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
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells.
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The protein, named p115 and encoded by the gene then called C1, is expressed predominantly in hematopoietic cells and contains GAP and SH3 homology regions.
"The protein encoded by C1, p115, is synthesized predominantly in cells of hematopoietic origin."
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p115 localises to a narrow cytoplasmic region just below the plasma membrane and inhibits stress fibre organisation, from which the authors inferred down-regulation of Rho-like GTPases.
"Its localization in a narrow cytoplasmic region just below the plasma membrane and its inhibitory effect on stress fiber organization indicate that p115 may down regulate rho-like GTPases in hematopoietic cells."
Cloning of rat ARHGAP4/C1, a RhoGAP family member expressed in the nervous system that colocalizes with the Golgi complex and microtubules.
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Recombinant ARHGAP4 stimulates GTP hydrolysis by RAC1, CDC42 and RHOA in vitro. This is the only direct measurement of the activity for this gene in any species.
"In vitro, recombinant ARHGAP4 stimulated the GTPase activity of three members of Rho GTPases, Rac1, Cdc42 and RhoA."
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Endogenous ARHGAP4 localises to the Golgi complex and redistributes to microtubules, for example during mitosis.
"Subcellularly, endogenous ARHGAP4 expression localized to the Golgi complex and could redistribute to the microtubules, for example during mitosis."
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ARHGAP4 mRNA is expressed across the developing and adult nervous systems. This is the basis of the GO:0007399 IEP row, that is, expression-pattern evidence.
"ARHGAP4 mRNA expression was observed in multiple tissues with marked expression throughout the developing and adult nervous systems."
ARHGAP4 is a novel RhoGAP that mediates inhibition of cell motility and axon outgrowth.
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ARHGAP4 inhibits migration of NIH/3T3 cells and outgrowth of hippocampal axons.
"Our studies show that ARHGAP4 inhibits the migration of NIH/3T3 cells and the outgrowth of hippocampal axons."
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The FCH (F-BAR) domain targets ARHGAP4 to the leading edge of migrating cells and to axon growth cones.
"Our structure/function analyses show that the FCH domain appears to be important for spatially localizing ARHGAP4 to the leading edges of migrating NIH/3T3 cells and to axon growth cones."
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The GAP domain and the C-terminus are both required for the inhibition of cell and axon motility, so the phenotype depends on catalysis and not on localisation alone.
"Our analyses also show that the GAP domain and C-terminus are necessary for ARHGAP4-mediated inhibition of cell and axon motility."
Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis.
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Hem-1 (NCKAP1L) scaffolds a family of neutrophil leading-edge complexes, of which the WAVE2 complex is one member, and some of which contain polarity-regulating proteins other than the WAVE2 components.
"A subset of these leading edge complexes are biochemically separable from the WAVE2 complex and contain a diverse set of potential polarity-regulating proteins."
Deciphering the Molecular and Functional Basis of RHOGAP Family Proteins: A SYSTEMATIC APPROACH TOWARD SELECTIVE INACTIVATION OF RHO FAMILY PROTEINS.
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The isolated RHOGAP catalytic domain is non-selective and sometimes inefficient in cell-free assays, so substrate specificity in cells must come from the other domains of the protein.
"We have found that the RHOGAP domain itself is nonselective and in some cases rather inefficient under cell-free conditions."
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The authors therefore propose that specificity and catalytic tuning are conferred by the non-catalytic domains.
"Thus, we propose that other domains of RHOGAPs confer substrate specificity and fine-tune their catalytic efficiency in cells."
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Fourteen of the 66 human RHOGAPs were assayed against 12 RHO proteins. ARHGAP4 is in the catalogue of 66 but is not one of the 14.
"The activity of 14 representatives of the RHOGAP family toward 12 RHO family proteins was determined in real time."
Severe combined immunodeficiency associated with nephrogenic diabetes insipidus and a deletion in the Xq28 region.
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Patients whose deletions remove all of ARHGAP4 except exon 1 have nephrogenic diabetes insipidus without immunodeficiency, so near-complete loss of ARHGAP4 does not by itself cause an immune phenotype.
"Other patients with NDI, but without immunodeficiency, have had deletions that remove all ARHGAP4 except exon 1"
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The authors attribute the SCID in their patient to loss of a conserved regulatory region between ARHGAP4 and ARD1A rather than to loss of ARHGAP4 itself.
"These results are consistent with an X-linked form of SCID, due to the loss of regulatory elements that control the response to hypoxia in hematopoietic cells."
Compound deletion of the rhoGAP C1 and V2 vasopressin receptor genes in a patient with nephrogenic diabetes insipidus.
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A patient hemizygous for a 21.5 kb deletion removing AVPR2 and most of the C1/ARHGAP4 locus was followed clinically and by laboratory testing for 16 years, with no abnormality beyond the AVPR2-attributable NDI, so ARHGAP4 is not essential for normal human development.
"On the basis of our observations, the rhoGAP C1 protein is not essential for normal development in the human."
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Because ARHGAP4 is hematopoietically enriched, immunologic and hematologic testing was done specifically, and was normal; the authors attribute this to compensation by other GAP-family members.
"Therefore, we postulate that the loss of rhoGAP C1 function is most likely compensated by other members of the GAP family."
Immunological profile in a family with nephrogenic diabetes insipidus with a novel 11 kb deletion in AVPR2 and ARHGAP4 genes.
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Peripheral blood mononuclear cells from patients lacking half of ARHGAP4 show no compensatory change in RhoGAP family gene expression, so whatever offsets the loss does not do it by transcriptional upregulation of paralogs.
"Gene expression profiling of PBMC lacking ARHGAP4 revealed that expression of RhoGAP family genes was not influenced greatly by the lack of ARHGAP4."
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Partial loss of ARHGAP4 produced measurable but subclinical immunologic changes and no susceptibility to infection.
"ARHGAP4 may play some role in lymphocyte differentiation but partial loss of ARHGAP4 does not result in clinical immunodeficiency."
A novel contiguous gene deletion of AVPR2 and ARHGAP4 genes in male dizygotic twins with nephrogenic diabetes insipidus and intellectual disability.
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Reviewing all characterised deletions spanning ARHGAP4, the authors find the clinical consequences of losing it still undefined.
"The clinical features of loss of ARHGAP4 function remain unclear despite several reports of different patterns of deletions inactivating different functional regions of the protein."
ARHGAP4/MYH9/β-catenin/c-Jun positive feedback loop promotes colorectal cancer stemness.
ARHGAP4 mutated in a Chinese intellectually challenged family.
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A T491M variant segregates in one X-linked intellectual disability family, with the authors themselves calling for replication before the association is accepted.
"The relation between ARHGAP4 mutation and MR clinical characteristic is needed to be illuminated with participation of more MR patients."
ARHGAP4 variants are associated with X-linked early-onset temporal lobe epilepsy.
ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell migration, and invasion.
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ARHGAP4 forms a complex with SEPT2 and SEPT9, and perturbing it reorganises focal adhesions and alters migration and invasion.
"ARHGAP4, one of the Rho-GAPs, forms a complex with SEPT2 and SEPT9"
WITHDRAWN: ARHGAP4/ MYH9/ β-catenin/ c-Jun positive feedback loop regulates colorectal cancer stemness.
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This version of the colorectal cancer stemness work was withdrawn for a publishing error, not for a problem with the data.
"This article has been withdrawn at the request of the author(s) and/or editor due to an error in the publishing process."
RAC1 GAPs stimulate RAC1 GTPase activity
Affinage mechanistic annotation for ARHGAP4 (human)
ARHGAP4 bioinformatics analyses