Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Combined Automated Annotation using Multiple IEA Methods
Identification and characterization of a novel Rho-specific guanine nucleotide exchange factor.
-
Purified p114-Rho-GEF binds RhoA in the nucleotide-free and GTP-gamma-S states but not Rac1 or Cdc42, and catalyses nucleotide exchange on RhoA.
"p114-Rho-GEF interacted specifically with RhoA, in its nucleotide-free and guanosine 5'-[gamma-thio]triphosphate-bound states, but not with Rac1 and Cdc42, and efficiently catalysed guanine nucleotide exchange of RhoA"
-
Overexpression in sparse cells induces stress fibres and Rho-dependent SRF transcription, the gain-of-function counterpart of the stress-fibre phenotype seen on depletion in monolayers.
"the overexpression of p114-Rho-GEF in J82 and HEK-293 cells induced the formation of actin stress fibres and stimulated serum-response-factor-mediated gene transcription in a Rho-dependent manner"
G Protein betagamma subunits stimulate p114RhoGEF, a guanine nucleotide exchange factor for RhoA and Rac1: regulation of cell shape and reactive oxygen species production.
-
In cells, p114RhoGEF activated RhoA and Rac1 but not Cdc42, with cell rounding and stress fibres as the RhoA readout and NADPH-oxidase-dependent ROS as the Rac1 readout.
"we have determined that p114RhoGEF activated RhoA and Rac1 but not Cdc42 proteins"
-
The Rac1 arm of this gene's described biology rests entirely on the ROS readout in this paper.
"Functional significance of Rac1 activation was established by the ability of p114RhoGEF to induce production of reactive oxygen species (ROS) followed by activation of NADPH oxidase enzyme complex"
Cytoskeletal modification of Rho guanine nucleotide exchange factor activity: identification of a Rho guanine nucleotide exchange factor as a binding partner for Sept9b, a mammalian septin.
-
ARHGEF18 was identified as a Sept9b-binding protein and named SA-RhoGEF, the source of UniProt's septin-associated RhoGEF AltName.
"We have identified a Rho-guanine nucleotide exchange factor (GEF) as a binding partner for a mammalian septin Sept9b using yeast two-hybrid screening"
-
Sept9b inhibits SA-RhoGEF-dependent Rho activation, the opposite sign to the later reports that SEPTIN9 activates ARHGEF18 at the ciliary base and at mitochondrial fission sites.
"In transient expression analyses, Sept9b inhibited SA-RhoGEF-dependent Rho activation in COS7 and HeLa cells"
Proteomic analysis of exosomes from human neural stem cells by flow field-flow fractionation and nanoflow liquid chromatography-tandem mass spectrometry.
Involvement of p114-RhoGEF and Lfc in Wnt-3a- and dishevelled-induced RhoA activation and neurite retraction in N1E-115 mouse neuroblastoma cells.
-
p114-RhoGEF and GEF-H1/Lfc are the two RhoGEFs responsible for Wnt-3a and Dishevelled-induced RhoA activation in neuroblastoma cells, and both bind Dvl and Daam1.
"Here we identified p114-RhoGEF and Lfc (also called GEF-H1) as the Rho-GEFs responsible for Wnt-3a-induced RhoA activation in N1E-115 mouse neuroblastoma cells"
Spatially restricted activation of RhoA signalling at epithelial junctions by p114RhoGEF drives junction formation and morphogenesis.
-
p114RhoGEF associates with the apical junctional complex and tight junctions, overlapping occludin but not E-cadherin.
"Junctional p114RhoGEF overlapped with occludin, a tight junction protein, but not E-cadherin, an adherens junction component, indicating that p114RhoGEF associates with the apical junctional complex and tight junctions"
-
Depletion lowers active RhoA without affecting Rac or Cdc42, which contradicts the Rac1 claim of PMID:14512443.
"p114RhoGEF is a widely expressed gene and, in vitro, functions as a specific activator of RhoA17-19. Accordingly, depletion of p114RhoGEF resulted in reduced levels of active RhoA in HCE cells without significantly affecting Rac and Cdc42"
-
The protein forms a junctional signalling module with myosin IIA and ROCK II, and cingulin is required for its junctional recruitment.
"p114RhoGEF immunoprecipitates contained myosin IIA and the RhoA effector Rock II"
-
Depletion attenuates barrier formation, the functional readout of tight junction maturation.
"Depletion of p114RhoGEF strongly attenuated barrier formation and only reached 40% of the values of control cultures"
-
The requirement is stage-specific, since spreading and initial adhesion are unaffected and only junctional maturation fails.
"Thus, p114RhoGEF is not required for spreading and initiation of adhesion, but for junctional maturation."
-
A conserved Dbl-domain tyrosine is required for exchange activity; this is the substitution that resolves to canonical Tyr-606.
"we substituted a conserved tyrosine residue in the Dbl domain necessary for GEF activity"
-
Loss of junctions raises non-junctional Rho signalling, which is why a RhoA activator can be annotated as a negative regulator of stress fibre assembly.
"RhoA activity is downregulated in response to cell confluence; hence, interfering with junction formation stimulates RhoA signalling in the rest of the cell"
Lulu2 regulates the circumferential actomyosin tensile system in epithelial cells through p114RhoGEF.
-
Lulu2 (EPB41L4B) binds and activates p114RhoGEF at apical cell-cell junctions to organise the circumferential actomyosin belt.
"In its regulation of the belt, Lulu2 interacts with and activates p114RhoGEF, a Rho-specific guanine nucleotide exchanging factor (GEF), at apical cell-cell junctions"
-
PATJ recruits p114RhoGEF to apical cell-cell boundaries through a PDZ interaction, the basis of the apical plasma membrane annotation.
"We further found that Patj, an apical cell polarity regulator, recruits p114RhoGEF to apical cell-cell boundaries via PDZ (PSD-95/Dlg/ZO-1) domain-mediated interaction"
Stimulation of cortical myosin phosphorylation by p114RhoGEF drives cell migration and tumor cell invasion.
-
p114RhoGEF associates with non-muscle myosin IIA and drives collective epithelial migration and tumour cell invasion through cortical myosin activation.
"we demonstrate that p114RhoGEF, an activator of RhoA that associates with non-muscle myosin IIA, regulates collective cell migration of epithelial sheets and tumor cell invasion"
Activated RhoA is a positive feedback regulator of the Lbc family of Rho guanine nucleotide exchange factor proteins.
-
Activated RhoA binds the PH domains of the Lbc-family RhoGEFs, including p114RhoGEF, as a positive-feedback mechanism.
"This demonstrates feasibility of the hypothesis that binding of activated RhoA to the PH domains acts as a positive feedback mechanism"
LKB1 controls human bronchial epithelial morphogenesis through p114RhoGEF-dependent RhoA activation.
-
LKB1 and p114RhoGEF act together to control RhoA activity and promote apical junction assembly in bronchial epithelium, independently of LKB1 kinase activity.
"Together, LKB1 and p114RhoGEF control RhoA activity in these cells to promote apical junction assembly"
ArhGEF18 regulates RhoA-Rock2 signaling to maintain neuro-epithelial apico-basal polarity and proliferation.
-
ArhGEF18-mediated RhoA activation maintains apicobasal polarity of the retinal neuroepithelium and sets the ratio of neurogenic to proliferative divisions.
"We show that ArhGEF18-mediated activation of the small GTPase RhoA is required to maintain apicobasal polarity at the onset of retinal differentiation and to control the ratio of neurogenic to proliferative cell divisions"
-
The human protein rescues the medaka mutant, establishing functional conservation across vertebrates.
"The human ArhGEF18 homologue can rescue the mutant phenotype, suggesting a conserved function in vertebrate neuroepithelia"
ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation.
-
ZO-1 and paracingulin (CGNL1, called JACOP) are both required to recruit p114RhoGEF to endothelial junctions, and p114RhoGEF co-precipitates with JACOP.
"p114RhoGEF and JACOP coimmunoprecipitated from endothelial cell extracts, and both ZO-1 and JACOP were required for junctional recruitment of p114RhoGEF"
-
p114RhoGEF depletion removes junctional vinculin and induces focal adhesions and stress fibres, which is the basis of both IMP rows.
"p114RhoGEF depletion led to a loss of junctional vinculin and induction of vinculin-stained focal adhesions and stress fibers comparable to depletions of ZO-1 and JACOP"
-
Vinculin is in the p114RhoGEF complex but not the ZO-1 complex, which is what makes the protein localization to cell-cell junction annotation specific rather than a general junction phenotype.
"p114RhoGEF, and not ZO-1, immunoprecipitates contained vinculin"
CRB3A Controls the Morphology and Cohesion of Cancer Cells through Ehm2/p114RhoGEF-Dependent Signaling.
-
CRB3A recruits p114RhoGEF and its activator Ehm2 to the cell periphery and raises RhoA activation, converting an ameboid morphology into an epithelial one with a circumferential actomyosin belt.
"CRB3A recruits p114RhoGEF and its activator Ehm2 to the cell periphery using both functional motifs of its cytoplasmic tail and increases RhoA activation levels"
p114RhoGEF governs cell motility and lumen formation during tubulogenesis through a ROCK-myosin-II pathway.
-
p114RhoGEF knockdown leaves early tubulogenesis intact but impairs later lumen consolidation, producing multiple lumens per tube.
"this knockdown impaired later stages of tubulogenesis, resulting in multiple lumens in a tube"
Biallelic Mutation of ARHGEF18, Involved in the Determination of Epithelial Apicobasal Polarity, Causes Adult-Onset Retinal Degeneration.
-
Biallelic ARHGEF18 variants cause adult-onset recessive retinal degeneration, and the gene is described as a RHOA activator.
"ARHGEF18 encodes ARHGEF18, a guanine nucleotide exchange factor that activates RHOA, a small GTPase protein that is a key component of tight junctions and adherens junctions"
-
The RP78 missense allele hits a conserved DH-domain residue required for RHOA interaction and activation; UniProt records it as VARIANT 458 T to A.
"the p.Thr270Ala missense variant affects a highly conserved residue in the DBL homology domain, which is required for the interaction and activation of RHOA"
The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier.
-
EPB41L5 binds and recruits ARHGEF18 to the leading edge of podocytes to control actomyosin contractility and focal adhesion maturation.
"by binding and recruiting the RhoGEF ARGHEF18 to the leading edge, EPB41L5 directly controls actomyosin contractility and subsequent maturation of focal adhesions, cell spreading, and migration"
Expression of novel "LOCGEF" isoforms of ARHGEF18 in eosinophils.
-
Alternative N-terminal isoforms of ARHGEF18 sit at the plasma membrane in resting eosinophils and redistribute to the two poles on cytokine-induced polarisation.
"Immunofluorescence microscopy revealed striking relocalization of LOCGEFs from the plasma membrane to the two poles upon polarization of eosinophils by IL5, IL33 and CCL11"
-
The canonical p114 isoform is absent from eosinophils, so the junctional mechanism cannot be assumed to operate there.
"No p114 transcript or protein band was detected in eosinophils."
Crystal structures of the PH domains from Lbc family of RhoGEFs bound to activated RhoA GTPase.
-
The PH domain of p114RhoGEF was solved at 1.4 angstrom in complex with RhoA (PDB 6BCB); this is the only structure of any part of ARHGEF18.
"Here we present two crystal structures at resolutions of 1.4 Å and 2.0 Å of RhoA complexed with the PH domain from p114RhoGEF (PDB access code 6BCB) and AKAP-LbcRhoGEF (PDB access code 6BCA), respectively"
-
Direct PH-domain binding to activated Rho GTPases is a property of the whole Lbc family.
"All 7 Lbc RhoGEFs associate directly with activated Rho GTPases via their PH domains"
A Gα12-specific Binding Domain in AKAP-Lbc and p114RhoGEF.
-
A C-terminal region of p114RhoGEF binds G alpha 12 through a mechanism distinct from the RH domain interface used by the RH-RhoGEFs.
"We identified a Gα12-binding region near the C-terminus of AKAP-Lbc, closely homologous to a region of p114RhoGEF that we also discovered to interact with Gα12"
Apical polarity proteins recruit the RhoGEF Cysts to promote junctional myosin assembly.
-
Drosophila Cysts is the single ortholog of mammalian p114RhoGEF, GEF-H1, p190RhoGEF and AKAP-13, which is what makes the PAINT node seeded by all four a legitimate ancestral inference.
"To explore the regulation of Rho GTPases in vivo, we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the Drosophila orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13"
-
Cysts activates Rho1 at junctions and stabilises junctional myosin, the fly equivalent of the mammalian junctional module.
"Cysts activates Rho1 at adherens junctions and stabilizes junctional myosin"
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Roles of protein-protein interactions and monolayer mechanics in tricellulin localization to tricellular tight junctions.
-
Occludin is a proximity partner of tricellulin at cell-cell junctions and its knockout perturbs tricellulin localisation at tricellular tight junctions, so occludin is present and functionally required at tricellular contacts.
"BioID proteomics identified several proximity partners of tricellulin, and knockout studies on angulin-1/LSR, occludin and afadin provided evidence that these proteins control tricellulin accumulation to tTJs to different extents and mechanisms."
-
Occludin nevertheless does not accumulate at tricellular tight junctions as prominently as tricellulin, so it is predominantly bicellular; it cannot license the bicellular subtype but does not exclude tricellular contacts either.
"tricellulin is in close proximity to occludin and afadin at cell-cell junctions, but neither one of these other proteins displays similar prominent accumulation to tTJs as tricellulin"
Septin-mediated RhoA activation engages the exocyst complex to recruit the cilium transition zone.
-
SEPTIN9 binds and activates ARHGEF18 at the ciliary base, the opposite sign to the inhibition reported for Sept9b in PMID:15558029.
"SEPTIN9 regulates RhoA signaling at the base of cilia by binding and activating the RhoA guanine nucleotide exchange factor, ARHGEF18"
p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
Disassembly of tight junctions
SMURF1 binds phosphorylated PARD6A
SMURF1 ubiquitinates RHOA
TGFBR1 is recruited to tight junction by binding Pard6a
TGFBR2 is recruited to tight junctions-associated, Pard6a-bound, TGFBR1 after TGF-beta stimulation
TGFBR2 phosphorylates Pard6a
Affinage mechanistic annotation for ARHGEF18 (human)
ARHGEF18 (p114RhoGEF) bioinformatics