490,491,492,493,494,495,496,
497,498,500,674,675,677,747,748,749,750,751,757,75
8,759,760,800,802,803,810,811,812,840,842,870,871,
934,942,943,974,976
P56524-21.0622071.055599.2210.4540.7911.0360.5411.1020.4911.216228,229,230,231,233,234,235,236,237,238,239,562,56
3,564,637,638,639,645,646,647,648,688,690,691,698,
699,700,728,730,758,759,760,822,830,831,861,862,86
4

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of P56524-1_P56524-1_2vqm_A.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P56524-1_2vqm_A_P56524-2.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of P56524-1_P56524-2.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/P56524-1_vs_P56524-2.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/P56524-1_vs_P56524-2.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to HDAC4


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
P56524HDAC4DB07879N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamideexperimental
P56524HDAC4DB01593Zincapproved, investigationalcofactor
P56524HDAC4DB086132,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOLexperimental
P56524HDAC4DB06176Romidepsinapproved, investigationalinhibitor
P56524HDAC4DB14487Zinc acetateapproved, investigational
P56524HDAC4DB14548Zinc sulfate, unspecified formapproved, experimentalcofactor
P56524HDAC4DB14533Zinc chlorideapproved, investigationalcofactor

Related Diseases to HDAC4


check button Previous studies relating to the alternative splicing of HDAC4 and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term


Clinically important variants in HDAC4


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance