General Information of Drug Therapeutic Target (DTT) (ID: TT25NY8)

DTT Name Ras-like protein TC25 (RAC1)
Synonyms p21-Rac1; TC25; MIG5; Cell migration-inducing gene 5 protein
Gene Name RAC1
DTT Type
Literature-reported target
[1]
UniProt ID
RAC1_HUMAN
TTD ID
T65721
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.6.5.2
Sequence
MQAIKCVVVGDGAVGKTCLLISYTTNAFPGEYIPTVFDNYSANVMVDGKPVNLGLWDTAG
QEDYDRLRPLSYPQTDVFLICFSLVSPASFENVRAKWYPEVRHHCPNTPIILVGTKLDLR
DDKDTIEKLKEKKLTPITYPQGLAMAKEIGAVKYLECSALTQRGLKTVFDEAIRAVLCPP
PVKKRKRKCLLL
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.
KEGG Pathway
MAPK signaling pathway (hsa04010 )
Ras signaling pathway (hsa04014 )
Rap1 signaling pathway (hsa04015 )
cAMP signaling pathway (hsa04024 )
Chemokine signaling pathway (hsa04062 )
Sphingolipid signaling pathway (hsa04071 )
Phagosome (hsa04145 )
PI3K-Akt signaling pathway (hsa04151 )
Wnt signaling pathway (hsa04310 )
Axon guidance (hsa04360 )
VEGF signaling pathway (hsa04370 )
Osteoclast differentiation (hsa04380 )
Focal adhesion (hsa04510 )
Adherens junction (hsa04520 )
Tight junction (hsa04530 )
Neutrophil extracellular trap formation (hsa04613 )
Toll-like receptor signaling pathway (hsa04620 )
Natural killer cell mediated cytotoxicity (hsa04650 )
B cell receptor signaling pathway (hsa04662 )
Fc epsilon RI signaling pathway (hsa04664 )
Fc gamma R-mediated phagocytosis (hsa04666 )
Leukocyte transendothelial migration (hsa04670 )
Neurotrophin signaling pathway (hsa04722 )
Regulation of actin cytoskeleton (hsa04810 )
Non-alcoholic fatty liver disease (hsa04932 )
AGE-RAGE signaling pathway in diabetic complications (hsa04933 )
Pancreatic secretion (hsa04972 )
Amyotrophic lateral sclerosis (hsa05014 )
Prion disease (hsa05020 )
Pathways of neurodegeneration - multiple diseases (hsa05022 )
Bacterial invasion of epithelial cells (hsa05100 )
Epithelial cell signaling in Helicobacter pylori infection (hsa05120 )
Pathogenic Escherichia coli infection (hsa05130 )
Shigellosis (hsa05131 )
Salmonella infection (hsa05132 )
Yersinia infection (hsa05135 )
Human cytomegalovirus infection (hsa05163 )
Kaposi sarcoma-associated herpesvirus infection (hsa05167 )
Epstein-Barr virus infection (hsa05169 )
Human immunodeficiency virus 1 infection (hsa05170 )
Pathways in cancer (hsa05200 )
Viral carcinogenesis (hsa05203 )
Proteoglycans in cancer (hsa05205 )
Chemical carcinogenesis - reactive oxygen species (hsa05208 )
Colorectal cancer (hsa05210 )
Renal cell carcinoma (hsa05211 )
Pancreatic cancer (hsa05212 )
Choline metabolism in cancer (hsa05231 )
Diabetic cardiomyopathy (hsa05415 )
Viral myocarditis (hsa05416 )
Lipid and atherosclerosis (hsa05417 )
Fluid shear stress and atherosclerosis (hsa05418 )
Reactome Pathway
PIP3 activates AKT signaling (R-HSA-1257604 )
Signaling by SCF-KIT (R-HSA-1433557 )
Translocation of SLC2A4 (GLUT4) to the plasma membrane (R-HSA-1445148 )
Nef and signal transduction (R-HSA-164944 )
NRAGE signals death through JNK (R-HSA-193648 )
Regulation of actin dynamics for phagocytic cup formation (R-HSA-2029482 )
Constitutive Signaling by Aberrant PI3K in Cancer (R-HSA-2219530 )
DAP12 signaling (R-HSA-2424491 )
FCERI mediated MAPK activation (R-HSA-2871796 )
DSCAM interactions (R-HSA-376172 )
CD28 dependent Vav1 pathway (R-HSA-389359 )
EPHB-mediated forward signaling (R-HSA-3928662 )
Ephrin signaling (R-HSA-3928664 )
EPH-ephrin mediated repulsion of cells (R-HSA-3928665 )
Sema3A PAK dependent Axon repulsion (R-HSA-399954 )
SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion (R-HSA-399955 )
PCP/CE pathway (R-HSA-4086400 )
Sema4D mediated inhibition of cell attachment and migration (R-HSA-416550 )
DCC mediated attractive signaling (R-HSA-418885 )
Activation of RAC1 (R-HSA-428540 )
Inactivation of CDC42 and RAC1 (R-HSA-428543 )
VEGFA-VEGFR2 Pathway (R-HSA-4420097 )
Signal transduction by L1 (R-HSA-445144 )
VEGFR2 mediated vascular permeability (R-HSA-5218920 )
RHO GTPases activate PKNs (R-HSA-5625740 )
RHO GTPases activate CIT (R-HSA-5625900 )
RHO GTPases activate KTN1 (R-HSA-5625970 )
RHO GTPases activate IQGAPs (R-HSA-5626467 )
RHO GTPases activate PAKs (R-HSA-5627123 )
RHO GTPases Activate WASPs and WAVEs (R-HSA-5663213 )
RHO GTPases Activate Formins (R-HSA-5663220 )
RHO GTPases Activate NADPH Oxidases (R-HSA-5668599 )
MAPK6/MAPK4 signaling (R-HSA-5687128 )
Neutrophil degranulation (R-HSA-6798695 )
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558 )
PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases (R-HSA-8849471 )
MET activates RAP1 and RAC1 (R-HSA-8875555 )
RAC1 GTPase cycle (R-HSA-9013149 )
NTRK2 activates RAC1 (R-HSA-9032759 )
Activated NTRK2 signals through CDK5 (R-HSA-9032845 )
Activation of RAC1 downstream of NMDARs (R-HSA-9619229 )
FCGR3A-mediated phagocytosis (R-HSA-9664422 )
WNT5 (R-HSA-9673324 )
Azathioprine ADME (R-HSA-9748787 )
Factors involved in megakaryocyte development and platelet production (R-HSA-983231 )
GPVI-mediated activation cascade (R-HSA-114604 )

References

1 RAC1: an emerging therapeutic option for targeting cancer angiogenesis and metastasis. Mol Cancer Ther. 2013 Oct;12(10):1925-34.