Target Information
Target General Information | Top | |||||
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Target ID |
T53890
(Former ID: TTDR01136)
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Target Name |
Gankyrin (PSMD10)
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Synonyms |
p28(GANK); 26S proteasome regulatory subunit p28; 26S proteasome non-ATPase regulatory subunit 10
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Gene Name |
PSMD10
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Target Type |
Literature-reported target
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[1] | ||||
Function |
In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis. Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC).
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UniProt ID | ||||||
Sequence |
MEGCVSNLMVCNLAYSGKLEELKESILADKSLATRTDQDSRTALHWACSAGHTEIVEFLL
QLGVPVNDKDDAGWSPLHIAASAGRDEIVKALLGKGAQVNAVNQNGCTPLHYAASKNRHE IAVMLLEGGANPDAKDHYEATAMHRAAAKGNLKMIHILLYYKASTNIQDTEGNTPLHLAC DEERVEEAKLLVSQGASIYIENKEEKTPLQVAKGGLGLILKRMVEG Click to Show/Hide
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3D Structure | Click to Show 3D Structure of This Target | PDB |
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: Urea | Ligand Info | |||||
Structure Description | Snapshots of Human PSMD10(Gankyrin) unfolding by urea: 1 hour incubation | PDB:7VXW | ||||
Method | X-ray diffraction | Resolution | 2.22 Å | Mutation | No | [2] |
PDB Sequence |
GCVSNLMVCN
12 LAYSGKLEEL22 KESILADKSL32 ATRTDQDSRT42 ALHWACSAGH52 TEIVEFLLQL 62 GVPVNDKDDA72 GWSPLHIAAS82 AGRDEIVKAL92 LGKGAQVNAV102 NQNGCTPLHY 112 AASKNRHEIA122 VMLLEGGANP132 DAKDHYEATA142 MHRAAAKGNL152 KMIHILLYYK 162 ASTNIQDTEG172 NTPLHLACDE182 ERVEEAKLLV192 SQGASIYIEN202 KEEKTPLQVA 212 KGGLGLILKR222 MVEG
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Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
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 | 25 | Degree centrality | 2.69E-03 | Betweenness centrality | 3.76E-04 |
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Closeness centrality | 2.30E-01 | Radiality | 1.40E+01 | Clustering coefficient | 6.47E-01 |
Neighborhood connectivity | 4.79E+01 | Topological coefficient | 1.77E-01 | Eccentricity | 11 |
Download | Click to Download the Full PPI Network of This Target | ||||
Target Regulators | Top | |||||
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Target-regulating microRNAs | ||||||
Target-interacting Proteins |
References | Top | |||||
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REF 1 | A cleaved form of MAGE-A4 binds to Miz-1 and induces apoptosis in human cells. J Biol Chem. 2004 Apr 9;279(15):15505-14. | |||||
REF 2 | Snapshots of urea-induced early structural changes and unfolding of an ankyrin repeat protein at atomic resolution. Protein Sci. 2022 Dec;31(12):e4515. |
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