Target Information
| Target General Information | Top | |||||
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| Target ID |
T46216
(Former ID: TTDI03065)
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| Target Name |
Bromodomain-containing protein 9 (BRD9)
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| Synonyms |
Rhabdomyosarcoma antigen MU-RMS-40.8
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| Gene Name |
BRD9
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Acute myeloid leukaemia [ICD-11: 2A60] | |||||
| Function |
Plays a role in chromatin remodeling and regulation of transcription. Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated. Component of SWI/SNF chromatin remodeling subcomplex GBAF that carries out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner.
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| BioChemical Class |
Bromodomain
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| UniProt ID | ||||||
| Sequence |
MGKKHKKHKAEWRSSYEDYADKPLEKPLKLVLKVGGSEVTELSGSGHDSSYYDDRSDHER
ERHKEKKKKKKKKSEKEKHLDDEERRKRKEEKKRKREREHCDTEGEADDFDPGKKVEVEP PPDRPVRACRTQPAENESTPIQQLLEHFLRQLQRKDPHGFFAFPVTDAIAPGYSMIIKHP MDFGTMKDKIVANEYKSVTEFKADFKLMCDNAMTYNRPDTVYYKLAKKILHAGFKMMSKQ AALLGNEDTAVEEPVPEVVPVQVETAKKSKKPSREVISCMFEPEGNACSLTDSTAEEHVL ALVEHAADEARDRINRFLPGGKMGYLKRNGDGSLLYSVVNTAEPDADEEETHPVDLSSLS SKLLPGFTTLGFKDERRNKVTFLSSATTALSMQNNSVFGDLKSDEMELLYSAYGDETGVQ CALSLQEFVKDAGSYSKKVVDDLLDQITGGDHSRTLFQLKQRRNVPMKPPDEAKVGDTLG DSSSSVLEFMSMKSYPDVSVDISMLSSLGKVKKELDPDDSHLNLDETTKLLQDLHEAQAE RGGSRPSSNLSSLSNASERDQHHLGSPSRLSVGEQPDVTHDPYEFLQSPEPAASAKT 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: Sunitinib | Ligand Info | |||||
| Structure Description | Crystal structure of the bromodomain of human BRD9 bound to sunitinib | PDB:6V0X | ||||
| Method | X-ray diffraction | Resolution | 1.50 Å | Mutation | No | [4] |
| PDB Sequence |
STPIQQLLEH
147 FLRQLQRKDP157 HGFFAFPVTD167 AIAPGYSMII177 KHPMDFGTMK187 DKIVANEYKS 197 VTEFKADFKL207 MCDNAMTYNR217 PDTVYYKLAK227 KILHAGFKM
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| Ligand Name: I-BRD9 | Ligand Info | |||||
| Structure Description | Crystal structure of the bromodomain of human BRD9 bound to I-BRD9 | PDB:6V1B | ||||
| Method | X-ray diffraction | Resolution | 1.35 Å | Mutation | No | [4] |
| PDB Sequence |
ESTPIQQLLE
146 HFLRQLQRKD156 PHGFFAFPVT166 DAIAPGYSMI176 IKHPMDFGTM186 KDKIVANEYK 196 SVTEFKADFK206 LMCDNAMTYN216 RPDTVYYKLA226 KKILHAGFKM236 MSKERLLALK 246 RSMS
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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 | 4.38E-07 |
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| Closeness centrality | 2.06E-01 | Radiality | 1.36E+01 | Clustering coefficient | 8.29E-01 |
| Neighborhood connectivity | 2.55E+01 | Topological coefficient | 2.52E-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 | ||||||
| References | Top | |||||
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| REF 1 | Discovery of I-BRD9, a Selective Cell Active Chemical Probe for Bromodomain Containing Protein 9 Inhibition. J Med Chem. 2016 Feb 25;59(4):1425-39. | |||||
| REF 2 | Structure-Based Design of an in Vivo Active Selective BRD9 Inhibitor. J Med Chem. 2016 May 26;59(10):4462-75. | |||||
| REF 3 | 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 4 | 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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