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
Chemical Structure based Activity Landscape of Target
Target Regulators
Target Affiliated Biological Pathways
References
Drug Binding Sites of Target  Top
Ligand Name: 4,5,-IP2 Ligand Info
Structure Description Crystal structure of the syntenin PDZ1 and PDZ2 tandem in complex with the Frizzled 7 C-terminal fragment and PIP2 PDB:4Z33
Method X-ray diffraction Resolution 2.45 Å Mutation No [3]
PDB Sequence
KGETAV
Residue
Distance (Å)
LYS1
3.400
Residue
Distance (Å)
Ligand Name: Nervonic acid Ligand Info
Structure Description Crystal structure of Frizzled 7 CRD in complex with C24 fatty acid PDB:5URV
Method X-ray diffraction Resolution 2.20 Å Mutation No [4]
PDB Sequence
HGFCQPISIP
25
LCTDIAYNQT
35
ILPNLLGHTN
45
QEDAGLEVHQ
55
FYPLVKVQCS
65

PELRFFLCSM
75
YAPVCTVLDQ
85
AIPPCRSLCE
95
RARQGCEALM
105
NKFGFQWPER
115

LRCENFPVHG
125
AGEICVGQ
Residue
Distance (Å)
GLU52
3.641
GLN55
3.590
PHE56
3.345
TYR57
4.964
PRO58
3.558
LEU59
3.707
Residue
Distance (Å)
LYS61
3.884
TYR76
4.123
MET105
3.652
PHE108
3.970
PHE110
3.670
PRO113
3.799
Click to View More Binding Site Information of This Target with Different Ligands
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 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).
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 Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
There is no similarity protein (E value < 0.005) for this target
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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KEGG Pathway Pathway ID Affiliated Target Pathway Map
mTOR signaling pathway hsa04150 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Wnt signaling pathway hsa04310 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Hippo signaling pathway hsa04390 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Signaling pathways regulating pluripotency of stem cells hsa04550 Affiliated Target
  Class: Cellular Processes => Cellular community - eukaryotes Pathway Hierarchy
Melanogenesis hsa04916 Affiliated Target
  Class: Organismal Systems => Endocrine system Pathway Hierarchy
Degree 11 Degree centrality 1.18E-03 Betweenness centrality 2.35E-04
Closeness centrality 2.06E-01 Radiality 1.36E+01 Clustering coefficient 3.82E-01
Neighborhood connectivity 2.08E+01 Topological coefficient 2.00E-01 Eccentricity 12
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