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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Functional analysis of ARHGAP6, a novel GTPase-activating protein for RhoA.
Expression in Escherichia coli of human ARHGAP6 gene and purification of His-tagged recombinant protein.
Regulation of phospholipase C-delta1 by ARGHAP6, a GTPase-activating protein for RhoA: possible role for enhanced activity of phospholipase C in hypertension.
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Under in vitro conditions ARHGAP6 activates PLC-delta1 by a direct mechanism - occluding the sites at which inhibitory phospholipids bind - raising the enzyme's maximal rate and its calcium responsiveness.
"ARHGAP6 increased the V(max) of PLC-delta1 and enhanced its response to Ca(2+) stimulation."
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The hypertension link is correlative, not a manipulation: ARHGAP6 mRNA and protein are higher in mononuclear cells from hypertensive patients, alongside higher PLC activity, IP3 and DAG. This is why the IP3 and DAG numbers are not offered as support for the process annotation.
"Enhanced expression of ARHGAP6 was associated with an elevated level of PLC activity and increased levels of IP(3) (1.6-fold) and DAG (2.3-fold)."
Genetic screening in C. elegans identifies rho-GTPase activating protein 6 as novel HERG regulator.
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ARHGAP6 lowers HERG/KCNH2 current and cell-surface channel density, and the effect survives both a dominant-negative Rho and a GAP-dead ARHGAP6 while being lost when PLC is inhibited - so it is a GAP-independent, PLC-routed output.
"ARHGAP6 effects were maintained when we introduced a dominant negative rho-GTPase, or ARHGAP6 devoid of rhoGAP function, indicating ARHGAP6 regulation of HERG is independent of rho activation."
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The channel effect is not an overexpression artefact: suppressing endogenous ARHGAP6 in an atrial myocyte line raises IKr by about half.
"In an atrial myocyte cell line, suppression of endogenous ARHGAP6 by virally transduced shRNA led to a 53% enhancement of I(Kr)."
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The mechanism is a reduction in the number of channels at the membrane rather than a change in gating.
"Biochemical measurements of cell-surface associated HERG revealed that ARHGAP6 reduced membrane expression of HERG by 35%, which correlates well with the reduction in current."
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The catalytic arginine finger of ARHGAP6 is R433, and R433G is the established loss-of-GAP reagent. The result is Prakash et al. 2000's (PMID:10699171), whose abstract names the residue only as 'a conserved arginine residue in the rhoGAP domain'; this paper is where the position is stated explicitly, and is quoted for that reason.
"Mutation of the conserved arginine at position 433 to a glycine (R433G) abolishes the rhoGAP activity of ARHGAP6"
Inhibitory effects of Arhgap6 on cervical carcinoma cells.
ARHGAP6 regulates the proliferation, migration and invasion of lung cancer cells.
Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.
ARHGAP6 Promotes Apoptosis and Inhibits Glycolysis in Lung Adenocarcinoma Through STAT3 Signaling Pathway.
Quantitative fragmentomics allow affinity mapping of interactomes.
ARHGAP6 Suppresses Breast Cancer Tumor Growth by Promoting Ferroptosis via RhoA-ROCK1-p38 MAPK Signaling.
Cloning and characterization of a novel rho-type GTPase-activating protein gene (ARHGAP6) from the critical region for microphthalmia with linear skin defects.
RHOA GAPs stimulate RHOA GTPase activity
RAC3 GAPs stimulate RAC3 GTPase activity
ARHGAP6 bioinformatics: what PMID:36115835 measured, per partner
ARHGAP6 bioinformatics: UniProt vs GOA, and what depends on the gap
ARHGAP6 bioinformatics: are the `protein binding` rows many findings or one?
ARHGAP6 bioinformatics: the RhoGAP catalytic arginine finger, with controls
Affinage mechanistic annotation for ARHGAP6 (human)
UniProtKB entry O43182 (RHG06_HUMAN)