Target Information
| Target General Information | Top | |||||
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| Target ID |
T57050
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| Target Name |
Zinc finger-containing ubiquitin peptidase 1 (ZUP1)
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| Synonyms |
Zinc finger with UFM1-specific peptidase domain protein; ZUFSP; Lys-63-specific deubiquitinase ZUFSP; DUB; C6orf113
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| Gene Name |
ZUP1
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| Target Type |
Patented-recorded target
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[1] | ||||
| Function |
Shows only weak activity against 'Lys-11' and 'Lys-48'-linked chains. Plays an important role in genome stability pathways, functioning to prevent spontaneous DNA damage and also promote cellular survival in response to exogenous DNA damage. Modulates the ubiquitination status of replication protein A (RPA) complex proteins in response to replication stress. Deubiquitinase with endodeubiquitinase activity that specifically interacts with and cleaves 'Lys-63'-linked long polyubiquitin chains.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.19.12
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| Sequence |
MLSCNICGETVTSEPDMKAHLIVHMESEIICPFCKLSGVNYDEMCFHIETAHFEQNTLER
NFERINTVQYGTSDNKKDNTLQCGMEVNSSILSGCASNHPKNSAQNLTKDSTLKHEGFYS ENLTESRKFLKSREKQSSLTEIKGSVYETTYSPPECPFCGKIEEHSEDMETHVKTKHANL LDIPLEDCDQPLYDCPMCGLICTNYHILQEHVDLHLEENSFQQGMDRVQCSGDLQLAHQL QQEEDRKRRSEESRQEIEEFQKLQRQYGLDNSGGYKQQQLRNMEIEVNRGRMPPSEFHRR KADMMESLALGFDDGKTKTSGIIEALHRYYQNAATDVRRVWLSSVVDHFHSSLGDKGWGC GYRNFQMLLSSLLQNDAYNDCLKGMLIPCIPKIQSMIEDAWKEGFDPQGASQLNNRLQGT KAWIGACEVYILLTSLRVKCHIVDFHKSTGPLGTHPRLFEWILNYYSSEGEGSPKVVCTS KPPIYLQHQGHSRTVIGIEEKKNRTLCLLILDPGCPSREMQKLLKQDIEASSLKQLRKSM GNLKHKQYQILAVEGALSLEEKLARRQASQVFTAEKIP 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: Allylamine | Ligand Info | |||||
| Structure Description | Crystal structure of the covalent complex between deubiquitinase ZUFSP (ZUP1) and Ubiquitin-PA | PDB:6EI1 | ||||
| Method | X-ray diffraction | Resolution | 1.73 Å | Mutation | No | [2] |
| PDB Sequence |
LQQEEDRKRR
249 SEESRQEIEE259 FQKLQRQYGL269 DNSGGYKQQQ279 LRNMEIEVNR289 GRMPPSEFHR 299 RKADMMESLA309 LGFDDGKTKT319 SGIIEALHRY329 YQNAATDVRR339 VWLSSVVDHF 349 HSSLGDKGWG359 CGYRNFQMLL369 SSLLQNDAYN379 DCLKGMLIPC389 IPKIQSMIED 399 AWKEGFDPQG409 ASQLNNRLQG419 TKAWIGACEV429 YILLTSLRVK439 CHIVDFHKST 449 GPLGTHPRLF459 EWILNYYSSS473 PKVVCTSKPP483 IYLQHQGHSR493 TVIGIEEKKN 503 RTLCLLILDP513 GCPSREMQKL523 LKQDIEASSL533 KQLRKSMGNL543 KHKQYQILAV 553 EGALSLEEKL563 ARRQASQVFT573 AEKIP
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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 | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 2.10E-01 | Radiality | 1.37E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.52E+02 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| References | Top | |||||
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| REF 1 | Deubiquitinases (DUBs) and DUB inhibitors: a patent review.Expert Opin Ther Pat. 2015;25(10):1191-1208. | |||||
| REF 2 | A family of unconventional deubiquitinases with modular chain specificity determinants. Nat Commun. 2018 Feb 23;9(1):799. | |||||
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