Target Information
| Target General Information | Top | |||||
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| Target ID |
T23984
(Former ID: TTDI03064)
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| Target Name |
Bromodomain-containing protein 7 (BRD7)
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| Synonyms |
Protein CELTIX-1; CELTIX1; BP75; 75 kDa bromodomain protein
Click to Show/Hide
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| Gene Name |
BRD7
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
May play a role in chromatin remodeling. Activator of the Wnt signaling pathway in a DVL1-dependent manner by negatively regulating the GSK3B phosphotransferase activity. Induces dephosphorylation of GSK3B at 'Tyr-216'. Down-regulates TRIM24-mediated activation of transcriptional activation by AR. Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation at 'Lys-9' (H3K9ac). Binds to the ESR1 promoter. Recruits BRCA1 and POU2F1 to the ESR1 promoter. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Promotes acetylation of TP53 at 'Lys-382', and thereby promotes efficient recruitment of TP53 to target promoters. Inhibits cell cycle progression from G1 to S phase. Acts both as coactivator and as corepressor.
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| BioChemical Class |
Bromodomain
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| UniProt ID | ||||||
| Sequence |
MGKKHKKHKSDKHLYEEYVEKPLKLVLKVGGNEVTELSTGSSGHDSSLFEDKNDHDKHKD
RKRKKRKKGEKQIPGEEKGRKRRRVKEDKKKRDRDRVENEAEKDLQCHAPVRLDLPPEKP LTSSLAKQEEVEQTPLQEALNQLMRQLQRKDPSAFFSFPVTDFIAPGYSMIIKHPMDFST MKEKIKNNDYQSIEELKDNFKLMCTNAMIYNKPETIYYKAAKKLLHSGMKILSQERIQSL KQSIDFMADLQKTRKQKDGTDTSQSGEDGGCWQREREDSGDAEAHAFKSPSKENKKKDKD MLEDKFKSNNLEREQEQLDRIVKESGGKLTRRLVNSQCEFERRKPDGTTTLGLLHPVDPI VGEPGYCPVRLGMTTGRLQSGVNTLQGFKEDKRNKVTPVLYLNYGPYSSYAPHYDSTFAN ISKDDSDLIYSTYGEDSDLPSDFSIHEFLATCQDYPYVMADSLLDVLTKGGHSRTLQEME MSLPEDEGHTRTLDTAKEMEITEVEPPGRLDSSTQDRLIALKAVTNFGVPVEVFDSEEAE IFQKKLDETTRLLRELQEAQNERLSTRPPPNMICLLGPSYREMHLAEQVTNNLKELAQQV TPGDIVSTYGVRKAMGISIPSPVMENNFVDLTEDTEEPKKTDVAECGPGGS 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: Bromosporine | Ligand Info | |||||
| Structure Description | Crystal structure of the bromodomain of human BRD7 bound to bromosporine | PDB:6V1H | ||||
| Method | X-ray diffraction | Resolution | 1.93 Å | Mutation | No | [2] |
| PDB Sequence |
EQTPLQEALN
141 QLMRQLQRKD151 PSAFFSFPVT161 DFIAPGYSMI171 IKHPMDFSTM181 KEKIKNNDYQ 191 SIEELKDNFK201 LMCTNAMIYN211 KPETIYYKAA221 KKLLHSGMKI231 LSQERIQSLK 241 QSIDFMA
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| Ligand Name: BI 7273 | Ligand Info | |||||
| Structure Description | Crystal structure of the bromodomain of human BRD7 bound to BI7273 | PDB:6V1E | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
EQTPLQEALN
141 QLMRQLQRKD151 PSAFFSFPVT161 DFIAPGYSMI171 IKHPMDFSTM181 KEKIKNNDYQ 191 SIEELKDNFK201 LMCTNAMIYN211 KPETIYYKAA221 KKLLHSGMKI231 LSQERIQSLK 241 QSIDFMADL
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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).
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
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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| Degree | 15 | Degree centrality | 1.61E-03 | Betweenness centrality | 2.83E-04 |
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| Closeness centrality | 2.42E-01 | Radiality | 1.42E+01 | Clustering coefficient | 6.10E-01 |
| Neighborhood connectivity | 5.19E+01 | Topological coefficient | 1.08E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| 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 | LP99: Discovery and Synthesis of the First Selective BRD7/9 Bromodomain Inhibitor. Angew Chem Int Ed Engl. 2015 May 18;54(21):6217-21. | |||||
| REF 2 | Structural Basis of Inhibitor Selectivity in the BRD7/9 Subfamily of Bromodomains. J Med Chem. 2020 Mar 26;63(6):3227-3237. | |||||
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