Target Information
Target General Information | Top | |||||
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Target ID |
T46128
(Former ID: TTDI02331)
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Target Name |
Melanocytes lineage-specific antigen GP100 (PMEL)
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Synonyms |
Silver locus protein homolog; SILV; Premelanosome protein; PMEL17; P100; P1; Melanomaassociated ME20 antigen; Melanoma-associated ME20 antigen; Melanocyte protein Pmel 17; Melanocyte protein PMEL; Mbeta; ME20S; ME20M; ME20-M; D12S53E
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Gene Name |
PMEL
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Stomach cancer ICD-11: 2B72 | |||||
Function |
Involved in the maturation of melanosomes from stage I to II. The transition from stage I melanosomes to stage II melanosomes involves an elongation of the vesicle, and the appearance within of distinct fibrillar structures. Release of the soluble form, ME20-S, could protect tumor cells from antibody mediated immunity. Plays a central role in the biogenesis of melanosomes.
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UniProt ID | ||||||
Sequence |
MDLVLKRCLLHLAVIGALLAVGATKVPRNQDWLGVSRQLRTKAWNRQLYPEWTEAQRLDC
WRGGQVSLKVSNDGPTLIGANASFSIALNFPGSQKVLPDGQVIWVNNTIINGSQVWGGQP VYPQETDDACIFPDGGPCPSGSWSQKRSFVYVWKTWGQYWQVLGGPVSGLSIGTGRAMLG THTMEVTVYHRRGSRSYVPLAHSSSAFTITDQVPFSVSVSQLRALDGGNKHFLRNQPLTF ALQLHDPSGYLAEADLSYTWDFGDSSGTLISRALVVTHTYLEPGPVTAQVVLQAAIPLTS CGSSPVPGTTDGHRPTAEAPNTTAGQVPTTEVVGTTPGQAPTAEPSGTTSVQVPTTEVIS TAPVQMPTAESTGMTPEKVPVSEVMGTTLAEMSTPEATGMTPAEVSIVVLSGTTAAQVTT TEWVETTARELPIPEPEGPDASSIMSTESITGSLGPLLDGTATLRLVKRQVPLDCVLYRY GSFSVTLDIVQGIESAEILQAVPSGEGDAFELTVSCQGGLPKEACMEISSPGCQPPAQRL CQPVLPSPACQLVLHQILKGGSGTYCLNVSLADTNSLAVVSTQLIMPGQEAGLGQVPLIV GILLVLMAVVLASLIYRRRLMKQDFSVPQLPHSSSHWLRLPRIFCSCPIGENSPLLSGQQ V 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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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Tebentafusp | Drug Info | Approved | Gastric cancer | [2] | |
Clinical Trial Drug(s) | [+] 5 Clinical Trial Drugs | + | ||||
1 | Melanoma vaccine | Drug Info | Phase 3 | Melanoma | [3] | |
2 | Multi-epitope peptide melanoma vaccine | Drug Info | Phase 3 | Melanoma | [3] | |
3 | Gp100:209-217(210M) peptide vaccine | Drug Info | Phase 2 | Melanoma | [4] | |
4 | Multi-epitope tyrosinase/gp100 vaccine | Drug Info | Phase 2 | Melanoma | [5] | |
5 | AE-08 | Drug Info | Phase 1 | Melanoma | [6] | |
Discontinued Drug(s) | [+] 1 Discontinued Drugs | + | ||||
1 | Melanoma vaccine (ALVAC) | Drug Info | Discontinued in Phase 2 | Melanoma | [7] | |
Mode of Action | [+] 1 Modes of Action | + | ||||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Tebentafusp | Drug Info | [8] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
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 | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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Closeness centrality | 3.76E-04 | Radiality | 1.48E-02 | Clustering coefficient | 1.00E+00 |
Neighborhood connectivity | 3.50E+00 | Topological coefficient | 7.00E-01 | Eccentricity | 3 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
References | Top | |||||
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REF 1 | National Cancer Institute Drug Dictionary (drug id 685201). | |||||
REF 2 | FDA Approved Drug Products from FDA Official Website. 2022. Application Number: 761228. | |||||
REF 3 | ClinicalTrials.gov (NCT00036816) Vaccine Therapy in Treating Patients With Melanoma of the Eye. U.S. National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT00003895) Vaccine Therapy in Treating HLA-A2 Positive Patients With Melanoma. U.S. National Institutes of Health. | |||||
REF 5 | ClinicalTrials.gov (NCT00003362) Vaccine Therapy Plus Immune Adjuvants in Treating Patients With Advanced Melanoma. U.S. National Institutes of Health. | |||||
REF 6 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800037366) | |||||
REF 7 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014153) | |||||
REF 8 | Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors | |||||
REF 9 | Safety and immunogenicity of vaccination with MART-1 (26-35, 27L), gp100 (209-217, 210M), and tyrosinase (368-376, 370D) in-adjuvant with PF-3512676 and GM-CSF in metastatic melanoma. Correction in: volume 35 on page 650. | |||||
REF 10 | National Cancer Institute Drug Dictionary (drug id 476335). | |||||
REF 11 | Synthesis of labeled BCX-4208, a potent inhibitor of purine nucleoside phosphorylase. Drug Test Anal. 2009 Mar;1(3):125-7. | |||||
REF 12 | Preclinical qualification of a new multi-antigen candidate vaccine for metastatic melanoma. J Immunother. 2010 Oct;33(8):743-58. |
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