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
Drug Property Profile of Target
Target Poor or Non Binders
Target Regulators
Target Profiles in Patients
Target Affiliated Biological Pathways
References
Drug Binding Sites of Target  Top
Ligand Name: D-myo-inositol 1,4,5-trisphosphate Ligand Info
Structure Description PI(4,5)P2 lipid binding induced a reorientation of FGF2 molecules near membrane surface to facilitate the unconventional oligomerization-dependent secretion process as revealed by a combined FTIR/NMR/X-ray study PDB:5X1O
Method X-ray diffraction Resolution 1.90 Å Mutation No [17]
PDB Sequence
KDPKRLYCKN
27
GGFFLRIHPD
37
GRVDGVREKS
47
DPHIKLQLQA
57
EERGVVSIKG
67

VCANRYLAMK
77
EDGRLLASKC
87
VTDECFFFER
97
LESNNYNTYR
107
SRKYTSWYVA
117

LKRTGQYKLG
127
SKTGPGQKAI
137
LFLPMSA
Residue
Distance (Å)
ARG39
4.683
VAL40
4.010
ASP41
4.766
ARG72
4.919
ALA75
4.629
LYS77
2.432
GLU78
3.046
ASP79
4.613
ARG81
2.190
Residue
Distance (Å)
LEU82
2.914
LEU83
3.299
ALA84
4.585
SER85
2.539
GLU91
3.626
GLN123
2.985
TYR124
2.292
LEU126
4.471
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
MAPK signaling pathway hsa04010 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Ras signaling pathway hsa04014 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Rap1 signaling pathway hsa04015 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
Calcium signaling pathway hsa04020 Affiliated Target
  Class: Environmental Information Processing => Signal transduction Pathway Hierarchy
PI3K-Akt signaling pathway hsa04151 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
Regulation of actin cytoskeleton hsa04810 Affiliated Target
  Class: Cellular Processes => Cell motility Pathway Hierarchy
  Click to Show/Hide the Information of Affiliated Human Pathways
Degree 39 Degree centrality 4.19E-03 Betweenness centrality 2.69E-03
Closeness centrality 2.44E-01 Radiality 1.43E+01 Clustering coefficient 1.39E-01
Neighborhood connectivity 3.15E+01 Topological coefficient 5.40E-02 Eccentricity 11
Download Click to Download the Full PPI Network of This Target

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