Target Information
| Target General Information | Top | |||||
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| Target ID |
T98698
(Former ID: TTDI03261)
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| Target Name |
Histone deacetylase 7 (HDAC7)
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| Synonyms |
Histone deacetylase 7A; HDAC7A; HD7a; HD7
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| Gene Name |
HDAC7
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
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 by repressing transcription of myocyte enhancer factors such as MEF2A, MEF2B and MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. May be involved in Epstein-Barr virus (EBV) latency, possibly by repressing the viral BZLF1 gene. Positively regulates the transcriptional repressor activity of FOXP3. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).
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| BioChemical Class |
Carbon-nitrogen hydrolase
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| UniProt ID | ||||||
| EC Number |
EC 3.5.1.98
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| Sequence |
MDLRVGQRPPVEPPPEPTLLALQRPQRLHHHLFLAGLQQQRSVEPMRLSMDTPMPELQVG
PQEQELRQLLHKDKSKRSAVASSVVKQKLAEVILKKQQAALERTVHPNSPGIPYRTLEPL ETEGATRSMLSSFLPPVPSLPSDPPEHFPLRKTVSEPNLKLRYKPKKSLERRKNPLLRKE SAPPSLRRRPAETLGDSSPSSSSTPASGCSSPNDSEHGPNPILGSEALLGQRLRLQETSV APFALPTVSLLPAITLGLPAPARADSDRRTHPTLGPRGPILGSPHTPLFLPHGLEPEAGG TLPSRLQPILLLDPSGSHAPLLTVPGLGPLPFHFAQSLMTTERLSGSGLHWPLSRTRSEP LPPSATAPPPPGPMQPRLEQLKTHVQVIKRSAKPSEKPRLRQIPSAEDLETDGGGPGQVV DDGLEHRELGHGQPEARGPAPLQQHPQVLLWEQQRLAGRLPRGSTGDTVLLPLAQGGHRP LSRAQSSPAAPASLSAPEPASQARVLSSSETPARTLPFTTGLIYDSVMLKHQCSCGDNSR HPEHAGRIQSIWSRLQERGLRSQCECLRGRKASLEELQSVHSERHVLLYGTNPLSRLKLD NGKLAGLLAQRMFVMLPCGGVGVDTDTIWNELHSSNAARWAAGSVTDLAFKVASRELKNG FAVVRPPGHHADHSTAMGFCFFNSVAIACRQLQQQSKASKILIVDWDVHHGNGTQQTFYQ DPSVLYISLHRHDDGNFFPGSGAVDEVGAGSGEGFNVNVAWAGGLDPPMGDPEYLAAFRI VVMPIAREFSPDLVLVSAGFDAAEGHPAPLGGYHVSAKCFGYMTQQLMNLAGGAVVLALE GGHDLTAICDASEACVAALLGNRVDPLSEEGWKQKPNLNAIRSLEAVIRVHSKYWGCMQR LASCPDSWVPRVPGADKEEVEAVTALASLSVGILAEDRPSEQLVEEEEPMNL Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Vorinostat | Ligand Info | |||||
| Structure Description | Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with SAHA | PDB:3C0Z | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [3] |
| PDB Sequence |
TLPFTTGLIY
524 DSVMLKHQCS534 CGDNSRHPEH544 AGRIQSIWSR554 LQERGLRSQC564 ECLRGRKASL 574 EELQSVHSER584 HVLLYGTNPL594 SRLKLDNGKL604 AGLLAQVMLP617 CGGVGVDTDT 627 IWNELHSSNA637 ARWAAGSVTD647 LAFKVASREL657 KNGFAVVRPP667 GHHADHSTAM 677 GFCFFNSVAI687 ACRQLQQQSK697 ASKILIVDWD707 VHHGNGTQQT717 FYQDPSVLYI 727 SLHRHDDGNF737 FPGSGAVDEV747 GAGSGEGFNV757 NVAWAGGLDP767 PMGDPEYLAA 777 FRIVVMPIAR787 EFSPDLVLVS797 AGFDAAEGHP807 APLGGYHVSA817 KCFGYMTQQL 827 MNLAGGAVVL837 ALEGGHDLTA847 ICDASEACVA857 ALLGNRVDPL867 SEEGWKQKPN 877 LNAIRSLEAV887 IRVHSKYWGC897 MQR
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| Ligand Name: Trichostatin A | Ligand Info | |||||
| Structure Description | Crystal structure of catalytic domain of human histone deacetylase HDAC7 in complex with Trichostatin A (TSA) | PDB:3C10 | ||||
| Method | X-ray diffraction | Resolution | 2.00 Å | Mutation | No | [3] |
| PDB Sequence |
TLPFTTGLIY
524 DSVMLKHQCS534 CGDNSRHPEH544 AGRIQSIWSR554 LQERGLRSQC564 ECLRGRKASL 574 EELQSVHSER584 HVLLYGTNPL594 SRLKLDNGKL604 AGLLAQVMLP617 CGGVGVDTDT 627 IWNELHSSNA637 ARWAAGSVTD647 LAFKVASREL657 KNGFAVVRPP667 GHHADHSTAM 677 GFCFFNSVAI687 ACRQLQQQSK697 ASKILIVDWD707 VHHGNGTQQT717 FYQDPSVLYI 727 SLHRHDDGNF737 FPGSGAVDEV747 GAGSGEGFNV757 NVAWAGGLDP767 PMGDPEYLAA 777 FRIVVMPIAR787 EFSPDLVLVS797 AGFDAAEGHP807 APLGGYHVSA817 KCFGYMTQQL 827 MNLAGGAVVL837 ALEGGHDLTA847 ICDASEACVA857 ALLGNRVDPL867 SEEGWKQKPN 877 LNAIRSLEAV887 IRVHSKYWGC897 MQR
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neutrophil extracellular trap formation | hsa04613 | Affiliated Target |
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| Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
| Degree | 10 | Degree centrality | 1.07E-03 | Betweenness centrality | 2.09E-05 |
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| Closeness centrality | 2.38E-01 | Radiality | 1.42E+01 | Clustering coefficient | 3.33E-01 |
| Neighborhood connectivity | 6.03E+01 | Topological coefficient | 1.59E-01 | Eccentricity | 11 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | HDAC inhibitors: a 2013-2017 patent survey.Expert Opin Ther Pat. 2018 Apr 19:1-17. | |||||
| REF 2 | Selective class IIa histone deacetylase inhibition via a nonchelating zinc-binding group. Nat Chem Biol. 2013 May;9(5):319-25. | |||||
| REF 3 | Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem. 2008 Apr 25;283(17):11355-63. | |||||
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