Target Information

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Target General Information
Drugs and Modes of Action
Drug Binding Sites of Target
Different Human System Profiles of Target
Target Regulators
Target Affiliated Biological Pathways
References
Drug Binding Sites of Target  Top
Ligand Name: Alpha-D-Mannose Ligand Info
Structure Description FAB fragment complexed with C-mannosylated tryptophan peptide PDB:6PLH
Method X-ray diffraction Resolution 1.60 Å Mutation No [5]
PDB Sequence
TWSEWSDP
Residue
Distance (Å)
GLU15
4.763
TRP16
1.494
Residue
Distance (Å)
SER17
2.414
ASP18
4.543
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Different Human System Profiles of Target  Top
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
Protein Name Pfam ID Percentage of Identity (%) E value
Interleukin 21 receptor (IL21R) 100.000 (538/538) 0.00E+00
Interleukin-9 receptor (IL9R) 28.464 (76/267) 1.31E-11
Interleukin 2 receptor beta (IL2RB)
PF18707
26.582 (84/316) 3.59E-11
Interleukin 4 receptor alpha (IL4R)
PF09238
24.706 (63/255) 4.71E-08
Interleukin 7 receptor alpha (IL7R)
PF00041 ; 
PF18447
22.485 (38/169) 4.06E-07
Erythropoietin Receptor (EPOR)
PF09067 ; 
PF00041
23.529 (68/289) 1.74E-05
Leptin receptor (LEPR)
PF06328 ; 
PF18589
34.821 (39/112) 5.61E-05
Interleukin 3 receptor (CSF2RB) 21.523 (65/302) 7.14E-05
Thrombopoietin receptor (MPL)
PF09067 ; 
PF00041
29.412 (45/153) 3.11E-04
Cytokine receptor common subunit gamma (IL2RG)
PF09240
24.359 (57/234) 6.04E-04
Interleukin 5 receptor alpha (IL5RA)
PF09240
24.074 (39/162) 1.00E-03
Cytokine receptor-like factor 1 (CRLF1)
PF09067 ; 
PF00041
25.786 (41/159) 1.00E-03
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KEGG Pathway Pathway ID Affiliated Target Pathway Map
Cytokine-cytokine receptor interaction hsa04060 Affiliated Target
  Class: Environmental Information Processing => Signaling molecules and interaction Pathway Hierarchy
JAK-STAT signaling pathway hsa04630 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Th17 cell differentiation hsa04659 Affiliated Target
  Class: Organismal Systems => Immune system Pathway Hierarchy
Degree 2 Degree centrality 2.15E-04 Betweenness centrality 2.02E-04
Closeness centrality 1.77E-01 Radiality 1.29E+01 Clustering coefficient 0.00E+00
Neighborhood connectivity 9.50E+00 Topological coefficient 5.00E-01 Eccentricity 13
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