Target Information
| Target General Information | Top | |||||
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| Target ID |
T77393
(Former ID: TTDI03618)
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| Target Name |
WD repeat-containing protein 5 (WDR5)
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| Synonyms |
BMP2-induced 3-kb gene protein; BIG3
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| Gene Name |
WDR5
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation. Contributes to histone modification.
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| UniProt ID | ||||||
| Sequence |
MATEEKKPETEAARAQPTPSSSATQSKPTPVKPNYALKFTLAGHTKAVSSVKFSPNGEWL
ASSSADKLIKIWGAYDGKFEKTISGHKLGISDVAWSSDSNLLVSASDDKTLKIWDVSSGK CLKTLKGHSNYVFCCNFNPQSNLIVSGSFDESVRIWDVKTGKCLKTLPAHSDPVSAVHFN RDGSLIVSSSYDGLCRIWDTASGQCLKTLIDDDNPPVSFVKFSPNGKYILAATLDNTLKL WDYSKGKCLKTYTGHKNEKYCIFANFSVTGGKWIVSGSEDNLVYIWNLQTKEIVQKLQGH TDVVISTACHPTENIIASAALENDKTIKLWKSDC Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| 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: Arginine | Ligand Info | |||||
| Structure Description | Crystal structure of human WDR5 in complex with L-arginine | PDB:6OI0 | ||||
| Method | X-ray diffraction | Resolution | 1.92 Å | Mutation | No | [2] |
| PDB Sequence |
VKPNYALKFT
40 LAGHTKAVSS50 VKFSPNGEWL60 ASSSADKLIK70 IWGAYDGKFE80 KTISGHKLGI 90 SDVAWSSDSN100 LLVSASDDKT110 LKIWDVSSGK120 CLKTLKGHSN130 YVFCCNFNPQ 140 SNLIVSGSFD150 ESVRIWDVKT160 GKCLKTLPAH170 SDPVSAVHFN180 RDGSLIVSSS 190 YDGLCRIWDT200 ASGQCLKTLI210 DDDNPPVSFV220 KFSPNGKYIL230 AATLDNTLKL 240 WDYSKGKCLK250 TYTGHKNEKY260 CIFANFSVTG270 GKWIVSGSED280 NLVYIWNLQT 290 KEIVQKLQGH300 TDVVISTACH310 PTENIIASAA320 LENDKTIKLW330 KSDC |
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| Ligand Name: Tilarginine | Ligand Info | |||||
| Structure Description | Crystal structure of human WDR5 in complex with monomethyl L-arginine | PDB:6OI1 | ||||
| Method | X-ray diffraction | Resolution | 1.68 Å | Mutation | No | [2] |
| PDB Sequence |
VKPNYALKFT
40 LAGHTKAVSS50 VKFSPNGEWL60 ASSSADKLIK70 IWGAYDGKFE80 KTISGHKLGI 90 SDVAWSSDSN100 LLVSASDDKT110 LKIWDVSSGK120 CLKTLKGHSN130 YVFCCNFNPQ 140 SNLIVSGSFD150 ESVRIWDVKT160 GKCLKTLPAH170 SDPVSAVHFN180 RDGSLIVSSS 190 YDGLCRIWDT200 ASGQCLKTLI210 DDDNPPVSFV220 KFSPNGKYIL230 AATLDNTLKL 240 WDYSKGKCLK250 TYTGHKNEKY260 CIFANFSVTG270 GKWIVSGSED280 NLVYIWNLQT 290 KEIVQKLQGH300 TDVVISTACH310 PTENIIASAA320 LENDKTIKLW330 KSDC |
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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 | 57 | Degree centrality | 6.12E-03 | Betweenness centrality | 3.92E-03 |
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| Closeness centrality | 2.42E-01 | Radiality | 1.42E+01 | Clustering coefficient | 1.09E-01 |
| Neighborhood connectivity | 2.61E+01 | Topological coefficient | 3.49E-02 | 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-interacting Proteins | ||||||
| References | Top | |||||
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| REF 1 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2831). | |||||
| REF 2 | A Binary Arginine Methylation Switch on Histone H3 Arginine 2 Regulates Its Interaction with WDR5. Biochemistry. 2020 Oct 6;59(39):3696-3708. | |||||
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