Target Information
| Target General Information | Top | |||||
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| Target ID |
T00938
(Former ID: TTDI02203)
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| Target Name |
Melanoma antigen gp75 (TYRP1)
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| Synonyms |
Tyrosinaserelated protein 1; TYRP1; TRP; Glycoprotein 75; Catalase B; 5,6dihydroxyindole2carboxylic acid oxidase
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| Gene Name |
TYRP1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 4 Target-related Diseases | + | ||||
| 1 | Motor neuron disease [ICD-11: 8B60] | |||||
| 2 | Multiple sclerosis [ICD-11: 8A40] | |||||
| 3 | Tonus and reflex abnormality [ICD-11: MB47] | |||||
| 4 | Melanoma [ICD-11: 2C30] | |||||
| Function |
Oxidation of 5,6-dihydroxyindole-2-carboxylic acid (DHICA)into indole-5,6-quinone-2-carboxylic acid. May regulate or influence the type of melanin synthesized.
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| BioChemical Class |
Tyrosinase
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| UniProt ID | ||||||
| EC Number |
EC 1.14.18.-
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| Sequence |
MSAPKLLSLGCIFFPLLLFQQARAQFPRQCATVEALRSGMCCPDLSPVSGPGTDRCGSSS
GRGRCEAVTADSRPHSPQYPHDGRDDREVWPLRFFNRTCHCNGNFSGHNCGTCRPGWRGA ACDQRVLIVRRNLLDLSKEEKNHFVRALDMAKRTTHPLFVIATRRSEEILGPDGNTPQFE NISIYNYFVWTHYYSVKKTFLGVGQESFGEVDFSHEGPAFLTWHRYHLLRLEKDMQEMLQ EPSFSLPYWNFATGKNVCDICTDDLMGSRSNFDSTLISPNSVFSQWRVVCDSLEDYDTLG TLCNSTEDGPIRRNPAGNVARPMVQRLPEPQDVAQCLEVGLFDTPPFYSNSTNSFRNTVE GYSDPTGKYDPAVRSLHNLAHLFLNGTGGQTHLSPNDPIFVLLHTFTDAVFDEWLRRYNA DISTFPLENAPIGHNRQYNMVPFWPPVTNTEMFVTAPDNLGYTYEIQWPSREFSVPEIIA IAVVGALLLVALIFGTASYLIRARRSMDEANQPLLTDQYQCYAEEYEKLQNPNQSVV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T31MUM | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | FLX-787 | Drug Info | Phase 2 | Amyotrophic lateral sclerosis | [2] | |
| 2 | Flanvotumab | Drug Info | Phase 1 | Melanoma | [3] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Activator | [+] 1 Activator drugs | + | ||||
| 1 | FLX-787 | Drug Info | [1] | |||
| 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: L-tyrosine | Ligand Info | |||||
| Structure Description | Crystal structure of human tyrosinase related protein 1 in complex with tyrosine | PDB:5M8P | ||||
| Method | X-ray diffraction | Resolution | 2.80 Å | Mutation | No | [5] |
| PDB Sequence |
QFPRQCATVE
34 ALRSGMCCPD44 LSPVSGPGTD54 RCGSSSGRGR64 CEAVTADSRP74 HSPQYPHDGR 84 DDREVWPLRF94 FNRTCHCNGN104 FSGHNCGTCR114 PGWRGAACDQ124 RVLIVRRNLL 134 DLSKEEKNHF144 VRALDMAKRT154 THPLFVIATR164 RSEEILGPDG174 NTPQFENISI 184 YNYFVWTHYY194 SVKKTFLGVG204 QESFGEVDFS214 HEGPAFLTWH224 RYHLLRLEKD 234 MQEMLQEPSF244 SLPYWNFATG254 KNVCDICTDD264 LMGSRSNFDS274 TLISPNSVFS 284 QWRVVCDSLE294 DYDTLGTLCN304 STEDGPIRRN314 PAGNVARPMV324 QRLPEPQDVA 334 QCLEVGLFDT344 PPFYSNSTNS354 FRNTVEGYSD364 PTGKYDPAVR374 SLHNLAHLFL 384 NGTGGQTHLS394 PNDPIFVLLH404 TFTDAVFDEW414 LRRYNADIST424 FPLENAPIGH 434 NRQYNMVPFW444 PPVTNTEMFV454 TAPDNLGYTY464 EIQWPS
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| Ligand Name: Phenylthiourea | Ligand Info | |||||
| Structure Description | Crystal structure of human tyrosinase related protein 1 mutant (T391V-R374S-Y362F) in complex with phenylthiourea (PTU) | PDB:5M8S | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [6] |
| PDB Sequence |
QFPRQCATVE
34 ALRSGMCCPD44 LSPVSGPGTD54 RCGSSSGRGR64 CEAVTADSRP74 HSPQYPHDGR 84 DDREVWPLRF94 FNRTCHCNGN104 FSGHNCGTCR114 PGWRGAACDQ124 RVLIVRRNLL 134 DLSKEEKNHF144 VRALDMAKRT154 THPLFVIATR164 RSEEILGPDG174 NTPQFENISI 184 YNYFVWTHYY194 SVKKTFLGVG204 QESFGEVDFS214 HEGPAFLTWH224 RYHLLRLEKD 234 MQEMLQEPSF244 SLPYWNFATG254 KNVCDICTDD264 LMGSRSNFDS274 TLISPNSVFS 284 QWRVVCDSLE294 DYDTLGTLCN304 STEDGPIRRN314 PAGNVARPMV324 QRLPEPQDVA 334 QCLEVGLFDT344 PPFYSNSTNS354 FRNTVEGFSD364 PTGKYDPAVS374 SLHNLAHLFL 384 NGTGGQVHLS394 PNDPIFVLLH404 TFTDAVFDEW414 LRRYNADIST424 FPLENAPIGH 434 NRQYNMVPFW444 PPVTNTEMFV454 TAPDNLGYTY464 EIQWPS
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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 Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
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 Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Tyrosine metabolism | hsa00350 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Melanogenesis | hsa04916 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 2.77E-04 | Radiality | 1.43E-02 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 3.00E+00 | Topological coefficient | 1.00E+00 | Eccentricity | 4 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| BioCyc | [+] 1 BioCyc Pathways | + | ||||
| 1 | Eumelanin biosynthesis | |||||
| KEGG Pathway | [+] 3 KEGG Pathways | + | ||||
| 1 | Tyrosine metabolism | |||||
| 2 | Metabolic pathways | |||||
| 3 | Melanogenesis | |||||
| Pathwhiz Pathway | [+] 1 Pathwhiz Pathways | + | ||||
| 1 | Degradation of Superoxides | |||||
| PID Pathway | [+] 1 PID Pathways | + | ||||
| 1 | Direct p53 effectors | |||||
| References | Top | |||||
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| REF 1 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 2 | Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA) | |||||
| REF 3 | ClinicalTrials.gov (NCT01137006) An Open-Label, Dose-Escalation Study of IMC-20D7S In Patients With Malignant Melanoma. U.S. National Institutes of Health. | |||||
| REF 4 | National Cancer Institute Drug Dictionary (drug id 675217). | |||||
| REF 5 | Structure of Human Tyrosinase Related Protein?1 Reveals a Binuclear Zinc Active Site Important for Melanogenesis. Angew Chem Int Ed Engl. 2017 Aug 7;56(33):9812-9815. | |||||
| REF 6 | Phenylthiourea Binding to Human Tyrosinase-Related Protein 1. doi:10.3390/ijms21030915. | |||||
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