Affinage

ARHGAP1

Rho GTPase-activating protein 1 · UniProt Q07960

Length
439 aa
Mass
50.4 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARHGAP1 (p50RhoGAP/Cdc42GAP) is a ubiquitously expressed Rho-family GTPase-activating protein that terminates Cdc42/Rho signaling to control actin-dependent processes including filopodia formation, cell polarity, directional migration, and apoptotic survival (PMID:8288572, PMID:16914516). Crystal structures of its GAP domain bound to Cdc42 establish the catalytic mechanism: the protein contributes an arginine finger (Arg305) that stabilizes the GTP-hydrolysis transition state while clamping the switch I and switch II regions of the bound GTPase, with the R305A (and equivalently R282A/R85) mutant abolishing catalysis (PMID:9262406, PMID:9846874, PMID:20660160). Biochemically, ARHGAP1 binds Rho, Rac, and Cdc42 comparably but strongly prefers Cdc42 as a substrate for hydrolysis stimulation while also accelerating RhoA GTP hydrolysis several-thousand-fold (PMID:8262058, PMID:8288572, PMID:9548756). Its activity is spatially and intramolecularly tuned through its N-terminal BCH/Sec14-like domain, which sequesters RhoA in cis to suppress the adjacent GAP domain and which targets the protein to endosomal membranes in a complex with Rab11 (PMID:20660160, PMID:16380373); the BCH domain also mediates competitive interactions with BNIP-2 and BNIP-Sα that displace ARHGAP1 from Cdc42 or RhoA (PMID:10954711, PMID:16331259). At the migrating leading edge, Nudel competes with Cdc42 for ARHGAP1 binding to sustain local Cdc42 activation, and ROS generated by NADPH oxidase (p47phox) suppress ARHGAP1 activity downstream of agonist stimulation (PMID:18331715, PMID:19812368). Gene knockout in mice and fibroblasts produces Cdc42 gain-of-function, demonstrating that ARHGAP1 governs filopodia and polarity in fibroblasts, hematopoietic stem/progenitor survival via the Cdc42-JNK apoptosis axis, perinatal body growth, and smooth muscle contraction through a Cdc42-PAK-vimentin pathway (PMID:16914516, PMID:16174757, PMID:16157885, PMID:19494238). In vivo, ARHGAP1 spatially restricts active Rho to the apex of premigratory neural crest cells to permit apical detachment during EMT (PMID:23804498).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1994 High

    Established the basic identity and biochemical activity of ARHGAP1, answering whether the 50 kDa protein was a general RhoGAP or one with substrate selectivity.

    Evidence Protein purification, cDNA cloning, and in vitro GTPase/binding assays of human p50rhoGAP

    PMID:8262058 PMID:8288572

    Open questions at the time
    • Substrate preference defined biochemically but cellular significance unresolved
    • Structural basis of selectivity unknown
  2. 1998 High

    Resolved the catalytic mechanism by defining how ARHGAP1 accelerates GTP hydrolysis, addressing how a GAP enhances an intrinsically slow GTPase.

    Evidence X-ray crystallography of isolated GAP domain and of Cdc42-GAP transition-state mimic complexes with R305A mutagenesis, plus quantitative RhoA kinetics

    PMID:9009196 PMID:9262406 PMID:9548756 PMID:9846874

    Open questions at the time
    • Structures use isolated GAP domain, not full-length protein
    • Does not address intramolecular or spatial regulation in cells
  3. 2000 Medium

    Identified the BCH domain as a protein-protein interaction module that competes for Cdc42/RhoA, raising the question of how RTK and adaptor signals feed into ARHGAP1 regulation.

    Evidence Yeast two-hybrid, GST pulldown, co-IP, in vitro phosphorylation and GTPase assays with BNIP-2 and FGFR1

    PMID:10551883 PMID:10954711

    Open questions at the time
    • Functional consequence of BNIP-2 competition in cells not established
    • Single-lab interaction data
  4. 2006 High

    Demonstrated in vivo physiological roles via genetic knockout, answering what cellular and organismal processes ARHGAP1-controlled Cdc42 activity governs.

    Evidence Cdc42GAP knockout mice and MEFs with GTPase, migration, apoptosis, hematopoietic reconstitution, and JNK pathway readouts

    PMID:16157885 PMID:16174757 PMID:16914516

    Open questions at the time
    • Knockout is a Cdc42 gain-of-function model; does not isolate Rho/Rac contributions
    • Tissue-specific mechanisms partly inferred
  5. 2006 Medium

    Linked ARHGAP1 to membrane trafficking by showing Sec14-like domain targeting to endosomes and Rab11 complex formation, addressing where in the cell it acts.

    Evidence Subcellular fractionation, transferrin uptake assay, colocalization, and BRET

    PMID:16380373

    Open questions at the time
    • Single-lab data; reciprocal validation limited
    • Functional consequence of Rab11 complex on Rho signaling not fully defined
  6. 2010 High

    Resolved how ARHGAP1 activity is autoregulated by showing the BCH domain sequesters RhoA in cis from the adjacent GAP domain, explaining substrate gating within the protein.

    Evidence Domain deletion, site-directed mutagenesis, RhoA pulldown, and cell morphology assays

    PMID:16331259 PMID:20660160

    Open questions at the time
    • Structural model of the closed/open intramolecular state lacking
    • Signals that relieve BCH autoinhibition in vivo unclear
  7. 2009 High

    Defined spatial and signal-dependent regulation at the leading edge and in smooth muscle, answering how local GAP activity is dynamically modulated by upstream signals.

    Evidence Nudel competition Co-IP/RNAi with Cdc42 activity readouts; ROS/p47phox-dependent suppression of GAP activity with PAK-vimentin-contraction readouts

    PMID:18331715 PMID:19494238 PMID:19812368

    Open questions at the time
    • Molecular target of ROS on ARHGAP1 (oxidized residue) not identified
    • Crosstalk between Nudel and ROS regulation not integrated
  8. 2013 High

    Showed in vivo spatial control of Rho during morphogenesis, establishing ARHGAP1 as a positional regulator of GTPase activity during EMT.

    Evidence Zebrafish FRET Rho biosensor imaging with morpholino loss-of-function and ROCK pharmacology in neural crest cells

    PMID:23804498

    Open questions at the time
    • Mechanism localizing ARHGAP1 to the apical domain unknown
    • Relationship to mammalian roles not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the distinct regulatory inputs (BCH autoinhibition, Nudel sequestration, ROS oxidation, Rab11 endosomal targeting) are integrated to produce substrate- and location-specific GTPase inactivation in vivo remains unresolved.
  • No full-length structure capturing autoinhibited vs active states
  • Direct ROS-modified residue unidentified
  • Integration of competing regulators at a single subcellular site untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140096 catalytic activity, acting on a protein 3 GO:0008289 lipid binding 1
Localization
GO:0005768 endosome 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
BNIP2BNIPSACDC42NDEL1RAB11RAC1RHOA

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Crystal structure of the GAP domain of p50rhoGAP (ARHGAP1) in complex with Cdc42Hs-GMPPNP resolved at 2.7Å, showing that Cdc42Hs interacts through its switch I and II regions with a shallow pocket on rhoGAP lined with conserved residues, and that Arg85 of rhoGAP interacts with the P-loop of Cdc42Hs, proposed to stabilize the GTP hydrolysis transition state. X-ray crystallography (2.7Å resolution) with biochemical data Nature High 9262406
1997 Crystal structure of the isolated GAP domain of human p50rhoGAP (ARHGAP1) resolved at high resolution; the structure comprises nine α-helices arranged around a four-helix bundle core; conserved residues are clustered on one face proposed as the G-protein interaction site; Arg85 and Asn194 are proposed to be involved in G-protein binding and GTPase enhancement. X-ray crystallography Nature High 9009196
1998 Crystal structures of Cdc42 bound to wild-type Cdc42GAP (ARHGAP1) and to the catalytically compromised Cdc42GAP(R305A) mutant in aluminum fluoride transition-state mimics; these structures confirm that Cdc42GAP contributes Arg305 (the arginine finger) to the active site to stabilize the transition state for GTP hydrolysis, analogous to RasGAP; Cdc42GAP stabilizes both switch I and switch II domains of Cdc42. X-ray crystallography of transition-state mimics; site-directed mutagenesis (R305A) Nature structural biology High 9846874
1993 In vitro GTPase assays and fibroblast microinjection showed that rhoGAP (ARHGAP1/p50rhoGAP) has striking preferential GAP activity for G25K (Cdc42) compared with Rho and Rac; microinjection of rhoGAP did not specifically inhibit rho-mediated stress fiber formation, consistent with its substrate preference for Cdc42/G25K in vivo. In vitro GTPase assay; microinjection into Swiss 3T3 fibroblasts The EMBO journal High 8262058
1994 Purification and cDNA cloning of human rhoGAP (ARHGAP1/p50rhoGAP) identified a 50 kDa ubiquitously expressed protein; in vitro GTPase assays showed that Rho, Rac, and G25K/CDC42 all bind equally well to rhoGAP, but G25K/CDC42 is the preferred substrate for GTP hydrolysis stimulation; the protein contains a proline-rich sequence suggesting it is an SH3-binding protein. Protein purification, cDNA cloning, in vitro GTPase assay, binding assay The Journal of biological chemistry High 8288572
1998 Kinetic analysis of RhoA GTP hydrolysis stimulated by the GAP domain of p50RhoGAP (ARHGAP1) showed at least 4000-fold stimulation of intrinsic RhoA GTPase rate; p50RhoGAP has a low Km for activated RhoA (~2.83 µM) and shows product inhibition by binding the GDP-bound form of RhoA (Kd ~6 µM); p50RhoGAP remains partially active toward effector domain mutants of RhoA (Y34K, T37A), indicating distinct structural determinants of interaction compared with p190. In vitro kinetic GTPase assay with recombinant proteins; binding studies Biochemistry High 9548756
2005 The Sec14-like domain of p50RhoGAP (ARHGAP1) targets the protein to endosomal membranes where it colocalizes with internalized transferrin receptor and Rab5/Rab11; overexpression of p50RhoGAP or its Sec14-like domain alone inhibits transferrin uptake; bioluminescence resonance energy transfer demonstrated that p50RhoGAP forms a molecular complex with Rab11 on endosomal membranes, mediated by the Sec14-like domain, linking Rab and Rho GTPase regulation at endosomes. Subcellular fractionation, co-localization imaging, transferrin uptake assay, BRET The Journal of biological chemistry Medium 16380373
2006 Gene targeting of Cdc42GAP (ARHGAP1) in primary mouse embryonic fibroblasts (Cdc42GAP−/− MEFs) resulted in elevated Cdc42 activity (gain-of-function model); these cells displayed spontaneous filopodia, defective adhesion to fibronectin, impaired wound-healing, polarity establishment, and directional migration, with deficiencies in PAK1, GSK3β, myosin light chain, and FAK phosphorylation, demonstrating that ARHGAP1-regulated Cdc42 activity controls filopodia induction, polarity, and migration in primary fibroblasts. Gene targeting/knockout, GTPase activity assay, cell migration assay, phosphorylation analysis Molecular biology of the cell High 16914516
2005 Genetic deletion of Cdc42GAP (ARHGAP1) in mice resulted in 3-fold elevated Cdc42 activity in hematopoietic tissues with normal Rac and RhoA activities; Cdc42GAP−/− mice were anemic with reduced hematopoietic stem/progenitor cell (HSP) numbers due to increased JNK-mediated apoptosis; HSPs showed impaired cortical F-actin assembly, deficient adhesion and migration, and defective engraftment, establishing ARHGAP1 as a critical regulator of Cdc42 activity in hematopoiesis. Gene targeting/knockout, GTPase activity assay, hematopoietic reconstitution, apoptosis assay, adhesion and migration assays Blood High 16174757
2005 Genetic disruption of Cdc42GAP (ARHGAP1) in mice caused approximately 25–40% reduction in body size and growth retardation during the perinatal period; Cdc42GAP−/− cells and tissues showed significantly elevated Cdc42 activity; increased basal apoptosis was attributed to altered c-Jun N-terminal kinase (JNK) apoptotic signals, establishing ARHGAP1 as a regulator of perinatal growth through the Cdc42-JNK apoptosis pathway. Gene targeting/knockout, Cdc42 GTPase activity assay, apoptosis assays, JNK pathway analysis Proceedings of the National Academy of Sciences of the United States of America High 16157885
2008 Nudel, a cytoplasmic dynein regulator, competes with Cdc42 for binding to Cdc42GAP (ARHGAP1), thereby inhibiting Cdc42GAP-mediated inactivation of Cdc42 in a dose-dependent manner; both Nudel and Cdc42GAP localize to the leading edge in migrating cells; Nudel localization requires Erk1/2-mediated phosphorylation; RNAi depletion of Nudel abolishes Cdc42 activation and cell migration, establishing Nudel as a regulator that sequesters ARHGAP1 to sustain active Cdc42 at the leading edge. Co-IP, in vitro competition binding assay, RNAi knockdown, cell migration assay, Cdc42 activity assay, immunofluorescence Developmental cell High 18331715
2009 Cdc42GAP (ARHGAP1) was cloned from smooth muscle; wild-type Cdc42GAP but not the catalytic mutant R282A enhanced Cdc42 GTP hydrolysis in vitro; agonist stimulation of smooth muscle cells with 5-HT decreased Cdc42GAP activity through reactive oxygen species (ROS); expression of wild-type Cdc42GAP inhibited agonist-induced Cdc42 activation, PAK phosphorylation at Thr-423, vimentin phosphorylation at Ser-56, vimentin remodeling, and smooth muscle contraction, establishing ARHGAP1 as a regulator of the Cdc42-PAK-vimentin axis in smooth muscle. In vitro GTPase assay, retroviral expression of wild-type and R282A mutant, ROS inhibitor pharmacology, phosphorylation analysis, contraction assay American journal of physiology. Cell physiology High 19494238
2009 p47(phox), a regulatory subunit of NADPH oxidase, mediates agonist-induced ROS production that suppresses Cdc42GAP (ARHGAP1) activity in smooth muscle cells; shRNA knockdown of p47(phox) attenuated ROS production, preserved Cdc42GAP activity, and reduced Cdc42 activation, PAK1 phosphorylation, vimentin phosphorylation, and smooth muscle contraction in response to 5-HT. shRNA knockdown, in vitro Cdc42GAP activity assay, ROS measurement, phosphorylation analysis, contraction assay American journal of physiology. Cell physiology Medium 19812368
2000 BNIP-2 and Cdc42GAP (ARHGAP1) directly bind each other and compete for binding to Cdc42 via their conserved BCH (BNIP-2 and Cdc42GAP Homology) domains; the BCH domain of Cdc42GAP can bind Cdc42 but is catalytically inactive; BNIP-2 BCH can stimulate Cdc42 GTPase activity via an arginine-patch motif; yeast two-hybrid and GST pulldown confirmed homo- and hetero-complex formation via BCH domains. GST pulldown, co-immunoprecipitation, yeast two-hybrid, in vitro GTPase assay The Journal of biological chemistry Medium 10954711
1999 BNIP-2 interacts with Cdc42GAP (ARHGAP1) via their BCH domains, and they compete for binding to Cdc42; fibroblast growth factor receptor-1 (FGFR1) phosphorylates BNIP-2 on tyrosine; tyrosine phosphorylation of BNIP-2 by FGFR1 impaired its association with Cdc42GAP and abolished BNIP-2's GAP-like activity toward Cdc42, establishing a regulatory crosstalk between receptor tyrosine kinase signaling and Cdc42GAP activity. Co-immunoprecipitation, in vitro phosphorylation assay, in vitro GTPase assay, transient transfection The Journal of biological chemistry Medium 10551883
2010 The BCH domain of p50RhoGAP/Cdc42GAP (ARHGAP1) sequesters RhoA from inactivation by the adjacent GAP domain in cis; deletion of the BCH domain enhanced GAP activity and caused drastic cell rounding reversed by constitutively active RhoA or by inactivating the GAP domain; the BCH domain selectively targeted RhoA (not Cdc42 or Rac1) regardless of nucleotide-binding state; a RhoA-binding motif (residues 85–120) and an intramolecular interaction motif (residues 169–197) within the BCH domain were identified by mutagenesis as necessary for suppression of GAP activity. Domain deletion, site-directed mutagenesis, cell morphology assay, RhoA pull-down, GTPase assay Molecular biology of the cell High 20660160
2006 Overexpression of BNIP-Sα displaces p50RhoGAP/Cdc42GAP (ARHGAP1) from RhoA through competitive interactions via overlapping binding motifs in the BCH domain (residues 133–177), thereby facilitating RhoA activation; cell rounding and apoptosis induced by BNIP-Sα were completely prevented by dominant-negative RhoA or by deletion of the RhoA-binding motif, establishing that competitive displacement of ARHGAP1 from RhoA drives the cellular phenotype. Co-immunoprecipitation, mutagenesis, cell morphology assay, apoptosis assay Oncogene Medium 16331259
2013 In zebrafish, Arhgap1 restricts Rho activation to the apical region of premigratory neural crest cells during epithelial-to-mesenchymal transition (EMT); loss of Arhgap1 caused Rho activation to spread beyond the apical region, preventing proper apical detachment; imaging of endogenous active Rho in vivo showed a discrete apical cap of active Rho during EMT, and Rho-ROCK signaling was essential for apical detachment, establishing ARHGAP1 as a spatial regulator of Rho during EMT in vivo. In vivo FRET-based Rho activity biosensor imaging, morpholino-based loss-of-function, pharmacological ROCK inhibition Development (Cambridge, England) High 23804498
2000 IGFBP-5(201–218) stimulation of mesangial cells caused rapid aggregation of Cdc42GAP (ARHGAP1) as detected by immunofluorescence, concurrent with filopodia formation and actin reorganization; staurosporin inhibited both migration and Cdc42GAP aggregation only when added in the first hour, suggesting Cdc42GAP aggregation is downstream of an IGFBP-5 receptor serine/threonine kinase. Immunofluorescence microscopy, pharmacological inhibition, wounding assay Kidney international Low 10792618
2004 ARHGAP8, a novel RHOGAP protein, shares identical domain architecture with ARHGAP1/CDC42GAP/p50RHOGAP including a C-terminal RHOGAP domain, a central SH3-binding motif, and an N-terminal BCH/Sec14p-like domain, indicating that ARHGAP1 defines a structural subfamily among RhoGAP proteins. Sequence/domain analysis, genomic organization comparison Gene Low 15225876

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity. Developmental cell 424 11782313
1998 Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. Nature 355 9582072
1997 Crystal structure of a small G protein in complex with the GTPase-activating protein rhoGAP. Nature 235 9262406
1993 rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. The EMBO journal 224 8262058
2018 Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A. Proceedings of the National Academy of Sciences of the United States of America 210 29440427
2001 p190 RhoGAP is the principal Src substrate in brain and regulates axon outgrowth, guidance and fasciculation. Nature cell biology 207 11283609
1995 A dual functional signal mediator showing RhoGAP and phospholipase C-delta stimulating activities. The EMBO journal 195 7835339
2000 The adhesion signaling molecule p190 RhoGAP is required for morphogenetic processes in neural development. Development (Cambridge, England) 183 11044403
1998 Structures of Cdc42 bound to the active and catalytically compromised forms of Cdc42GAP. Nature structural biology 180 9846874
2007 Angiopoietin-1 requires p190 RhoGAP to protect against vascular leakage in vivo. The Journal of biological chemistry 156 17562701
2002 Human RhoGAP domain-containing proteins: structure, function and evolutionary relationships. FEBS letters 142 12297274
2006 Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts. Molecular biology of the cell 135 16914516
1999 Regulation of p190 Rho-GAP by v-Src is linked to cytoskeletal disruption during transformation. Journal of cell science 133 10036244
1994 Characterization of rhoGAP. A GTPase-activating protein for rho-related small GTPases. The Journal of biological chemistry 132 8288572
2005 The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells. Cancer research 131 16024604
2008 The PAR-6 polarity protein regulates dendritic spine morphogenesis through p190 RhoGAP and the Rho GTPase. Developmental cell 119 18267090
2008 DLC-1 suppresses non-small cell lung cancer growth and invasion by RhoGAP-dependent and independent mechanisms. Molecular carcinogenesis 116 17932950
2008 A tip-localized RhoGAP controls cell polarity by globally inhibiting Rho GTPase at the cell apex. Current biology : CB 115 19108776
1997 The structure of the GTPase-activating domain from p50rhoGAP. Nature 106 9009196
2010 Motorized RhoGAP myosin IXb (Myo9b) controls cell shape and motility. Proceedings of the National Academy of Sciences of the United States of America 105 20566876
2001 Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein. The Journal of cell biology 104 11238453
2008 Polarization of the C. elegans embryo by RhoGAP-mediated exclusion of PAR-6 from cell contacts. Science (New York, N.Y.) 99 18583611
2015 The RhoGAP SPIN6 associates with SPL11 and OsRac1 and negatively regulates programmed cell death and innate immunity in rice. PLoS pathogens 98 25658451
2002 SYD-1, a presynaptic protein with PDZ, C2 and rhoGAP-like domains, specifies axon identity in C. elegans. Nature neuroscience 93 12379863
2009 Role of DLC-1, a tumor suppressor protein with RhoGAP activity, in regulation of the cytoskeleton and cell motility. Cancer metastasis reviews 91 19221866
2002 Fear memory formation involves p190 RhoGAP and ROCK proteins through a GRB2-mediated complex. Neuron 88 12441060
2000 RAFTK/Pyk2 tyrosine kinase mediates the association of p190 RhoGAP with RasGAP and is involved in breast cancer cell invasion. Oncogene 87 10713673
2004 Thy-1 regulates fibroblast focal adhesions, cytoskeletal organization and migration through modulation of p190 RhoGAP and Rho GTPase activity. Experimental cell research 86 15093746
2007 Regulation of cell diameter, For3p localization, and cell symmetry by fission yeast Rho-GAP Rga4p. Molecular biology of the cell 79 17377067
2006 Protein tyrosine phosphatase receptor type Z is involved in hippocampus-dependent memory formation through dephosphorylation at Y1105 on p190 RhoGAP. Neuroscience letters 75 16513268
2005 Genetic deletion of Cdc42GAP reveals a role of Cdc42 in erythropoiesis and hematopoietic stem/progenitor cell survival, adhesion, and engraftment. Blood 75 16174757
2006 The RhoGAP crossveinless-c links trachealess and EGFR signaling to cell shape remodeling in Drosophila tracheal invagination. Genes & development 74 16818611
2012 Myosin-IXA regulates collective epithelial cell migration by targeting RhoGAP activity to cell-cell junctions. Current biology : CB 72 22305756
1999 Inhibition of RhoGAP activity is sufficient for the induction of Rho-mediated actin reorganization. European journal of cell biology 72 10494860
2015 The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis. eLife 71 26252513
2008 Coordination of Rho and Rac GTPase function via p190B RhoGAP. Current biology : CB 71 18948007
2003 FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains. International journal of molecular medicine 71 12736724
2007 The RhoGAP RGA-2 and LET-502/ROCK achieve a balance of actomyosin-dependent forces in C. elegans epidermis to control morphogenesis. Development (Cambridge, England) 69 17537791
2007 Convergent use of RhoGAP toxins by eukaryotic parasites and bacterial pathogens. PLoS pathogens 68 18166080
2011 SH3BP1, an exocyst-associated RhoGAP, inactivates Rac1 at the front to drive cell motility. Molecular cell 67 21658605
2008 Nudel binds Cdc42GAP to modulate Cdc42 activity at the leading edge of migrating cells. Developmental cell 64 18331715
2005 RA-RhoGAP, Rap-activated Rho GTPase-activating protein implicated in neurite outgrowth through Rho. The Journal of biological chemistry 60 16014623
1998 Regulation of RhoA GTP hydrolysis by the GTPase-activating proteins p190, p50RhoGAP, Bcr, and 3BP-1. Biochemistry 60 9548756
2012 ARHGAP21 is a RhoGAP for RhoA and RhoC with a role in proliferation and migration of prostate adenocarcinoma cells. Biochimica et biophysica acta 57 23200924
2011 DLC1 interaction with S100A10 mediates inhibition of in vitro cell invasion and tumorigenicity of lung cancer cells through a RhoGAP-independent mechanism. Cancer research 57 21372205
2011 Skeletal muscle differentiation and fusion are regulated by the BAR-containing Rho-GTPase-activating protein (Rho-GAP), GRAF1. The Journal of biological chemistry 57 21622574
2007 ARHGAP4 is a novel RhoGAP that mediates inhibition of cell motility and axon outgrowth. Molecular and cellular neurosciences 55 17804252
2008 Rho-kinase contributes to sustained RhoA activation through phosphorylation of p190A RhoGAP. The Journal of biological chemistry 53 19103606
2009 The SAM domain of the RhoGAP DLC1 binds EF1A1 to regulate cell migration. Journal of cell science 51 19158340
2009 Tensin1 requires protein phosphatase-1alpha in addition to RhoGAP DLC-1 to control cell polarization, migration, and invasion. The Journal of biological chemistry 51 19826001
2004 ARAP3 is transiently tyrosine phosphorylated in cells attaching to fibronectin and inhibits cell spreading in a RhoGAP-dependent manner. Journal of cell science 51 15546919
2021 Osteoclast-derived small extracellular vesicles induce osteogenic differentiation via inhibiting ARHGAP1. Molecular therapy. Nucleic acids 50 33664997
2005 Sec14 homology domain targets p50RhoGAP to endosomes and provides a link between Rab and Rho GTPases. The Journal of biological chemistry 49 16380373
1994 p190 RhoGAP, the major RasGAP-associated protein, binds GTP directly. Molecular and cellular biology 49 7935432
2013 Rho activation is apically restricted by Arhgap1 in neural crest cells and drives epithelial-to-mesenchymal transition. Development (Cambridge, England) 48 23804498
2004 A PLCdelta1-binding protein, p122/RhoGAP, is localized in caveolin-enriched membrane domains and regulates caveolin internalization. Genes to cells : devoted to molecular & cellular mechanisms 47 14723705
2003 Identification and characterization of human KIAA1391 and mouse Kiaa1391 genes encoding novel RhoGAP family proteins with RA domain and ANXL repeats. International journal of oncology 47 14532992
2004 ARHGAP8 is a novel member of the RHOGAP family related to ARHGAP1/CDC42GAP/p50RHOGAP: mutation and expression analyses in colorectal and breast cancers. Gene 46 15225876
2006 Inactivation of Rho GTPases by p190 RhoGAP reduces human pancreatic cancer cell invasion and metastasis. Cancer science 45 16776779
2005 Cdc42GAP regulates c-Jun N-terminal kinase (JNK)-mediated apoptosis and cell number during mammalian perinatal growth. Proceedings of the National Academy of Sciences of the United States of America 44 16157885
2003 Concerted regulation of cell dynamics by BNIP-2 and Cdc42GAP homology/Sec14p-like, proline-rich, and GTPase-activating protein domains of a novel Rho GTPase-activating protein, BPGAP1. The Journal of biological chemistry 44 12944407
1996 An X chromosome-linked gene encoding a protein with characteristics of a rhoGAP predominantly expressed in hematopoietic cells. Proceedings of the National Academy of Sciences of the United States of America 44 8570618
2007 Gem associates with Ezrin and acts via the Rho-GAP protein Gmip to down-regulate the Rho pathway. Molecular biology of the cell 43 17267693
2005 Activation of EGF receptor endocytosis and ERK1/2 signaling by BPGAP1 requires direct interaction with EEN/endophilin II and a functional RhoGAP domain. Journal of cell science 42 15944398
1999 Tyrosine phosphorylation of the Bcl-2-associated protein BNIP-2 by fibroblast growth factor receptor-1 prevents its binding to Cdc42GAP and Cdc42. The Journal of biological chemistry 42 10551883
2017 miR-130b directly targets ARHGAP1 to drive activation of a metastatic CDC42-PAK1-AP1 positive feedback loop in Ewing sarcoma. International journal of cancer 41 28748534
2000 IGFBP-5(201-218) stimulates Cdc42GAP aggregation and filopodia formationin migrating mesangial cells. Kidney international 41 10792618
2008 p190A RhoGAP is a glycogen synthase kinase-3-beta substrate required for polarized cell migration. The Journal of biological chemistry 40 18502760
2008 p190B RhoGAP regulates endothelial-cell-associated proteolysis through MT1-MMP and MMP2. Journal of cell science 40 18505793
2004 A vascular cell-restricted RhoGAP, p73RhoGAP, is a key regulator of angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 40 15302923
2009 Cdc42GAP, reactive oxygen species, and the vimentin network. American journal of physiology. Cell physiology 39 19494238
2000 The BNIP-2 and Cdc42GAP homology domain of BNIP-2 mediates its homophilic association and heterophilic interaction with Cdc42GAP. The Journal of biological chemistry 39 10954711
2006 The effect of missense mutations in the RhoGAP-homology domain on ocrl1 function. Molecular genetics and metabolism 38 16777452
2001 The BNIP-2 and Cdc42GAP homology/Sec14p-like domain of BNIP-Salpha is a novel apoptosis-inducing sequence. The Journal of biological chemistry 38 11741952
2017 p190-B RhoGAP and intracellular cytokine signals balance hematopoietic stem and progenitor cell self-renewal and differentiation. Nature communications 36 28176763
2006 BNIP-Salpha induces cell rounding and apoptosis by displacing p50RhoGAP and facilitating RhoA activation via its unique motifs in the BNIP-2 and Cdc42GAP homology domain. Oncogene 36 16331259
2010 Extracellular signal-regulated kinase promotes Rho-dependent focal adhesion formation by suppressing p190A RhoGAP. Molecular and cellular biology 35 20439493
2003 p250GAP, a neural RhoGAP protein, is associated with and phosphorylated by Fyn. Biochemical and biophysical research communications 35 12788081
2012 Rnd1 and Rnd3 targeting to lipid raft is required for p190 RhoGAP activation. Molecular biology of the cell 34 22357615
2012 The RhoGAP protein Deleted in Liver Cancer 3 (DLC3) is essential for adherens junctions integrity. Oncogenesis 34 23552697
2002 The Rho-GAP Bem2p plays a GAP-independent role in the morphogenesis checkpoint. The EMBO journal 33 12145202
2013 PKA-induced dimerization of the RhoGAP DLC1 promotes its inhibition of tumorigenesis and metastasis. Nature communications 32 23511482
2005 BNIP-2 induces cell elongation and membrane protrusions by interacting with Cdc42 via a unique Cdc42-binding motif within its BNIP-2 and Cdc42GAP homology domain. Experimental cell research 32 15652341
2000 Evidence for a novel Cdc42GAP domain at the carboxyl terminus of BNIP-2. The Journal of biological chemistry 32 10799524
2014 Functional cross-talk between ras and rho pathways: a Ras-specific GTPase-activating protein (p120RasGAP) competitively inhibits the RhoGAP activity of deleted in liver cancer (DLC) tumor suppressor by masking the catalytic arginine finger. The Journal of biological chemistry 31 24443565
2013 The human minor histocompatibility antigen 1 is a RhoGAP. PloS one 31 24086303
2003 Protein tyrosine phosphatase PTP20 induces actin cytoskeleton reorganization by dephosphorylating p190 RhoGAP in rat ovarian granulosa cells stimulated with follicle-stimulating hormone. Molecular endocrinology (Baltimore, Md.) 31 12554790
2005 PARG1, a protein-tyrosine phosphatase-associated RhoGAP, as a putative Rap2 effector. Biochemical and biophysical research communications 30 15752761
2017 Regulation of white and brown adipocyte differentiation by RhoGAP DLC1. PloS one 29 28358928
2007 The neurite outgrowth multiadaptor RhoGAP, NOMA-GAP, regulates neurite extension through SHP2 and Cdc42. The Journal of cell biology 29 17664338
2014 Arhgap28 is a RhoGAP that inactivates RhoA and downregulates stress fibers. PloS one 28 25211221
2010 The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation. Molecular and cellular biology 28 20530197
2010 P190B RhoGAP has pro-tumorigenic functions during MMTV-Neu mammary tumorigenesis and metastasis. Breast cancer research : BCR 28 20860838
2017 The RhoGAP Stard13 controls insulin secretion through F-actin remodeling. Molecular metabolism 26 29310936
2024 Recurrent RhoGAP gene fusion CLDN18-ARHGAP26 promotes RHOA activation and focal adhesion kinase and YAP-TEAD signalling in diffuse gastric cancer. Gut 25 38621923
2013 The RhoGAP ARHGAP19 controls cytokinesis and chromosome segregation in T lymphocytes. Journal of cell science 25 24259668
2020 Comprehensive analysis on the whole Rho-GAP family reveals that ARHGAP4 suppresses EMT in epithelial cells under negative regulation by Septin9. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 24 32378260
2010 The BNIP-2 and Cdc42GAP homology (BCH) domain of p50RhoGAP/Cdc42GAP sequesters RhoA from inactivation by the adjacent GTPase-activating protein domain. Molecular biology of the cell 24 20660160
2009 Role of p47(phox) in regulating Cdc42GAP, vimentin, and contraction in smooth muscle cells. American journal of physiology. Cell physiology 24 19812368
2008 Phosphoinositides affect both the cellular distribution and activity of the F-BAR-containing RhoGAP Rgd1p in yeast. The Journal of biological chemistry 24 18845541

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