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Information on EC 3.6.5.2 - small monomeric GTPase
for references in articles please use BRENDA:EC3.6.5.2
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EC Tree 3 Hydrolases
3.6 Acting on acid anhydrides
3.6.5 Acting on GTP to facilitate cellular and subcellular movement
3.6.5.2 small monomeric GTPase
IUBMB Comments
A family of about 50 enzymes with a molecular mass of 21 kDa that are distantly related to the α-subunit of heterotrimeric G-protein GTPase (EC 3.6.5.1). They are involved in cell-growth regulation (Ras subfamily), membrane vesicle traffic and uncoating (Rab and ARF subfamilies), nuclear protein import (Ran subfamily) and organization of the cytoskeleton (Rho and Rac subfamilies).
The enzyme appears in viruses and cellular organisms
- 3.6.5.2
- actin
- oncogene
- cytoskeleton
- endosomes
- colorectal
- pancreatic
- metastasis
- endothelial
- adenocarcinoma
-
gtp-bound
- tumorigenesis
- carcinogenesis
-
endocytic
- integrins
- gdp
-
gtpase-activating
-
dominant-negative
- phosphatidylinositol
- mapk
- vesicular
- erk
- microtubule
- synaptic
-
exocytosis
- filopodia
-
cargo
-
neurite
-
traffic
- myosin
- 3-kinase
- guanosine
-
cell-cell
-
protrusion
-
cytokinesis
-
ruffle
- proto-oncogene
-
farnesylation
-
prenylation
-
geranylgeranylation
-
rock
-
adhesions
- lamellipodia
-
adherens
-
pleckstrin
- raf
- aminoacyl-trnas
- melanosomes
-
farnesyltransferase
-
rho-associated
- actomyosin
- analysis
- drug development
- pharmacology
- medicine
showSynonyms
k-ras, cdc42, h-ras, small gtpase, ef-tu, rho gtpase, rab11, rab3a, rab27a, rap1a, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADP-ribosylation factor 6
Alp41
Alp41/Arl2
ARD1
-
ARF subfamily, stimulates cholera toxin ADP ribosyltransferase, involved in vesicular trafficking, key regulator for interaction of non-clathrin coat proteins with Golgi stacks and clathrin adaptor particles with the trans-Golgi network
Arf 1
Arf6
Cdc42
Der
Der GTPase
double Era-like protein
EC 3.6.1.47
-
-
formerly
-
EF-Tu
FgCdc42
FgRac1
FgRHO1
FgRHO2
FgRHO3
FgRHO4
Gem
-
Ras-related, involved in receptor-mediated signal transduction at the plasma membrane
GTP-phosphohydrolase
-
-
-
-
GTPase
GTPase Alp41/Arl2
guanine triphosphatase
-
-
-
-
guanosine 5'-triphosphatase
-
-
-
-
guanosine triphosphatase
-
-
-
-
Kir
-
Ras-related, involved in processes of invasion or metastasis in mammalia cells
monomeric G protein
monomeric GTPase
OsRac1
p21 ras
PRA
Pra2
Pra3
Rab
Rab1a
Rab1B
Rab2A
Rab2B
Rab6A
Rab6B
Rac
Rac-like GTP-binding protein 1
Rac1
Rac2
Rac3
Rad
RalA
Ran
RAP
Rap GTPase
Rap1
Rap1b
RAS
Ras GTPase
Ras proximity 1
Ras related GTPase Rap
Ras-associated protein 1
Rho
Rho family small GTPase
Rho GTPase
Rho1
RhoA
RhoB
rhoB p20
RhoE
RhoEalpha
RhoGTPase
RhoH
ribosomal GTPase
-
-
-
-
ribosome-small-subunit-dependent GTPase A
RsgA
small GTPase
small GTPase Rac
small nuclear GTPase Ran
small Rho GTPase
vacuolar Rab GTPase
YjeQ
Ypt1
Ypt7p
additional information
GTPase
-
-
-
-
Rho1
-
Rho1 is important for the localization of the Sec3 component of the exocyst complex
RhoH
initially named translation three four, RhoH is a GTPase-deficient so-called atypical Rho GTPase, RhoH is only found in vertebrates
RhoH
initially named translation three four, RhoH is a GTPase-deficient so-called atypical Rho GTPase, RhoH is only found in vertebrates
additional information
member of a novel small monomeric GTPase gene family
additional information
member of a novel small monomeric GTPase gene family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GTP + H2O = GDP + phosphate
A family of about 50 enzymes with a molecular mass of 21 kDa that are distantly related to the alpha-subunit of heterotrimeric G-protein GTPase, EC 3.6.1.46. They are involved in cell-growth regulation, Ras subfamily, membrane vesicle traffic and uncoating, Rab and ARF subfamilies, nuclear protein import, Ran subfamily, and organization of the cytoskeleton, Rho and Rac subfamilies
-
-
-
GTP + H2O = GDP + phosphate
a family of about 50 enzymes with a molecular mass of 21 kDa that are distantly related to the alpha-subunit of heterotrimeric G-protein GTPase, EC 3.6.1.46, they are involved in cell-growth regulation, Ras subfamily, membrane vesicle traffic and uncoating, Rab and ARF subfamilies, nuclear protein import, Ran subfamily, and organization of the cytoskeleton, Rho and Rac subfamilies
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphorous acid anhydride hydrolysis
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
GTP phosphohydrolase (cell-regulating)
A family of about 50 enzymes with a molecular mass of 21 kDa that are distantly related to the alpha-subunit of heterotrimeric G-protein GTPase (EC 3.6.5.1). They are involved in cell-growth regulation (Ras subfamily), membrane vesicle traffic and uncoating (Rab and ARF subfamilies), nuclear protein import (Ran subfamily) and organization of the cytoskeleton (Rho and Rac subfamilies).
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CAS REGISTRY NUMBER
COMMENTARY
9059-32-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
guanosine 5'-O-(3-thio)triphosphate + H2O
guanosine 5'-diphosphate + thiophosphate
-
Substrates: -
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?
MEK kinase 1 + H2O
?
-
Substrates: RhoA binds and activates MEK kinase 1
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?
p21-activated kinase 1 + H2O
activated p21-activated kinase 1 + ?
-
Substrates: Gamide signals Rac/Cdc42 to activate p21-activated kinase 1
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?
Rho-activated kinase + H2O
activated Rho-activated kinase + ?
-
Substrates: Ggly signals Rac/Cdc42 to activate Rho-activated kinase
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?
GTP + H2O
GDP + phosphate
-
Substrates: the enzyme is involved in nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Nuclear import of Ran relies on a small RanGTP-binding protein, nuclear transport factor 2
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?
GTP + H2O
GDP + phosphate
-
Substrates: Arabidopsis thaliana circadian clock is regulated by the small GTPase LIP1. LIP1 plays a unique negative role in controlling circadian light input and is required for precise entrainment of the plant
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?
GTP + H2O
GDP + phosphate
Substrates: transport of precursor proteins across chloroplast membranes involves the GTPases Toc33/34 and Toc159 at the outer chloroplast envelope
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?
GTP + H2O
GDP + phosphate
-
Substrates: assay at pH 7.8, 30°C, 30 min
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?
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchange factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: RHO-1 plays a role in hypodermal P cell migration to a ventral position during larval development
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?
GTP + H2O
GDP + phosphate
Substrates: GTP binds to Der in a cooperative manner and the interruption of cooperative nucleotide association disrupts the interaction of Der with the 50S subunit
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rab11 plays a central role in the transport and secretion of pathogenic factors
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?
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
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ir
GTP + H2O
GDP + phosphate
Substrates: GTP binds to Der in a cooperative manner and the interruption of cooperative nucleotide association disrupts the interaction of Der with the 50S subunit
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?
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
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ir
GTP + H2O
GDP + phosphate
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Substrates: -
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?
GTP + H2O
GDP + phosphate
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Substrates: -
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rac-1 coordinates changes in chondrocyte phenotype and function and stimulates the maturation process essential for skeletal development
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?
GTP + H2O
GDP + phosphate
-
Substrates: GhRac1 GTPase may be a potential regulator of fiber elongation by controlling cytoskeletal assembly
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?
GTP + H2O
GDP + phosphate
-
Substrates: -
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ir
GTP + H2O
GDP + phosphate
-
Substrates: high affinity for GTP, significant GTPase activity
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ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchange factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: cycling between the active GTP bound and the inactive GDP bound state, slow GTPase activity
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ir
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
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ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: RhoA promotes actin-myosin contractility and, thereby, the formation of stress fibers and focal adhesions, regulating cell shape, attachment and motility
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rac1 promotes actin polymerization and the formation of lamellipodia of migrating cells
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?
GTP + H2O
GDP + phosphate
-
Substrates: Cdc42 causes formation of filopodia, which might be involved in the recognition of the extracellular environment
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?
GTP + H2O
GDP + phosphate
Substrates: Rab21 has a role in the dynamics of the early endocytic pathway
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?
GTP + H2O
GDP + phosphate
Substrates: Rac1 regulates gene expression, cell cycle progression and rearrangement of the actin cytoskeleton, Rac1 is ubiquitously expressed and regulates a wide variety of cellular processes
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?
GTP + H2O
GDP + phosphate
Substrates: Rac2 may be responsible for the regulation of the oxidative burst in hematopoietic cells
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?
GTP + H2O
GDP + phosphate
Substrates: Rac3 is ubiquitously expressed and regulates a wide variety of cellular processes
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rab27a has a determinant role in melanocytes and lymphocytes, role in melanosome peripheral transfer, required for cytotoxic granule exocytosis
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?
GTP + H2O
GDP + phosphate
-
Substrates: intrinsic GTPase reaction mechanism, biphasic reaction
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?
GTP + H2O
GDP + phosphate
Substrates: nucleotide binding and hydrolysis properties, comparison with the properties of the Rac isoforms Rac2 and Rac3, enzyme structure
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?
GTP + H2O
GDP + phosphate
Substrates: nucleotide binding and hydrolysis properties, comparison with the properties of the Rac isoforms Rac1 and Rac3, Rac2 structure, altered dynamics of Rac2 at the switch I region may be responsible for the differing biochemical properties compared with Rac1 and 3
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?
GTP + H2O
GDP + phosphate
Substrates: nucleotide binding and hydrolysis properties, comparison with the properties of the Rac isoforms Rac1 and Rac2
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?
GTP + H2O
GDP + phosphate
-
Substrates: Trp-73 is a key position for interaction with the specific effectors of Rab27a, both in melanocytes and cytotoxic cells, Trp-73 is essential for the intrinsic GTPase activity, Gln-78 may stabilize the catalytic transition state between switch I and II
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?
GTP + H2O
GDP + phosphate
-
Substrates: tuberous sclerosis complex TSC2 displays activity of a GTPase-activating protein specifically towards the small G protein Rheb and inhibits its ability to stimulate the mTOR signalling pathway
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?
GTP + H2O
GDP + phosphate
Substrates: RHEBL1 may play an important role in the NF-kappa B-mediated gene transcription
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?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein. Altering the intracellular trafficking of P-glycoprotein by modulation of its small GTPase regulators can be potential strategy to overcome multidrug resistance, a major obstacle in cancer chemotherapy
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?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells
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?
GTP + H2O
GDP + phosphate
-
Substrates: the small GTPase Rac plays a crucial role in activation of Nox2- and Nox1-based oxidases i all the possible combinations of the organizer p47phox or Noxo1 with the activator p67phox or Noxa1
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?
GTP + H2O
GDP + phosphate
-
Substrates: small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran has important roles during mitosis, when the nucleus is reorganized to allow chromosome segregation. Ran directs the assembly of the mitotic spindle, nuclear-envelope dynamics and the timing of cell-cycle transitions
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?
GTP + H2O
GDP + phosphate
-
Substrates: two conformational states of Ras GTPase exhibit differential GTP-binding kinetics
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?
GTP + H2O
GDP + phosphate
-
Substrates: -
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?
GTP + H2O
GDP + phosphate
Substrates: -
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?
GTP + H2O
GDP + phosphate
Substrates: -
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?
GTP + H2O
GDP + phosphate
Substrates: enzyme Rheb contains a high basal GTP level
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?
GTP + H2O
GDP + phosphate
-
Substrates: acts on the intracellular membrane through the trafficking pathway
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?
GTP + H2O
GDP + phosphate
Substrates: transport of precursor proteins across chloroplast membranes involves the GTPases Toc33/34 and Toc159 at the outer chloroplast envelope
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?
GTP + H2O
GDP + phosphate
-
Substrates: small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran has important roles during mitosis, when the nucleus is reorganized to allow chromosome segregation. Ran directs the assembly of the mitotic spindle, nuclear-envelope dynamics and the timing of cell-cycle transitions
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?
GTP + H2O
GDP + phosphate
-
Substrates: two conformational states of Ras GTPase exhibit differential GTP-binding kinetics
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?
GTP + H2O
GDP + phosphate
-
Substrates: -
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?
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
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ir
GTP + H2O
GDP + phosphate
Substrates: -
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?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rnd1 is involved in signaling pathways of neuronal activity-dependent dendritic development
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?
GTP + H2O
GDP + phosphate
-
Substrates: Rho A-linked pathway important in the endothelin-1 signaling to c-fos SRC
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ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchange factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: slow time-dependent GTPase activity
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ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
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ir
GTP + H2O
GDP + phosphate
-
Substrates: -
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ir
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
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ir
GTP + H2O
GDP + phosphate
-
Substrates: Rho3p and Rho4p are involved in regulating cell polarity by controlling polarized exocytosis. It is proposed that Wsc1p participates in the regulation of a Rho3/4-dependent cellular mechanism
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?
GTP + H2O
GDP + phosphate
-
Substrates: GTP binds to Der in a cooperative manner and the interruption of cooperative nucleotide association disrupts the interaction of Der with the 50S subunit
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?
GTP + H2O
GDP + phosphate
Substrates: GTP binds to Der in a cooperative manner and the interruption of cooperative nucleotide association disrupts the interaction of Der with the 50S subunit
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?
GTP + H2O
GDP + phosphate
Substrates: nucleotide binding pocket and binding structures, overview
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GTP + H2O
GDP + phosphate
-
Substrates: GTPase TcRho1 is required for differentiation of epimastigote to trypomastigote forms during the parasite cell cycle. TcRho1 plays a conserved regulatory role in cell-substrate adhesion in both NIH-3T3 fibroblasts and Trypanosoma cruzi epimastigotes. TcRho1 may regulate the substrate-adhesion in Trypanosoma cruzi,a critical step for successful progression of the parasite life cycle
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guanosine 5'-O-(3-thiotriphosphate) + H2O
guanosine 5'-O-diphosphate + thiophosphate
-
Substrates: poorly hydrolyzable, GTP[S]-activated Rac1 and Cdc42, but not RhoA, stimulate activity of phospholipase C-beta2 protein in complex with Rho GDP dissociation inhibitor protein LyGDL
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?
guanosine 5'-O-(3-thiotriphosphate) + H2O
guanosine 5'-O-diphosphate + thiophosphate
-
Substrates: no detectable hydrolysis of GTP at the ARF domain p3, 35-40% of the GTP bound to ARD1 domain p8 hydrolyzed in 1 h at room temperature
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?
guanosine 5'-O-(3-thiotriphosphate) + H2O
guanosine 5'-O-diphosphate + thiophosphate
-
Substrates: poorly hydrolyzable, GTP[S]-activated Rac1 and Cdc42, but not RhoA, stimulate activity of phospholipase C-beta2 protein in complex with Rho GDP dissociation inhibitor protein LyGDL
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?
guanosine 5'-O-(3-thiotriphosphate) + H2O
guanosine 5'-O-diphosphate + thiophosphate
-
Substrates: -
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?
additional information
?
-
-
Substrates: role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response
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?
additional information
?
-
-
Substrates: small GTPase Rab2 functions in the removal of apoptotic cells
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?
additional information
?
-
-
Substrates: GTPase-mediated regulation of the unfolded protein response in Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48
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?
additional information
?
-
-
Substrates: Campylobacter jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 play a crucial role in this entry process
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?
additional information
?
-
Substrates: Rhb1 is involved in the cell wall integrity pathway via activation of mitogen-activated protein kinase Mkc1
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?
additional information
?
-
-
Substrates: Rhb1 is involved in the cell wall integrity pathway via activation of mitogen-activated protein kinase Mkc1
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?
additional information
?
-
Substrates: p21-activated kinase Cla4 is a major downstream partner of Rac. Rac has strong effect on hyphal morphology
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?
additional information
?
-
-
Substrates: p21-activated kinase Cla4 is a major downstream partner of Rac. Rac has strong effect on hyphal morphology
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?
additional information
?
-
-
Substrates: small GTPases are involved in chemotaxis
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additional information
?
-
-
Substrates: Rho1 activity is required for proper development of the circular visceral mesoderm upon which the gland migrates, Rho1 GTPase regulates salivary gland invagination by maintaining apical localization of Crumbs, Drosophila atypical protein kinase C and Stardust and that this occurs partially through regulation of Crumbs RNA level and apical localization of the transcript and by inducing apical constriction and cell shape change through Rho-kinase
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additional information
?
-
-
Substrates: crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
A0A098E0E9
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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?
additional information
?
-
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
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Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
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Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
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Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
A0A098E0E9
Substrates: FgRac1 interacts with the PBD domain of FgCla4
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additional information
?
-
Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
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additional information
?
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Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
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additional information
?
-
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Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
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additional information
?
-
-
Substrates: Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac
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additional information
?
-
-
Substrates: the Ral-exocyst pathway participates in the regulation of platelet dense granule secretion by enhancing the Ca2+ sensitivity of the secretion
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additional information
?
-
-
Substrates: small GTPase Rac is directly involved in activation of the superoxide-producing NADPH oxidase Nox1
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additional information
?
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Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
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?
additional information
?
-
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoA activity is required for modulating cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rho and Rac play a role in the regulation cytoskeletal remodeling and EC barrier regulation
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rap1 plays a critical role in the regulation of beta1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoA may serve as intermediary for functional receptor for thromboxane A2-signaling axis to regulate tumor cell motility
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme Rheb does not co-localize with microtubules but interacts with unpolymerized free alphabeta-tubulin, alphabeta-tubulin is a Rheb-binding protein. Rheb binds to deacetylated soluble alphabeta-tubulin
Products: -
Products: -
?
additional information
?
-
Substrates: kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development overview
Products: -
Products: -
?
additional information
?
-
Substrates: kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development overview
Products: -
Products: -
?
additional information
?
-
Substrates: kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development overview
Products: -
Products: -
?
additional information
?
-
Substrates: binding of GppNHp by Rab8 leads to the active form of Rab8, like with GTP, but GppNHp is unhydrolyzable, binding studies
Products: -
Products: -
?
additional information
?
-
-
Substrates: binding of GppNHp by Rab8 leads to the active form of Rab8, like with GTP, but GppNHp is unhydrolyzable, binding studies
Products: -
Products: -
?
additional information
?
-
-
Substrates: Ras binds guanine nucleotides in its guanine nucleotide-binding cleft composed of G-box elements that are conserved among all GTPase proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone
Products: -
Products: -
?
additional information
?
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac1 and Cdc42 are not required for differentiation and migration of neural crest cells, but are essential for mitotic activity and cell-cycle control in neural crest cell target structures
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac2 selectively controls phagosomal alkalinization and antigen crosspresentation in CD8+ dendritic cells, Rac2 determines the subcellular assembly of the NADPH oxidase complex to phagosomes in CD8+ cells whereas in CD8- cells Rac1 mediates the assembly of NOX2 at the plasma membrane
Products: -
Products: -
?
additional information
?
-
-
Substrates: RalA is a critical component in biphasic insulin release from pancreatic beta cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the small GTPase RhoA is crucial for MC3T3-E1 osteoblastic cell survival
Products: -
Products: -
?
additional information
?
-
-
Substrates: in 3T3-L1 adipocytes, stimulation of lipolysis increases the association of Rab18 with lipid droplets, suggesting that recruitment of Rab18 is regulated by the metabolic state of individual lipid droplets
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac1 is a central regulator of rapid encoding of novel spatial information in vivo, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac GTPases play an important role in enucleation of mammalian erythroblasts
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rab and Ral GTPases function in exocyst assembly and vesicle-tethering processes, whereas the Rho family of GTPases functions in the local activation of the exocyst complex to facilitate downstream vesicle-fusion events
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rap1 plays a critical role in the regulation of beta1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization
Products: -
Products: -
?
additional information
?
-
Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
Products: -
Products: -
?
additional information
?
-
Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
Products: -
Products: -
?
additional information
?
-
Substrates: recombinant RhoA activity reduces Ba2+ currents through CaV2.1, CaV2.2 and CaV2.3 Ca2+ channels independently of CaVbeta subunit. This inhibition occurs independently of RGKs activity and without modification of biophysical properties and global level of expression of the channel subunit
Products: -
Products: -
?
additional information
?
-
Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
Products: -
Products: -
?
additional information
?
-
Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
Products: -
Products: -
?
additional information
?
-
Substrates: interaction site of HsRac1 with p67phox, an essential component of the NADPH oxidase complex
Products: -
Products: -
?
additional information
?
-
-
Substrates: interaction site of HsRac1 with p67phox, an essential component of the NADPH oxidase complex
Products: -
Products: -
?
additional information
?
-
Substrates: no activity with unhydrolyzable GTPgammaS, which is used for association/dissociation and binding analysis
Products: -
Products: -
?
additional information
?
-
-
Substrates: no activity with unhydrolyzable GTPgammaS, which is used for association/dissociation and binding analysis
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac1 can interact with the PBD domain of p21-activated kinase 1 (PAK1)
Products: -
Products: -
?
additional information
?
-
-
Substrates: RalA is a critical component in biphasic insulin release from pancreatic beta cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rho1p and its downstream regulatory pathways are involved in controlling cell size in Saccharomyces cerevisiae
Products: -
Products: -
?
additional information
?
-
-
Substrates: vacuole fusion assays
Products: -
Products: -
?
additional information
?
-
-
Substrates: vacuole fusion assays
Products: -
Products: -
?
additional information
?
-
Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
Products: -
Products: -
?
additional information
?
-
-
Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
Products: -
Products: -
?
additional information
?
-
Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoA activity is required for modulating cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding
Products: -
Products: -
?
additional information
?
-
Substrates: the enzyme interacts with tubulin and co-localises to the flagellar pocket with BBS1 when this protein is overexpressed
Products: -
Products: -
?
additional information
?
-
-
Substrates: the enzyme interacts with tubulin and co-localises to the flagellar pocket with BBS1 when this protein is overexpressed
Products: -
Products: -
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
p21-activated kinase 1 + H2O
activated p21-activated kinase 1 + ?
-
Substrates: Gamide signals Rac/Cdc42 to activate p21-activated kinase 1
Products: -
Products: -
?
Rho-activated kinase + H2O
activated Rho-activated kinase + ?
-
Substrates: Ggly signals Rac/Cdc42 to activate Rho-activated kinase
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: the enzyme is involved in nucleocytoplasmic transport, mitotic spindle assembly and nuclear envelope formation. Nuclear import of Ran relies on a small RanGTP-binding protein, nuclear transport factor 2
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Arabidopsis thaliana circadian clock is regulated by the small GTPase LIP1. LIP1 plays a unique negative role in controlling circadian light input and is required for precise entrainment of the plant
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: transport of precursor proteins across chloroplast membranes involves the GTPases Toc33/34 and Toc159 at the outer chloroplast envelope
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: RHO-1 plays a role in hypodermal P cell migration to a ventral position during larval development
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Rab11 plays a central role in the transport and secretion of pathogenic factors
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Substrates: -
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Substrates: -
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Rac-1 coordinates changes in chondrocyte phenotype and function and stimulates the maturation process essential for skeletal development
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: GhRac1 GTPase may be a potential regulator of fiber elongation by controlling cytoskeletal assembly
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: -
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: high affinity for GTP, significant GTPase activity
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: cycling between the active GTP bound and the inactive GDP bound state, slow GTPase activity
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: RhoA promotes actin-myosin contractility and, thereby, the formation of stress fibers and focal adhesions, regulating cell shape, attachment and motility
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Rac1 promotes actin polymerization and the formation of lamellipodia of migrating cells
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Cdc42 causes formation of filopodia, which might be involved in the recognition of the extracellular environment
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: Rab21 has a role in the dynamics of the early endocytic pathway
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: Rac1 regulates gene expression, cell cycle progression and rearrangement of the actin cytoskeleton, Rac1 is ubiquitously expressed and regulates a wide variety of cellular processes
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: Rac2 may be responsible for the regulation of the oxidative burst in hematopoietic cells
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: Rac3 is ubiquitously expressed and regulates a wide variety of cellular processes
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Rab27a has a determinant role in melanocytes and lymphocytes, role in melanosome peripheral transfer, required for cytotoxic granule exocytosis
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: tuberous sclerosis complex TSC2 displays activity of a GTPase-activating protein specifically towards the small G protein Rheb and inhibits its ability to stimulate the mTOR signalling pathway
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: RHEBL1 may play an important role in the NF-kappa B-mediated gene transcription
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein. Altering the intracellular trafficking of P-glycoprotein by modulation of its small GTPase regulators can be potential strategy to overcome multidrug resistance, a major obstacle in cancer chemotherapy
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: the small GTPase Rac plays a crucial role in activation of Nox2- and Nox1-based oxidases i all the possible combinations of the organizer p47phox or Noxo1 with the activator p67phox or Noxa1
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran has important roles during mitosis, when the nucleus is reorganized to allow chromosome segregation. Ran directs the assembly of the mitotic spindle, nuclear-envelope dynamics and the timing of cell-cycle transitions
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: -
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: -
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: enzyme Rheb contains a high basal GTP level
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: acts on the intracellular membrane through the trafficking pathway
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
Substrates: transport of precursor proteins across chloroplast membranes involves the GTPases Toc33/34 and Toc159 at the outer chloroplast envelope
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: small nuclear GTPase Ran controls the directionality of macromolecular transport between the nucleus and the cytoplasm. Ran has important roles during mitosis, when the nucleus is reorganized to allow chromosome segregation. Ran directs the assembly of the mitotic spindle, nuclear-envelope dynamics and the timing of cell-cycle transitions
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
Substrates: -
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression
Products: -
Products: -
?
GTP + H2O
GDP + phosphate
-
Substrates: Rho A-linked pathway important in the endothelin-1 signaling to c-fos SRC
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: slow time-dependent GTPase activity
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: increased rate of nucleotide dissociation by interaction with guanosine exchanges factors that facilitates loading with GTP
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: -
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: unidirectional cycle in which exchange of GDP for GTP turns on a switch and GTP hydrolysis turns it off
Products: -
Products: -
ir
GTP + H2O
GDP + phosphate
-
Substrates: Rho3p and Rho4p are involved in regulating cell polarity by controlling polarized exocytosis. It is proposed that Wsc1p participates in the regulation of a Rho3/4-dependent cellular mechanism
Products: -
Products: -
?
additional information
?
-
-
Substrates: role of small GTPases in endothelial cytoskeletal dynamics and the shear stress response
Products: -
Products: -
?
additional information
?
-
-
Substrates: small GTPase Rab2 functions in the removal of apoptotic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: GTPase-mediated regulation of the unfolded protein response in Caenorhabditis elegans is dependent on the AAA+ ATPase CDC-48
Products: -
Products: -
?
additional information
?
-
-
Substrates: Campylobacter jejuni invade host target cells by a unique mechanism and the activation of the Rho GTPase members Rac1 and Cdc42 play a crucial role in this entry process
Products: -
Products: -
?
additional information
?
-
Substrates: Rhb1 is involved in the cell wall integrity pathway via activation of mitogen-activated protein kinase Mkc1
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rhb1 is involved in the cell wall integrity pathway via activation of mitogen-activated protein kinase Mkc1
Products: -
Products: -
?
additional information
?
-
Substrates: p21-activated kinase Cla4 is a major downstream partner of Rac. Rac has strong effect on hyphal morphology
Products: -
Products: -
?
additional information
?
-
-
Substrates: p21-activated kinase Cla4 is a major downstream partner of Rac. Rac has strong effect on hyphal morphology
Products: -
Products: -
?
additional information
?
-
-
Substrates: small GTPases are involved in chemotaxis
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rho1 activity is required for proper development of the circular visceral mesoderm upon which the gland migrates, Rho1 GTPase regulates salivary gland invagination by maintaining apical localization of Crumbs, Drosophila atypical protein kinase C and Stardust and that this occurs partially through regulation of Crumbs RNA level and apical localization of the transcript and by inducing apical constriction and cell shape change through Rho-kinase
Products: -
Products: -
?
additional information
?
-
-
Substrates: crystal cell rupture after injury in Drosophila requires the JNK pathway, small GTPases and the TNF homolog Eiger
Products: -
Products: -
?
additional information
?
-
Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
Products: -
Products: -
?
additional information
?
-
Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
Products: -
Products: -
?
additional information
?
-
-
Substrates: RASL11A is down-regulated in prostate tumors and may have a tumor suppressor role in prostate cancer
Products: -
Products: -
?
additional information
?
-
-
Substrates: Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac
Products: -
Products: -
?
additional information
?
-
-
Substrates: the Ral-exocyst pathway participates in the regulation of platelet dense granule secretion by enhancing the Ca2+ sensitivity of the secretion
Products: -
Products: -
?
additional information
?
-
-
Substrates: small GTPase Rac is directly involved in activation of the superoxide-producing NADPH oxidase Nox1
Products: -
Products: -
?
additional information
?
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoA activity is required for modulating cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rho and Rac play a role in the regulation cytoskeletal remodeling and EC barrier regulation
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rap1 plays a critical role in the regulation of beta1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoA may serve as intermediary for functional receptor for thromboxane A2-signaling axis to regulate tumor cell motility
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: at least 3 mitogen-activated protein kinases (MAPKs) are direct targets of Rac1: MLK2, MLK3, and MEKK4
Products: -
Products: -
?
additional information
?
-
Substrates: enzyme Rheb does not co-localize with microtubules but interacts with unpolymerized free alphabeta-tubulin, alphabeta-tubulin is a Rheb-binding protein. Rheb binds to deacetylated soluble alphabeta-tubulin
Products: -
Products: -
?
additional information
?
-
-
Substrates: Knock down of Rab21 impairs integrin-mediated cell adhesion and motility, its overexpression stimulates cell migration and cancer cell adhesion to collagen and human bone
Products: -
Products: -
?
additional information
?
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the small GTPase RhoH is an atypical regulator of haematopoietic cells
Products: -
Products: -
?
additional information
?
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: RhoH inhibits IkappaB degradation and acts as a specific negative regulator for Rac and RhoA-induced p38 activity
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac1 and Cdc42 are not required for differentiation and migration of neural crest cells, but are essential for mitotic activity and cell-cycle control in neural crest cell target structures
Products: -
Products: -
?
additional information
?
-
-
Substrates: Rac2 selectively controls phagosomal alkalinization and antigen crosspresentation in CD8+ dendritic cells, Rac2 determines the subcellular assembly of the NADPH oxidase complex to phagosomes in CD8+ cells whereas in CD8- cells Rac1 mediates the assembly of NOX2 at the plasma membrane
Products: -
Products: -
?
additional information
?
-
-
Substrates: RalA is a critical component in biphasic insulin release from pancreatic beta cells
Products: -
Products: -
?
additional information
?
-
-
Substrates: the small GTPase RhoA is crucial for MC3T3-E1 osteoblastic cell survival
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Substrates: in 3T3-L1 adipocytes, stimulation of lipolysis increases the association of Rab18 with lipid droplets, suggesting that recruitment of Rab18 is regulated by the metabolic state of individual lipid droplets
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Substrates: Rac1 is a central regulator of rapid encoding of novel spatial information in vivo, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place
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Substrates: Rac GTPases play an important role in enucleation of mammalian erythroblasts
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Substrates: Rab and Ral GTPases function in exocyst assembly and vesicle-tethering processes, whereas the Rho family of GTPases functions in the local activation of the exocyst complex to facilitate downstream vesicle-fusion events
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Substrates: Rap1 plays a critical role in the regulation of beta1-integrin affinity, adhesion, and migration in endothelial cells and in postnatal neovascularization
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Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
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Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
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Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
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Substrates: Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states: in the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position
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Substrates: interaction site of HsRac1 with p67phox, an essential component of the NADPH oxidase complex
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Substrates: interaction site of HsRac1 with p67phox, an essential component of the NADPH oxidase complex
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Substrates: Rac1 can interact with the PBD domain of p21-activated kinase 1 (PAK1)
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Substrates: RalA is a critical component in biphasic insulin release from pancreatic beta cells
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Substrates: Rho1p and its downstream regulatory pathways are involved in controlling cell size in Saccharomyces cerevisiae
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Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
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Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
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Substrates: Alp41 GTPase interacts with cofactor C, but with cofactor D, Alp1D, only when bound to GDP
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Substrates: RhoA activity is required for modulating cell migration and proliferation through cytoskeleton reorganization and focal adhesion formation in response to wounding
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Substrates: the enzyme interacts with tubulin and co-localises to the flagellar pocket with BBS1 when this protein is overexpressed
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Substrates: the enzyme interacts with tubulin and co-localises to the flagellar pocket with BBS1 when this protein is overexpressed
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Mg2+
Mg2+
-
coordinated to oxygens of beta- and gamma-phosphates of GTP, essential for GTP hydrolysis
Mg2+
-
in absence of Mg2+ rapid release of GDP but dissociation rate of GTP very slow
Mg2+
-
the Mg2+ cofactor acts as a stabilizer for the bound nucleotides by slowing down the off and on rates, Mg2+ has only a minor effect on the intrinsic hydrolysis rate of GTP, kinetic study of the interaction of GTP with Cdc42 in the absence and presence of Mg2+
Mg2+
nucleotide binding to Ras is greatly enhanced by Mg2+
Mg2+
-
1 mM required for optimal activity, involved in binding of beta- and gamma-phosphates of GTP
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2E)-2-[(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
inhibition of GEF-Rac1 interaction (selective for Trio)
2-(morpholin-4-ylmethyl)-5-[(5-[[7-(trifluoromethyl)quinolin-4-yl]sulfanyl]pentyl)oxy]-4H-pyran-4-one
inhibition of Rac1 nucleotide binding possiblly using an allosteric mechanism
2-amino-8-hydroxy-9-[3-hydroxy-2-(hydroxymethyl)cyclopentyl]-5,9-dihydro-6H-purin-6-one
inhibition of Rac1-dependent NADPH oxidase activity
3-(2-hydroxyphenyl)-N-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide
inhibition of GEF-Rac1 interaction (Tiam1, Trio, and Vav2), the compound inhibits lamellipodia formation and smooth muscle cell migration
3-([(2E)-2-cyano-3-(4-methoxy-3-[(naphthalen-1-ylcarbonyl)oxy]phenyl)prop-2-enoyl]amino)benzoic acid
5-(3-chloro-4-[(3-fluorobenzyl)oxy]-5-methoxybenzyl)-1-(4-hydroxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
5-chloro-3-(2-oxo-2-(4-[3-(trifluoromethyl)phenyl]piperazin-1-yl)ethyl)-1H-indole-2-carboxylic acid
9-methoxy-5-(3-nitrophenyl)-2-phenyl-3,10b-dihydropyrazolo[1,5-c][1,3]benzoxazine
inhibition of effector-Rac1 interaction (p67phox)
atorvastatin
-
marketed as Lipitor, i.e. [R-(R*,R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-heptanoic acid, inhibits RhoA activity by reducing Rho geranylgeranylation
Calmodulin
-
binding of calmodulin to GST-immobilized Kir/Gem peptide inhibits GTP binding
cerivastatin
-
marketed as Baycol/Lipobay, i.e. (E,3R,5S)-7-[4-(4-fluorophenyl)-5-(methoxymethyl)-2,6-dipropan-2-yl-pyridin-3-yl]-3,5-dihydroxy-hept-6-enoic acid, RhoA inhibitor
EDTA
inhibits nucleotide binding to Ras; inhibits nucleotide binding to Ras; inhibits nucleotide binding to Ras
ethyl ([2-(2-methoxy-4-((Z)-[1-(4-methylphenyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl)phenoxy)ethyl]sulfanyl)acetate
GTPgammaS
-
Arl6 is competitively inhibited by the increasing concentrations of non-radioactive GTPgammaS
lovastatin
-
marketed as Mevacor, i.e. 8-[2-(4-hydroxy-6-oxo-oxan-2-yl)ethyl]-3,7-dimethyl-1,2,3,7,8,8a-[hexahydronaphthalen-1-yl]2-methylbutanoate
N-(2-chlorobenzyl)-N-[[(4-methylphenyl)sulfonyl]carbamoyl]-L-alanine
-
Rho toxin from Clostridium botulinum, ADP-ribosylates and specifically inactivates rho-1
N-[4-methoxy-3-(piperidin-1-ylsulfonyl)phenyl]-1H-indazole-3-carboxamide
inhibition of GEF-Rac1 interaction (Tiam1)
N4-(9-ethyl-9H-carbazol-3-yl)-N2-[3-(morpholin-4-yl)propyl]pyrimidine-2,4-diamine
inhibition of GEF-Rac1 interaction (selective for Vav2)
N6-(2-[[5-(diethylamino)pentan-2-yl]amino]-6-methylpyrimidin-4-yl)-2-methylquinoline-4,6-diamine
a selective inhibitor for Rac1. The small molecule fits into the surface groove of Rac1 involved in the binding with GEFs, thus interfering with the Tiam1-Rac1 interaction
p21 activated kinase
PAK, inhibits nucleotide dissociation from enzyme; PAK, inhibits nucleotide dissociation from enzyme
-
PlexA
plexins (Plexs) comprise a large family of cell surface receptors for semaphorins (Semas) that function as evolutionarily conserved guidance molecules. Rap GTPase but not Ras GTPase homologs are inactivated by the GAP activity of several vertebrate plexins. GTPase activating protein (GAP) activity for Ras family small GTPases has been implicated in plexin signaling cascades through its RasGAP domain. Neuronal expression of mutant PlexA robustly restores defasciculation defects in PlexA null mutants when the catalytic arginine fingers of the PlexA RasGAP domain critical for GAP activity are disrupted. Deleting the RasGAP domain abolishes the ability of PlexA to rescue the PlexA guidance phenotypes. PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases
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Rap1Gap
-
the GTPase activating protein catalyzes the hydrolysis of GTP by its asparagine side chain rendering Rap1 inactive
-
simvastatin
-
marketed as Zocor, i.e. [(1S,3R,7R,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxo-oxan-2-yl]ethyl]3.7-dimethyl]-1,2,3,7,8,8a-[hexahydronaphthalen-1-yl]2,2-dimethylbutanoate
statin
improves redox state in saphenous vein grafts in patients undergoing to coronary artery bypass grafting by inhibiting Rac1-mediated activation of NADPH oxidase
Yersinia outer protein T
-
Yersinia outer protein T is a cysteine protease that cleaves Rho protein directly upstream of the post-translationally modified cysteine, thereby releasing the GTPase from the membrane leading to inactivation, farnesylated RhoA is a preferred substrate of Yersinia outer protein T compared with the geranylgeranylated GTPase, geranylgeranylated RhoA, however, is the preferred substrate for Yersinia outer protein T-catalyzed cleavage with a 3fold faster turnover rate over Rac and Cdc42
-
3-([(2E)-2-cyano-3-(4-methoxy-3-[(naphthalen-1-ylcarbonyl)oxy]phenyl)prop-2-enoyl]amino)benzoic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
3-([(2E)-2-cyano-3-(4-methoxy-3-[(naphthalen-1-ylcarbonyl)oxy]phenyl)prop-2-enoyl]amino)benzoic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
3-([(2E)-2-cyano-3-(4-methoxy-3-[(naphthalen-1-ylcarbonyl)oxy]phenyl)prop-2-enoyl]amino)benzoic acid
-
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
3-([(2E)-2-cyano-3-(4-methoxy-3-[(naphthalen-1-ylcarbonyl)oxy]phenyl)prop-2-enoyl]amino)benzoic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
5-(3-chloro-4-[(3-fluorobenzyl)oxy]-5-methoxybenzyl)-1-(4-hydroxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
-
5-(3-chloro-4-[(3-fluorobenzyl)oxy]-5-methoxybenzyl)-1-(4-hydroxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
-
5-(3-chloro-4-[(3-fluorobenzyl)oxy]-5-methoxybenzyl)-1-(4-hydroxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
-
-
5-(3-chloro-4-[(3-fluorobenzyl)oxy]-5-methoxybenzyl)-1-(4-hydroxyphenyl)pyrimidine-2,4,6(1H,3H,5H)-trione
-
5-chloro-3-(2-oxo-2-(4-[3-(trifluoromethyl)phenyl]piperazin-1-yl)ethyl)-1H-indole-2-carboxylic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
5-chloro-3-(2-oxo-2-(4-[3-(trifluoromethyl)phenyl]piperazin-1-yl)ethyl)-1H-indole-2-carboxylic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
5-chloro-3-(2-oxo-2-(4-[3-(trifluoromethyl)phenyl]piperazin-1-yl)ethyl)-1H-indole-2-carboxylic acid
-
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
5-chloro-3-(2-oxo-2-(4-[3-(trifluoromethyl)phenyl]piperazin-1-yl)ethyl)-1H-indole-2-carboxylic acid
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
ethyl ([2-(2-methoxy-4-((Z)-[1-(4-methylphenyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl)phenoxy)ethyl]sulfanyl)acetate
-
ethyl ([2-(2-methoxy-4-((Z)-[1-(4-methylphenyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl)phenoxy)ethyl]sulfanyl)acetate
-
ethyl ([2-(2-methoxy-4-((Z)-[1-(4-methylphenyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl)phenoxy)ethyl]sulfanyl)acetate
-
-
ethyl ([2-(2-methoxy-4-((Z)-[1-(4-methylphenyl)-2,4,6-trioxotetrahydropyrimidin-5(2H)-ylidene]methyl)phenoxy)ethyl]sulfanyl)acetate
-
GDP
the activation state of Rac1 depends on the release of guanosine diphosphate and the binding of guanosine triphosphate. This cycling is regulated by the guanine nucleotide exchange factors, as activators, and by the GTPase activating proteins; the activation state of Rac1 depends on the release of guanosine diphosphate and the binding of guanosine triphosphate. This cycling is regulated by the guanine nucleotide exchange factors, as activators, and by the GTPase activating proteins; the activation state of Rac1 depends on the release of guanosine diphosphate and the binding of guanosine triphosphate. This cycling is regulated by the guanine nucleotide exchange factors, as activators, and by the GTPase activating proteins
GDP
Rab proteins exist in the active GTP-bound and inactive GDP-bound conformations with the GTP/GDP exchange mediated by GTP exchange factors (GEF53) and it is the GTP-bound active form of Rab that promotes membrane trafficking upon interaction with effector proteins
guanine nucleotide dissociation inhibitor GDI
-
inhibits the dissociation of GDP from and the binding of GTP to rhoB p20
-
guanine nucleotide dissociation inhibitor GDI
-
down-regulating GTPase activity, inhibition of nucleotide dissociation
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guanine nucleotide dissociation inhibitor GDI
-
down-regulating GTPase activity, inhibition of nucleotide dissociation
-
guanine nucleotide dissociation inhibitor GDI
-
down-regulating GTPase activity, inhibition of nucleotide dissociation
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N-(2-acetylphenyl)-4-([2-(4-chloro-2-methylphenoxy)propanoyl]amino)benzamide
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
N-(2-acetylphenyl)-4-([2-(4-chloro-2-methylphenoxy)propanoyl]amino)benzamide
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
N-(2-acetylphenyl)-4-([2-(4-chloro-2-methylphenoxy)propanoyl]amino)benzamide
-
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
N-(2-acetylphenyl)-4-([2-(4-chloro-2-methylphenoxy)propanoyl]amino)benzamide
the compound is both biologically active against bacterial cells and a putative enzymatic inhibitor of Der GTPase homologue
additional information
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exposure of confluent lung endothelial cell monolayers to wild type Pseudomonase aeruginosa strain PAK causes a significant decrease in Rac1 activity within 10 min
-
additional information
structure-based design of enzyme Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der, computer-aided pharmacophore modeling. Analysis of the interactions of the inhibitory compounds with the Der GTP-binding site to understand the mechanism of inhibition. No or poor inhibition by 3-[(4Z)-5-hydroxy-3-methyl-4-([5-(2-methyl-5-nitrophenyl)furan-2-yl]methylidene)-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 3-[(4Z)-4-([5-(3-acetylphenyl)furan-2-yl]methylidene)-5-hydroxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 2-((Z)-[3-(4-carboxyphenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl)benzoic acid, (4E)-4-(2-[2-(3-methoxyphenoxy)ethoxy]benzylidene)-1-phenylpyrazolidine-3,5-dione, 3,4-bis([(3,4-dimethylphenoxy)acetyl]amino)benzoic acid, 2-(5,5-dimethyl-3-methylidenehexyl)-1-methyl-5-(3-adamantylbutyl)-3-propylbenzene, and 2-(3-([((2-[2-(dimethylamino)ethyl]-1H-indol-3-yl)methyl)sulfanyl]methyl)-5-methyl-1H-indol-2-yl)-N,N-dimethylethanamine
-
additional information
structure-based design of enzyme Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der, computer-aided pharmacophore modeling. Analysis of the interactions of the inhibitory compounds with the Der GTP-binding site to understand the mechanism of inhibition. No or poor inhibition by 3-[(4Z)-5-hydroxy-3-methyl-4-([5-(2-methyl-5-nitrophenyl)furan-2-yl]methylidene)-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 3-[(4Z)-4-([5-(3-acetylphenyl)furan-2-yl]methylidene)-5-hydroxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 2-((Z)-[3-(4-carboxyphenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl)benzoic acid, (4E)-4-(2-[2-(3-methoxyphenoxy)ethoxy]benzylidene)-1-phenylpyrazolidine-3,5-dione, 3,4-bis([(3,4-dimethylphenoxy)acetyl]amino)benzoic acid, 2-(5,5-dimethyl-3-methylidenehexyl)-1-methyl-5-(3-adamantylbutyl)-3-propylbenzene, and 2-(3-([((2-[2-(dimethylamino)ethyl]-1H-indol-3-yl)methyl)sulfanyl]methyl)-5-methyl-1H-indol-2-yl)-N,N-dimethylethanamine
-
additional information
-
regulation of Cdc42 activity; regulation of Rac1 activity; regulation of RhoA activity
-
additional information
accumulation of acetylated alpha-tubulin by TSA treatment decreases the phosphorylation level of S6K1
-
additional information
three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity
-
additional information
three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity
-
additional information
three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity; three categories of selective Rac1 inhibitors affect different steps of the GTP/GDP pathway of enzyme activation: antagonists of Rac1-guanine nucleotide exchange factor interaction, allosteric inhibitors of nucleotide binding to Rac1, and antagonists of Rac1-mediated NADPH oxidase activity
-
additional information
Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
-
additional information
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Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
-
additional information
most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation
-
additional information
most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation
-
additional information
most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation; most RhoGTPases bind to chaperones, called guanine nucleotide dissociation inhibitors (RhoGDIs), which are cytosolic proteins that lack enzymatic activity. GDIs retain RhoGTPases in the inactive conformation, sequester them from cellular membranes and protect the GTPase from effector binding and proteolytic degradation
-
additional information
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RhoE downregulates the activity of RhoA by activating p190RhoGAP
-
additional information
RhoA- or ROCK-induced inhibitions are partially relieved upon incubation of the oocytes with the ROCK inhibitor Y27632
-
additional information
-
structure-based design of enzyme Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der, computer-aided pharmacophore modeling. Analysis of the interactions of the inhibitory compounds with the Der GTP-binding site to understand the mechanism of inhibition. No or poor inhibition by 3-[(4Z)-5-hydroxy-3-methyl-4-([5-(2-methyl-5-nitrophenyl)furan-2-yl]methylidene)-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 3-[(4Z)-4-([5-(3-acetylphenyl)furan-2-yl]methylidene)-5-hydroxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 2-((Z)-[3-(4-carboxyphenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl)benzoic acid, (4E)-4-(2-[2-(3-methoxyphenoxy)ethoxy]benzylidene)-1-phenylpyrazolidine-3,5-dione, 3,4-bis([(3,4-dimethylphenoxy)acetyl]amino)benzoic acid, 2-(5,5-dimethyl-3-methylidenehexyl)-1-methyl-5-(3-adamantylbutyl)-3-propylbenzene, and 2-(3-([((2-[2-(dimethylamino)ethyl]-1H-indol-3-yl)methyl)sulfanyl]methyl)-5-methyl-1H-indol-2-yl)-N,N-dimethylethanamine
-
additional information
structure-based design of enzyme Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der, computer-aided pharmacophore modeling. Analysis of the interactions of the inhibitory compounds with the Der GTP-binding site to understand the mechanism of inhibition. No or poor inhibition by 3-[(4Z)-5-hydroxy-3-methyl-4-([5-(2-methyl-5-nitrophenyl)furan-2-yl]methylidene)-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 3-[(4Z)-4-([5-(3-acetylphenyl)furan-2-yl]methylidene)-5-hydroxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 2-((Z)-[3-(4-carboxyphenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl)benzoic acid, (4E)-4-(2-[2-(3-methoxyphenoxy)ethoxy]benzylidene)-1-phenylpyrazolidine-3,5-dione, 3,4-bis([(3,4-dimethylphenoxy)acetyl]amino)benzoic acid, 2-(5,5-dimethyl-3-methylidenehexyl)-1-methyl-5-(3-adamantylbutyl)-3-propylbenzene, and 2-(3-([((2-[2-(dimethylamino)ethyl]-1H-indol-3-yl)methyl)sulfanyl]methyl)-5-methyl-1H-indol-2-yl)-N,N-dimethylethanamine
-
additional information
-
structure-based design of enzyme Der inhibitors using the X-ray crystal structure of Thermotoga maritima Der, computer-aided pharmacophore modeling. Analysis of the interactions of the inhibitory compounds with the Der GTP-binding site to understand the mechanism of inhibition. No or poor inhibition by 3-[(4Z)-5-hydroxy-3-methyl-4-([5-(2-methyl-5-nitrophenyl)furan-2-yl]methylidene)-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 3-[(4Z)-4-([5-(3-acetylphenyl)furan-2-yl]methylidene)-5-hydroxy-3-methyl-4,5-dihydro-1H-pyrazol-1-yl]benzoic acid, 2-((Z)-[3-(4-carboxyphenyl)-4-oxo-2-thioxo-1,3-thiazolidin-5-ylidene]methyl)benzoic acid, (4E)-4-(2-[2-(3-methoxyphenoxy)ethoxy]benzylidene)-1-phenylpyrazolidine-3,5-dione, 3,4-bis([(3,4-dimethylphenoxy)acetyl]amino)benzoic acid, 2-(5,5-dimethyl-3-methylidenehexyl)-1-methyl-5-(3-adamantylbutyl)-3-propylbenzene, and 2-(3-([((2-[2-(dimethylamino)ethyl]-1H-indol-3-yl)methyl)sulfanyl]methyl)-5-methyl-1H-indol-2-yl)-N,N-dimethylethanamine
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACAP3
aGTPase-activating protein (GAP) specific to small GTPase Arf6. ACAP3 is involved in neuronal migration in the developing cerebral cortex of mice, regulation mechanism, detailed overview. ACAP3 is abundantly expressed in the developing cerebral cortex. GAP activity of ACAP3 is required for neuronal migration. Knockdown of ACAP3 in the developing cortical neurons of mice in utero significantly abrogates neuronal migration in the cortical layer, which is restored by ectopic expression of wild-type ACAP3, but not by its GAP-inactive mutant
-
alphabeta-tubulin
soluble alphabeta-tubulin acts as a constitutively active Rheb activator that performs direct Rheb-binding, the deacetylated form has a high binding affinity for Rheb. Deacetylated soluble tubulin has a positive role in Rheb function by increasing the GTP-bound Rheb levels. Overexpression of alpha-tubulin K40A increases Rheb-induced S6K1 phosphorylation
-
CAPRI
-
a member of the GAP1 family of GTPase-activating proteins, GAPs, for small G proteins functioning as an amplitude sensor for intracellular Ca2+ levels stimulated by extracellular signals. It has a catalytic domain with dual Ras-GAP and RapGAP activities, and acts as dimer and monomer. CAPRI switches between its two GAP activities, RasGAP and Rap1GAP, mechanism, overview. Structure and activity of the C-terminal tail of Mus musclus CAPRI, activities on endogenous Rap1 in vivo of the recombinant full-length and C-terminal part of murine CAPRI in CHO cells, overview. Wild-type and monomeric CAPRI translocate to the plasma membrane similarly, but monomers are stronger RasGAPs at the membrane level
-
Epidermal growth factor
stimulates Rac1 as cardiovascular stimulus
exoenzyme S
-
arginine 146 essential for the stimulation of GTPase activity
-
forskolin
-
the adenylyl cyclase activator strongly and specifically activates Rap1 in microvascular smooth muscle cells
geranylgeranyl transferase I
-
RhoA is activated by geranylgeranylation, which promotes its membrane anchoring, the geranylgeranyl transferase I inhibitor GGTI-2166to is used to inhibit geranylgeranylation
-
guanidine nucleotide exchange protein
-
activates. Activated Ras then stimulates Raf, mitogen-activatde protein kinase cascades
-
guanine nucleotide exchange factors
GEF, GTP-binding to small GTPases is catalyzed by GEFs, Trp71 of Rac1 is a critical site for the discrimination of a subset of GEF, including Tiam1 and Trio
-
Insulin-like growth factor
stimulates Rac1 as cardiovascular stimulus
-
interleukin 1beta
stimulates Rac1 as cardiovascular stimulus
-
lipopolysaccharide
Rap2a is activated by lipopolysaccharide in macrophages. In contrast to mRNA levels, Rap2a protein levels are increased after lipopolysaccharide treatments of macrophages
mastoparan
stimulates GTP binding in the presence of Mg2+ and guanine nucleotide exchange, mastoparan mimics the GPCR mode of action
nucleoside diphosphate kinase
-
truncated 12-kDa form, builds complex with Pra with increased GTP and dGTP synthesis activity and decreased CTP and UTP or dCTP and dUTP synthesis activity relative to their synthesis by uncomplexed Ndk
-
platelet-derived growth factor
stimulates Rac1 as cardiovascular stimulus
-
pyruvate kinase
-
builds complex with Pra with specific GTP synthesis activity
Rac
-
activation of Rho, cross-talk between Ras- and Rho subfamilies
-
Sodium fluoride
stimulates of guanine nucleotide exchange, based on the formation of a fluoroaluminate complex which can pass the membrane and occupy the position next to bound GDP and thus stimulates an active state conformation
SOS980-989 peptide
the recombinant SOS980-989 peptide contains the H-Ras-SOScat interaction contact region, which is known to be able to compete with SOScat for binding to H-Ras
-
sphingosine 1 phosphate
stimulates Rac1 as cardiovascular stimulus
T-lymphoma invasion and metastasis factor 1
Tiam1, a GEF, structure analysis in complex with Rac1, specific site of GEF-Rac1 interaction, in particular Trp71
-
Tbc1/cofactor C
acts as a GTPase-activating protein, GAP, in regulating GTPase Alp41/Arl2. Tbc1 and Alp41 directly interact. Tbc1 is the orthologue of cofactor C and is able to form a supercomplex with Alp1D and Alp21E. Temperature-sensitive mutants of tbc1 show loss of microtubules. If Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state
-
TGF-beta1
TGF-beta1 activates Rap1 through cAMP and Epac1/Epac2. 2',5-dideoxyadenosine is an inhibitor of adenlyate cyclase on Rap1 activity
-
tumor necrosis factor-alpha
stimulates Rac1 as cardiovascular stimulus
-
U46619
-
small GTPase RhoA is activated by the activation of functional receptors for thromboxane A2 like U46619
UNC-73
-
Trio-like guanine nucleotide exchange factor encoded by unc-73, acts as an activator of RHO-1 in the migration process, the UNC-73 GEF2 domain may have the exchange activity on RHO-1 in vivo
-
vascular endothelial growth factor
stimulates Rac1 as cardiovascular stimulus
-
cytotoxic necrotizing factor 1
activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli, while the isomeric cytotoxicnecrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails tocause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Cytotoxic-necrotizing factors encompass a class of auto-transporter toxins produced by Escherichia coli (CNF1-3) or Yersiniapseudotuberculosis (CNFy). CNF1 deamidates Gln63 in RhoA. CNF1-induced RhoB response depends on the deamidation of Rho proteins
-
cytotoxic necrotizing factor 1
activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli, while the isomeric cytotoxicnecrotizing factor from Yersinia pseudotuberculosis (CNFy) drives GTP-loading of basal RhoB but fails to cause activation of the rhoB promoter and thus its expression. CNF1 inhibits cytokinesis and induces the formation of bi-nucleated (tetraploid) cells. Cytotoxic-necrotizing factors encompass a class of auto-transporter toxins produced by Escherichia coli (CNF1-3) or Yersinia pseudotuberculosis (CNFy). CNF1 specifically deamidates RhoA. CNF1-induced RhoB response depends on the deamidation of Rho proteins
-
GTP
the activation state of Rac1 depends on the release of guanosine diphosphate and the binding of guanosine triphosphate. This cycling is regulated by the guanine nucleotide exchange factors, as activators, and by the GTPase activating proteins. The activation process of Rac1 combines the GDP/GTP switch, catalyzed by GEF and GAP, with a cytosol/membrane alternation, regulated by GDI and protein prenylation, detailed overview
GTP
the activation state of Rac1 depends on the release of guanosine diphosphate and the binding of guanosine triphosphate. This cycling is regulated by the guanine nucleotide exchange factors, as activators, and by the GTPase activating proteins
GTP
Rab proteins exist in the active GTP-bound and inactive GDP-bound conformations with the GTP/GDP exchange mediated by GTP exchange factors (GEF53) and it is the GTP-bound active form of Rab that promotes membrane trafficking upon interaction with effector proteins
GTPase activating protein GAP
-
for Ras-related proteins, stimulates intrinsic GTPase reaction
-
GTPase activating protein GAP
-
p190, binding to and activation of RhoA and cdc42
-
GTPase activating protein GAP
-
Rap-GAP in neutrophil cytosol, increased rate of GTP hydrolysis
-
GTPase activating protein GAP
-
Rap2-GAP, stimulation of both Rap1 and Rap2 proteins
-
GTPase activating protein GAP
-
complex formation with Ran, stimulates intrinsic GTPase activity
-
GTPase activating protein GAP
-
for Ras-related proteins, stimulates intrinsic GTPase reaction
-
GTPase activating protein GAP
-
stimulating intrinsic GTPase acitivity
-
GTPase activating protein GAP
-
for Ras-related proteins, stimulates intrinsic GTPase reaction
-
GTPase activating protein GAP
-
Gyp1p, Gyp7p, specificity for Ypt/Rab GTPases, enhancement of intrinsic GTP hydrolysis rate
-
GTPase activating protein GAP
-
stimulating intrinsic GTPase acitivity
-
GTPase activating protein GAP
-
complex formation with Ran, stimulates intrinsic GTPase activity
-
guanine nucleotide exchange factor
-
Ypt1p requires guanine nucleotide exchange factor for the GDP-GTP exchange and subsequent activation of the signaling process
-
guanine nucleotide exchange factor Epac
-
specifically increases Rap1 activity
-
guanine nucleotide exchange factor Epac
-
specifically increases Rap1 activity
-
guanine nucleotide exchange factor GEF
-
activation of RhoGTPases through direct protein-protein interaction
-
guanine nucleotide exchange factor GEF
-
facilitates loading with GTP
-
guanine nucleotide exchange factor GEF
-
activation of RhoGTPases through direct protein-protein interaction
-
heparin-binding epidermal growth factor-like growth factor
-
induces rapid and strong RhoA activation
-
heparin-binding epidermal growth factor-like growth factor
-
induces rapid and strong RhoA activation
-
Insulin
-
RalA is activated upon insulin stimulation in a dose-dependent manner
-
lysophosphatidic acid
stimulates Rac1 as cardiovascular stimulus
lysophosphatidic acid
-
activation of Rho, assembly of contractile actin-myosin filaments and focal adhesion complexes
Rac-specific GEF Tiam1
stimulates the GDP exchange reaction, increases the GDP dissociation rate, activates Rac1 less efficiently than Rac2
-
Rac-specific GEF Tiam1
stimulates the GDP exchange reaction, increases the GDP dissociation rate, activates Rac2 more efficiently than the Rac isoforms Rac1 and Rac3
-
Rac-specific GEF Tiam1
activates Rac3, but less efficiently than the Rac isoform Rac2
-
additional information
-
exposure of confluent lung endothelial cell monolayers to wild type Pseudomonase aeruginosa strain PAK causes a significant increase in RhoA activity within 10 min
-
additional information
the recruited CFP-tagged RhoA on the parasitophorous vacuole membrane cannot be activated by epithelial growth factor and no translocation is observed, unlike the unassociated RhoA in the host cell cytosol that migrates to the cell membrane towards the epithelial growth factor activation spot
-
additional information
the recruited CFP-tagged RhoA on the parasitophorous vacuole membrane cannot be activated by epithelial growth factor and no translocation is observed, unlike the unassociated RhoA in the host cell cytosol that migrates to the cell membrane towards the epithelial growth factor activation spot
-
additional information
some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Other mechanisms of regulating RhoH activity include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyltransferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling
-
additional information
-
some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Other mechanisms of regulating RhoH activity include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyltransferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling
-
additional information
-
Rho kinase is an important downstream effector of RhoA GTPases
-
additional information
-
Rac and Rho are also activated by mechanical stimulation like shear stress and cyclic stretch
-
additional information
-
reduced human Mammarian enabled protein expression enhances Rac1 activity
-
additional information
-
Ras inhibition and downregulation is expected to enhance RhoA activity
-
additional information
Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
-
additional information
-
Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
-
additional information
wild-type RhoA activation by Ect2cat is known to be lower than that of Ras by SOScat because of the lower affinity of GTP for wild-type RhoA than for Ras
-
additional information
wild-type RhoA activation by Ect2cat is known to be lower than that of Ras by SOScat because of the lower affinity of GTP for wild-type RhoA than for Ras
-
additional information
wild-type RhoA activation by Ect2cat is known to be lower than that of Ras by SOScat because of the lower affinity of GTP for wild-type RhoA than for Ras
-
additional information
some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Other mechanisms of regulating RhoH activity include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyltransferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling
-
additional information
-
some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Other mechanisms of regulating RhoH activity include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyltransferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling
-
additional information
-
Rac is activated via stimulation of the G-protein-coupled seven-span transmembrane receptor CXCR4 by stromal derived factor-1, by adhesion via beta1 integrins, and via stimulation of c-kit by the stem cell factor
-
additional information
-
growth factor receptor-induced activation of Cdc42 activates Rac, which in turn stimulates Rho activity
-
additional information
-
mDia2 is a downstream effector of the Rho GTPases Rac1 and Rac2, Rac1 and Rac2 bind to mDia2 GBD in a GTP-dependent manner
-
additional information
putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation
-
additional information
-
the small GTPase RhoA is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase RhoA is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase RhoA is upregulated during cell invasion by Candida albicans
-
additional information
-
the small GTPase Cdc42 is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase Cdc42 is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase Cdc42 is upregulated during cell invasion by Candida albicans
-
additional information
-
the small GTPase Rac1 is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase Rac1 is upregulated during cell invasion by Candida albicans
-
additional information
the small GTPase Rac1 is upregulated during cell invasion by Candida albicans
-
additional information
-
GTPase-activating proteins are required for hydrolysis of the bound GTP
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
detailed kinetic study of the interaction of GTP with Cdc42 in the absence and presence of Mg2+, biphasic reaction
-
additional information
additional information
-
nucleotide association and dissociation kinetics
-
additional information
additional information
nucleotide association and dissociation kinetics
-
additional information
additional information
kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development, overview. Nucleotide exchange kinetics with small GTPases can be used to obtain important information about the binding kinetics of GTP molecules under different activation states and with different activator molecules
-
additional information
additional information
kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development, overview. Nucleotide exchange kinetics with small GTPases can be used to obtain important information about the binding kinetics of GTP molecules under different activation states and with different activator molecules
-
additional information
additional information
kinetic analysis of the GTPase nucleotide exchange reaction via homogeneous quenching resonance energy transfer assay, method development, overview. Nucleotide exchange kinetics with small GTPases can be used to obtain important information about the binding kinetics of GTP molecules under different activation states and with different activator molecules
-
additional information
additional information
Michaelis-Menten kinetics, MICAL1-Rab8 interaction analysis, overview. Analysis of the effect of Rab8-GppNHp on the apparent steady-state kinetic parameters of the NADPH oxidase in the coupled assay
-
additional information
additional information
-
Michaelis-Menten kinetics, MICAL1-Rab8 interaction analysis, overview. Analysis of the effect of Rab8-GppNHp on the apparent steady-state kinetic parameters of the NADPH oxidase in the coupled assay
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0005
GTP
-
quite low, increased GTP hydrolysis by action of guanine nucleotide release proteins, promoting replacement of bound GDP by GTP
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1
(2E)-2-[(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
Homo sapiens
pH and temperature not specified in the publication
0.005
2-(morpholin-4-ylmethyl)-5-[(5-[[7-(trifluoromethyl)quinolin-4-yl]sulfanyl]pentyl)oxy]-4H-pyran-4-one
Homo sapiens
pH and temperature not specified in the publication
0.156
2-amino-8-hydroxy-9-[3-hydroxy-2-(hydroxymethyl)cyclopentyl]-5,9-dihydro-6H-purin-6-one
Homo sapiens
pH and temperature not specified in the publication
0.0087 - 0.0088
3-(2-hydroxyphenyl)-N-[4-(piperidin-1-ylsulfonyl)phenyl]-1H-pyrazole-5-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.01
9-methoxy-5-(3-nitrophenyl)-2-phenyl-3,10b-dihydropyrazolo[1,5-c][1,3]benzoxazine
Homo sapiens
pH and temperature not specified in the publication
0.024
N-[4-methoxy-3-(piperidin-1-ylsulfonyl)phenyl]-1H-indazole-3-carboxamide
Homo sapiens
pH and temperature not specified in the publication
0.0011
N4-(9-ethyl-9H-carbazol-3-yl)-N2-[3-(morpholin-4-yl)propyl]pyrimidine-2,4-diamine
Homo sapiens
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
diverse genes encoding fourteen PpRAB, seven PpARF/ARL/SAR, two PpROP and one PpRAN GTPases, overview
-
-
brenda
-
-
-
brenda
isozyme FgRac1; Rho GTPase isozyme FgRac1
UniProt
brenda
isozyme FgRHO2; Rho GTPase isozyme FgRHO2
A0A098E0E9
UniProt
brenda
isozyme FgRHO3; Rho GTPase isozyme FgRHO3
UniProt
brenda
isozyme FgRHO4; Rho GTPase isozyme FgRHO4
UniProt
brenda
-
644107, 644115, 644116, 644118, 644119, 644121, 644122, 644124, 644126, 644128, 644129, 644130, 644131, 644132, 644137, 657726
-
-
brenda
-
670240, 684840, 684860, 684912, 685346, 685410, 685786, 685986, 686009, 686026, 686763, 687512, 687719, 687915, 688689, 688831, 689138, 696043, 696313, 696514, 696950, 697093
-
-
brenda
two closely related isoforms, Rap1A and Rap1B encoded by genes rap1a and rap1b
-
-
brenda
two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
SwissProt
brenda
-
669377, 669955, 684144, 684912, 686026, 687531, 687901, 688152, 688162, 688916, 688962, 689138, 695347, 695454, 696950
-
-
brenda
-
A1XKQ6, A1XKQ7, A1XKQ8, A1XKQ9, A1XKR0, A1XKR1, A1XKR2, A1XKR3, A1XKR5, A1XKR6, A1XKR7, A1XKR8, A1XKR9, A1XKS0, A1XKS1, A1XKS2, A1XKS3, A1XKS4, A1XKS5, A1XKS6, A1XKS7, A1XKS8, A1XKS9, A1XKT0, A1XKT1, A1XKT2, A1XKT3, A1XKT4, A1XKT5, A1XKT6, A1XKT7, A1XKT8, A1XKT9, A1XKU0, A1XKU1, A1XKU2, A1XKU3, A1XKU4, O97342, Q4H115, Q4H116
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
tumor-induced dysregulation of endocytic activity of dendritic cells is mediated by reduced activity of several members of the small Rho GTPase family
brenda
-
human alveolar epithelial cell HAEC exposed to hypoxia, RhoA/ROCK activation is necessary for Na,K-ATPase endocytosis via a mechanism that requires mitochondrial reactive oxygen species
brenda
-
tumor-induced dysregulation of endocytic activity of dendritic cells is mediated by reduced activity of several members of the small Rho GTPase family
brenda
two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
brenda
-
mRNA levels of RasL10B are down-regulated in all breast cancer cells tested (HBL100, MCF7, MDA-MB-468, MDA-MB-231 and MDA-MB-435. RasL10B) is a member of ras superfamily with tumor suppressor potential
brenda
-
small GTPase protein Rac-1 is activated with maturation and regulates cell morphology and function in chondrocytes
brenda
two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
brenda
the enzyme is expressed in the R7 photoreceptor, localization study, overview
brenda
-
GhRac1 is highly expressed during the elongation stage of fiber development with expression decreasing dramatically when the rate of the fiber elongation declines
brenda
-
differential expression dynamics of small GTPases encoding genes during fruit development and ripening, overview
brenda
-
important role for Rho-GTPases in the morphology and function of glomerular epithelial cells. Activation of RhoA appears to be protective against complement-mediated injury
brenda
lung cancer patients with metastasis and poor survival show low hRAB37 protein expression coinciding with low TIMP1 in tumours, hRAB37 is downregulated mainly by promoter hypermethylation in lung cancer cells and patients, low mRNA expression of hRAB37 gene is associated with tumour metastasis in lung cancer patients
brenda
-
tumor-induced dysregulation of endocytic activity of dendritic cells is mediated by reduced activity of several members of the small Rho GTPase family
brenda
-
expression of Rap2C may be down-regulated diring the late phase of megakaryocyte differentiation and platelet formation
brenda
-
small GTPase Rac-1 is a regulator of mesangial cell morphology and thrombospondin-1 expression
brenda
-
transient transcriptional upregulation of PpARF genes and of PpRAB genes of the A and D clades appears to coincide with peaks of growth speed and sugar accumulation and with the final phases of ripening
brenda
-
a transient increase in Rac activity coupled with a transient decrease in RhoA activity occurs in honey bees with 4 days foraging experience compared with same-aged new foragers
brenda
-
signal relay in which pollen receptor kinase AtPRK2a at the plasma membrane recruits AtRopGEF12 through its C terminus to maintain polar Rop activity in the pollen tube
brenda
adjacent, two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb, the abundance of the RASL11A transcript is diminished in prostate tumors in comparison to normal adjacent prostate tissue
brenda
-
macrovascular lung pulmonary artery endothelial cell
brenda
-
tumor-induced dysregulation of endocytic activity of dendritic cells is mediated by reduced activity of several members of the small Rho GTPase family
brenda
-
small Rho GTPases are important for acinus formation
brenda
smGTP gene displays low levels of expression prior to harvesting and increased 12 h after harvest. Low level of expression as the seed head emerges and shows a strong induction in late to post-anthesis tissues. Surprisingly very little expression is observed in seed heads at the milk and ripe seed head stages. A low level of smGTP expression is observed in stem and leaf tissue at this stage of development
brenda
-
proliferation of dermal fibroblasts is crucial for the maintenance of skin. Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity
brenda
-
Rac1 appears to be important for parenchyma expansion at the beginning of cytodifferentiation, while RhoC, Cdc42 and the inactive phosphorylated form of Rac1 seemed associated with lumen formation and cell polarization in terminal tubules in the developing submandilbular gland
brenda
-
conversion of plasma membrane topology during epithelial tube connection requires Arf-like 3 small GTPase
brenda
low content in late trophozoites, very low in early trophozoites
brenda
additional information
-
in the adult mouse brain, Rab23 is detected in betaIII tubulin positive neuronal cell bodies and are most prominent in cortex, hypothalamus and the cerebellum
brenda
upon infection with Candida albicans, a significant increase in the mRNA level is observed
brenda
-
prepared from tumor-bearing mice ex vivo. Tumor-induced dysregulation of endocytic activity of dendritic cells is mediated by reduced activity of several members of the small Rho GTPase family
brenda
-
RhoV mRNA is maternally expressed and accumulates shortly after gastrulation in the neural crest forming region. Rho functions in pathways that control neural crest cells specification
brenda
Rac2 is predominantly expressed in cells of the hematopoietic lineage
brenda
RhoH is specifically expressed in hematopoietic cells
brenda
Rac2 is mainly present in the hematopoietic cells
brenda
RhoH is specifically expressed in hematopoietic cells
brenda
-
Vascular endothelial cadherin-mediated cell-cell adhesion is regulated by a Small GTPase, Rap1
brenda
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Ras is detected in glomerular cells, proximal convoluted tubule cells, distal convoluted tubule cells, cortical collecting tubule cells, medullar collecting duct cells, interstitial cells and subcapsular fibroblast. Ras plays a role in renal fibrosis
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Ras is detected in medullary endothelial cells, medullary interstitial cells, cortical interstitial cells and glomerular endothelial cells. Ras plays a role in renal fibrosis
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ARF6 is an essential component in the signaling pathway coupling hepatocyte growth factor signaling to hepatic cord formation
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TLRs agonists induce changes in the expression of Rap2a in macrophages. In contrast to mRNA levels, Rap2a protein levels are increased after LPS treatments of macrophages
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Rac1 activity serves as a regulator of cell senescence through modulation of cellular ROS, genomic stability, and p53 activity
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constitutively active RhoA in primary culture of spinal motoneurons
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hippocampal neuron. Rnd1 plays a critical role in neuronal activity-dependent dendritic development in hippocampal neurons. Overexpression of Rnd1 promotes dendritic growth and branching in cultured hippocampal neurons. Suppression of endogenous Rnd1 expression by RNA interference significantly inhibits neuronal activity-dependent dendritic development
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Rap1 and Rap2 share the ability to suppress synaptic transmission by inhibiting surface expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors containing the glutamate receptor alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor subunit GluR2. Rap1 and Rap2 have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites. Rap2 in particular induced the retraction of axons and dendrites and the loss of spines and excitatory synapses, in a cell type-specific and activity-regulated fashion
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Rap1b is the predominant Rap1 isoform expressed in neutrophils
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Rap1b is the predominant Rap1 isoform expressed in neutrophils
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Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption
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uninfected normal cells have negligible quantities of mRNA for RhoA, upon infection with Candida albicans a significant increase in the mRNA level is observed
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uninfected normal cells have considerable levels of Cdc42, upon infection with Candida albicans and a significant increase in the mRNA level
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uninfected normal cells have negligible quantities of mRNA for Rac1, upon infection with Candida albicans a significant increase in the mRNA level is observed
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Rad GTPase is overexpressed in skeletal muscle of humans with type II diabetes
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RhoH is expressed strongest in T-lymphocytes and acts as a positive regulatory factor for thymocyte selection and T-cell receptor signalling
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RhoH is expressed strongest in T-lymphocytes and acts as a positive regulatory factor for thymocyte selection and T-cell receptor signalling
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two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
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additional information
the RASL11A transcript is ubiquitously expressed in human tissues, no expression in thymus and leukocytes
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additional information
the RASL11A transcript is ubiquitously expressed in human tissues, no expression in thymus and leukocytes
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additional information
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the RASL11A transcript is ubiquitously expressed in human tissues, no expression in thymus and leukocytes
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additional information
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mutant Rab27a is isolated from patients with Griscelli syndrome type 2
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additional information
RhoH is underexpressed in hairy cell leukaemia and acute myeloid leukaemia cells
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additional information
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RhoH is underexpressed in hairy cell leukaemia and acute myeloid leukaemia cells
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additional information
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the enzyme expression is frequently lost in lung adenocarcinoma cells
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additional information
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Rab23 is absent from glial fibrillary acidic protein positive astrocytes or CNPase positive oligodendrocytes
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additional information
Rap1b is expressed in all tissues, including endothelial cells
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additional information
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Rap1b is expressed in all tissues, including endothelial cells
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additional information
transcript levels and expression of the enzyme are significantly increased in the erythrocytic phase in particular during schizont and gametocyte formation
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additional information
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transcript levels and expression of the enzyme are significantly increased in the erythrocytic phase in particular during schizont and gametocyte formation
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additional information
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Pc-Rac1 is expressed in all examined tissues with the highest expression level in hemocytes
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
Rab21 is predominantly localized to the early endocytic pathway, on vesicles containing early-endosomal antigen 1, transferrin receptor and internalized ligands
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Rab1b-labeled vesicles, distribute peripherally from the Golgi perinuclear area
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human Mammarian enabled protein colocalizes with Rac1 in lamellipodia
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associates with both intracellular vesicles and microtubules
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part of invadosomes, specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities
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colocalization with tissue inhibitor of metalloproteinase 1 (TIMP1)
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additional information
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recombinant enzyme is expressed in cytoplasm of COS-7 cells
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the subcellular localization of LIP1 is not significantly affected by light
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Rho GTPase, partially cytosolic in association with guanine nucleotide dissociation inhibitor
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recombinant Pra2 is predominantly localized on Golgi stacks and endosomes
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GCC185 localizes to the Golgi by cooperative interaction with Rab6 GTPase
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co-localization with effector protein GARI-L4
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recombinant Pra2 is predominantly localized on Golgi stacks and endosomes
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recombinant Pra3 is likely to be localized on the trans-Golgi network and/or the prevacuolar compartment
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part of invadosomes, specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities
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only the membrane-localised form of RhoH is able to downregulate Rac1 efficiently
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only the membrane-localised form of RhoH is able to downregulate Rac1 efficiently
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direct interaction with nucleoporin Nsp1p
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RanGTPase activating protein-Ran complex, stimulation of GTP hydrolysis, terminating export
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the subcellular localization of LIP1 is not significantly affected by light
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RanGTP form, mediates termination of import and initiation of export
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the nuclear localization of Rad is important for its suppressive effect on NFkappaB
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RalA is predominantly localized on the plasma membrane
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purified YsxC binds preferentially to the 50S subunit of Bacillus subtilis ribosomes. This interaction is modulated by nucleotides and is stronger in the presence of a nonhydrolyzable GTP analogue than with GTP. YsxC interacts with at least four ribosomal proteins from the 50S subunit. YsxC plays a role in ribosome assembly
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RsgA has the capacity to coexist with mRNA in the ribosome while it promotes dissociation of tRNA from the ribosome
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Escherichia coli A19
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RsgA has the capacity to coexist with mRNA in the ribosome while it promotes dissociation of tRNA from the ribosome
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additional information
RhoA and Rac1 GTPases from the host cell accumulate on the parasitophorous vacuole membrane, PVM, regardless of the virulence of the Toxoplasma gondii strains after invasion, and this accumulation is dependent on their GTPase activity. The recruited Rac1 on the PVM is in the GTP-bound active form
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additional information
RhoA and Rac1 GTPases from the host cell accumulate on the parasitophorous vacuole membrane, PVM, regardless of the virulence of the Toxoplasma gondii strains after invasion, and this accumulation is dependent on their GTPase activity. The recruited Rac1 on the PVM is in the GTP-bound active form
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additional information
RhoA and Rac1 GTPases from the host cell accumulate on the parasitophorous vacuole membrane, PVM, regardless of the virulence of the Toxoplasma gondii strains after invasion, and this accumulation is dependent on their GTPase activity. The decisive domains for the RhoA accumulation on the PVM include the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which are related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited RhoA on the PVM is in the GTP-bound active form
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brenda
additional information
RhoA and Rac1 GTPases from the host cell accumulate on the parasitophorous vacuole membrane, PVM, regardless of the virulence of the Toxoplasma gondii strains after invasion, and this accumulation is dependent on their GTPase activity. The decisive domains for the RhoA accumulation on the PVM include the GTP/Mg2+ binding site, the mDia effector interaction site, the G1 box, the G2 box and the G5 box, respectively, which are related to the binding of GTP for enzymatic activity and mDia for the regulation of microtubules. The recruited RhoA on the PVM is in the GTP-bound active form
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additional information
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partially associated with non-acidified vesicles in the endocytic pathway, likely recycling endosomes
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additional information
subcellular distribution of wild-type, T33N and Q78L mutant Rab21
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additional information
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subcellular distribution of wild-type, T33N and Q78L mutant Rab21
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additional information
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GFP-Rab1 localizes in autophagosomes marked with either RFP-light chain 3 or endogenous light chain 3
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additional information
conditions of podosome assembly, detailed overview
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additional information
conditions of podosome assembly, detailed overview
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additional information
conditions of podosome assembly, detailed overview
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additional information
conditions of podosome assembly, detailed overview
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additional information
enzyme Rheb does not co-localize with microtubules but interacts with unpolymerized free alphabeta-tubulin. And Rheb does not co-localize with the ordered microtubule structure in either interphase or mitotic phase
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additional information
pterostilbene evokes redistribution of Rab13 from the cell surface and diffuse cytoplasmic location to exclusively cytoplasmic, punctuated autophagosomes as shown by Rab13 co-localization with LC3 in HUVECs
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additional information
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pterostilbene evokes redistribution of Rab13 from the cell surface and diffuse cytoplasmic location to exclusively cytoplasmic, punctuated autophagosomes as shown by Rab13 co-localization with LC3 in HUVECs
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additional information
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RalA localizes independently of intracellular insulin granules
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additional information
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RalA localizes independently of intracellular insulin granules
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Highest Expressing Human Cell Lines
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
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Rac and RhoA belong to the Rho family of GTPases, small monomeric G proteins
evolution
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
the enzyme belongs to the Rho GTPase family of enzymes
evolution
Rab proteins are members of the Ras superfamily of GTPases that switch between GDP-bound (inactive) and GTP-bound (active) forms
evolution
the enzyme belongs to the superfamily of small GTPase proteins
evolution
Ras proximity 1 (Rap1) belongs to the Ras superfamily of GTPases that cycle between GTP-bound active and GDPbound inactive forms through GEFs and GAPs
evolution
Ras homologue enriched in the brain (Rheb) belongs to the Ras superfamily, sharing high homology with human Rap2, yeast RAS1, and human H-Ras
evolution
Drosophila Rap1 is a member of the Ras family of GTPases
evolution
the enzyme belongs to the Rac/ROP family small GTPases
evolution
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Ypt1p is a member of the Rab family of small GTPases. A large number of small GTPases belonging to the Rab family play a role in vesicular trafficking
evolution
the subfamily of Ras-like small GTPases contains numerous members including classical Ras (H-, K-, and N-Ras), R-Ras, TC21/R-Ras2, MRas/R-Ras3, DexRas1/RasD1, RalA/B, Rheb, Rit, Rin, Rap1 and Rap2, and atypical kappaB-Ras1 and kappaB-Ras2
evolution
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Ras proximity 1 (Rap1) belongs to the Ras superfamily of GTPases that cycle between GTP-bound active and GDPbound inactive forms through GEFs and GAPs
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evolution
Drosophila melanogaster w1118
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Drosophila Rap1 is a member of the Ras family of GTPases
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evolution
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the enzyme belongs to the Rac/ROP family small GTPases
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malfunction
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in cultured human microvascular endothelial cells, knockdown of either Rap1a or 1b appears to diminish adhesion to the extracellular matrix and impair cell migration, and also increases permeability. Loss of Rap1a or 1b unexpectedly blocked angiogenesis by abolishing the angiogenic response to FGF2 or to VEGF, leading to an inability for these cells to form tubular structures. Ablation of either isoforms leads to decrease in FGF-2 mediated ERK, p38 and Rac activation which are all important angiogenesis signaling molecules. Overexpressing activated Rap 1a in dermal microvascular endothelial cells show defective angiogenesis through regulation of thrombospondin-1
malfunction
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the loss of Rap1b leads to deficiencies both in B cell migration and in adhesion. Platelets from Rap1b null mice exhibit defective aggregation in response to integrin stimulation. These mice exhibit protection from arterial thrombosis and provide an independent role for this Rap1 isoform
malfunction
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overexpression of dominant-negative Sar1 and Rab1b mutants and the use of siRNAs impair autophagosome generation as determined by LC3 puncta formation and light chain 3 (LC3)-II processing. Recombinant expression of Sar1 mutants H79G or Sar1 T39N induce Golgi fragmentation
malfunction
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
malfunction
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, septum defect and nuclear division phenotype of DELTAFgrho4 deletion mutant, overview
malfunction
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. FgRac1 deletion mutants display a precocious, multi-site germ tube formation as well as hyperbranching of hyphae. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
malfunction
Dysfunction of hRAB37 or TIMP1 abrogates metastasis suppression
malfunction
ectopic expression of active RhoA suppresses podosome formation in response to phorbol ester by global inhibition of actin turnover
malfunction
misregulation of the enzyme is involved in several diseases, especially cancer
malfunction
a dominant active mutant of Cdc42 promotes the formation of invadopodia. Small interfering RNA-mediated Fgd1 knockdown inhibits TGFbeta-induced Cdc42 activation and reduces podosome formation and associated extracellular matrix degradation
malfunction
Rac1-deficient macrophages show impaired podosome formation with fewer cells displaying podosomes that lack the adhesion ring, but migrate at a speed similar to that of wild-type macrophages
malfunction
Rac2 deficiency results in complete loss of podosomes in macrophages
malfunction
upon long term treatment with CNF1, RhoB-/- mouse embryonic fibroblasts exhibit DNA fragmentation, phosphatidylserine exposure, and loss of membrane integrity, while RhoB+/- MEFs persist as bi-nucleated (tetraploid) cells without any signs of cell death
malfunction
Rap1b deficiency increases neutrophil transmigration, Rap1b loss promotes transendothelial migration via transcellular route. Rap1b-deficient mice exhibits enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit enhanced chemokinesis and chemotaxis. Rap1b deficiency promotes the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro is selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Pharmacological inhibition of Akt activation rescued Rap1b-/- neutrophil phenotype. Rap1a expression does not compensate for Rap1b loss in blood cells. Phenotype, overview
malfunction
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deletion of Cdc42 in mature B cells results in an antibody response of reduced magnitude and lower affinity to soluble T cell-dependent antigen. B cells that lack Cdc42 remain dominant for 2 weeks postinduction with tamoxifen, following which Cdc42-sufficient B cells gradually dominate with very few Cdc42-deficient B cells being detected after 6 weeks. Deletion of Cdc42 in mature B cells alters their ability to activate T cells. B cells that lack Cdc42 fail to form long protrusions on Ab-coated surfaces. Reduced spreading and upregulation of CIP4 in Cdc42-deficient B cells. Deletion of Cdc42 in B cells leads to impaired humoral immune response, phenotype, overview
malfunction
expression of constitutively active RhoA in primary culture of spinal motoneurons also drastically reduces high-voltage-activated Ca2+ current amplitude
malfunction
RNAi knockdown of Trypanosom brucei Arl6 results in shortening of the trypanosome flagellum without loss of motility
malfunction
increased expression of GCF2 is found in human chemotherapeutic agent cisplatin-resistant cells, and overexpression in GCF2-transfected cells results in loss of RhoA expression and disruption of the actin-filamin network. The membrane transporter MRP1 is internalized from the cell surface into the cytoplasm, rendering cells sensitive to doxorubicin by more than 10fold due to increased accumulation of doxorubicin in the cells. The GCF2 transfectants also show reduced accumulation of cisplatin and increased resistance. siRNA targeted to GCF2 suppresses the expression of GCF2 in cisplatin-resistant cells, reactivates RhoA expression, and restores the fine structure of actin microfilaments. MRP1 is also relocated to the cell surface. siRNA targeted to RhoA increased resistance 3fold in KB-3-1 and KB-CP.5 cells. Phenotypes, overview. Silencing RhoA increases resistance against cisplatin
malfunction
if Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state. Overproduction of GTP or GDP form of Alp41 is toxic to the cell
malfunction
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overexpression of Rad in cells lowers both the basal and TNFalpha-stimulated transcriptional activity of NFkappaB. Compared with control cells, Rad-overexpressing cells display more cytoplasmic distribution of the NFkappaB subunit RelA/p65,while Rad knockdown cells have higher levels of nuclear RelA/p65. Depleting Rad does not affect the kinetics of TNFalpha-induced IkappaB degradation. Rad depletion alters the expression of an array of NFkappaB target genes, including upregulating MMP9, depletion of Rad enhances MMP9 expression and cell invasion. Knockdown of Rad expression in cells increases both basal and TNFalpha-stimulated MMP9 activities and cell invasion
malfunction
gain-of-function studies using dominant-negative and constitutively active forms of Rap1 indicate that Rap1 contributes to axonal growth and guidance
malfunction
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RNA interference of Pc-Rac1 affects the mRNA expression levels of immune-related genes lectin, Toll, crustin, TNF, ALF and cactus
malfunction
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temperature-sensitive growth phenotype of the ypt1-G80D mutant strain. Complete knockout of the YPT1 gene in yeast is lethal. Abrogation of heat-shock-induced Ypt1p chaperone function by the G80D mutation lowers cell viability largely by hindering metabolism and cellular energy generation. Mutant Ypt1pG80D retains GTPase activity but loses molecular chaperone activity
malfunction
both knockdown and overexpression of Rap2a small GTPase in macrophages result in impairment of NF-kappaB activity and inflammatory gene expression. Silencing of Rap2a impairs LPS-induced production of IL-6 cytokine and KC/Cxcl1 chemokine, and also NF-kappaB activity. Overexpression of Rap2a does also lead to marked inhibition of NF-kappaB activation induced by LPS, Pam3CSK4, and downstream TLR signaling molecules. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation
malfunction
knockdown of Rab13 blocks pterostilbene-induced mTOR inhibition and autophagy, whereas overexpression of the GTP-containing active form of Rab13 induces mTOR inhibition and autophagy in HUVECs. Upregulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells. Knockdown of Grb2 suppresses pterostilbene or upregulation of the active form of Rab13-induced autophagy. Knockdown of Rab13 inhibits the digestion of cytoplasmic components in pterostilbene-treated HUVECs numerous autophagosome- or autolysosome-like vesicular structures
malfunction
ARF6Q67L promotes spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. ARF6Q67L tumors show upregulation of Pik3r1 expression, which encodes the p85 regulatory subunit of PI3K. Tumor cells expressing ARF6Q67L displays increased PI3K protein levels and activity, enhances PI3K distribution to cellular protrusions, and increases AKT activation in invadopodia. Aberrant ARF6 activation in human melanoma samples is associated with reduced survival
malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
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malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, septum defect and nuclear division phenotype of DELTAFgrho4 deletion mutant, overview
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malfunction
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all single deletion mutants of the isozymes show impaired growth, particularly in conidial morphology, when compared to the wild-type progenitor. FgRac1 deletion mutants display a precocious, multi-site germ tube formation as well as hyperbranching of hyphae. Conidia morphology of wild-type strain PH-1 and FgRHO deletion mutants, overview
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malfunction
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Rap1b deficiency increases neutrophil transmigration, Rap1b loss promotes transendothelial migration via transcellular route. Rap1b-deficient mice exhibits enhanced neutrophil recruitment to inflamed lungs and enhanced susceptibility to endotoxin shock. Rap1b-/- neutrophils exhibit enhanced chemokinesis and chemotaxis. Rap1b deficiency promotes the transcellular route of diapedesis through endothelial cell. Increased transcellular migration of Rap1b-deficient neutrophils in vitro is selectively mediated by enhanced PI3K-Akt activation and invadopodia-like protrusions. Akt inhibition in vivo suppresses excessive Rap1b-deficient neutrophil migration and associated endotoxin shock. Pharmacological inhibition of Akt activation rescued Rap1b-/- neutrophil phenotype. Rap1a expression does not compensate for Rap1b loss in blood cells. Phenotype, overview
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malfunction
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deletion of Cdc42 in mature B cells results in an antibody response of reduced magnitude and lower affinity to soluble T cell-dependent antigen. B cells that lack Cdc42 remain dominant for 2 weeks postinduction with tamoxifen, following which Cdc42-sufficient B cells gradually dominate with very few Cdc42-deficient B cells being detected after 6 weeks. Deletion of Cdc42 in mature B cells alters their ability to activate T cells. B cells that lack Cdc42 fail to form long protrusions on Ab-coated surfaces. Reduced spreading and upregulation of CIP4 in Cdc42-deficient B cells. Deletion of Cdc42 in B cells leads to impaired humoral immune response, phenotype, overview
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malfunction
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if Tbc1 loses its GAP activity as in the tbc1-11 mutant, Alp41 will no longer be converted from its active, GTP-bound state to the inactive, GDP-bound state. Overproduction of GTP or GDP form of Alp41 is toxic to the cell
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malfunction
Drosophila melanogaster w1118
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gain-of-function studies using dominant-negative and constitutively active forms of Rap1 indicate that Rap1 contributes to axonal growth and guidance
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metabolism
RhoGTPases are involved in podosome assembly and sequential mechanism for invadopodium formation, regulation, detailed overview
metabolism
six Rab isoforms are involved in regulating Golgi morphology in HeLa-S3 cells
metabolism
Rac/Rop proteins are Rho-type small GTPases that act as molecular switches in plants. They are key components in many major plant signaling pathways, such as innate immunity, pollen tube growth, and root hair formation
metabolism
high-voltage-activated Ca2+ channels are known regulators of synapse formation and transmission and play fundamental roles in neuronal pathophysiology. Small GTPases of Rho and RGK families, via their action on both cytoskeleton and Ca2+ channels are key molecules for these processes
metabolism
photoreceptor R7 is specified by the combined actions of the receptor tyrosine kinase (RTK) and Notch (N) signaling pathways. These pathways interact in a complex manner that includes antagonistic effects on photoreceptor specification and involve the small GTPase Rap. RTK promotes the photoreceptor fate, whereas N inhibits it
metabolism
a complex regulatory pathway downstream from GCF2 involves the small GTPase RhoA, actin/filamin dynamics, and membrane protein trafficking, overview
metabolism
the tubulin cofactor pathway consists of a specific set of chaperones that aid the folding of alpha- and beta-tubulin monomers into a functional heterodimer, with the introduction of cofactor C, GTP hydrolysis occurs, triggering the release of the newly folded alpha/beta-tubulin heterodimer for addition to the plus end of the microtubule, modeling of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP
metabolism
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Rac1 can interact with the PBD domain of p21-activated kinase 1 (PAK1)
metabolism
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identification of diverse putative Ypt1p-regulatory proteins under heat-shock, overview
metabolism
Rap2a is activated by lipopolysaccharide in macrophages, and although putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation. Dysregulation of Rap2a expression in an inflammatory context may significantly alter the status of NF-kappaB activation
metabolism
ACAP3, the GTPase-activating protein specific to the small GTPase Arf6, regulates neuronal migration in the developing cerebral cortex. ACAP3 is involved in neuronal migration in the developing cerebral cortex of mice. Knockdown of ACAP3 in the developing cortical neurons of mice in utero significantly abrogates neuronal migration in the cortical layer, which is restored by ectopic expression of wild-type ACAP3, but not by its GAP-inactive mutant
metabolism
an increasing number of Rab GTPases have been shown to play either critical or accessory roles in various stages of autophagy. Rab1, Rab4, Rab5, Rab11, Rab12, Rab17, Rab23, Rab26, Rab30 and Rab32 participate in autophagosome formation. Rab13 is required for pterostilbene-induced autophagy
metabolism
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the tubulin cofactor pathway consists of a specific set of chaperones that aid the folding of alpha- and beta-tubulin monomers into a functional heterodimer, with the introduction of cofactor C, GTP hydrolysis occurs, triggering the release of the newly folded alpha/beta-tubulin heterodimer for addition to the plus end of the microtubule, modeling of the final stages of the tubulin cofactor pathway that includes a dual role for both Tbc1 and Alp1D in opposing regulation of the microtubule. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP
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metabolism
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ACAP3, the GTPase-activating protein specific to the small GTPase Arf6, regulates neuronal migration in the developing cerebral cortex. ACAP3 is involved in neuronal migration in the developing cerebral cortex of mice. Knockdown of ACAP3 in the developing cortical neurons of mice in utero significantly abrogates neuronal migration in the cortical layer, which is restored by ectopic expression of wild-type ACAP3, but not by its GAP-inactive mutant
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physiological function
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small monomeric GTPases have a function in fruit development and ripening. PpARF and PpRAB of the A and D clades are putatively controlling the exocytic delivery of cell wall components and modifying enzymes
physiological function
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the GTP-bound Rap mediates signaling by associating with, and activating effector proteins. Whereas Rap1a and 1b appear to be key regulators in differing cell types of the blood, neutrophils and platelets, both appear to contribute to the normal function of endothelial cells and to angiogenesis. Endothelial cell junctional proteins are involved in regulating vascular permeability. This dynamic regulation is regulated in part by Rap1 in response to cAMP activation through Epac1. In cultured human umbilical vein endothelial cells activation of Epac1-Rap1 by cAMP enhances endothelial barrier function by altering actin cytoskeleton organization, activating microtubule growth and results in a redistribution of adherens junctional proteins involving MAGI-1 protein. Rap1a and b are involved in the activation of beta1-integrins in endothelial cells and play a key role in integrin dependent angiogenic functions such as sprouting, tube formation, migration and adhesion. In smooth muscle cells, Rap1 may elicit a protective response to maintain vessel wall integrity in response to cellular stress
physiological function
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Rap1A and Rap1B have differing roles in the cardiovasculature. Activation of Rap1a and 1b in various cell types of the cardiovasculature lead to alterations in cell attachment, migration and cell junction formation. Rap1b is necessary for proper development, homing and T cell dependant immunity. Rap1b protein regulates the SERCA 3b-associated Ca2+ pool through its cAMP-dependent phosphorylation, and therefore plays a role in the transition between platelet activation and inhibition. Whereas Rap1a and 1b appear to be key regulators in differing cell types of the blood, neutrophils and platelets, both appear to contribute to the normal function of endothelial cells and to angiogenesis. In smooth muscle cells, Rap1 may elicit a protective response to maintain vessel wall integrity in response to cellular stress
physiological function
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Rac and RhoA belong to the small, monomeric G proteins of the Rho family of GTPases, that, when activated, initiate a signaling cascade that reorganizes the neuronal cytoskeleton. Rho GTPases regulate cellular morphogenesis through direct interactions with actin and microtubule-organizing proteins. Rho GTPases are cycling between the inactive GDP-bound and the active GTP-bound forms is controlled by guanine nucleotide exchange factors, GTPase activating proteins, and guanine nucleotide dissociation inhibitors
physiological function
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Sar1 and Rab1b are monomeric GTPases that control traffic from the endoplasmic reticulum to the Golgi, Sar1 is responsible for export from the endoplasmic reticulum and is required for the initial steps in the secretory pathway, activity of both proteins is required for autophagosome formation under starvation or rapamycin treatment
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRho3 demonstrates functions only in vegetative growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgRho4 is multifunctional and is involved in sexual development and pathogenesis. While FgRho4 is involved in cell wall integrity, and FgRho4 shows a role in nuclear division and septum formation. FgRho4 is also important for hyphal growth and conidiation. Isozyme FgRho4 plays a positive role in deoxynivalenol production. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgCdc42 is multifunctional and is involved in sexual development and pathogenesis. Isozyme FgCdc42 is important for hyphal growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. FgRac1 interacts with FgCla4 via its PBD domain and genetically acts upstream of FgCla4 to affect hyphal growth and conidiation. Isozyme FgRac1 is important for hyphal growth and conidiation. FgRac1 negatively controls deoxynivalenol production. FgCla4 is a downstream target of FgRac1, but is dispensable for sexual development. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
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enzyme Der is an essential and widely conserved GTPase that assists assembly of a large ribosomal subunit in bacteria. Enzyme Der associates specifically with the 50S subunit in a GTP-dependent manner and the cells depleted of GTPase Der accumulate the structurally unstable 50S subunit, which dissociates into an aberrant subunit at a lower Mg2+ concentration. The enzyme Der is an essential and ubiquitous protein in bacteria
physiological function
Rab small GTPases are master regulators of membrane trafficking and guide vesicle targeting. Rab proteins transport cargo proteins to target membrane, organelle and cellular compartment to coordinate the cell membrane dynamics, cytoskeleton organization, signal transduction and membrane trafficking. Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 (TIMP1) for exocytosis and thus suppresses tumour metastasis in a nucleotide-dependent manner. hRAB37 is involved in transportation of exocytotic vesicles and is involved in the exocytotic pathway of nascent secretory protein from the Golgi to the plasma membrane but not in the recycling endosome-mediated secretory pathway. Tissue inhibitor of metalloproteinase 1 is a secreted protein that inhibits MMPs and extracellular matrix turnover thereby decreasing cell motility. Rab-controlled trafficking pathways are altered during tumorigenesis. Tissue inhibitor of metalloproteinase 1 (TIMP1), a secreted glycoprotein that inhibits extracellular matrix turnover, is a cargo of hRAB37. hRAB37 regulates the exocytosis of TIMP1 in a nucleotide-dependent manner to inactivate matrix metalloproteinase 9 (MMP9) migration axis in vitro and in vivo
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly
physiological function
small GTPases are central signaling proteins in all eukaryotic cells acting as a molecular switches that are active in the GTP-state and inactive in the GDP-state. GTP-loading is highly regulated by guanine nucleotide exchange factors
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Fgd1 is the GEF mediating Cdc42 activation and subsequent podosome formation in TGFbeta-stimulated BAE cells. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Essential role of Cdc42 in podosome formation, Cdc42 stands as a central player in the regulation of podosome dynamics as it orchestrates podosome actin polymerization via its canonical effector, WASp. When activated by a GEF, Cdc42 binds to WASp. This binding, together with phosphorylation of WASp on tyrosine, induces a dramatic conformational change. The hydrophobic core is disrupted, releasing the verprolin homology domain-cofilin homology domain-acidic region domain (VCA domain) and enabling its interaction with the Arp2/3 complex, thereby promoting actin nucleation. Constitutively active Cdc42 induces podosome formation in vascular smooth muscle cells
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, e.g. Dock 5, FARP2 (FRG), a Dbl family GEF specific for Rac1. And guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis. Dock5 and Vav3 regulate Rac1 activation at distinct locations in osteoclasts and at different phases of the bone-resorption cycle
physiological function
remodeling of the actin cytoskeleton heavily relies on the regulation of RhoGTPases which have important and conserved roles in almost all its functions. Their activity is tightly regulated by three classes of molecules: guanine nucleotide exchange factors, GEFs, which exchange GDP for GTP hence activating in the hydrolysis of bound GTP to GDP thus contributing to inactivation, and guanine dissociation inhibitors, GDIs, which sequester membrane-anchored GTPases into the cytosol and thus affect their distribution, localization and protein levels. In the mechanism driving invadosome assembly adhesive and soluble ligands act via transmembrane receptors that propagate signals to the cytoskeleton via small G proteins of the Rho family, assisted by tyrosine kinases and scaffold proteins to induce invadosome formation and rearrangements. Oncogene expression and cell-cell interactions may also trigger their assembly. Osteoclasts generated from the Rac double knockout mouse are devoid of podosomes and sealing zone, and show impaired bone resorption capacities. Rac1 and Rac2 have overlapping roles in podosome assembly and sealing zone-like structure formation by localizing Arp2/3 at podosome sites during osteoclastogenesis.. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
physiological function
cell adhesion and migration are regulated through the concerted action of cytoskeletal dynamics and adhesion proteins, the activity of which is governed by RhoGTPases. Specific RhoGTPase signaling requires spatio-temporal activation and coordination of subsequent protein-protein and protein-lipid interactions. The nature, location and duration of these interactions are dependent on polarized extracellular triggers, such as cell-cell contact, and intracellular modifying events, such as phosphorylation. RhoA, RhoB, and RhoC are highly homologous GTPases that, however, succeed in generating specific intracellular responses
physiological function
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activity of Ypt7p in proteoliposome lipid mixing: Ypt7p is required for the lipid mixing of proteoliposomes lacking cardiolipin [1,3-bis-(sn-3-phosphatidyl)-sn-glycerol]. Omission of other lipids with negatively charged and/or small head groups does not cause Ypt7p dependence for lipid mixing. Disruption of cardiolipin synthase, CRD1, does not alter dependence on Rab GTPases for vacuole fusion. Lipid mixing of proteoliposomes lacking cardiolipin is completely dependent on the presence of Ypt7p. The recruitment of the HOPS, homotypic fusion and protein sorting, complex to membranes is the main function of enzyme Ypt7p. Ypt7p therefore must stimulate membrane fusion by a mechanism that is in addition to recruitment of HOPS to the membrane. Lipid mixing required soluble NSF (N-ethylmaleimide-sensitive factor)-attachment protein receptor proteins, Sec18p and Sec17p (yeast NSF and alpha-SNAP) and the HOPS (homotypic fusion and protein sorting)-class C vacuole protein sorting complex, but not the vacuolar Rab GTPase Ypt7p
physiological function
a pathway involving GTPase Rac1 positively regulates the activity of the rhoB promoter and RhoB expression. The cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivatingRho/Ras proteins but also by the Rac1-activating toxin CNF1. Critical role of transcriptional activation in CNF1-induced RhoB expression. Regulation of the rhoB promoter, overview
physiological function
a pathway involving GTPase Rac1 positively regulates the activity of the rhoB promoter and RhoB expression. Critical role of transcriptional activation in CNF1-induced RhoB expression. Regulation of the rhoB promoter, overview. RhoB dependent suppression of CNF1-induced polyploidy and cell death
physiological function
the cytoprotective RhoB response is not only evoked by bacterial protein toxins inactivatingRho/Ras proteins but also by the Rac1-activating toxin CNF
physiological function
Rab small GTPases are membrane trafficking proteins. Rab2A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab2B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule. Golgi-associated Rab2B interactor-like 4 (GARI-L4) is a Golgi-resident Rab2B-specific binding protein whose knockdown also induces fragmentation of the Golgi like the knockdown of Rab2B. Effector protein GARI-L4 is required for the compacted Golgi morphology in HeLa-S3 cells
physiological function
Rab small GTPases are membrane trafficking proteins. Rab1B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab1A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab6A non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rab small GTPases are membrane trafficking proteins. Rab8B non-redundantly regulates Golgi morphology possibly through interaction with an isoform-specific effector molecule
physiological function
Rac/Rop protein OsRac1 plays an important role in regulating the production of reactive oxygen species by the NADPH oxidase OsRbohB during innate immunity. Direct OsRac1-OsRbohB interactions activate NADPH oxidase in plants
physiological function
Rac1 is one of the biologically important genes in coronary heart diseases, i.e. cardiomyocyte hypertrophy and atherosclerosis, overview. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder. Rac1 facilitates the formation of the lamellipodia structures by initiating peripheral actin polymerization through the Arp2/3 complex that is activated by either the Wiskott-Aldrich syndrome protein (WASP) family or the WAVE (WASP with a V-domain) family proteins. Rac1, through the calmodulin-binding GAP, that is enriched at the leading edge of migrating cells, influences the organization of microtubules, and thus cell shape and polarity. In addition to the cytoskeletal and microtubules effects, Rac1 regulates several signal transduction pathways that lead to alterations in gene expression. Cellular effects of Rac1 activation in cardiomyocytes, smooth muscle cells, endothelial cells, and leukocytes, overview
physiological function
Rac1 is one of the biologically important genes in coronary heart diseases. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder
physiological function
Rac1 is one of the biologically important gene in coronary heart diseases. Rac directly regulates the activity of the NADPH oxidase and the generation of reactive oxygen species (ROS), important players of cardiovascular disorder
physiological function
small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs). Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
physiological function
small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs), Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
physiological function
the small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Role for Rap1b as a key suppressor of neutrophil migration and lung inflammation, which may represent an unappreciated regulatory pathway of neutrophil-related aberrant inflammatory responses. Rap1b inhibits Akt activation via CD11b outside-in signaling, Rap1b negatively regulates PI3K-Akt signaling via the phosphatase SHP-1
physiological function
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role of intrinsic expression of Cdc42 by mature B cells in their activation and function, Cdc42 expression in B cells is essential for efficient IL-2 secretion of CD4+ T cells in cognate T-B cell interaction
physiological function
RhoA inhibits HVA CaV2 Ca2+ channels in a CaVbeta subunit-independent manner, recombinant RhoA activity reduces Ba2+ currents through CaV2.1, CaV2.2 and CaV2.3 Ca2+ channels independently of CaVbeta subunit. This inhibition occurs independently of RGKs activity and without modification of biophysical properties and global level of expression of the channel subunit. High-voltage-activated Ca2+ channels regulation by RhoA might govern synaptic transmission during development and potentially contribute to pathophysiological processes when axon regeneration and growth cone kinetics are impaired. Effects of RhoA on CaV2 trafficking to the plasma membrane, regulation of Ca2+ channel expression and activity by small GTPases, overview
physiological function
requirement for rap gene function in photoreceptor R7, localization of rap gene activity, overview. Overactivity of Ras GTPase activating proteins or underactivity of Ras guanine exchange factors, among other possibilities might account for the limitation in the Ras pathway
physiological function
the transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin. GC-binding factor 2 (GCF2)/leucine-rich repeat (in FLII) interacting protein 1 (LRRFIP1) directly interacts with Dishevelled protein to regulate RhoA activity
physiological function
Rheb acts as a molecular switch in several cellular processes, such as misfolded protein metabolism, cellular apoptosis, vesicle formation and myogenesis. The Ras homologue enriched in brain (Rheb) regulates diverse cellular functions by modulating its nucleotide-bound status. Deacetylated alphabeta-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading, regulatory mechanism of Rheb, overview. Modulation of both soluble and acetylated alphabeta-tubulin levels affects the level of GTP-bound Rheb. This occurs in the mitotic phase in which the level of acetylated alphabeta-tubulin is increased but that of GTP-bound Rheb is decreased. Rheb is an upstream key activator for the mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which has a central role in cell growth by regulating protein synthesis, through modulating mTOR kinase activity. Tubulin-mediated Rheb regulation, detailed overview
physiological function
dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GTPase activating protein for GTPase Alp41/Arl2, Tbc1 and Alp41 directly interact, mutational analysis, overview. Tbc1 is the cofactor C involved in correct folding of alphabeta-tubulin heterodimers, critical for microtubule dynamics. The expression of GDP- or GTP-bound Alp41 shows a microtubule loss phenotype, continuous cycling between these forms seems important for its functions. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP, GDP-bound Alp41 sequesters overproduced Alp1D from microtubules and rescues abnormal microtubule structures
physiological function
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the enzyme Ryh1 activates the target of rapamycin complex 2, TORC2, a protein kinase complex that is required for the TORC2-Gad8 pathway, which is essential for growth under glucose-limited conditions. the nucleotide-binding state of Ryh1 is regulated in response to glucose mediating the nutrient signal to TORC2. In glucose-rich growth media, the GTP-bound form of Ryh1 induces TORC2-dependent phosphorylation of Gad8, a downstream target of TORC2 in fission yeast. Upon glucose deprivation, Ryh1 becomes inactive, which turns off the TORC2-Gad8 pathway. During glucose starvation, Gad8 phosphorylation by TORC2 gradually recovers independently of Ryh1, implying an additional TORC2 activator that is regulated negatively by glucose. The paired positive and negative regulatory mechanisms may allow fine-tuning of the TORC2-Gad8 pathway
physiological function
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Rad is a Ras-related small GTPase shown to inhibit cancer cell migration, and its expression is frequently lost in lung cancer cells. Rad can negatively regulate the NFkappaB pathway. Rad-mediated regulation of NFkappaB is through an IkappaB-independent mechanism. Expression of a nucleus-localized mutant Rad is sufficient to inhibit the NFkappaB transcriptional activity, whereas expressing the scaffolding protein 14-3-3gamma to retain Rad in the cytoplasm alleviates the suppressive effect of Rad on NFkappaB. The Rad-p65 interaction primarily occurs in the nucleus. Rad may directly impede the interaction between RelA/p65 and DNA. Role of nuclear Rad in inhibiting the NFkappaB pathway function
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRHO1 is essential for fungal survival. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Rho GTPase FgRho2 is multifunctional and is involved in sexual development and pathogenesis. FgRho2 is involved in cell wall integrity. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
physiological function
small GTPase Rap1 plays an important role controlling intersegmental nerve b motor axon guidance during neural development. Rap1 contributes to axonal growth and guidance. Genetic interaction analyses demonstrate that the Sema-1a/PlexA-mediated repulsive guidance function is regulated positively by Rap1. The axon guidance function of Rap1 small GTPase is independent of PlexA Ras GAP activity in Drosophila melanogaster. PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases
physiological function
small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Small GTPases exhibit both GDP/GTP-binding activity and GTPase activity, and work as molecular switches by cycling between GDP-bound inactive and GTP-bound active forms. Rac/ROP family small GTPases are master regulators, controlling various signalling systems in plants such as those governing pollen tube growth, root hair development, auxin signaling, and disease resistance
physiological function
Rab proteins exist in the active GTP-bound and inactive GDP-bound conformations with the GTP/GDP exchange mediated by GTP exchange factors (GEF53) and it is the GTP-bound active form of Rab that promotes membrane trafficking upon interaction with effector proteins. Proteins of the Rab family of Ras-related small GTPases, e.g. Rab8, are MICAL regulators. The small GTPase Rab8 activates human MICAL1, small-angle X-ray scattering studies on the oligomerization state of MICAL1 (molecule interacting with casl1) and its complex with Rab8, overview. Rab8, in the active GTP-bound state, stabilizes the active MICAL1 conformation causing a specific increase of kcat
physiological function
ARL2 plays an essential role in the cellular actions of tubulin binding cofactor B (TBCD) but, rather than competing with the binding of beta-tubulin, facilitates it. The ARL2-TBCD interaction is critical for proper maintenance of microtubule densities in cells. The TBCD-ARL2-beta-tubulin trimer represents a functional complex whose activity is fundamental to microtubule dynamics. Correlation between the ability of ARL2 and ARL2 mutants to bind TBCD and to alter microtubule dynamics in a cell-based assay
physiological function
the putitative, Ras-like G-protein might be involved in a non-canonical signaling pathway in Plasmodium falciparum
physiological function
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Pc-Rac1 is involved in the innate immune responses in Procambarus clarkii
physiological function
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Ypt1p, a Rab family small GTPase protein, exhibits a stress-driven structural and functional switch from a GTPase to a molecular chaperone, and mediates thermo tolerance in Saccharomyces cerevisiae. The enzyme Ypt1p has another function in addition to its well-known GTPase function, which is temperature-dependent and promotes the survival and growth of cells under heat-stress. The GTPase activity of Ypt1p is not essential for the growth of yeast at elevated temperatures. Ypt1p controls an abundance of proteins involved in metabolism, protein synthesis, cellular energy generation, stress response, and DNA regulation. Ypt1p is essential for multiple steps of the yeast secretory pathway, including endoplasmic reticulum to cis-Golgi and cis- to medial-Golgi transport. Ypt1p essentially regulates fundamental cellular processes under heat-stress conditions by acting as a molecular chaperone
physiological function
small Ras GTPases are key molecules that regulate a variety of cellular responses in different cell types. Rap2a. Rap2a can inhibit the LPS-induced phosphorylation of the NF-kappaB subunit p65 at serine 536. Rap2a is implicated in TLR-mediated responses by contributing to balanced NF-kappaB activity status in macrophages. Rap2a GTPase is involved in TLR signaling pathway to NF-kappaB. Rap2a exhibits a more potent inhibitory effect on Mal/TIRAP and TRAF6-induced NF-kappaB activation. In contrast, Rap2a fails to inhibit NF-kappaB activity induced directly by the monomer p65(RelA). Thus, Rap2a interferes in NF-kappaB activation by affecting upstream signaling events to p65(RelA)
physiological function
Arf6 is a critical regulator of membrane dynamics-based cellular events such as reorganization of actin cytoskeleton and membrane trafficking. Like other small GTPases, Arf6 acts as a molecular switch by cycling between GDP-bound inactive and GTP-bound active forms in cellular signaling pathways. Arf6 is activated in response to agonist stimulation of the cell interacts with its downstream effectors to regulate their intracellular location and activity
physiological function
Macroautophagy (i.e. autophagy) a highly conserved intracellular process by which cytosolic components and damaged organelles are enclosed and degraded by a double membrane-bound structure, can be viewed as a continuous and dynamic membrane transport and fusion process. The GTP-bound active form of Rab13 promotes the interaction between Rab13 and growth factor receptor-bound protein 2 (Grb2). It promotes macroautophagy in vascular endothelial cells. Rab13 activates the downstream AMP-activated protein kinase (AMPK) and blocks mammalian target of rapamycin (mTOR) signaling by its functional interaction with Grb2 to regulate autophagy in HUVECs. Rab13 is a regulator of autophagy in VECs under nutrient-enriched conditions. Upregulation of the active form of Rab13 increases its interaction with Grb2, which is required to activate AMPK, leading to the inhibition of mTOR and subsequently inducing autophagy. Rab13 regulated autophagy by interacting with Grb2 in HUVECs
physiological function
the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. ARF6 activation accelerate metastasis and increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade. ARF6 activation increases metastatic disease burden, a role for ARF6 in proliferation or survival is also possible
physiological function
the small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state. Constitutive activation of the small GTPase ARF6 (ARF6Q67L) is sufficient to accelerate metastasis in mice with BRAFV600E/Cdkn2aNULL melanoma at a similar incidence and severity to Pten loss, a major driver of PI3K activation and melanoma metastasis. ARF6 activation increases lung colonization from circulating melanoma cells, suggesting that the prometastatic function of ARF6 extends to late steps in metastasis. ARF6 is necessary and sufficient for activation of both PI3K and AKT, and PI3K and AKT are necessary for ARF6-mediated invasion. Critical role for ARF6 in multiple steps of the metastatic cascade
physiological function
the enzyme Rac2 enhances osteoclast differentiation. The enzyme Rac2 and guanine nucleotide exchange factor Vav1 may counteract to fine-tune osteoclast differentiation and bone resorption
physiological function
the small GTPase Ran is the main regulator of the nucleo-cytoplasmic import and export through the nuclear pore complex. It controls cell cycle progression by regulating the microtubule polymerization and mitotic spindle formation, playing an essential role in tumor progression and metastasis. The enzyme is a molecular switch cycling between GDP-bound cytosolic inactive- and GTP-bound nucleus-located active states
physiological function
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the enzyme plays a key role in regulating Bamboo mosaic virus movement by vesicle transport from the Golgi apparatus to the plasma membrane
physiological function
enzyme DiRAS3 exhibits tumor suppressor properties
physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRho3 demonstrates functions only in vegetative growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgRho4 is multifunctional and is involved in sexual development and pathogenesis. While FgRho4 is involved in cell wall integrity, and FgRho4 shows a role in nuclear division and septum formation. FgRho4 is also important for hyphal growth and conidiation. Isozyme FgRho4 plays a positive role in deoxynivalenol production. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. The Rho GTPase FgCdc42 is multifunctional and is involved in sexual development and pathogenesis. Isozyme FgCdc42 is important for hyphal growth and conidiation. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. FgRac1 interacts with FgCla4 via its PBD domain and genetically acts upstream of FgCla4 to affect hyphal growth and conidiation. Isozyme FgRac1 is important for hyphal growth and conidiation. FgRac1 negatively controls deoxynivalenol production. FgCla4 is a downstream target of FgRac1, but is dispensable for sexual development. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Isozyme FgRHO1 is essential for fungal survival. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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Rho GTPases have multiple cellular and metabolic functions, including vesicular trafficking and pathogenesis, as signaling molecules in fungi. Rho GTPases are known to regulate asexual development in filamentous fungi. Rho GTPase FgRho2 is multifunctional and is involved in sexual development and pathogenesis. FgRho2 is involved in cell wall integrity. FgRho GTPase isozymes contribute diversely to growth, conidiogenesis, sexual reproduction, deoxynivalenol production and pathogenesis
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physiological function
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small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs). Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
-
physiological function
-
small GTPase Rap1 regulates cell migration through regulation of small GTPase RhoA activity in response to transforming growth factor-beta1. GTP-RhoA and GTP-Rap1 levels are reciprocally regulated in a time-dependent manner following TGF-beta1 stimulation. Ras-related, small GTPases act as molecular switches that control a variety of cellular processes by cycling between alternative conformational states. In the active state, they are bound with GTP, and in the inactive state, they are bound with GDP. In their active state, GTPases recognize their target effector proteins and evoke responses until GTP hydrolysis returns the switch to the off position. GTP-binding to small GTPases is catalyzed by guanine nucleotide exchange factors (GEFs), and hydrolysis of the bound GTP is accelerated by GTPase activating proteins (GAPs), Downstream effector proteins of Rap1, including RapL, AF6, and ARAP3 transmit the activated Rap1 signals within the cells. Rap1 regulates GTPase RhoA activity, but RhoA does not regulate the Rap1 activity
-
physiological function
-
the small GTPase Rap1b negatively regulates neutrophil chemotaxis and transcellular diapedesis by inhibiting Akt activation. The inhibitory action of Rap1b on PI3K signaling may be mediated by activation of phosphatase SHP-1. Role for Rap1b as a key suppressor of neutrophil migration and lung inflammation, which may represent an unappreciated regulatory pathway of neutrophil-related aberrant inflammatory responses. Rap1b inhibits Akt activation via CD11b outside-in signaling, Rap1b negatively regulates PI3K-Akt signaling via the phosphatase SHP-1
-
physiological function
-
role of intrinsic expression of Cdc42 by mature B cells in their activation and function, Cdc42 expression in B cells is essential for efficient IL-2 secretion of CD4+ T cells in cognate T-B cell interaction
-
physiological function
-
activity of Ypt7p in proteoliposome lipid mixing: Ypt7p is required for the lipid mixing of proteoliposomes lacking cardiolipin [1,3-bis-(sn-3-phosphatidyl)-sn-glycerol]. Omission of other lipids with negatively charged and/or small head groups does not cause Ypt7p dependence for lipid mixing. Disruption of cardiolipin synthase, CRD1, does not alter dependence on Rab GTPases for vacuole fusion. Lipid mixing of proteoliposomes lacking cardiolipin is completely dependent on the presence of Ypt7p. The recruitment of the HOPS, homotypic fusion and protein sorting, complex to membranes is the main function of enzyme Ypt7p. Ypt7p therefore must stimulate membrane fusion by a mechanism that is in addition to recruitment of HOPS to the membrane. Lipid mixing required soluble NSF (N-ethylmaleimide-sensitive factor)-attachment protein receptor proteins, Sec18p and Sec17p (yeast NSF and alpha-SNAP) and the HOPS (homotypic fusion and protein sorting)-class C vacuole protein sorting complex, but not the vacuolar Rab GTPase Ypt7p
-
physiological function
-
dual role of fission yeast Tbc1/cofactor C orchestrates microtubule homeostasis in tubulin folding and acts as a GTPase activating protein for GTPase Alp41/Arl2, Tbc1 and Alp41 directly interact, mutational analysis, overview. Tbc1 is the cofactor C involved in correct folding of alphabeta-tubulin heterodimers, critical for microtubule dynamics. The expression of GDP- or GTP-bound Alp41 shows a microtubule loss phenotype, continuous cycling between these forms seems important for its functions. Alp41 GTPase interacts with cofactor D, Alp1D, only when bound to GDP, GDP-bound Alp41 sequesters overproduced Alp1D from microtubules and rescues abnormal microtubule structures
-
physiological function
-
Arf6 is a critical regulator of membrane dynamics-based cellular events such as reorganization of actin cytoskeleton and membrane trafficking. Like other small GTPases, Arf6 acts as a molecular switch by cycling between GDP-bound inactive and GTP-bound active forms in cellular signaling pathways. Arf6 is activated in response to agonist stimulation of the cell interacts with its downstream effectors to regulate their intracellular location and activity
-
physiological function
Drosophila melanogaster w1118
-
small GTPase Rap1 plays an important role controlling intersegmental nerve b motor axon guidance during neural development. Rap1 contributes to axonal growth and guidance. Genetic interaction analyses demonstrate that the Sema-1a/PlexA-mediated repulsive guidance function is regulated positively by Rap1. The axon guidance function of Rap1 small GTPase is independent of PlexA Ras GAP activity in Drosophila melanogaster. PlexA-mediated motor axon guidance is dependent on the presence of the PlexA RasGAP domain, but not on its GAP activity toward Ras family small GTPases
-
physiological function
-
small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Small GTPases exhibit both GDP/GTP-binding activity and GTPase activity, and work as molecular switches by cycling between GDP-bound inactive and GTP-bound active forms. Rac/ROP family small GTPases are master regulators, controlling various signalling systems in plants such as those governing pollen tube growth, root hair development, auxin signaling, and disease resistance
-
additional information
-
co-ordinated differential expression of a set of genes encoding small GTPases of the ARF and RAB families which takes place during key moments of fruit development and maturation
additional information
-
activation of Rap1 by Epac1 leads to increased integrin activity and adhesion of endothelial progenitor cells, CD34+ hematopoietic progenitor cells and mesenchylmal stem cells, which show increased homing and neovascularization capabilities
additional information
-
disruption of the secretory pathway by brefeldin A does not affect autophagosome formation
additional information
each of the two Der GTP-binding domains expressed separately has an intrinsic GTPase activity, though the activity of the N-terminal GD1 domain is stronger than that of the GD2 domain
additional information
-
each of the two Der GTP-binding domains expressed separately has an intrinsic GTPase activity, though the activity of the N-terminal GD1 domain is stronger than that of the GD2 domain
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rac1 deletion in cathepsin-K+ differentiating Rac2 deficient osteoclasts has no effect on actin ring formation. In contrast to osteoclasts, Rac1 and Rac2 play distinct roles in macrophage podosome formation
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
Rho GTPase structure-function analysis, comparisons of RhoA, RhoB, and RhoC enzymes, overview. Multiple regions in RhoA/B/C cooperate to provide specificity in binding to regulators and effectors. These specific interactions are highly regulated in time and space. Visualization and analyzsis of localized GTPase activation using biosensors that allow imaging of isoform-specific, localized regulation
additional information
the solvent accessibility values of all residues located in Switch I are for Phe35, Tyr39, Thr42, Val43, Phe44, and Asp45 16, 100, 55, 54, 54, and 69%, respectively
additional information
-
the solvent accessibility values of all residues located in Switch I are for Phe35, Tyr39, Thr42, Val43, Phe44, and Asp45 16, 100, 55, 54, 54, and 69%, respectively
additional information
structure analysis and comparison of trypanosomal and human Arl6/BBS3 proteins, overview. Analysis of the TbArl6 active site confirms that it lacks the key glutamine that activates the nucleophile during GTP hydrolysis in other small GTPases. The trypanosomal proteins are significantly shorter at their N-termini suggesting a different method of membrane insertion compared to humans. Two surface patches may be important for protein-protein interactions
additional information
-
structure analysis and comparison of trypanosomal and human Arl6/BBS3 proteins, overview. Analysis of the TbArl6 active site confirms that it lacks the key glutamine that activates the nucleophile during GTP hydrolysis in other small GTPases. The trypanosomal proteins are significantly shorter at their N-termini suggesting a different method of membrane insertion compared to humans. Two surface patches may be important for protein-protein interactions
additional information
overexpression of any type of Rhebs (wild-type, constitutively active form, and dominant-negative form) does not affect the intact microtubule structure, and the vesicle-formed Rheb does not colocalize with the microtubule network during interphase and mitosis
additional information
real-time micrography of Toxoplasma gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA shows that this GTPase is recruited to the parasitophorous vacuole membrane at the very beginning of the invasion through the host cell membrane or from the cytosol
additional information
real-time micrography of Toxoplasma gondii tachyzoites invading COS-7 cells overexpressing CFP-RhoA shows that this GTPase is recruited to the parasitophorous vacuole membrane at the very beginning of the invasion through the host cell membrane or from the cytosol
additional information
establishment of a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells, protocol for visualizing spatiotemporal activity of plant Rac/ ROP GTPase in living plant cells, transfection of rice protoplasts, method, detailed overview
additional information
human MICAL1 is a member of a recently discovered family of multidomain proteins that couple a FAD-containing monooxygenase-like domain to typical protein interaction domains, MICAL1-Rab8 interaction analysis, quaternary structure, overview
additional information
-
human MICAL1 is a member of a recently discovered family of multidomain proteins that couple a FAD-containing monooxygenase-like domain to typical protein interaction domains, MICAL1-Rab8 interaction analysis, quaternary structure, overview
additional information
GST-TBCD with or without ARL2 from HEK cells co-purifies with different combinations of tubulins in novel complexes. The TBCD-alpha-tubulin-beta-tubulin trimer is analyzed, overview
additional information
-
GST-TBCD with or without ARL2 from HEK cells co-purifies with different combinations of tubulins in novel complexes. The TBCD-alpha-tubulin-beta-tubulin trimer is analyzed, overview
additional information
the enzyme has has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases
additional information
-
the enzyme has has GTP binding capacity and GTPase activity due to an EngA2 domain present in small Ras-like GTPases
additional information
-
Ypt1p cycles between an active GTP-bound form and an inactive GDP-bound form. Native-PAGE analysis confirms that heat-shock treatment induces the reversible formation of high-molecular-weight protein complexes containing Ypt1p in vivo
additional information
-
enzyme structure-activity analysis and Ras allosteric networks, detailed overview. The allosteric networks on Ras intimately link switch I and switch II to each other and to two other functionally important regions on the opposite side of the protein. Switch I is linked to helix 5 membrane-interacting residues at the back of the molecule, where Arg161 and Arg164 make salt bridges with the interswitch loop 3 residues Asp47 and Glu49. Switch II is normally disordered and disconnected from the network. When calcium and a negatively charged ligand bind, helix 3 shifts towards helix 4, and the entire switch II becomes ordered and linked to the Ca2+-binding pocket through an extensive water-mediated network
additional information
murine ectopic ARF6Q67L mutant increases Matrigel invasion of human A-2058 melanoma cells in vitro. The pan-AKT inhibitor MK2206 and the pan-Class I PI3K inhibitor GSK-0941 both abrogate ARF6Q67L-dependent Matrigel invasion, demonstrating that PI3K signaling is necessary for ARF6-mediated invasion
additional information
-
murine ectopic ARF6Q67L mutant increases Matrigel invasion of human A-2058 melanoma cells in vitro. The pan-AKT inhibitor MK2206 and the pan-Class I PI3K inhibitor GSK-0941 both abrogate ARF6Q67L-dependent Matrigel invasion, demonstrating that PI3K signaling is necessary for ARF6-mediated invasion
additional information
-
establishment of a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells, protocol for visualizing spatiotemporal activity of plant Rac/ ROP GTPase in living plant cells, transfection of rice protoplasts, method, detailed overview
-
Show AA Sequence and Transmembrane Helices (69131 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
21803
1 * 21803, multi-angle laser light scattering and sequence calculation
23000
26000
additional information
23000
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
26000
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
26000
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
additional information
when human ARL2 is expressed in bacteria, it purifies as a soluble, stable monomer with no evidence of any species greater than 20 kDa
additional information
-
when human ARL2 is expressed in bacteria, it purifies as a soluble, stable monomer with no evidence of any species greater than 20 kDa
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
heteromer
monomer
additional information
dimer
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
dimer
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
dimer
the small GTPase Toc33/34 can homodimerize. Dimerization is independent of nucleotide loading state. GTPase activation by dimerization is sparse. The dimer is not self-activating, possibly lacking an additional regulatory layer
heteromer
-
association in a high molecular weight complex with different other proteins, gel filtration
monomer
1 * 27504, mutant enzyme C75S/C80S, calculated from amino acid sequence
monomer
1 * 21803, multi-angle laser light scattering and sequence calculation
additional information
Der has a C-terminal KH-like (RNA-binding module-like) domain flanked by two tandemly repeated GTP-binding domains at the N-terminus
additional information
Der has a C-terminal KH-like (RNA-binding module-like) domain flanked by two tandemly repeated GTP-binding domains at the N-terminus
additional information
structural core of RhoGTPases: the G domain, the Rho insert region, and the C-terminus of RhoGTPases, structure analysis, detailed overview. The hypervariable region also functions as protein binding site and determines, at least in part, specific binding to regulatory or effector proteins. In most RhoGTPases, including RhoA and RhoC, this region of around 10 residues harbors a polybasic stretch that binds the inner leaflet of the plasma membrane. RhoA, RhoB and RhoC have a very similar structure of the G domain and the insert region
additional information
structural core of RhoGTPases: the G domain, the Rho insert region, and the C-terminus of RhoGTPases, structure analysis, detailed overview. The hypervariable region also functions as protein binding site and determines, at least in part, specific binding to regulatory or effector proteins. In most RhoGTPases, including RhoA and RhoC, this region of around 10 residues harbors a polybasic stretch that binds the inner leaflet of the plasma membrane. RhoA, RhoB and RhoC have a very similar structure of the G domain and the insert region
additional information
structural core of RhoGTPases: the G domain, the Rho insert region, and the C-terminus of RhoGTPases, structure analysis, detailed overview. The hypervariable region also functions as protein binding site and determines, at least in part, specific binding to regulatory or effector proteins. In most RhoGTPases, including RhoA and RhoC, this region of around 10 residues harbors a polybasic stretch that binds the inner leaflet of the plasma membrane. RhoA, RhoB and RhoC have a very similar structure of the G domain and the insert region
additional information
-
Der has a C-terminal KH-like (RNA-binding module-like) domain flanked by two tandemly repeated GTP-binding domains at the N-terminus
additional information
Der has a C-terminal KH-like (RNA-binding module-like) domain flanked by two tandemly repeated GTP-binding domains at the N-terminus
additional information
-
Der has a C-terminal KH-like (RNA-binding module-like) domain flanked by two tandemly repeated GTP-binding domains at the N-terminus
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
lipoprotein
phosphoprotein
side-chain modification
additional information
lipoprotein
the C-terminus of RhoGTPases comprises, next to the hypervariable region, the CAAX-box to which a lipid anchor is attached allowing GTPase binding to membranes. RhoA, RhoB and RhoC differ in this posttranslational lipid modification which has consequences for their subcellular localization. The lipid anchor regulates the interaction with RhoGDIs and with regions within the plasma membrane (RhoA, RhoC) or endosomal vesicles (RhoB). RhoA and RhoC are geranylgeranylated, whereas RhoB has both a palmitoyl anchor and a farnesyl or geranylgeranyl group
phosphoprotein
PKA- and PKG-mediated phosphorylation of RhoA on Ser188, which is located in the hypervariable C-terminus. This phosphorylation serves as a Rho-inactivating signal, as it promotes GDI binding and membrane dissociation and protects RhoA from proteolytic degradation. In addition, this phosphorylation interferes with RhoA binding to ROCK further underscoring a role of the C-terminus in effector interactions
phosphoprotein
RhoC, but not RhoA, is phosphorylated on Ser73 in the alpha2-helix by the kinase Akt in SUM149 breast cancer cells54 although Ser73 is highly conserved among all 3 Rho-isoforms. Intriguingly, phosphorylation of RhoC is required for downstream signaling and invasiveness, which contrasts markedly with the inactivating phosphorylation at Ser188 in RhoA
side-chain modification
wild type and activated RhoA is ubiquitylated on Lys6 and Lys7 in the beta1-strand by the E3 ubiquitin ligase Smurf1 resulting in local RhoA degradation
additional information
the CKIF motif in human RhoH is a target for the in vitro modification by farnesyl-transferase and geranylgeranyl-transferase
additional information
-
the CKIF motif in human RhoH is a target for the in vitro modification by farnesyl-transferase and geranylgeranyl-transferase
additional information
-
small GTPases are modified by isoprenylation of the cysteine of the CAAX box, cleavage of the AAX tripeptide, and methylation of the cysteine, isoprenylation and the endoproteolytic cleavage of the tripeptide of Rho GTPases are essential for YopT-induced cleavage, whereas carboxyl methylation is not required
additional information
the CKIF motif in mouse RhoH is a target for the in vitro modification by farnesyl-transferase and geranylgeranyl-transferase
additional information
-
the CKIF motif in mouse RhoH is a target for the in vitro modification by farnesyl-transferase and geranylgeranyl-transferase
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
sitting-drop vapor-diffusion technique, structure of the GMPPNP-bound state and GMP-bound state of Toc33 GTPase
enzyme in complex with GTP, sitting drop vapor diffusion method, using 100 mM MES, pH 5.5, 250 mM NaCl, 13% (w/v) PEG 8000
A0A135VL07
Thermotoga maritima crystal structure analysis, PDB ID 1MKY, computer-aided pharmacophore modeling and modeling of GTP and GDP binding to the enzyme, overview
1.65 A resolution, complex of RhoA-rhoGAP with the transition-state analogue GDPAIF4-, hanging drop vapour diffusion technique
-
crystals are obtained at 20°C by vapour diffusion using a crystallization robot. The crystals are found to belong to space group P2(1), with unit-cell parameters a = 52.2, b = 58.6, c =53.4 A, beta= 97.9°, and contains two Rad molecules in the crystallographic asymmetric unit, 1.8 A resolution
-
GTPase domain of human Rheb recombinantly expressed in Escherichia coli, purified and cocrystallized in complexes with GDP, GTP and GppNHp using the hanging-drop vapour-diffusion method. Crystals of the hRheb/GDP complex belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 44.5, b = 52.3, c = 70.6 A. The hRheb/GppNHp complex crystallizes in two crystal forms: one has the same space group and unit-cell parameters as the hRheb/GDP complex and the other belongs to space group C222(1), with unit-cell parameters a = 102.9, b = 99.2, c = 48.0 A. The hRheb/GTP complex also crystallizes in two crystal forms: one belongs to space group C222(1), with unit-cell parameters a = 102.4, b = 98.3, c = 47.9 A, and the other belongs to space group P2(1), with unit-cell parameters a = 77.3, b = 47.9, c = 71.9 A, beta = 89°. All these crystals diffract X-rays to better than 2.8 A resolution
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hanging-drop vapor-diffusion method, Rab11b-GDP and Rab11b-GppNHp crystal structures solved to 1.55 and 1.95 A resolution, respectively
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purified enzyme hydrogenated H-RAS, residues 1-166, Sitting drop vapour diffusion, 1:1 ratio of protein solution, containing 20 mM HEPES, pH 7.5, 50 mM NaCl, 5 mM MgCl2, 1 mM DTT, and reservoir solution containing 200 mM calcium acetate, 20% w/v PEG 3350, 0.1% w/v n-octyl-beta-D-glucoside. Once the crystals has stopped growing, the hydrogenated reservoir solution is replaced with an identical reservoir solution prepared with D2O. A single crystal of the small GTPase Ras is used to collect three neutron data sets at pD 8.4, 9.0 and 9.4, in crystallo titration study using neutron protein crystallography (NPC), a method that lacks radiation damage of the cyrstals. Structure analysis at resolution of 1.9-2.1 A
-
solution structure of free RalB bound to the GTP analogue GMPPNP, nuclear magnetic resonance spectroscopy
-
vapor diffusion hanging-drop method, three-dimensional crystal structure of Rab4a in its GppNHp-bound state to 1.6 A resolution and in its GDP-bound state to 1.8 A resolution
-
sitting-drop vapor-diffusion technique, structure of the GMPPNP-bound state of Toc33/34 GTPase
crystallization of M-ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate-bound forms, hanging-drop vapour diffusion method at 20°C using the reservoir solution containing 20% w/v polyethylene glycol 8000 and 50 mM potassium phosphate at a protein concentration of 10 mg/ml
-
hanging drop vapour diffusion method, using 1.0 M sodium citrate trihydrate, 0.1 M sodium cacodylate, at pH 6.5
-
purified recombinant GST-tagged OsRac1 complexed with non-hydrolyzable GTP analogue guanosine 5'-(beta,gamma-imido)triphosphate, sitting-drop vapor-diffusion method, mixing of 0.007 ml of 4 mg/ml protein with 0.007 ml of reservoir solution containing 100mM MES, pH 6.0, and 10-30% PEG 6000, 25% v/v glycerol as a cryoprotectant, X-ray diffraction structure determination and analysis at 1.9 A resolution, molecular replacement
crystal structure analysis, PDB ID 1MKY, computer-aided pharmacophore modeling and modeling of GTP and GDP binding to the enzyme, overview
purified enzyme complexed with non-hydrolysable GTP analog GppNp, mixing of 8 mM guanosine 5'-[beta,gamma-imido]triphosphate (GppNp) and 92 mg/ml TbArl6 protein are mixed with 0.2 M CsCl and 2.2 M (NH4)2SO4, X-ray diffraction structure determination and analysis at 2.0 A resolution, molecular replacement using the human Arl6 structure, PDB ID 2h57, as the search model
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Q74L
-
the mutant is preferentially GTP bound and therefore in an active state
S29N
-
the mutant is preferentially GDP bound and therefore in an inactive state
C192S
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
FgCDC42 cDNA is amplified from cDNA of PH-1 with a site mutation C192S to ensure that FgCdc42 protein cannot be prenylated and is soluble
C196S
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
FgRAC1 cDNA is amplified from cDNA of PH-1 with a site mutation C196S to ensure that FgRac1 protein cannot be prenylated and is soluble
G15V/D121A
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
constitutively active (G15V) and dominant negative mutations (D121A) are generated in the BD-FgCdc42 background
G17V/D123A
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
constitutively active (G17V) and dominant negative mutations (D123A) are generated in the BD-FgRac1 background
C192S
-
FgCDC42 cDNA is amplified from cDNA of PH-1 with a site mutation C192S to ensure that FgCdc42 protein cannot be prenylated and is soluble
-
C196S
-
FgRAC1 cDNA is amplified from cDNA of PH-1 with a site mutation C196S to ensure that FgRac1 protein cannot be prenylated and is soluble
-
G15V/D121A
-
constitutively active (G15V) and dominant negative mutations (D121A) are generated in the BD-FgCdc42 background
-
G17V/D123A
-
constitutively active (G17V) and dominant negative mutations (D123A) are generated in the BD-FgRac1 background
-
A152P
-
mutation dramatically affects both GTP and GDP nucleotide-binding activity of Rab27a, probably by disrupting protein folding
C75S/C80S
the mutation significantly improves soluble protein expression in Escherichia coli
chimeras between RhoA/Cdc42
-
residues 85-122 contain specific binding determinants for guanosine nucleotide activating protein, p190
D90A
-
RhoA, significant decrease in p190-mediated stimulation of GTPase activity
F50A
site-directed mutagenesis, the mutation disrupts the interaction with TBCD, increased expression levels compared to wild-type
F50A/Q70L
site-directed mutagenesis, cells expressing mutant L3A/F50A show a reversal of the microtubule loss phenotype, with about 20% of transfected cells showing only intermediate loss in microtubule densities
G169A
-
the mutation causes the Bardet-Biedl syndrome, the mutant protein is destabilized probably due to the weak affinity to guanine nucleotides
H79G
-
a GTPase-defective Sar1 mutant. Overexpression of the GTPase-defective mutant Sar1 H79G, in its GTP-bound form, allows the development of ERES, but the transport to the Golgi apparatus is blocked because this mutant inhibits COPII coat dissociation, and its expression induces Golgi fragmentation as indicated by Rab6 dispersion and inhibits autophagosome formation
I6R
site-directed mutagenesis, the mutation disrupts the interaction with TBCD
I6R/Q70L
site-directed mutagenesis, the addition of the I6R mutation to Q70L does not reverse the effects of the dominant mutant on microtubule densities
L130P
-
mutation dramatically affects both GTP and GDP nucleotide-binding activity of Rab27a, probably by disrupting protein folding
L170W
-
the mutation causes the Bardet-Biedl syndrome, the mutant protein is destabilized probably due to the weak affinity to guanine nucleotides
L3A
site-directed mutagenesis, the mutation disrupts the interaction with TBCD
L3A/Q70L
site-directed mutagenesis, cells expressing mutant L3A/Q70L show a reversal of the microtubule loss phenotype, with about 10% of transfected cells showing only intermediate loss in microtubule densities
N-terminal truncation
-
Kir/Gem peptide, C-terminal calmodulin-binding domain, high affinity for dansyl-calmodulin
N121I
-
a dominant-negative GFP-tagged Rab1b mutant, inhibits autophagosome formation
Q67L
-
a GTPase-deficient Rab1b mutant, the distribution of Rab1b in the acidic compartments responds to inhibition of autophagy
Q70L
site-directed mutagenesis, ARL2 dominant activating mutation. Expression of ARL2 Q70L mutant causes the loss of polymerized microtubules in cultured cells
Q72L
-
the mutant decreases the GTP hydrolysis activity and stabilizes the active form of the protein
Q78L
T30N
site-directed mutagenesis, ARL2 dominant inactivating mutation, shows decreased expression levels compared to wild-type
T31M
-
the mutation causes the Bardet-Biedl syndrome, the mutant protein is destabilized probably due to the weak affinity to guanine nucleotides
T31N
-
the guanine nucleotide-free Arl6 mutant protein is unstable and degraded in living cells
T31R
-
the mutation selectively abrogates the GTP-binding ability of Arl6 without affecting GDP-binding/dissociating properties
T33N
mutant enzyme is defective in GTP binding, cells expressing mutant Rab21 show defects in endocytosis of transferrin and epidermal growth factor and fail to effectively deliver the latter ligand to late endosomes and lysosomes for degradation, subcellular distribution
T39N
-
a dominant-negative Sar1 mutant, expression induces Golgi fragmentation as indicated by Rab6 dispersion and inhibits autophagosome formation
W73G
-
mutant protein has GTP-binding activity but is inefficient in hydrolyzing GTP, in contrast to Q78L it neither interacts with the Rab27a effector melanophilin nor modifies melanosome distribution and cytotoxic granule exocytosis, mutation may increase switch flexibility and thus impair the dynamics of the conformational changes associated with each nucleotide binding
AS28N
-
the mutant significantly inhibits KCl-induced insulin secretion but has no significant effect on glucose/carbachol-and glucose/KCl-induced insulin secretion despite an inhibitory trend
D57N
-
the dominant negative Rac GTPase mutation does not only inhibit Rac1, Rac2, and Rac3 activities, but may also inhibit Cdc42
E78L/C123S/C188S
-
the mutant may modulate effector recognition by forming an intramolecular disulfide bridge
Q67L
Q92L
-
the mutant with the stabilized GTP-bound form, and the GTP failing to be hydrolyzed, can have a negative effect on Bamboo mosaic virus accumulation
S46N
-
the mutation can disrupt the binding of Mg2+ essential for GTP binding and consequently locks the GTPase in an inactive form (GDP-bound)
C32S/Q68L
design OsRac1 mutants that display reduced binding to the NADPH oxidase OsRbohB. Tyr39 and Asp45 substitutions suppress ROS production in rice cells, these residues are critical for interaction with and activation of NADPH oxidase OsRbohB
G19V
the constitutively activated mutant of OsRac1 increases resistance to rice bacterial blight disease and subsequent cell death
G19V/D38A
site-directed mutagenesis, the Switch I mutant shows unaltered binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/D45A
site-directed mutagenesis, the Switch I mutant shows markedly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/F35A
site-directed mutagenesis, the Switch I mutant shows markedly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/F44A
site-directed mutagenesis, the Switch I mutant shows moderately reduced binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/I40A
site-directed mutagenesis, the Switch I mutant shows slightly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/P36A
site-directed mutagenesis, the Switch I mutant shows almost unaltered binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/P41A
site-directed mutagenesis, the Switch I mutant shows slightly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/T37A
site-directed mutagenesis, the Switch I mutant shows slightly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/T42A
site-directed mutagenesis, the Switch I mutant shows markedly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/V43A
site-directed mutagenesis, the Switch I mutant shows moderately reduced binding with OsRbohB(138-313) compared to the wild-type enzyme
G19V/Y39A
site-directed mutagenesis, the Switch I mutant shows markedly attenuated binding with OsRbohB(138-313) compared to the wild-type enzyme
T24N
a dominant-negative mutant of OsRac1 that decrease the resistance reaction to rice bacterial blight disease and subsequent cell death
AS28N
-
the mutant significantly inhibits KCl-induced insulin secretion but has no significant effect on glucose/carbachol-and glucose/KCl-induced insulin secretion despite an inhibitory trend
D124N
-
Ypt1, changed nucleotide specificity from guanine to xanthine, complete inhibition of guanosine nucleotide exchange factor-mediated nucleotide exchange
G80D
-
the Ypt1pG80D mutant protein has normal GTPase function and the ypt1-G80D mutant strain displays normal growth and nearly normal endoplasmic reticulum-to-Golgi vesicle trafficking at typical growth temperature (30°C), but experiences growth retardation at an elevated temperature (37°C). Ypt1pG80D does not undergo a heat-shock-induced structural change in vivo. Ypt1pG80D loses molecular chaperone activity. Sodium 4-phenylbutyric acid (PBA), a chemical chaperone, increases the thermotolerance of mutant ypt1-G80D cells, although it is not restored to the level seen for the wild-type YPT1 strain
R142G K143M K144I
-
triple mutation prevents interaction with Nsp1p nucleoporin
additional information
Q78L
-
constitutively GTP-bound, active mutant, mutant protein has GTP-binding activity but is inefficient in hydrolyzing GTP
Q67L
ARF6Q67L promotes spontaneous metastasis from significantly smaller primary tumors than PTENNULL, implying an enhanced ability of ARF6-GTP to drive distant spread. In mice with metastases, there is a dramatic increase in metastatic volume in the ARF6Q67L cohort
additional information
-
eliminating or reducing rho-1 gene function by using a dominant-negative transgene or dsRNA interference results in a severe defect in migration of hypodermal P cells to a ventral position
additional information
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
A0A098E0E9
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
-
construction of deletion mutants of the isozymes, phenotypes, overview
additional information
-
construction of deletion mutants of the isozymes, phenotypes, overview
-
additional information
-
mutations in the Rab27a gene cause pigment as well as cytotoxic granule transport defects, accounting for the partial albinism and severe immune disorder characteristics of the Griscelli syndrome type 2
additional information
-
overexpressing activated Rap 1a in dermal microvascular endothelial cells
additional information
quantitative analyses of vesicular stomatitis virus ts045 G protein fused to green fluorescent protein exocytosis from endoplasmic reticulum through the Golgi to the PM22,23 in Rab37 knockdown (Rab37KD) or control COS1 cells
additional information
-
quantitative analyses of vesicular stomatitis virus ts045 G protein fused to green fluorescent protein exocytosis from endoplasmic reticulum through the Golgi to the PM22,23 in Rab37 knockdown (Rab37KD) or control COS1 cells
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
-
knockdown of Rab isoform Rab2B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
-
knockdown of Rab isoform Rab1B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
-
knockdown of Rab isoform Rab1A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
-
knockdown of Rab isoform Rab6A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
-
knockdown of Rab isoform Rab8B induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of siRNA-resistant Rab constructs
additional information
construction of truncaction mutant DELTA1-9. All Arl2 mutants co-purify to similar levels as wild-type ARL2 with TBCD and tubulin in a complex, with no apparent differences in the composition of the trimer
additional information
-
construction of truncaction mutant DELTA1-9. All Arl2 mutants co-purify to similar levels as wild-type ARL2 with TBCD and tubulin in a complex, with no apparent differences in the composition of the trimer
additional information
-
the chocolate mutation is attributed to a G146T transversion in the conserved GTP/GDP-interacting domain of Rab38, recombinant Rab38chocolate proteins retain GTP-binding activity but fail to undergo prenyl modification, the genetic abnormality of Rab38 affects multiple lysosome-related organelles, resulting in lung disease in addition to oculocutaneous albinism
additional information
-
generation of Cdc42-deficient B cells, tamoxifen induction of Cdc42 excision
additional information
knockdown and overexpression of Rap2a small GTPase in macrophages resulting in impairment of NF-kappaB activity and inflammatory gene expression
additional information
-
generation of Cdc42-deficient B cells, tamoxifen induction of Cdc42 excision
-
additional information
-
truncation of C-terminal 32 residues leads to dissociation from the plasma membrane and redistribution to the cytosol
additional information
overproduction of GTP or GDP form of Alp41 is toxic to the cell
additional information
-
overproduction of GTP or GDP form of Alp41 is toxic to the cell
additional information
-
overproduction of GTP or GDP form of Alp41 is toxic to the cell
-
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GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
the purified recombinant His6-tagged enzyme is stable only for 3.5 hours
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STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-70°C, 50 mM Tris-HCl, 10 mM MgCl2, 1 mM dithiothreitol, 0.5% glycerol, pH 7.6, 50% glycerol
-
-70°C, 50 mM Tris-HCl, pH 7.5, 0.01 mM GDP, 150 mM NaCl, 1 mM Mg2+, 1 mM DTT, 10% glycerol, v/v
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PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
DEAE cellulose chromatography, heparin-Sepharose column chromatography, and Q-Sepharose column chromatography
-
glutathione-Sepharose bead chromatography
GppNHp-bound Rab27a in complex with the Rab27-binding domain of exophilin4/Slp2-a effector, glutathione Sepharose 4B resin chromatography and Superdex-75 gel filtration
-
GST-tagged Rheb by glutathione affinity chromatography, recombinant enzyme from HEK-293 cells by tandem affinity purification through IgG-binding and anti-Flag affinity chromatography
Ni-NTA column chromatography and Enrich SEC 70 gel filtration
Q Sepharose column chromatography, ammonium sulfate precipitation, glutathione 4B-Sepharose bead chromatography, and Superdex 200 gel filtration
-
recombinant enzymes, affinity chromatography
recombinant glutathione S-transferase (GST)-Wrch- and hexa-histidine (His6)-tagged Wrch-1 protein from Escherichia coli
-
recombinant GST-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3)pLysS by glutathione affinity chromatography, the GST-tag is removed by thrombin cleavage, followed by heparin affinity chromatography, DnaK removal by ATP affinity chromatography, and dialysis
-
recombinant GST-tagged wild-type and mutant enzymes from HEK cells by glutathione affinity chromatography. Purification GST-TBCD with or withoout ARL2 from HEK cells results in the co-purification of different combinations of tubulins in novel complexes
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His6-tagged enzyme from Escherichia coli strain Rosetta by nickel affinity chromatography and blue native PAGE
recombinant N-terminally GST-tagged wild-type and mutant enzymes from Escherichia coli Rosetta (DE3) by glutathione affinity chromatography
recombinant N-terminally His6-tagged TbArl6 by affinity chromatgraphy and gelfiltration
the cytosolic G domain of psToc34 (lacking the C-terminal membrane anchor) is purified mainly in the GDP-bound form after recombinant protein production in Escherichia coli
Ni-NTA column chromatography and Enrich SEC 70 gel filtration
A0A135VL07
Ni-NTA column chromatography and Enrich SEC 70 gel filtration
-
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by nickel affinity chromatography
-
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CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of rhoB mRNA level by semi-quantitative real-time RT-PCR
coexpression of GFP-LC3 and either Sar1 wild-type or the mutants Sar1 H79G or Sar1 T39N in CHO cells, effect of overexpression of Sar1 and its mutants in the secretory pathway, overview. Overexpression of GFP-tagged Rab1b wild-type or mutant Rab1b in CHO cells. Overexpression of GFP-tagged Rab1b N121I mutant in Vero monkey cells and human HaCaT cells
-
complete coding sequence of ARL9, from testis, maps to chromosome 4q12
complete coding sequence of RASL11A, from prostate, maps to chromosome 13q12.2
determination of transcriptional expression profiles of monomeric GTPases, analysed by real-time quantitative reverse transcription-PCR
-
expressed in Escherichia coli
expressed in Escherichia coli BL21 cells
expressed in Escherichia coli BL21(DE3) LysS cells. Three crystal structures of Rab27b-GDP were solved in three different space groups: P6522, C2 and P212121
-
expressed in Escherichia coli BL21(DE3) or BL21-CodonPlus (DE3)-RIL cells
expressed in Escherichia coli BL21-Codon-Plus(DE3) cells, and in MDCKII and Flp-In-293 cells
-
expressed in Escherichia coli strain BL21(DE3)
expression in Escherichia coli
expression in Sf9 cells
gene PfG, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic tree, RT-PCR enzyme expression analysis, recombinant expression of His6-tagged enzyme in Escherichia coli strain Rosetta, subcloning in Escherichia coli strain NEB 5-alpha
gene RAB13, semiquantitative RT-PCR and quantitative real-time PCR expression analysis
gene rac1, DNA and amino acid sequence determination and analysis, sequence comparisons and phylogenetic analysis, real-time PCR enzyme expression analysis
-
gene YPT1, recombinant expression of GST-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3)pLysS
-
heterologous expression of RhoA in Xenopus laevis oocytes. Expression of constitutively active RhoA in primary culture of spinal motoneurons also drastically reduces high-voltage-activated Ca2+ current amplitude
OsRac1, DNA and amino acid sequence determination and analysis, recombinant expression of N-terminally GST-tagged wild-type and mutant enzymes in Escherichia coli Rosetta (DE3), transient coexpression of OsRac1 andthe NADPH oxidase OsRbohB in Nicotiana benthamiana leaves enhancing ROS production
production of Entamoeba histolytica transformants overexpressing EhRab11B
-
quantitative RT-PCR enzyme expression analysis, cotransfection of the NF-kappaB reporter with TLR2, TLR3, and TLR4, CD14, MD2 and Rap2a encoding plasmids into HEK-293 cells, and further treating the cells with the TLR ligands
Rab1A, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rab1B, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rab21 cDNA from K-562 cell, expression in HeLa cells CCL-2 and in hepatocellular carcinoma Hep3B cells
Rab2A, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rab2B, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rab6A, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rab8B, genome-wide screening for human Rabs that are involved in Golgi morphology in HeLa-S3 cells using specific siRNAs
Rac1, expression in Escherichia coli as glutathione S-transferase fusion protein
Rac2, expression in Escherichia coli as glutathione S-transferase fusion protein
Rac3, expression in Escherichia coli as glutathione S-transferase fusion protein
recombinant expression of dual tagged Rheb in HEK-293 cells or of GST-tagged Rheb
recombinant expression of enzyme mutants FgRac1-G17V/D123A and FgCdc42-G15V/D121A in Saccharomyces cerevisiae strain AH109 in the yeast two-hybrid assay
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
recombinant expression of GST-tagged RhoA wild-type (amino acids 1-193) in Escherichia coli
recombinant expression of H-Ras wild-type (amino acids 2-189) and H-Ras mutant Q61G (amino acids 2-189) in Escherichia coli
recombinant expression of HA- and GST-tagged wild-type and mutant enzymes in HEK cells, recombinant optimized expression of Arl2 in HeLa cells
recombinant expression of His6-tagged Alp41 in Escherichia coli, coexpression with activator Tbc1. HAT-tagged Tbc1 coimmunoprecipitates with GFP-tagged Alp41
recombinant expression of K-Ras wild-type (amino acids 2-189) in Escherichia coli
recombinant expression of Raichu-OsRac1 in rice protoplasts from strain C5924 with high efficiency
recombinant expression of the enzyme
A0A2H3GRH7, A0A098DKM1, I1R9M1, A0A2H3FHS0, Q4I2W2, A0A098E0E9
recombinant expression of the enzyme in Escherichia coli strain BL21(DE3)
recombinant expression of the His-tagged enzyme in Escherichia coli strain BL21(DE3)
wild-type and mutant Rab27a cDNA, expression in Escherichia coli BL21 and in 293T cells, expression of mutant Rab27a in the mouse melanocyte cell line melan-a
-
expression in Escherichia coli
-
recombinant expression of the His-tagged enzyme in Escherichia coli strain BL21(DE3)
recombinant expression of the His-tagged enzyme in Escherichia coli strain BL21(DE3)
-
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
8CPT-2Me-cAMP suppresses GTP-RhoA levels
expression levels of Rap2a in macrophages might be tightly regulated to avoid unbalanced immune response
hRAB37 is downregulated mainly by promoter hypermethylation in lung cancer cells
knockdown of Rab isoform Rab2A induces fragmentation of the Golgi in HeLa-S3 cells, its phenotype is rescued by re-expression of its siRNA-resistant Rab construct alone, not by any of the other five Rab isozymes
overexpression of any type of Rhebs (wild-type, constitutively active form, and dominant-negative form) does not affect the intact microtubule structure, and the vesicle-formed Rheb does not co-localize with the microtubule network
putative activator TLR-inducible Ras guanine exchange factor RasGEF1b is sufficient to induce, it is not fully required for Rap2a activation. In contrast to mRNA levels, Rap2a protein levels are increased after lipopolysaccharide treatments of macrophages
Rab13 is the most significantly upregulated gene in pterostilbene-treated human umbilical VECs (HUVECs)
RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediate early gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and genotoxic agents. Clostridial glucosylating toxins evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. Long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. Deamidase-deficient CNF1-C866S fails to activate the rhoB promoter, CNF1-C866S only faintly induces expression of rhoB mRNA and RhoB protein. Critical role of Rac1 in CNF1-induced RhoB expression, overview
RhoB is the only member of the Rho subfamily of small GTPases, which is classified as an immediateearly gene product. RhoB is up-regulated in response to growth factors as well as cytotoxic and geno-toxic agents. Clostridial glucosylating toxins evoke pronounced RhoB expression, based on the inactivation of Rho/Ras proteins. Long lasting expression of RhoB in cultured cells upon activation of Rho proteins by the cytotoxic necrotizing factor 1 (CNF1) from Escherichia coli. CNF1-induced RhoB expression in primary and immortalized NIH3T3 fibroblasts. Deamidase-deficient CNF1-C866S fails to activate the rhoB promoter, CNF1-C866S only faintly induces expression of rhoB mRNA and RhoB protein. Critical role of Rac1 in CNF1-induced RhoB expression, overview
si-Rap1 augments GTP-RhoA levels and cell migration. si-RNAs of Epac1 and Epac2 reduced GTP-Rap1 levels leading to promotion of GTP-RhoA levels. si-RNA of ARAP3 (Rap-dependent RhoGAP) increased GTP-RhoA level and cell migration
si-RNAs of Epac1 and Epac2 reduced GTP-Rap1 levels
the transcriptional expression level of Pc-Rac1 is significantly upregulated in hemocytes and hepatopancreas after lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (poly I:C) induction. Induced expression pattern of Pc-Rac1 in various tissues by immunostimulating challenges
-
si-Rap1 augments GTP-RhoA levels and cell migration. si-RNAs of Epac1 and Epac2 reduced GTP-Rap1 levels leading to promotion of GTP-RhoA levels. si-RNA of ARAP3 (Rap-dependent RhoGAP) increased GTP-RhoA level and cell migration
si-Rap1 augments GTP-RhoA levels and cell migration. si-RNAs of Epac1 and Epac2 reduced GTP-Rap1 levels leading to promotion of GTP-RhoA levels. si-RNA of ARAP3 (Rap-dependent RhoGAP) increased GTP-RhoA level and cell migration
-
-
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APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
nucleotide exchange kinetics with small GTPases can be used to obtain important information about the binding kinetics of GTP molecules under different activation states and with different activator molecules
drug development
medicine
pharmacology
the enzyme is a pharmacological target for the treatment of cardiovascular diseases
drug development
the enzyme Der may be an ideal cellular target against which antibiotics can be developed, lead compounds inhibiting Der GTPase provide scaffolds for the development of antibiotics against antibiotic-resistant pathogenic bacteria
drug development
the enzyme Der may be an ideal cellular target against which antibiotics can be developed, lead compounds inhibiting Der GTPase provide scaffolds for the development of antibiotics against antibiotic-resistant pathogenic bacteria
drug development
the enzyme Der may be an ideal cellular target against which antibiotics can be developed, lead compounds inhibiting Der GTPase provide scaffolds for the development of antibiotics against antibiotic-resistant pathogenic bacteria
drug development
-
the enzyme Der may be an ideal cellular target against which antibiotics can be developed, lead compounds inhibiting Der GTPase provide scaffolds for the development of antibiotics against antibiotic-resistant pathogenic bacteria
medicine
-
Rab27a is associated with the Griscelli syndrome type 2, mutations in the Rab27a gene cause pigment as well as cytotoxic granule transport defects, accounting for the partial albinism and severe immune disorder characteristics of this syndrome
medicine
-
regulation of small Rho GTPases might serve as a new pharmacological tool for protection of dendridic cell vaccines from tumor-induced inhibition and functional failure
medicine
-
small Rho GTPases might serve as new targets for modulating functional activity of dendritic cell vaccines or endogenous dendritic cells in various immunotherapeutic or chemoimmunotherapeutic strategies
medicine
neither the overall survival nor the disease-free survival rate in diffuse large B-cell lymphoma can be linked to hypermutation of the RHOH gene
medicine
neither the overall survival nor the disease-free survival rate in diffuse large B-cell lymphoma can be linked to hypermutation of the RHOH gene
EXTERNAL LINKS (specific for EC-Number 3.6.5.2)
Transporter Classification Database (TCDB): 8.A.92.1.15, 9.A.3.1.1
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Release 2026.1 (March 2026)
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