Target Information
| Target General Information | Top | |||||
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| Target ID |
T81281
(Former ID: TTDI02403)
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| Target Name |
Desmoglein-3 (DSG3)
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| Synonyms |
PVA; DSG3; Cadherin family member 6; 130 kDa pemphigus vulgaris antigen
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| Gene Name |
DSG3
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Pemphigus [ICD-11: EB40] | |||||
| Function |
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
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| UniProt ID | ||||||
| Sequence |
MMGLFPRTTGALAIFVVVILVHGELRIETKGQYDEEEMTMQQAKRRQKREWVKFAKPCRE
GEDNSKRNPIAKITSDYQATQKITYRISGVGIDQPPFGIFVVDKNTGDINITAIVDREET PSFLITCRALNAQGLDVEKPLILTVKILDINDNPPVFSQQIFMGEIEENSASNSLVMILN ATDADEPNHLNSKIAFKIVSQEPAGTPMFLLSRNTGEVRTLTNSLDREQASSYRLVVSGA DKDGEGLSTQCECNIKVKDVNDNFPMFRDSQYSARIEENILSSELLRFQVTDLDEEYTDN WLAVYFFTSGNEGNWFEIQTDPRTNEGILKVVKALDYEQLQSVKLSIAVKNKAEFHQSVI SRYRVQSTPVTIQVINVREGIAFRPASKTFTVQKGISSKKLVDYILGTYQAIDEDTNKAA SNVKYVMGRNDGGYLMIDSKTAEIKFVKNMNRDSTFIVNKTITAEVLAIDEYTGKTSTGT VYVRVPDFNDNCPTAVLEKDAVCSSSPSVVVSARTLNNRYTGPYTFALEDQPVKLPAVWS ITTLNATSALLRAQEQIPPGVYHISLVLTDSQNNRCEMPRSLTLEVCQCDNRGICGTSYP TTSPGTRYGRPHSGRLGPAAIGLLLLGLLLLLLAPLLLLTCDCGAGSTGGVTGGFIPVPD GSEGTIHQWGIEGAHPEDKEITNICVPPVTANGADFMESSEVCTNTYARGTAVEGTSGME MTTKLGAATESGGAAGFATGTVSGAASGFGAATGVGICSSGQSGTMRTRHSTGGTNKDYA DGAISMNFLDSYFSQKAFACAEEDDGQEANDCLLIYDNEGADATGSPVGSVGCCSFIADD LDDSFLDSLGPKFKKLAEISLGVDGEGKEVQPPSKDSGYGIESCGHPIEVQQTGFVKCQT LSGSQGASALSTSGSVQPAVSIPDPLQHGNYLVTETYSASGSLVQPSTAGFDPLLTQNVI VTERVICPISSVPGNLAGPTQLRGSHTMLCTEDPCSRLI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | DSG3-CAART | Drug Info | Phase 1 | Pemphigus vulgaris | [2] | |
| 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: Alpha-D-Mannose | Ligand Info | |||||
| Structure Description | Crystal structure of human Desmoglein-3 ectodomain | PDB:5EQX | ||||
| Method | X-ray diffraction | Resolution | 3.05 Å | Mutation | No | [4] |
| PDB Sequence |
EWVKFAKPCR
10 EGEDNSKRNP20 IAKITSDYQA30 TQKITYRISG40 VGIDQPPFGI50 FVVDKNTGDI 60 NITAIVDREE70 TPSFLITCRA80 LNAQGLDVEK90 PLILTVKILD100 INDNPPVFSQ 110 QIFMGEIEEN120 SASNSLVMIL130 NATDADEPNH140 LNSKIAFKIV150 SQEPAGTPMF 160 LLSRNTGEVR170 TLTNSLDREQ180 ASSYRLVVSG190 ADKDGEGLST200 QCECNIKVKD 210 VNDNFPMFRD220 SQYSARIEEN230 ILSSELLRFQ240 VTDLDEEYTD250 NWLAVYFFTS 260 GNEGNWFEIQ270 TDPRTNEGIL280 KVVKALDYEQ290 LQSVKLSIAV300 KNKAEFHQSV 310 ISRYRVQSTP320 VTIQVINVRE330 GIAFRPASKT340 FTVQKGISSK350 KLVDYILGTY 360 QAIDEDTNKA370 ASNVKYVMGR380 NDGGYLMIDS390 KTAEIKFVKN400 MNRDSTFIVN 410 KTITAEVLAI420 DEYTGKTSTG430 TVYVRVPDF
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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 | 3 | Degree centrality | 3.22E-04 | Betweenness centrality | 1.68E-07 |
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| Closeness centrality | 1.61E-01 | Radiality | 1.24E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 5.33E+00 | Topological coefficient | 4.85E-01 | Eccentricity | 14 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Desmoglein 3: a help or a hindrance in cancer progression Cancers (Basel). 2015 Jan 26;7(1):266-86. | |||||
| REF 2 | ClinicalTrials.gov (NCT04422912) A Phase 1, Open-label, Safety and Dosing Study of Autologous Desmoglein 3 Chimeric Autoantibody Receptor T Cells (DSG3-CAART) in Subjects With Active, Anti-DSG3, Mucosal-dominant Pemphigus Vulgaris. U.S.National Institutes of Health. | |||||
| REF 3 | Antigen-specific B cell depletion for precision therapy of mucosal pemphigus vulgaris. J Clin Invest. 2020 Dec 1;130(12):6317-6324. | |||||
| REF 4 | Structural basis of adhesive binding by desmocollins and desmogleins. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):7160-5. | |||||
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