Target Information
Target General Information | Top | |||||
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Target ID |
T65721
(Former ID: TTDI01371)
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Target Name |
Ras-like protein TC25 (RAC1)
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Synonyms |
p21-Rac1; TC25; MIG5; Cell migration-inducing gene 5 protein
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Gene Name |
RAC1
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Target Type |
Literature-reported target
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Function |
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In neurons, is involved in dendritic spine formation and synaptic plasticity (By similarity). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3.
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UniProt ID | ||||||
EC Number |
EC 3.6.5.2
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Sequence |
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAG
QEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR DDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPP PVKKRKRKCLLL 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 |
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).
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
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Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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Leucine-rich repeat kinase 2 (LRRK2) | 24.590 (45/183) | 4.01E-07 | |
ADP-ribosylation factor-like protein 5A (ARL5A) | 23.030 (38/165) | 4.00E-03 |
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 |
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MAPK signaling pathway | hsa04010 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Ras signaling pathway | hsa04014 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Rap1 signaling pathway | hsa04015 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
cAMP signaling pathway | hsa04024 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Chemokine signaling pathway | hsa04062 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Sphingolipid signaling pathway | hsa04071 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Phagosome | hsa04145 | Affiliated Target |
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Class: Cellular Processes => Transport and catabolism | Pathway Hierarchy | ||
PI3K-Akt signaling pathway | hsa04151 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Wnt signaling pathway | hsa04310 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Axon guidance | hsa04360 | Affiliated Target |
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Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
VEGF signaling pathway | hsa04370 | Affiliated Target |
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Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
Osteoclast differentiation | hsa04380 | Affiliated Target |
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Class: Organismal Systems => Development and regeneration | Pathway Hierarchy | ||
Focal adhesion | hsa04510 | Affiliated Target |
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Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
Adherens junction | hsa04520 | Affiliated Target |
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Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
Tight junction | hsa04530 | Affiliated Target |
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Class: Cellular Processes => Cellular community - eukaryotes | Pathway Hierarchy | ||
Neutrophil extracellular trap formation | hsa04613 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Toll-like receptor signaling pathway | hsa04620 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Natural killer cell mediated cytotoxicity | hsa04650 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
B cell receptor signaling pathway | hsa04662 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Fc epsilon RI signaling pathway | hsa04664 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Fc gamma R-mediated phagocytosis | hsa04666 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Leukocyte transendothelial migration | hsa04670 | Affiliated Target |
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Class: Organismal Systems => Immune system | Pathway Hierarchy | ||
Neurotrophin signaling pathway | hsa04722 | Affiliated Target |
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Class: Organismal Systems => Nervous system | Pathway Hierarchy | ||
Regulation of actin cytoskeleton | hsa04810 | Affiliated Target |
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Class: Cellular Processes => Cell motility | Pathway Hierarchy | ||
Pancreatic secretion | hsa04972 | Affiliated Target |
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Class: Organismal Systems => Digestive system | Pathway Hierarchy | ||
Click to Show/Hide the Information of Affiliated Human Pathways |
Degree | 73 | Degree centrality | 7.84E-03 | Betweenness centrality | 5.03E-03 |
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Closeness centrality | 2.57E-01 | Radiality | 1.44E+01 | Clustering coefficient | 5.94E-02 |
Neighborhood connectivity | 2.63E+01 | Topological coefficient | 3.14E-02 | 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 |
References | Top | |||||
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REF 1 | RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol Cancer Ther. 2013 Oct;12(10):1925-34. |
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