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Information on EC 3.6.5.2 - small monomeric GTPase and Organism(s) Homo sapiens and UniProt Accession P60763

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IUBMB Comments
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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Homo sapiens
UNIPROT: P60763
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
k-ras, cdc42, h-ras, small gtpase, ef-tu, rho gtpase, rab11, rab3a, rab27a, rap1a, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
small GTPase
-
ADP-ribosylation factor 6
UniProt
ADP-ribosylation factor-like protein 2
UniProt
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
-
-
Arl6
-
-
Arl9
ADP-ribosylation factor-like 9
Cdc42
Cdc42Hs
-
Rho subfamily
GCC185
-
-
Gem
-
Ras-related, involved in receptor-mediated signal transduction at the plasma membrane
GTP-phosphohydrolase
-
-
-
-
GTPase
-
-
-
-
guanine triphosphatase
-
-
-
-
guanosine 5'-triphosphatase
-
-
-
-
guanosine triphosphatase
-
-
-
-
Kir
-
Ras-related, involved in processes of invasion or metastasis in mammalia cells
Krev-1
-
-
monomeric G protein
-
-
monomeric GTPase
-
-
p21 ras
-
-
Rab15
-
isoform
Rab1a
Rab1B
Rab27a
-
-
Rab27B
-
isoform
Rab2A
Rab2B
Rab30
-
isoform
Rab33A
-
isoform
Rab35
-
isoform
Rab36
-
isoform
Rab4a
-
-
Rab6A
Rab9A
-
isoform
Rab9B
-
isoform
Rad GTPase
-
-
RalB
-
-
Rap GTPase
-
-
Rap1A
-
-
Rap2
-
Ras-related
Rap2C
-
-
Ras GTPase
-
-
Ras homolog enriched in brain-like protein 1
-
Ras related GTPase Rap
-
-
Ras-associated protein 1
-
-
Ras-related small GTPase
-
-
RasL10B
-
-
Rasl11a
RAS-like, family 11, member A
Rheb GTPase
-
Rho GTPase
-
-
RhoGTPase
RhoH
initially named translation three four, RhoH is a GTPase-deficient so-called atypical Rho GTPase, RhoH is only found in vertebrates
ribosomal GTPase
-
-
-
-
Sar1
-
-
small GTPase
small GTPase Rab1
-
-
small GTPase Rab11b
-
-
small GTPase Rac
-
-
small GTPase Ral
-
-
small GTPase Ras-related protein in brain 13
-
small GTPase Rho
-
-
small GTPase RhoA
-
-
small GTPases Rab5
-
-
small GTPases Ral5
-
-
small nuclear GTPase Ran
-
-
small Rho GTPase
-
-
small Rho GTPase Rac1
-
-
Wrch-1
-
-
additional information
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
GTP + H2O = GDP + phosphate
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphorous acid anhydride hydrolysis
-
-
-
-
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).
CAS REGISTRY NUMBER
COMMENTARY hide
9059-32-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
GTP + H2O
GDP + phosphate
show the reaction diagram
GTP + H2O
GDP + phosphate
show the reaction diagram
guanosine 5'-O-(3-thio)triphosphate + H2O
guanosine 5'-diphosphate + thiophosphate
show the reaction diagram
-
-
-
-
?
guanosine 5'-O-(3-thiotriphosphate) + H2O
guanosine 5'-O-diphosphate + thiophosphate
show the reaction diagram
MEK kinase 1 + H2O
?
show the reaction diagram
-
RhoA binds and activates MEK kinase 1
-
-
?
p21-activated kinase 1 + H2O
activated p21-activated kinase 1 + ?
show the reaction diagram
-
Gamide signals Rac/Cdc42 to activate p21-activated kinase 1
-
-
?
Rho-activated kinase + H2O
activated Rho-activated kinase + ?
show the reaction diagram
-
Ggly signals Rac/Cdc42 to activate Rho-activated kinase
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
GTP + H2O
GDP + phosphate
show the reaction diagram
GTP + H2O
GDP + phosphate
show the reaction diagram
p21-activated kinase 1 + H2O
activated p21-activated kinase 1 + ?
show the reaction diagram
-
Gamide signals Rac/Cdc42 to activate p21-activated kinase 1
-
-
?
Rho-activated kinase + H2O
activated Rho-activated kinase + ?
show the reaction diagram
-
Ggly signals Rac/Cdc42 to activate Rho-activated kinase
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
p21 activated kinase
PAK, inhibits nucleotide dissociation from enzyme
-
(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
5'-p-fluorosulfonylbenzoylguanosine
-
irreversible substrate analogue-binding
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
CCG-1423
-
-
CCG-977
-
-
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
Clostridium botulinum exoenzyme C3
-
specific inhibitor
-
EDTA
inhibits nucleotide binding to Ras
GTP
-
inhibition of GTP[S]-binding at increasing concentrations
GTPgammaS
-
Arl6 is competitively inhibited by the increasing concentrations of non-radioactive GTPgammaS
guanine nucleotide dissociation inhibitor GDI
-
down-regulating GTPase activity, inhibition of nucleotide dissociation
-
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-[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
NSC23766
-
not very potent inhibitor of Rac1 and Cdc42
p21 activated kinase
PAK, inhibits nucleotide dissociation from enzyme
-
Rap1Gap
-
the GTPase activating protein catalyzes the hydrolysis of GTP by its asparagine side chain rendering Rap1 inactive
-
Rap1GAP1
-
a GTPase-activating protein that inhibits Rap1 activity
-
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
-
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
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
Rac-specific GEF Tiam1
activates Rac3, but less efficiently than the Rac isoform Rac2
-
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
-
angiotensin II
stimulates Rac1 as cardiovascular stimulus
C3G guanine nucleotide exchange factor
-
-
-
CalDAG-GEF
-
a guanine nucleotide exchange factor
-
cAMP
-
-
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
-
diacylglycerol
-
-
Ect2cat
RhoA activation
-
endothelin-1
stimulates Rac1 as cardiovascular stimulus
Epidermal growth factor
stimulates Rac1 as cardiovascular stimulus
farnesylthiosalicylic acid
-
markedly enhances RhoA level and activity
forskolin
-
the adenylyl cyclase activator strongly and specifically activates Rap1 in microvascular smooth muscle cells
GTPase activating protein GAP
-
guanine nucleotide exchange factor Epac
-
specifically increases Rap1 activity
-
guanine nucleotide exchange factor GEF
-
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
-
heparin-binding epidermal growth factor-like growth factor
-
induces rapid and strong RhoA activation
-
Insulin
-
activation of Rac, assembly of actin filaments
-
Insulin-like growth factor
stimulates Rac1 as cardiovascular stimulus
-
interleukin 1beta
stimulates Rac1 as cardiovascular stimulus
-
lysophosphatidic acid
melanophilin
-
Rab27a effector
-
p21-activated kinase 1
-
interacts with Rac and Cdc42
-
PDZ-GEF1
-
a guanine nucleotide exchange factor
-
PDZ-GEF2
-
a guanine nucleotide exchange factor
-
platelet derived growth factor
-
Rac activation, assembly of actin filaments
-
platelet-derived growth factor
stimulates Rac1 as cardiovascular stimulus
-
PLCepsilon
-
a guanine nucleotide exchange factor
-
Prorenin
stimulates Rac1 as cardiovascular stimulus
-
Rac-specific GEF Tiam1
-
Ras
-
cross-talk between Ras- and Rho subfamilies, activation of Rac
-
RasGRP2
-
a guanine nucleotide exchange factor
-
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
-
SOScat
activation of 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
-
thrombin
stimulates Rac1 as cardiovascular stimulus
-
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
vascular endothelial growth factor
stimulates Rac1 as cardiovascular stimulus
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0005
GTP
-
quite low, increased GTP hydrolysis by action of guanine nucleotide release proteins, promoting replacement of bound GDP by GTP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.001
GDP
-
inhibition of binding of GTP[S]
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
0.05
N6-(2-[[5-(diethylamino)pentan-2-yl]amino]-6-methylpyrimidin-4-yl)-2-methylquinoline-4,6-diamine
Homo sapiens
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.001
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
assay at
7.4
assay at
7.6
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
assay at
10
assay at
22
assay at room temperature
25
assay at
30
-
assay at
37
assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
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
Manually annotated by BRENDA team
two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
two isoforms of RASL11A transcript with different sizes of 1.6 and 1.2 kb
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
-
B-EBV lymphoblastoid cell line
Manually annotated by BRENDA team
-
expression of Rap2C may be down-regulated diring the late phase of megakaryocyte differentiation and platelet formation
Manually annotated by BRENDA team
-
Rho-mediated signaling in osteoblasts seems to introduce major biases to bone resorption
Manually annotated by BRENDA team
very weak expression of RASL11A
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team
-
small Rho GTPases are important for acinus formation
Manually annotated by BRENDA team
-
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
Manually annotated by BRENDA team
RhoH is expressed strongest in T-lymphocytes and acts as a positive regulatory factor for thymocyte selection and T-cell receptor signalling
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
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
Manually annotated by BRENDA team
-
Rab1b-labeled vesicles, distribute peripherally from the Golgi perinuclear area
-
Manually annotated by BRENDA team
-
human Mammarian enabled protein colocalizes with Rac1 in lamellipodia
Manually annotated by BRENDA team
part of invadosomes, specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities
Manually annotated by BRENDA team
colocalization with tissue inhibitor of metalloproteinase 1 (TIMP1)
Manually annotated by BRENDA team
additional information
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
evolution
the enzyme belongs to the superfamily of small GTPase proteins
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
evolution
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
RAC3_HUMAN
192
0
21379
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20000
recombinant Arl2, gel filtration
200000
Arl2-TBCD-tubulin complex, gel filtration
22000
-
SDS-PAGE
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
51000
x * 51000, GFP-Rab21, SDS-PAGE
additional information
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 51000, GFP-Rab21, SDS-PAGE
dimer
-
complex of 1 * 23000 for Cdc42Hs + 1 * 26000 for regulatory protein LyGDL, SDS-PAGE, immunostaining
monomer
-
1 * 22000, SDS-PAGE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
lipoprotein
phosphoprotein
side-chain modification
additional information
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
1.65 A resolution, complex of RhoA-rhoGAP with the transition-state analogue GDPAIF4-, hanging drop vapour diffusion technique
-
Arf1 complexed to GDP, common G domain topology
-
complex of Cdc42Hs-GMPP-NP-RhoGAP
-
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
-
hanging-drop method, Rad in the GDP-bound form at 1.8 A resolution
-
hanging-drop vapor-diffusion method, Rab11b-GDP and Rab11b-GppNHp crystal structures solved to 1.55 and 1.95 A resolution, respectively
-
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
-
Rac1, active conformation
-
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
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
A152P
-
mutation dramatically affects both GTP and GDP nucleotide-binding activity of Rab27a, probably by disrupting protein folding
chimeras between RhoA/Cdc42
-
residues 85-122 contain specific binding determinants for guanosine nucleotide activating protein, p190
D60I
site-directed mutagenesis
D60K
site-directed mutagenesis
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
Q89L
site-directed mutagenesis, a GTP-bound active mutant
S88D
-
Cdc42, enhancement of GTP-hydrolysis
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
T35A
-
Rap1A, blocks abilitiy of Rap-GAP to stimulate GTP hydrolysis
T39N
-
a dominant-negative Sar1 mutant, expression induces Golgi fragmentation as indicated by Rab6 dispersion and inhibits autophagosome formation
T43N
site-directed mutagenesis, a GDP-bound inactive mutant
W269G
-
Kir/Gem peptide, abolish affinity for dansyl-calmodulin
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
additional information
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-80°C, little loss of activity, several weeks
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant Rac3
glutathione Sepharose 4B column chromatography
-
glutathione-agarose bead 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
GTPase core domain overexpressed in Escherichia coli
-
GTPase domain of human Rheb recombinantly expressed in Escherichia coli
-
Q Sepharose column chromatography, ammonium sulfate precipitation, glutathione 4B-Sepharose bead chromatography, and Superdex 200 gel filtration
-
recombinant
-
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 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 Rac1
recombinant Rac2
recombinant wild-type and mutant Rab27a
-
to homogeneity, chromatography techniques
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
Rac3, expression in Escherichia coli as glutathione S-transferase fusion protein
analysis of rhoB mRNA level by semi-quantitative real-time RT-PCR
Cdc42, expression in Escherichia coli
-
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
expressed in Escherichia coli
-
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli BL21(DE3) 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 COS-7 cells
-
expression in COS7 cells
expression in Escherichia coli
-
expression in Sf9 cells
-
gene RAB13, semiquantitative RT-PCR and quantitative real-time PCR expression analysis
gene rad, recombinant expression of GST-tagged Rad in Escherichia coli
-
GTPase core domain is overexpressed in Escherichia coli
-
GTPase domain of human Rheb recombinantly expressed in Escherichia coli
-
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
recombinant expression of dual tagged Rheb in HEK-293 cells or of GST-tagged Rheb
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 K-Ras wild-type (amino acids 2-189) in Escherichia coli
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
ORGANISM
UNIPROT
LITERATURE
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
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pharmacology
the enzyme is a pharmacological target for the treatment of cardiovascular diseases
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
medicine
pharmacology
the enzyme is a pharmacological target for the treatment of cardiovascular diseases
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sauvage, C.; Rumigny, J.F.; Maitre, M.
Purification and characterization of G proteins from human brain: modification of GTPase activity upon phosphorylation
Mol. Cell. Biochem.
107
65-77
1991
Homo sapiens
Manually annotated by BRENDA team
Haberland, J.; Gerke, V.
Conserved charged residues in the leucin-rich repeat domain of the Ran GTPase activating protein are required for Ran binding and GTPase activation
Biochem. J.
343
653-662
1999
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Illenberger, D.; Schwald, F.; Pimmer, D.; Binder, W.; Maier, G.; Dietrich, A.; Gierschik, P.
Stimulation of phospholipase C-beta2 by the Rho GTPases Cdc42Hs and Rac1
EMBO J.
17
6241-6249
1998
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Gamblin S.J.; Smerdon, S.J.
GTPase-activating proteins and their complexes
Curr. Opin. Struct. Biol.
8
195-201
1998
Homo sapiens
Manually annotated by BRENDA team
Hall, A.
Rho GTPases and the actin cytoskeleton
Science
279
509-514
1998
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Vitale, N.; Moss, J.; Vaughan, M.
Molecular characterization of the GTPase-activating domain of ADP-ribosylation factor domain protein 1 (ARD1)
J. Biol. Chem.
273
2553-2560
1998
Homo sapiens
Manually annotated by BRENDA team
Rittinger, K.; Walker, P.A.; Eccleston, J.F.; Smerdon, S.J.; Gamblin, S.J.
Structure at 1.65 A of RhoA and its GTPase-activating protein in complex with a transition-state analogue
Nature
389
758-762
1997
Homo sapiens
Manually annotated by BRENDA team
Polakis, P.G.; Rubinfeld, B.; Evans, T.; McCormick, F.
Purification of a plasma membrane-associated GTPase-activating protein specific for rap1/Krec-1 from HL60 cells
Proc. Natl. Acad. Sci. USA
88
239-243
1991
Homo sapiens
Manually annotated by BRENDA team
Janoueix-Lerosey, I.; Polakis, P.; Tavitian, A.; de Gunzburg, J.
Regulation of the GTPase activity of the Ras-related Rap2 protein
Biochem. Biophys. Res. Commun.
189
455-464
1992
Homo sapiens
Manually annotated by BRENDA team
Geyer, M.; Wittinghofer, A.
GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding protein
Curr. Opin. Struct. Biol.
7
786-792
1997
Bos taurus, Homo sapiens, Rattus sp.
Manually annotated by BRENDA team
Fischer, R.; Wei, Y.; Anagli, J.; Berchtold, M.W.
Calmodulin binds to and inhibits GTP binding of the Ras-like GTPase Kir/Gem
J. Biol. Chem.
271
25067-25070
1996
Homo sapiens
Manually annotated by BRENDA team
Li, R.; Zhang, B.; Zheng, Y.
Structural determinants required for the interaction between Rho GTPase and the GTPase-activating domain p190
J. Biol. Chem.
272
32830-32835
1997
Homo sapiens
Manually annotated by BRENDA team
Jones, S.; Litt, R. J.; Richardson, C.J.; Segev, N.
Requirement of nucleotide exchange factor for Ypt1 GTPase mediated protein transport
J. Cell Biol.
130
1051-1061
1995
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Quilliam, L.A.; Der, C.J.; Clark, R.; O'Rourke, E.C.; Zhang, K.; McCormick, F.; Bokoch, G.M.
Biochemical characterization of baculovirus-expressed rap1A/Krev-1 and its regulation by GTPase-activating proteins
Mol. Cell. Biol.
10
2901-2908
1990
Homo sapiens
Manually annotated by BRENDA team
Bourne, H.R.; Sanders, D.A.; McCormick, F.
The GTPase superfamily: conserved structure and molecular mechanism
Nature
349
117-127
1991
Saccharomyces cerevisiae, Oryctolagus cuniculus, Escherichia coli, Homo sapiens, Escherichia coli EF-Tu
Manually annotated by BRENDA team
Zhao, J.; Wang, W.N.; Tan, Y.C.; Zheng, Y.; Wang, Z.X.
Effect of Mg2+ on the kinetics of guanine nucleotide binding and hydrolysis by Cdc42
Biochem. Biophys. Res. Commun.
297
653-658
2002
Homo sapiens
Manually annotated by BRENDA team
Louro, R.; Nakaya, H.I.; Paquola, A.C.; Martins, E.A.; da Silva, A.M.; Verjovski-Almeida, S.; Reis, E.M.
RASL11A, member of a novel small monomeric GTPase gene family, is down-regulated in prostate tumors
Biochem. Biophys. Res. Commun.
316
618-627
2004
Homo sapiens (Q6T310), Homo sapiens (Q6T311), Homo sapiens
Manually annotated by BRENDA team
Menasche, G.; Feldmann, J.; Houdusse, A.; Desaymard, C.; Fischer, A.; Goud, B.; de Saint Basile, G.
Biochemical and functional characterization of Rab27a mutations occurring in Griscelli syndrome patients
Blood
101
2736-2742
2003
Homo sapiens
Manually annotated by BRENDA team
Haeusler, L.C.; Blumenstein, L.; Stege, P.; Dvorsky, R.; Ahmadian, M.R.
Comparative functional analysis of the Rac GTPases
FEBS Lett.
555
556-560
2003
Homo sapiens, Homo sapiens (P60763)
Manually annotated by BRENDA team
Wennerberg, K.; Der, C.J.
Rho-family GTPases: It's not only Rac and Rho (and I like it)
J. Cell Sci.
117
1301-1312
2004
Homo sapiens
Manually annotated by BRENDA team
Simpson, J.C.; Griffiths, G.; Wessling-Resnick, M.; Fransen, J.A.; Bennett, H.; Jones, A.T.
A role for the small GTPase Rab21 in the early endocytic pathway
J. Cell Sci.
117
6297-6311
2004
Homo sapiens (Q9UL25), Homo sapiens
Manually annotated by BRENDA team
Yu, Y.; Chang, Y.; Li, S.; Hu, H.; Huang, Q.; Ding, J.
Expression, purification, crystallization and preliminary structural characterization of the GTPase domain of human Rheb
Acta Crystallogr. Sect. D
D60
1883-1887
2004
Homo sapiens
Manually annotated by BRENDA team
Yanuar, A.; Sakurai, S.; Kitano, K.; Hakoshima, T.
Expression, purification, crystallization and preliminary crystallographic analysis of human Rad GTPase
Acta Crystallogr. Sect. F
F61
978-980
2005
Homo sapiens
Manually annotated by BRENDA team
Paganini, S.; Guidetti, G.F.; Catricala, S.; Trionfini, P.; Panelli, S.; Balduini, C.; Torti, M.
Identification and biochemical characterization of Rap2C, a new member of the Rap family of small GTP-binding proteins
Biochimie
88
285-295
2006
Homo sapiens
Manually annotated by BRENDA team
Zou, H.; Hu, L.; Li, J.; Zhan, S.; Cao, K.
Cloning and characterization of a novel small monomeric GTPase, RasL10B, with tumor suppressor potential
Biotechnol. Lett.
28
1901-1908
2006
Homo sapiens
Manually annotated by BRENDA team
Huber, S.K.; Scheidig, A.J.
High resolution crystal structures of human Rab4a in its active and inactive conformations
FEBS Lett.
579
2821-2829
2005
Homo sapiens
Manually annotated by BRENDA team
Yanuar, A.; Sakurai, S.; Kitano, K.; Hakoshima, T.
Crystal structure of human Rad GTPase of the RGK-family
Genes Cells
11
961-968
2006
Homo sapiens
Manually annotated by BRENDA team
Shutes, A.; Berzat, A.C.; Chenette, E.J.; Cox, A.D.; Der, C.J.
Biochemical analyses of the Wrch atypical Rho family GTPases
Methods Enzymol.
406
11-26
2006
Homo sapiens
Manually annotated by BRENDA team
Yuan, J.; Shan, Y.; Chen, X.; Tang, W.; Luo, K.; Ni, J.; Wan, B.; Yu, L.
Identification and characterization of RHEBL1, a novel member of Ras family, which activates transcriptional activities of NF-kappa B
Mol. Biol. Rep.
32
205-214
2005
Homo sapiens (Q8TAI7)
Manually annotated by BRENDA team
Li, Y.; Inoki, K.; Guan, K.L.
Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity
Mol. Cell. Biol.
24
7965-7975
2004
Homo sapiens
Manually annotated by BRENDA team
Hirai, F.; Nakayamada, S.; Okada, Y.; Saito, K.; Kurose, H.; Mogami, A.; Tanaka, Y.
Small GTPase Rho signaling is involved in beta1 integrin-mediated up-regulation of intercellular adhesion molecule 1 and receptor activator of nuclear factor kappaB ligand on osteoblasts and osteoclast maturation
Biochem. Biophys. Res. Commun.
356
279-285
2007
Homo sapiens
Manually annotated by BRENDA team
Nikolova, E.; Mitev, V.; Zhelev, N.; Deroanne, C.F.; Poumay, Y.
The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc
Biochem. Biophys. Res. Commun.
359
834-839
2007
Homo sapiens
Manually annotated by BRENDA team
Liao, J.; Shima, F.; Araki, M.; Ye, M.; Muraoka, S.; Sugimoto, T.; Kawamura, M.; Yamamoto, N.; Tamura, A.; Kataoka, T.
Two conformational states of Ras GTPase exhibit differential GTP-binding kinetics
Biochem. Biophys. Res. Commun.
369
327-332
2008
Homo sapiens, Mus musculus, Suberites domuncula (A1XKQ5), Suberites domuncula (A1XKQ6), Suberites domuncula (A1XKQ7), Suberites domuncula (A1XKQ8), Suberites domuncula (A1XKQ9), Suberites domuncula (A1XKR0), Suberites domuncula (A1XKR1), Suberites domuncula (A1XKR2), Suberites domuncula (A1XKR3), Suberites domuncula (A1XKR5), Suberites domuncula (A1XKR6), Suberites domuncula (A1XKR7), Suberites domuncula (A1XKR8), Suberites domuncula (A1XKR9), Suberites domuncula (A1XKS0), Suberites domuncula (A1XKS1), Suberites domuncula (A1XKS2), Suberites domuncula (A1XKS3), Suberites domuncula (A1XKS4), Suberites domuncula (A1XKS5), Suberites domuncula (A1XKS6), Suberites domuncula (A1XKS7), Suberites domuncula (A1XKS8), Suberites domuncula (A1XKS9), Suberites domuncula (A1XKT0), Suberites domuncula (A1XKT1), Suberites domuncula (A1XKT2), Suberites domuncula (A1XKT3), Suberites domuncula (A1XKT4), Suberites domuncula (A1XKT5), Suberites domuncula (A1XKT6), Suberites domuncula (A1XKT7), Suberites domuncula (A1XKT8), Suberites domuncula (A1XKT9), Suberites domuncula (A1XKU0), Suberites domuncula (A1XKU1), Suberites domuncula (A1XKU2), Suberites domuncula (A1XKU3), Suberites domuncula (A1XKU4), Suberites domuncula (A1XKU5), Suberites domuncula (O97342), Suberites domuncula (Q4H115), Suberites domuncula (Q4H116)
Manually annotated by BRENDA team
Fu, D.; van Dam, E.M.; Brymora, A.; Duggin, I.G.; Robinson, P.J.; Roufogalis, B.D.
The small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein
Biochim. Biophys. Acta
1773
1062-1072
2007
Homo sapiens
Manually annotated by BRENDA team
Miyano, K.; Sumimoto, H.
Role of the small GTPase Rac in p22phox-dependent NADPH oxidases
Biochimie
89
1133-1144
2007
Homo sapiens
Manually annotated by BRENDA team
de Gorter, D.J.; Reijmers, R.M.; Beuling, E.A.; Naber, H.P.; Kuil, A.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.
The de Gorter, D.J.; Reijmers, R.M.; Beuling, E.A.; Naber, H.P.; Kuil, A.; Kersten, M.J.; Pals, S.T.; Spaargaren, M.: The small GTPase Ral mediates SDF-1-induced migration of B cells and multiple myeloma cells
Blood
111
3364-3372
2008
Homo sapiens
Manually annotated by BRENDA team
Burguete, A.S.; Fenn, T.D.; Brunger, A.T.; Pfeffer, S.R.
Rab and Arl GTPase family members cooperate in the localization of the golgin GCC185
Cell
132
286-298
2008
Homo sapiens
Manually annotated by BRENDA team
Crema, V.O.; Hamassaki, D.E.; Santos, M.F.
Small Rho GTPases are important for acinus formation in a human salivary gland cell line
Cell Tissue Res.
325
493-500
2006
Homo sapiens
Manually annotated by BRENDA team
Martinez-Salgado, C.; Rodriguez-Pena, A.B.; Lopez-Novoa, J.M.
Involvement of small Ras GTPases and their effectors in chronic renal disease
Cell. Mol. Life Sci.
65
477-492
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Selvakumar, B.; Hess, D.T.; Goldschmidt-Clermont, P.J.; Stamler, J.S.
Co-regulation of constitutive nitric oxide synthases and NADPH oxidase by the small GTPase Rac
FEBS Lett.
582
2195-2202
2008
Homo sapiens
Manually annotated by BRENDA team
Miyano, K.; Ueno, N.; Takeya, R.; Sumimoto, H.
Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1
J. Biol. Chem.
281
21857-21868
2006
Homo sapiens
Manually annotated by BRENDA team
Kawato, M.; Shirakawa, R.; Kondo, H.; Higashi, T.; Ikeda, T.; Okawa, K.; Fukai, S.; Nureki, O.; Kita, T.; Horiuchi, H.
Regulation of platelet dense granule secretion by the Ral GTPase-exocyst pathway
J. Biol. Chem.
283
166-174
2008
Homo sapiens
Manually annotated by BRENDA team
Dada, L.A.; Novoa, E.; Lecuona, E.; Sun, H.; Sznajder, J.I.
Role of the small GTPase RhoA in the hypoxia-induced decrease of plasma membrane Na,K-ATPase in A549 cells
J. Cell Sci.
120
2214-2222
2007
Homo sapiens
Manually annotated by BRENDA team
Scapin, S.M.; Carneiro, F.R.; Alves, A.C.; Medrano, F.J.; Guimaraes, B.G.; Zanchin, N.I.
The crystal structure of the small GTPase Rab11b reveals critical differences relative to the Rab11a isoform
J. Struct. Biol.
154
260-268
2006
Homo sapiens
Manually annotated by BRENDA team
Koziel, H.
Rho GTPases in alveolar macrophage phagocytosis
Methods Enzymol.
439
303-313
2008
Homo sapiens
Manually annotated by BRENDA team
Clarke, P.R.; Zhang, C.
Spatial and temporal coordination of mitosis by Ran GTPase
Nat. Rev. Mol. Cell Biol.
9
464-477
2008
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Kobayashi, T.; Hori, Y.; Ueda, N.; Kajiho, H.; Muraoka, S.; Shima, F.; Kataoka, T.; Kontani, K.; Katada, T.
Biochemical characterization of missense mutations in the Arf/Arl-family small GTPase Arl6 causing Bardet-Biedl syndrome
Biochem. Biophys. Res. Commun.
381
439-442
2009
Homo sapiens
Manually annotated by BRENDA team
Fenwick, R.; Prasannan, S.; Campbell, L.; Nietlispach, D.; Evetts, K.; Camonis, J.; Mott, H.; Owen, D.
Solution structure and dynamics of the small GTPase RalB in its active conformation: significance for effector protein binding
Biochemistry
48
2192-2206
2009
Homo sapiens
Manually annotated by BRENDA team
Li, H.; Ung, C.Y.; Ma, X.H.; Li, B.W.; Low, B.C.; Cao, Z.W.; Chen, Y.Z.
Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1
Bioinformatics
25
358-364
2009
Homo sapiens
Manually annotated by BRENDA team
Carmona, G.; Goettig, S.; Orlandi, A.; Scheele, J.; Baeuerle, T.; Jugold, M.; Kiessling, F.; Henschler, R.; Zeiher, A.M.; Dimmeler, S.; Chavakis, E.
Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis
Blood
113
488-497
2009
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Nie, D.; Guo, Y.; Yang, D.; Tang, Y.; Chen, Y.; Wang, M.T.; Zacharek, A.; Qiao, Y.; Che, M.; Honn, K.V.
Thromboxane A2 receptors in prostate carcinoma: expression and its role in regulating cell motility via small GTPase Rho
Cancer Res.
68
115-121
2008
Homo sapiens
Manually annotated by BRENDA team
Fueller, F.; Kubatzky, K.F.
The small GTPase RhoH is an atypical regulator of haematopoietic cells
Cell Commun. Signal.
6
6-6
2008
Homo sapiens (Q15669), Homo sapiens, Mus musculus (Q9D3G9), Mus musculus
Manually annotated by BRENDA team
Lu, Q.; Longo, F.M.; Zhou, H.; Massa, S.M.; Chen, Y.H.
Signaling through Rho GTPase pathway as viable drug target
Curr. Med. Chem.
16
1355-1365
2009
Homo sapiens
Manually annotated by BRENDA team
He, H.; Baldwin, G.S.
Rho GTPases and p21-activated kinase in the regulation of proliferation and apoptosis by gastrins
Int. J. Biochem. Cell Biol.
40
2018-2022
2008
Homo sapiens
Manually annotated by BRENDA team
Yin, J.; Lu, J.; Yu, F.S.
Role of small GTPase Rho in regulating corneal epithelial wound healing
Invest. Ophthalmol. Vis. Sci.
49
900-909
2008
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Birukov, K.G.
Small GTPases in mechanosensitive regulation of endothelial barrier
Microvasc. Res.
77
46-52
2009
Homo sapiens
Manually annotated by BRENDA team
Hayes, G.L.; Brown, F.C.; Haas, A.K.; Nottingham, R.M.; Barr, F.A.; Pfeffer, S.R.
Multiple Rab GTPase binding sites in GCC185 suggest a model for vesicle tethering at the trans-Golgi
Mol. Biol. Cell
20
209-217
2009
Homo sapiens
Manually annotated by BRENDA team
Higashi, M.; Ishikawa, C.; Yu, J.; Toyoda, A.; Kawana, H.; Kurokawa, K.; Matsuda, M.; Kitagawa, M.; Harigaya, K.
Human Mena associates with Rac1 small GTPase in glioblastoma cell lines
PLoS ONE
4
e4765
2009
Homo sapiens
Manually annotated by BRENDA team
Fueller, F.; Schmidt, G.
The polybasic region of Rho GTPases defines the cleavage by Yersinia enterocolitica outer protein T (YopT)
Protein Sci.
17
1456-1462
2008
Homo sapiens
Manually annotated by BRENDA team
Jeyaraj, S.C.; Unger, N.T.; Chotani, M.A.
Rap1 GTPases: an emerging role in the cardiovasculature
Life Sci.
88
645-652
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Zoppino, F.C.; Militello, R.D.; Slavin, I.; Alvarez, C.; Colombo, M.I.
Autophagosome formation depends on the small GTPase Rab1 and functional ER exit sites
Traffic
11
1246-1261
2010
Homo sapiens
Manually annotated by BRENDA team
Kopra, K.; Ligabue, A.; Wang, Q.; Syrjaenpaeae, M.; Blazevits, O.; Veltel, S.; van Adrichem, A.J.; Haenninen, P.; Abankwa, D.; Haermae, H.
A homogeneous quenching resonance energy transfer assay for the kinetic analysis of the GTPase nucleotide exchange reaction
Anal. Bioanal. Chem.
406
4147-4156
2014
Homo sapiens (P01112), Homo sapiens (P01116), Homo sapiens (P61586)
Manually annotated by BRENDA team
Lee, M.N.; Koh, A.; Park, D.; Jang, J.H.; Kwak, D.; Jeon, H.; Kim, J.; Choi, E.J.; Jeong, H.; Suh, P.G.; Ryu, S.H.
Deacetylated alphabeta-tubulin acts as a positive regulator of Rheb GTPase through increasing its GTP-loading
Cell. Signal.
25
539-551
2013
Homo sapiens (Q15382)
Manually annotated by BRENDA team
Hsiao, B.Y.; Chang, T.K.; Wu, I.T.; Chen, M.Y.
Rad GTPase inhibits the NFkappaB pathway through interacting with RelA/p65 to impede its DNA binding and target gene transactivation
Cell. Signal.
26
1437-1444
2014
Homo sapiens
Manually annotated by BRENDA team
Huelsenbeck, S.C.; Roggenkamp, D.; May, M.; Huelsenbeck, J.; Brakebusch, C.; Rottner, K.; Ladwein, M.; Just, I.; Fritz, G.; Schmidt, G.; Genth, H.
Expression and cytoprotective activity of the small GTPase RhoB induced by the Escherichia coli cytotoxic necrotizing factor 1
Int. J. Biochem. Cell Biol.
45
1767-1775
2013
Homo sapiens (P62745), Mus musculus (P62746), Mus musculus
Manually annotated by BRENDA team
Aizawa, M.; Fukuda, M.
Small GTPase Rab2B and its specific binding protein Golgi-associated Rab2B interactor-like 4 (GARI-L4) regulate Golgi morphology
J. Biol. Chem.
290
22250-22261
2015
Homo sapiens (P61006), Homo sapiens (P61019), Homo sapiens (P62820), Homo sapiens (Q8WUD1), Homo sapiens (Q9H0U4), Homo sapiens (Q9NRW1), Homo sapiens
Manually annotated by BRENDA team
Ferri, N.; Contini, A.; Bernini, S.K.; Corsini, A.
Role of small GTPase protein Rac1 in cardiovascular diseases: development of new selective pharmacological inhibitors
J. Cardiovasc. Pharmacol.
62
425-435
2013
Homo sapiens (P15153), Homo sapiens (P60763), Homo sapiens (P63000)
Manually annotated by BRENDA team
Shen, D.W.; Pouliot, L.M.; Gillet, J.P.; Ma, W.; Johnson, A.C.; Hall, M.D.; Gottesman, M.M.
The transcription factor GCF2 is an upstream repressor of the small GTPAse RhoA, regulating membrane protein trafficking, sensitivity to doxorubicin, and resistance to cisplatin
Mol. Pharm.
9
1822-1833
2012
Homo sapiens (P61586), Homo sapiens
Manually annotated by BRENDA team
Tsai, C.H.; Cheng, H.C.; Wang, Y.S.; Lin, P.; Jen, J.; Kuo, I.Y.; Chang, Y.H.; Liao, P.C.; Chen, R.H.; Yuan, W.C.; Hsu, H.S.; Yang, M.H.; Hsu, M.T.; Wu, C.Y.; Wang, Y.C.
Small GTPase Rab37 targets tissue inhibitor of metalloproteinase 1 for exocytosis and thus suppresses tumour metastasis
Nat. Commun.
5
4804
2014
Homo sapiens (Q96AX2), Homo sapiens
Manually annotated by BRENDA team
Schaefer, A.; Reinhard, N.R.; Hordijk, P.L.
Toward understanding RhoGTPase specificity: structure, function and local activation
Small GTPases
5
6
2014
Homo sapiens (P08134), Homo sapiens (P61586), Homo sapiens (P62745)
Manually annotated by BRENDA team
Spuul, P.; Ciufici, P.; Veillat, V.; Leclercq, A.; Daubon, T.; Kramer, I.; Genot, E.
Importance of RhoGTPases in formation, characteristics, and functions of invadosomes
Small GTPases
5
e28195
2014
Homo sapiens (P15153), Homo sapiens (P60953), Homo sapiens (P61586), Homo sapiens (P63000)
Manually annotated by BRENDA team
Knihtila, R.; Volmar, A.Y.; Meilleur, F.; Mattos, C.
Titration of ionizable groups in proteins using multiple neutron data sets from a single crystal application to the small GTPase Ras
Acta Crystallogr. Sect. F
75
111-115
2019
Homo sapiens
Manually annotated by BRENDA team
Zhang, L.; Dai, F.; Cui, L.; Zhou, B.; Guo, Y.
Up-regulation of the active form of small GTPase Rab13 promotes macroautophagy in vascular endothelial cells
Biochim. Biophys. Acta
1864
613-624
2017
Homo sapiens (P51153), Homo sapiens
Manually annotated by BRENDA team
Yoo, J.; Brady, S.; Acosta-Alvarez, L.; Rogers, A.; Peng, J.; Sorensen, L.; Wolff, R.; Mleynek, T.; Shin, D.; Rich, C.; Kircher, D.; Bild, A.; Odelberg, S.; Li, D.; Holmen, S.; Grossmann, A.
The small GTPase ARf6 activates PI3K in melanoma to induce a prometastatic state
Cancer Res.
79
2892-2908
2019
Homo sapiens (P62330), Homo sapiens, Mus musculus (P62331)
Manually annotated by BRENDA team
Francis, J.W.; Newman, L.E.; Cunningham, L.A.; Kahn, R.A.
A trimer consisting of the tubulin-specific chaperone D (TBCD), regulatory GTPase ARL2, and beta-tubulin is required for maintaining the microtubule network
J. Biol. Chem.
292
4336-4349
2017
Homo sapiens (P36404), Homo sapiens
Manually annotated by BRENDA team
Esposito, A.; Ventura, V.; Petoukhov, M.; Rai, A.; Svergun, D.; Vanoni, M.
Human MICAL1 activation by the small GTPase Rab8 and small-angle X-ray scattering studies on the oligomerization state of MICAL1 and its complex with Rab8
Protein Sci.
28
150-166
2019
Homo sapiens (P61006), Homo sapiens
Manually annotated by BRENDA team