Target Information
| Target General Information | Top | |||||
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| Target ID |
T56108
(Former ID: TTDI03589)
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| Target Name |
Tripartite motif-containing 24 (TRIM24)
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| Synonyms |
Tripartite motif-containing protein 24; Transcription intermediary factor 1-alpha; TIF1A; TIF1-alpha; TIF1; RNF82; RING-type E3 ubiquitin transferase TIF1-alpha; RING finger protein 82; E3 ubiquitin-protein ligase TRIM24
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| Gene Name |
TRIM24
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Interacts with chromatin depending on histone H3 modifications, having the highest affinity for histone H3 that is both unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-23' (H3K23ac). Has E3 protein-ubiquitin ligase activity. Promotes ubiquitination and proteasomal degradation of p53/TP53. Plays a role in the regulation of cell proliferation and apoptosis, at least in part via its effects on p53/TP53 levels. Up-regulates ligand-dependent transcription activation by AR, GCR/NR3C1, thyroid hormone receptor (TR) and ESR1. Modulates transcription activation by retinoic acid (RA) receptors, including RARA. Plays a role in regulating retinoic acid-dependent proliferation of hepatocytes. Transcriptional coactivator that interacts with numerous nuclear receptors and coactivators and modulates the transcription of target genes.
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| BioChemical Class |
Acyltransferase
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| UniProt ID | ||||||
| EC Number |
EC 2.3.2.27
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| Sequence |
MEVAVEKAVAAAAAASAAASGGPSAAPSGENEAESRQGPDSERGGEAARLNLLDTCAVCH
QNIQSRAPKLLPCLHSFCQRCLPAPQRYLMLPAPMLGSAETPPPVPAPGSPVSGSSPFAT QVGVIRCPVCSQECAERHIIDNFFVKDTTEVPSSTVEKSNQVCTSCEDNAEANGFCVECV EWLCKTCIRAHQRVKFTKDHTVRQKEEVSPEAVGVTSQRPVFCPFHKKEQLKLYCETCDK LTCRDCQLLEHKEHRYQFIEEAFQNQKVIIDTLITKLMEKTKYIKFTGNQIQNRIIEVNQ NQKQVEQDIKVAIFTLMVEINKKGKALLHQLESLAKDHRMKLMQQQQEVAGLSKQLEHVM HFSKWAVSSGSSTALLYSKRLITYRLRHLLRARCDASPVTNNTIQFHCDPSFWAQNIINL GSLVIEDKESQPQMPKQNPVVEQNSQPPSGLSSNQLSKFPTQISLAQLRLQHMQQQVMAQ RQQVQRRPAPVGLPNPRMQGPIQQPSISHQQPPPRLINFQNHSPKPNGPVLPPHPQQLRY PPNQNIPRQAIKPNPLQMAFLAQQAIKQWQISSGQGTPSTTNSTSSTPSSPTITSAAGYD GKAFGSPMIDLSSPVGGSYNLPSLPDIDCSSTIMLDNIVRKDTNIDHGQPRPPSNRTVQS PNSSVPSPGLAGPVTMTSVHPPIRSPSASSVGSRGSSGSSSKPAGADSTHKVPVVMLEPI RIKQENSGPPENYDFPVVIVKQESDEESRPQNANYPRSILTSLLLNSSQSSTSEETVLRS DAPDSTGDQPGLHQDNSSNGKSEWLDPSQKSPLHVGETRKEDDPNEDWCAVCQNGGELLC CEKCPKVFHLSCHVPTLTNFPSGEWICTFCRDLSKPEVEYDCDAPSHNSEKKKTEGLVKL TPIDKRKCERLLLFLYCHEMSLAFQDPVPLTVPDYYKIIKNPMDLSTIKKRLQEDYSMYS KPEDFVADFRLIFQNCAEFNEPDSEVANAGIKLENYFEELLKNLYPEKRFPKPEFRNESE DNKFSDDSDDDFVQPRKKRLKSIEERQLLK 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: 2,4-dimethoxy-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)benzenesulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of TRIM24 PHD-bromodomain complexed with 2,4-dimethoxy-N-(1-methyl-2-oxo-1,2,3,4-tetrahydroquinolin-6-yl)benzene-1-sulfonamide (3b) | PDB:4YAD | ||||
| Method | X-ray diffraction | Resolution | 1.73 Å | Mutation | No | [2] |
| PDB Sequence |
PNEDWCAVCQ
833 NGGELLCCEK843 CPKVFHLSCH853 VPTLTNFPSG863 EWICTFCRDL873 SKPEVEYDCD 883 APKKKTEGLV898 KLTPIDKRKC908 ERLLLFLYCH918 EMSLAFQDPV928 PLTVPDYYKI 938 IKNPMDLSTI948 KKRLQEDYSM958 YSKPEDFVAD968 FRLIFQNCAE978 FNEPDSEVAN 988 AGIKLENYFE998 ELLKNLYP
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| Ligand Name: N-(1,3-Dimethyl-2-Oxo-6-{3-[(3s)-Tetrahydrofuran-3-Ylmethoxy]phenoxy}-2,3-Dihydro-1h-Benzimidazol-5-Yl)-1-Methyl-1h-Imidazole-4-Sulfonamide | Ligand Info | |||||
| Structure Description | Crystal structure of TRIM24 PHD-bromodomain complexed with N-{1,3-dimethyl-2-oxo-6-[3-(oxolan-3-ylmethoxy)phenoxy]-2,3-dihydro-1H-1,3-benzodiazol-5-yl}-1-methyl-1H-imidazole-4-sulfonamide (7l) | PDB:4YBT | ||||
| Method | X-ray diffraction | Resolution | 1.82 Å | Mutation | No | [2] |
| PDB Sequence |
PNEDWCAVCQ
833 NGGELLCCEK843 CPKVFHLSCH853 VPTLTNFPSG863 EWICTFCRDL873 SKPEVEYDCD 883 APKKKTEGLV898 KLTPIDKRKC908 ERLLLFLYCH918 EMSLAFQDPV928 PLTVPDYYKI 938 IKNPMDLSTI948 KKRLQEDYSM958 YSKPEDFVAD968 FRLIFQNCAE978 FNEPDSEVAN 988 AGIKLENYFE998 ELLKNLYP
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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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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 | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 1.16E-05 |
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| Closeness centrality | 2.21E-01 | Radiality | 1.39E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 7.00E+01 | Topological coefficient | 5.04E-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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| 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 | Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF. J Med Chem. 2016 Feb 25;59(4):1642-7. | |||||
| REF 2 | Structure-Guided Design of IACS-9571, a Selective High-Affinity Dual TRIM24-BRPF1 Bromodomain Inhibitor. J Med Chem. 2016 Feb 25;59(4):1440-54. | |||||
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