Target Information
| Target General Information | Top | |||||
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| Target ID |
T95183
(Former ID: TTDI02577)
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| Target Name |
Ubiquitin carboxyl-terminal hydrolase 2 (USP2)
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| Synonyms |
Ubiquitin-specific-processing protease 2; Ubiquitin thioesterase 2; UBP41; Deubiquitinating enzyme 2; 41 kDa ubiquitin-specific protease
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| Gene Name |
USP2
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| Target Type |
Preclinical target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Postoperative inflammation [ICD-11: 1A00-CA43] | |||||
| Function |
Isoform 1 and isoform 4 possess both ubiquitin-specific peptidase and isopeptidase activities. Deubiquitinates MDM2 without reversing MDM2-mediated p53/TP53 ubiquitination and thus indirectly promotes p53/TP53 degradation and limits p53 activity. Has no deubiquitinase activity against p53/TP53. Prevents MDM2-mediated degradation of MDM4. Plays a role in the G1/S cell-cycle progression in normal and cancer cells. Regulates the circadian clock by modulating its intrinsic circadian rhythm and its capacity to respond to external cues. Associates with clock proteins and deubiquitinates core clock component PER1 but does not affect its overall stability. Regulates the nucleocytoplasmic shuttling and nuclear retention of PER1 and its repressive role on the clock transcription factors CLOCK and ARNTL/BMAL1. Plays a role in the regulation of myogenic differentiation of embryonic muscle cells. Hydrolase that deubiquitinates polyubiquitinated target proteins such as MDM2, MDM4 and CCND1.
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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 |
MSQLSSTLKRYTESARYTDAHYAKSGYGAYTPSSYGANLAASLLEKEKLGFKPVPTSSFL
TRPRTYGPSSLLDYDRGRPLLRPDITGGGKRAESQTRGTERPLGSGLSGGSGFPYGVTNN CLSYLPINAYDQGVTLTQKLDSQSDLARDFSSLRTSDSYRIDPRNLGRSPMLARTRKELC TLQGLYQTASCPEYLVDYLENYGRKGSASQVPSQAPPSRVPEIISPTYRPIGRYTLWETG KGQAPGPSRSSSPGRDGMNSKSAQGLAGLRNLGNTCFMNSILQCLSNTRELRDYCLQRLY MRDLHHGSNAHTALVEEFAKLIQTIWTSSPNDVVSPSEFKTQIQRYAPRFVGYNQQDAQE FLRFLLDGLHNEVNRVTLRPKSNPENLDHLPDDEKGRQMWRKYLEREDSRIGDLFVGQLK SSLTCTDCGYCSTVFDPFWDLSLPIAKRGYPEVTLMDCMRLFTKEDVLDGDEKPTCCRCR GRKRCIKKFSIQRFPKILVLHLKRFSESRIRTSKLTTFVNFPLRDLDLREFASENTNHAV YNLYAVSNHSGTTMGGHYTAYCRSPGTGEWHTFNDSSVTPMSSSQVRTSDAYLLFYELAS PPSRM 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: Thioguanine | Ligand Info | |||||
| Structure Description | Crystal structure of human USP2 in complex with ubiquitin and 6-thioguanine | PDB:5XU8 | ||||
| Method | X-ray diffraction | Resolution | 1.81 Å | Mutation | No | [3] |
| PDB Sequence |
QGLAGLRNLG
273 NTCFMNSILQ283 CLSNTRELRD293 YCLQRLYMRD303 LHHGSNAHTA313 LVEEFAKLIQ 323 TIWTSSPNDV333 VSPSEFKTQI343 QRYAPRFVGY353 NQQDAQEFLR363 FLLDGLHNEV 373 NRVNLDHLPD392 DEKGRQMWRK402 YLEREDSRIG412 DLFVGQLKSS422 LTCTDCGYCS 432 TVFDPFWDLS442 LPIAKRGYPE452 VTLMDCMRLF462 TKEDVLDGDE472 KPTCCRCRGR 482 KRCIKKFSIQ492 RFPKILVLHL502 KRFSESRIRT512 SKLTTFVNFP522 LRDLDLREFA 532 SENTNHAVYN542 LYAVSNHSGT552 TMGGHYTAYC562 RSPGTGEWHT572 FNDSSVTPMS 582 SSQVRTSDAY592 LLFYELA
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| Ligand Name: Ethylamine | Ligand Info | |||||
| Structure Description | Covalent Ubiquitin-USP2 Complex | PDB:2IBI | ||||
| Method | X-ray diffraction | Resolution | 2.20 Å | Mutation | Yes | [4] |
| PDB Sequence |
AQGLAGLRNL
272 GNTCFMNSIL282 QCLSNTRELR292 DYCLQRLYMR302 DLHHGSNAHT312 ALVEEFAKLI 322 QTIWTSSPND332 VVSPSEFKTQ342 IQRYAPRFVG352 YNQQDAQEFL362 RFLLDGLHNE 372 VNRVTLRPKN383 PENLDHLPDD393 EKGRQMWRKY403 LEREDSRIGD413 LFVGQLKSSL 423 TCTDCGYCST433 VFDPFWDLSL443 PIAKRGPEVT454 LMDCMRLFTK464 EDVLDGDAAP 474 TCCRCRGRKR484 CIKKFSIQRF494 PKILVLHLKR504 FSESRIRTSK514 LTTFVNFPLR 524 DLDLREFASE534 NTHAVYNLYA545 VSNHSGTTMG555 GHYTAYCRSP565 GTGEWHTFND 575 SSVTPMSSSQ585 VRTSDAYLLF595 YELAS
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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 | 6 | Degree centrality | 6.45E-04 | Betweenness centrality | 2.66E-06 |
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| Closeness centrality | 2.22E-01 | Radiality | 1.39E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 1.23E+02 | Topological coefficient | 3.46E-01 | 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 | The Deubiquitylase USP2 Regulates the LDLR Pathway by Counteracting the E3-Ubiquitin Ligase IDOL. Circ Res. 2016 Feb 5;118(3):410-9. | |||||
| REF 2 | Deubiquitylating enzymes and drug discovery: emerging opportunities. Nat Rev Drug Discov. 2018 Jan;17(1):57-78. | |||||
| REF 3 | 6-Thioguanine is a noncompetitive and slow binding inhibitor of human deubiquitinating protease USP2. Sci Rep. 2018 Feb 15;8(1):3102. | |||||
| REF 4 | Covalent Ubiquitin-USP2 Complex | |||||
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