Affinage

ARAP1

Arf-GAP with Rho-GAP domain, ANK repeat and PH domain-containing protein 1 · UniProt Q96P48

Length
1450 aa
Mass
162.2 kDa
Annotated
2026-06-09
45 papers in source corpus 21 papers cited in narrative 21 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

ARAP1 is a phosphoinositide-regulated dual GTPase-activating protein that integrates membrane lipid signals with Arf and Rho family GTPase output to control membrane trafficking and actin-dependent cell-surface dynamics (PMID:11804590). It carries both an Arf GAP and a Rho GAP activity: PtdIns(3,4,5)P3 binding to its first PH domain allosterically stimulates the Arf GAP catalytic activity that acts on Arf1 and Arf5, while the Rho GAP activity drives loss of stress fibers and inhibits cell spreading (PMID:11804590, PMID:19666464, PMID:22573888). Through these activities ARAP1 localizes to the Golgi and to late endosomal/multivesicular compartments and governs growth-factor receptor trafficking: it is recruited in a Rab5- and EGFR-dependent manner to early endocytic structures and retards the transit of EGFR into degradative compartments, thereby prolonging downstream ERK/JNK signaling (PMID:18939958, PMID:18764928). ARAP1 slows EGFR degradation by binding the adaptor CIN85 through a proline-arginine motif and competing with Cbl for the CIN85 SH3B domain, reducing EGFR ubiquitination — an interaction defined structurally and thermodynamically (PMID:21275903, PMID:29589748); PTK6 phosphorylates ARAP1 at Tyr231 to reinforce EGFR retention (PMID:20554524). The Arf GAP activity also sets the size of growth-factor-induced circular dorsal ruffles downstream of Arf1/Arf5 and supports macropinocytosis (PMID:22573888, PMID:39934854), and ARAP1 directs surface delivery of the death receptor DR4 and the AT1 angiotensin II receptor (PMID:18165900, PMID:14559250). The Rho GAP activity, dependent on Rap1/Rac1 binding through the Ras-association domain, suppresses RhoA-driven actin polymerization and cell migration in lymphocytes and tumor cells (PMID:38008882, PMID:41488654). In vivo, ARAP1 functions in osteoclast bone resorption via AP-3-dependent lysosomal protein transport (PMID:30240610), in renal vascular angiotensin II responsiveness and blood-pressure control (PMID:23844607, PMID:16801480), and in retinal pigment epithelium, where it is required for outer-segment phagocytosis and photoreceptor survival (PMID:35758026).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Established ARAP1 as a bifunctional PIP3-dependent Arf GAP and Rho GAP that couples phosphoinositide signaling to both Golgi/filopodial dynamics and stress-fiber loss, defining its core enzymatic identity.

    Evidence In vitro GAP assays plus overexpression and localization studies in cells

    PMID:11804590

    Open questions at the time
    • Did not define the physiological substrate Arf isoforms in vivo
    • Mechanism of PIP3 dependence not yet resolved at the domain level
  2. 2003 Medium

    Linked an ARAP1 isoform to G-protein-coupled receptor recycling, showing it promotes AT1A angiotensin receptor return to the plasma membrane to restore signaling competence.

    Evidence Yeast two-hybrid, reciprocal Co-IP, immunocytochemistry, and Ca2+ release assay in HEK-293 cells

    PMID:14559250

    Open questions at the time
    • Used a short 493-aa isoform distinct from full-length ARAP1
    • GAP-domain involvement in recycling not tested
  3. 2008 High

    Resolved ARAP1's role in EGFR trafficking from both ends of the endocytic route, showing it is recruited to early Rab5/EGFR structures and retards transit to EEA1 endosomes while also acting at late sorting/MVB compartments to slow receptor degradation and prolong signaling.

    Evidence siRNA knockdown, live-cell imaging, colocalization, subcellular fractionation, and ERK/JNK phospho-blots (two companion studies)

    PMID:18764928 PMID:18939958

    Open questions at the time
    • Did not identify the molecular tether retaining EGFR
    • Relative contribution of early vs late steps unresolved
  4. 2008 Medium

    Extended ARAP1's trafficking function to death-receptor delivery, implicating it in routing DR4 to the cell surface to enable TRAIL-induced apoptosis.

    Evidence Yeast two-hybrid, Co-IP, colocalization, siRNA, surface flow cytometry, and cell-death assays in tumor lines

    PMID:18165900

    Open questions at the time
    • GAP-domain dependence not dissected
    • Single-lab interaction without structural detail
  5. 2009 High

    Defined the mechanism of phosphoinositide control, showing PH1 binds PtdIns(3,4,5)P3 not to recruit ARAP1 but to allosterically stimulate its Arf GAP catalysis, which is required for EGFR trafficking function.

    Evidence In vitro lipid-binding and Arf GAP assays, mutagenesis, and EGFR trafficking readouts

    PMID:19666464

    Open questions at the time
    • Membrane recruitment mechanism left unexplained
    • Structural basis of allostery not solved
  6. 2010 High

    Identified an upstream regulatory input, showing PTK6 binds and phosphorylates ARAP1 at Tyr231 to enforce EGFR retention and sustain receptor signaling.

    Evidence Co-IP/MS, in vitro kinase assay, Y231F mutagenesis, and EGFR down-regulation and PTK6 siRNA assays

    PMID:20554524

    Open questions at the time
    • How Y231 phosphorylation alters ARAP1 activity is unknown
    • Crosstalk with PIP3 regulation untested
  7. 2011 High

    Established the adaptor mechanism by which ARAP1 slows EGFR degradation, showing it binds CIN85 via a PXPXXRX motif and competes with Cbl to reduce EGFR ubiquitination and divert it from the degradative pathway.

    Evidence Co-IP, mutagenesis, CIN85/ARAP1 siRNA, ubiquitination and degradation assays

    PMID:21275903

    Open questions at the time
    • Competition shown functionally but not yet structurally
    • Did not measure binding affinities
  8. 2012 High

    Placed Arf1/Arf5 as direct effectors of ARAP1 in actin remodeling, demonstrating that ARAP1 Arf GAP activity sets circular dorsal ruffle ring size.

    Evidence Microscopy with overexpression, knockdown, dominant-negative Arf1/Arf5, and GAP-dead mutant epistasis

    PMID:22573888

    Open questions at the time
    • Functional purpose of CDR size control not established
    • Link to receptor internalization untested
  9. 2012 Medium

    Located endogenous ARAP1 to renal vasculature/mesangium and revealed a negative feedback loop in which angiotensin II suppresses ARAP1 expression and AT1 blockade raises it.

    Evidence IHC localization with in vivo Ang II infusion, losartan, and mesangial cell culture

    PMID:22357923

    Open questions at the time
    • Molecular mechanism of transcriptional suppression unknown
    • Connection to AT1 trafficking not directly demonstrated in vivo
  10. 2013 Medium

    Provided genetic evidence that ARAP1 is required for AT1-dependent vasoconstriction, with knockout mice showing impaired angiotensin II vascular sensitivity and worsened sepsis-induced hypotension.

    Evidence Arap1 knockout mice, telemetry, isolated perfused kidney, LPS endotoxemia, and cytokine treatment of cells

    PMID:23844607

    Open questions at the time
    • Did not pinpoint the cellular site of action
    • Mechanistic link to AT1 receptor trafficking inferred not proven
  11. 2006 Medium

    Showed renal ARAP1 controls blood pressure, with proximal-tubule overexpression causing RAS-dependent, salt-sensitive hypertension.

    Evidence Proximal-tubule-specific transgenic mice with BP telemetry, RAS inhibition, and dietary salt manipulation

    PMID:16801480

    Open questions at the time
    • Molecular mechanism downstream of ARAP1 overexpression unresolved
    • Cell-autonomous tubular pathway not defined
  12. 2018 High

    Solved the structural and thermodynamic basis of the ARAP1–CIN85 interaction, mapping the SH3B-binding motif and confirming direct competition with Cbl by ITC and gel filtration.

    Evidence Structural domain-swap analysis, ITC, and competitive analytical gel-filtration chromatography

    PMID:29589748

    Open questions at the time
    • Did not test the structural model in cellular EGFR trafficking
    • In vivo stoichiometry with Cbl unknown
  13. 2018 Medium

    Extended ARAP1's dual-GAP logic to osteoclast bone resorption, with the RhoGAP domain acting at podosomes and the Arf GAP domain governing Arf1-dependent AP-3 recruitment for lysosomal protein transport.

    Evidence Co-IP, immunofluorescence, siRNA, domain-mutant analysis, and in vitro bone resorption assay

    PMID:30240610

    Open questions at the time
    • Single-lab interactome
    • How the two GAP activities are spatially coordinated is unclear
  14. 2017 Medium

    Implicated ARAP1 in photoreceptor survival, with knockout mice degenerating and initial localization pointing to a non-cell-autonomous Müller glia mechanism.

    Evidence Germline Arap1 knockout mice with OCT, fundus imaging, IHC, and ERG

    PMID:28324111

    Open questions at the time
    • Localization-based mechanism later revised
    • Molecular role in retina not defined
  15. 2022 High

    Identified the cellular basis of retinal degeneration, showing RPE-specific (not Müller glia) ARAP1 loss recapitulates the phenotype through a defect in outer-segment phagocytosis.

    Evidence Conditional cell-type-specific knockouts, in vivo phagocytosis quantification, and Co-IP mass spectrometry

    PMID:35758026

    Open questions at the time
    • MS interactors are candidate not validated
    • Direct molecular step in phagocytosis machinery unresolved
  16. 2020 Medium

    Connected ARAP1's CIN85/Cbl-competition mechanism to disease, showing it sustains EGFR/TGF-β/Smad3 signaling in high-glucose tubular cells, with the lncRNA ARAP1-AS2 binding ARAP1 to promote this axis.

    Evidence Co-IP, ubiquitination assay, RNA pulldown, and knockdown/overexpression

    PMID:32969198

    Open questions at the time
    • Functional consequence of lncRNA binding on ARAP1 activity unclear
    • Single-lab corroboration of prior model
  17. 2023 Medium

    Demonstrated a tumor-suppressive role in lung adenocarcinoma, with ARAP1 RhoGAP activity inhibiting migration and invasion by suppressing Rho-driven stress fibers.

    Evidence Wild-type vs RhoGAP-dead overexpression, transwell assays, mouse metastasis model, and F-actin staining

    PMID:38008882

    Open questions at the time
    • Endogenous loss-of-function not tested
    • RhoA as the specific GTPase inferred not directly measured
  18. 2025 Medium

    Defined how ARAP1 RhoGAP activity is targeted, showing its Ras-association domain binds Rap1 and Rac1 to enable RhoA inhibition and suppress chemokine-directed lymphocyte migration.

    Evidence Knockout cells, FRET RhoA biosensor, Rap1/Rac1 binding assays, live imaging, and domain-mutant rescue

    PMID:41488654

    Open questions at the time
    • Structural basis of RA-domain dual binding unknown
    • Coupling between RA-domain occupancy and GAP catalysis not resolved
  19. 2025 Medium

    Revealed an unexpected mitochondrial input and proteasomal control of ARAP1, linking mitochondrial activity to ARAP1-dependent CDR formation and macropinocytosis in hepatocellular carcinoma.

    Evidence CRISPR knockout, confocal/SEM, macropinocytosis assays, MG132, CCCP, and Golgicide A perturbations

    PMID:39934854

    Open questions at the time
    • Mechanism of mitochondrial localization unknown
    • How mitochondrial dysfunction blocks CDRs is undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how ARAP1's two GAP activities, multiple phosphoinositide and small-GTPase inputs, phosphorylation, and degradation are integrated to select among its diverse cargo and actin outputs in a given cell type.
  • No unifying structural model of full-length ARAP1 regulation
  • Spatial/temporal coordination of Arf vs Rho GAP activities unknown
  • Physiological substrate selectivity across tissues undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 3
Partners
AP-3ARF1ARF5CIN85EGFRPTK6RAC1RAP1

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 ARAP1 has PIP3-dependent Arf GAP activity and Rho GAP activity in vitro. Its Rho GAP activity mediates cell rounding and loss of stress fibers when overexpressed. Its Arf GAP activity mediates changes in the Golgi apparatus and formation of filopodia via increased cellular Cdc42 activity. Both activities contribute to inhibiting cell spreading. ARAP1 associates with the Golgi. In vitro GAP assays, overexpression in cells, immunofluorescence/localization studies Molecular cell High 11804590
2003 ARAP1 (the 493-aa isoform identified in this study, distinct from the multi-domain ARAP1) binds the carboxyl terminus of the AT1A angiotensin II receptor via yeast two-hybrid and co-immunoprecipitation, co-localizes with recycled AT1A at the plasma membrane, and promotes recycling of AT1A to the plasma membrane in HEK-293 cells, restoring Ca2+ release response to a second Ang II stimulation. Yeast two-hybrid, co-immunoprecipitation, immunocytochemistry, functional Ca2+ release assay Biochemical and biophysical research communications Medium 14559250
2008 ARAP1 rapidly and transiently associates with the cell edge and with Rab5/rabaptin-5/EGFR-positive punctate structures that precede EEA1-positive early endosomes after EGF treatment. Recruitment requires active Rab5 and an EGFR-derived signal. siRNA knockdown of ARAP1 accelerates association of EGF with EEA1 endosomes, accelerates EGFR degradation, and diminishes/shortens ERK and JNK phosphorylation, demonstrating that ARAP1 retards early endocytic trafficking of EGFR and prolongs downstream signaling. siRNA knockdown, live-cell imaging, immunofluorescence colocalization, western blot for ERK/JNK phosphorylation Traffic (Copenhagen, Denmark) High 18939958
2008 ARAP1 localizes to the Golgi complex and to internal membranes of multivesicular bodies/late endosomes. Its distribution is controlled by phosphorylation and by binding to 3- and 4-phosphorylated phosphoinositides through its PH domains. ARAP1 knockdown causes EGFR accumulation in sorting/late endosomal compartments and inhibits EGFR degradation, resulting in prolonged EGF signaling, placing ARAP1 at a late step of EGFR endocytic trafficking. siRNA knockdown, immunofluorescence, subcellular fractionation, western blot Traffic (Copenhagen, Denmark) High 18764928
2009 The first PH domain (PH1) of ARAP1 specifically binds PtdIns(3,4,5)P3 with ~1.6 µM affinity. PH1 does not mediate PtdIns(3,4,5)P3-dependent recruitment of ARAP1 to membranes in cells; instead, PtdIns(3,4,5)P3 binding to PH1 allosterically stimulates Arf GAP catalytic activity and is required for ARAP1's in vivo function in regulating EGFR endocytic trafficking. In vitro lipid-binding assay, in vitro Arf GAP activity assay, live-cell imaging, site-directed mutagenesis, EGFR trafficking assay The Journal of biological chemistry High 19666464
2010 PTK6 (Brk) associates with ARAP1 in an EGF/EGFR-dependent manner via its SH2 domain (requiring Arg105). PTK6 phosphorylates ARAP1 at Tyr231. Phosphorylation of ARAP1 at Y231 is required for ARAP1 to inhibit EGFR down-regulation; the Y231F mutant fails to do so. Silencing PTK6 in breast carcinoma cells decreases EGFR levels, placing ARAP1 phosphorylation by PTK6 as a mechanism that sustains EGFR signaling. Co-immunoprecipitation (Flag-PTK6 pull-down, MALDI-TOF MS identification of ARAP1), in vitro kinase assay, site-directed mutagenesis (Y231F), EGFR down-regulation assay, PTK6 siRNA The Journal of biological chemistry High 20554524
2011 ARAP1 associates with CIN85 via its PXPXXRX motif (requiring Arg86 and Arg90) interacting with CIN85 SH3 domains. A CIN85-binding-deficient ARAP1 mutant fails to rescue the effect of ARAP1 knockdown on EGFR trafficking to the early endosome. Overexpression of ARAP1 reduces Cbl-mediated ubiquitination of EGFR and slows Cbl-dependent EGFR degradation, with ARAP1 proposed to compete with Cbl for CIN85 binding to divert EGFR away from the early endosome/lysosome degradation pathway. Co-immunoprecipitation, site-directed mutagenesis, siRNA knockdown of CIN85/ARAP1, EGFR ubiquitination assay, EGFR degradation assay Biology of the cell High 21275903
2012 Growth factor stimulation induces localization of ARAP1 to the plasma membrane inside the ring structure of circular dorsal ruffles (CDRs). ARAP1 overexpression increases CDR ring size in an Arf GAP activity-dependent manner, while ARAP1 knockdown produces smaller CDRs. Expression of dominant-negative Arf1 or Arf5 (the substrates of ARAP1) also expands CDR size, placing Arf1 and Arf5 downstream of ARAP1 in CDR ring-size control. Fluorescence microscopy, ARAP1 overexpression, siRNA knockdown, dominant-negative Arf1/Arf5, Arf GAP-dead mutant Molecular biology of the cell High 22573888
2008 ARAP1 interacts with the intracellular portion of TRAIL death receptor DR4 (identified by yeast two-hybrid), co-precipitates with DR4, and co-localizes with it in the ER/Golgi, plasma membrane, and early endosomes of TRAIL-treated cells. ARAP1 knockdown significantly reduces DR4 surface localization in multiple tumor cell lines and slows TRAIL-induced cell death, implicating ARAP1 in DR4 trafficking to the cell surface. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence colocalization, siRNA knockdown, flow cytometry (surface DR4), cell death assay Apoptosis : an international journal on programmed cell death Medium 18165900
2018 In osteoclasts, ARAP1 is part of a protein complex at podosomes/sealing zones where its RhoGAP domain regulates actin dynamics. At endosomes, ARAP1 interacts with AP-3 adaptor complexes where its Arf GAP domain regulates Arf1-dependent AP-3 binding to membranes and lysosomal membrane protein transport to ruffled borders. ARAP1 or AP-3 depletion in osteoclasts impairs their capacity to digest bone in vitro. Co-immunoprecipitation, immunofluorescence, siRNA knockdown, bone resorption assay in vitro, domain-specific mutant analysis iScience Medium 30240610
2018 The ARAP1 PXPXXRX(except P)XXR/H/K motif binds the CIN85 SH3B domain with high affinity and specificity. Crystal/biochemical structure shows that the β2–β3 loops of CIN85 SH3 domains and the H87(ARAP1)/E132(CIN85) interaction are critical for binding specificity. ARAP1 competes with Cbl for CIN85 binding as demonstrated by competitive analytical gel-filtration chromatography and isothermal titration calorimetry. Biochemical binding assays, structural (domain-swap analysis, structure alignment), isothermal titration calorimetry (ITC), analytical gel-filtration chromatography Biochemistry High 29589748
2013 Arap1-deficient mice show accelerated sepsis-induced hypotension and reduced vascular sensitivity to angiotensin II (measured in isolated perfused kidney), confirming that Arap1 is required for normal AT1 receptor-dependent vasoconstriction. During endotoxemia, Arap1 expression is successively down-regulated in wildtype mice (to <10% baseline), and this down-regulation can be recapitulated in cultured mesangial cells by TNFα and IFNγ. Arap1 knockout mice, telemetry blood pressure measurement, isolated perfused kidney assay, LPS-induced endotoxemia model, cytokine treatment of cultured cells Critical care (London, England) Medium 23844607
2006 Proximal-tubule-specific overexpression of ARAP1 in transgenic mice causes hypertension (~20–25 mmHg increase in systolic BP), decreased urine volume, and kidney hypertrophy. The hypertension is completely normalized by renin-angiotensin system inhibition and prevented by low-salt diet, placing renal ARAP1 in regulation of BP via the intrarenal renin-angiotensin system. Transgenic mouse overexpression (proximal tubule-specific), telemetry/tail-cuff BP measurement, pharmacological RAS inhibition, dietary salt manipulation Hypertension (Dallas, Tex. : 1979) Medium 16801480
2012 In vivo, Arap1 protein is restricted to the renal vasculature and glomerular mesangial cells (absent from tubular epithelia). Angiotensin II infusion suppresses renal Arap1 mRNA and protein, while AT1 antagonism (losartan) increases Arap1 expression. Angiotensin II also suppresses Arap1 in cultured mesangial cells in a time- and dose-dependent manner, establishing a negative feedback loop between Ang II signaling and Arap1 expression. Immunohistochemistry (localization in mouse and human kidneys), in vivo Ang II infusion, losartan treatment, renal artery stenosis, water restriction models; western blot and RT-PCR of Arap1 American journal of physiology. Renal physiology Medium 22357923
2017 Arap1 knockout mice develop photoreceptor degeneration starting at 4 weeks postnatal. Immunohistochemistry detects Arap1 predominantly in Müller glia (not photoreceptors), implicating a non-cell-autonomous Müller glia-dependent mechanism for photoreceptor survival. Germline Arap1 knockout mice (KOMP2), optical coherence tomography, fundus photography, immunohistochemistry, electroretinography Investigative ophthalmology & visual science Medium 28324111
2022 Conditional knockout of Arap1 in RPE (Vmd2-Cre) but not Müller glia (Glast-Cre) recapitulates the photoreceptor degeneration of germline Arap1-/- mice. Arap1-/- mice show a clear phagocytic defect in RPE outer segment phagocytosis in vivo. Mass spectrometry of ARAP1 co-immunoprecipitation identifies candidate interactors involved in phagocytosis, cytoskeletal organization, intracellular trafficking and endocytosis, establishing that ARAP1 expression in RPE is required for photoreceptor survival via its role in RPE phagocytosis. Conditional (cell-type-specific) Arap1 knockout mice, in vivo outer segment phagocytosis quantification, mass spectrometry of ARAP1 co-IP Disease models & mechanisms High 35758026
2020 ARAP1 maintains persistent EGFR activation in high-glucose-treated renal tubular cells by reducing EGFR ubiquitination through competing with Cbl for CIN85 binding, as shown by co-immunoprecipitation and ubiquitination assays. The lncRNA ARAP1-AS2 directly interacts with ARAP1 (RNA pulldown), and overexpression of ARAP1-AS2 promotes this EGFR/TGF-β/Smad3 signaling. Co-immunoprecipitation, ubiquitination assay, RNA pulldown, dual-immunofluorescence, siRNA knockdown/overexpression Journal of cellular and molecular medicine Medium 32969198
2023 ARAP1 overexpression significantly inhibits migration and invasion of lung adenocarcinoma cells in vitro and in vivo, and this effect depends on its RhoGAP activity; the mechanism is suppression of Rho signaling leading to inhibition of stress fiber formation. Overexpression of wild-type vs. RhoGAP-dead ARAP1 mutant, transwell migration/invasion assays, mouse metastasis model, F-actin staining Discover oncology Medium 38008882
2015 ARAP1 knockdown in high-glucose-treated HK-2 renal tubular cells decreases Cdc42-GTP levels and reduces cytoskeleton reorganization, cell viability, migration, and EMT/fibrosis marker expression, placing ARAP1 upstream of Cdc42 activation in this cellular context. siRNA knockdown of ARAP1, Cdc42-GTP pull-down (CRIB assay), cell migration assay, western blot for EMT markers Journal of cellular physiology Low 31975379
2025 ARAP1 is transiently recruited to cell protrusions following chemokine stimulation in lymphocytes. Its Ras-association (RA) domain binds Rap1 and Rac1, and this binding is required for ARAP1-mediated RhoA inhibition. ARAP1-deficient cells show enhanced chemokine-directed migration with increased RhoA activation and F-actin polymerization. ARAP1 overexpression inhibits migration in a RhoGAP domain-dependent manner. ARAP1 knockout cells, FRET-based RhoA biosensor, Rap1/Rac1 pulldown/binding assay, live-cell imaging of ARAP1 localization, domain-mutant overexpression, migration assay Frontiers in immunology Medium 41488654
2025 In Hep3B hepatocellular carcinoma cells, ARAP1 localizes to circular dorsal ruffles (CDRs) and to mitochondria (not seen in control HCC lines). ARAP1 KO reduces CDR size, disrupts lamellipodia within CDRs, attenuates extracellular solute uptake (macropinocytosis), and reduces cell growth and malignant potential. ARAP1 is actively degraded via the proteasome in Hep3B cells (MG132 restores levels), and mitochondrial dysfunction (CCCP) blocks CDRs, linking mitochondrial activity to ARAP1-dependent CDR formation. ARAP1 CRISPR knockout, confocal microscopy, scanning electron microscopy, macropinocytosis uptake assay, proteasome inhibitor (MG132), mitochondrial inhibitor (CCCP), ARF1 inhibitor (Golgicide A), cell proliferation/invasion assays Cell communication and signaling : CCS Medium 39934854

Source papers

Stage 0 corpus · 45 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 ARAP1: a point of convergence for Arf and Rho signaling. Molecular cell 155 11804590
2014 A common functional regulatory variant at a type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell. American journal of human genetics 65 24439111
2003 Type 1 angiotensin II receptor-associated protein ARAP1 binds and recycles the receptor to the plasma membrane. Biochemical and biophysical research communications 53 14559250
2013 The angiotensin II AT1 receptor-associated protein Arap1 is involved in sepsis-induced hypotension. Critical care (London, England) 46 23844607
2019 YY1-Induced Upregulation of Long Noncoding RNA ARAP1-AS1 Promotes Cell Migration and Invasion in Colorectal Cancer Through the Wnt/β-Catenin Signaling Pathway. Cancer biotherapy & radiopharmaceuticals 42 31173500
2008 ARAP1 regulates endocytosis of EGFR. Traffic (Copenhagen, Denmark) 42 18939958
2006 Development of hypertension and kidney hypertrophy in transgenic mice overexpressing ARAP1 gene in the kidney. Hypertension (Dallas, Tex. : 1979) 41 16801480
2011 Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release. Diabetologia 36 21267535
2008 ARAP1 regulates EGF receptor trafficking and signalling. Traffic (Copenhagen, Denmark) 36 18764928
2020 Long non-coding RNA ARAP1-AS1 promotes tumorigenesis and metastasis through facilitating proto-oncogene c-Myc translation via dissociating PSF/PTB dimer in cervical cancer. Cancer medicine 33 31953923
2012 ARAP1 regulates the ring size of circular dorsal ruffles through Arf1 and Arf5. Molecular biology of the cell 32 22573888
2010 PTK6 inhibits down-regulation of EGF receptor through phosphorylation of ARAP1. The Journal of biological chemistry 31 20554524
2009 A PH domain in the Arf GTPase-activating protein (GAP) ARAP1 binds phosphatidylinositol 3,4,5-trisphosphate and regulates Arf GAP activity independently of recruitment to the plasma membranes. The Journal of biological chemistry 30 19666464
2020 The effect of lncRNA-ARAP1-AS2/ARAP1 on high glucose-induced cytoskeleton rearrangement and epithelial-mesenchymal transition in human renal tubular epithelial cells. Journal of cellular physiology 29 31975379
2020 Long non-coding RNA ARAP1-AS1 accelerates cell proliferation and migration in breast cancer through miR-2110/HDAC2/PLIN1 axis. Bioscience reports 29 32110804
2023 YY1-induced upregulation of LncRNA-ARAP1-AS2 and ARAP1 promotes diabetic kidney fibrosis via aberrant glycolysis associated with EGFR/PKM2/HIF-1α pathway. Frontiers in pharmacology 26 36874012
2019 Ursolic Acid Treatment Alleviates Diabetic Kidney Injury By Regulating The ARAP1/AT1R Signaling Pathway. Diabetes, metabolic syndrome and obesity : targets and therapy 26 31849504
2018 Long non-coding RNA ARAP1-AS1 promotes the progression of bladder cancer by regulating miR-4735-3p/NOTCH2 axis. Cancer biology & therapy 26 30404578
2008 Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane. Apoptosis : an international journal on programmed cell death 23 18165900
2020 LncRNA ARAP1-AS2 promotes high glucose-induced human proximal tubular cell injury via persistent transactivation of the EGFR by interacting with ARAP1. Journal of cellular and molecular medicine 21 32969198
2020 Long non-coding RNA ARAP1-AS1 promotes the proliferation and migration in cervical cancer through epigenetic regulation of DUSP5. Cancer biology & therapy 19 32985327
2011 ARAP1 association with CIN85 affects epidermal growth factor receptor endocytic trafficking. Biology of the cell 19 21275903
2021 Long Non-Coding RNA ARAP1-AS1 Facilitates the Progression of Cervical Cancer by Regulating miR-149-3p and POU2F2. Pathobiology : journal of immunopathology, molecular and cellular biology 18 33965958
2012 Angiotensin AT1 receptor-associated protein Arap1 in the kidney vasculature is suppressed by angiotensin II. American journal of physiology. Renal physiology 17 22357923
2021 Long non-coding RNA ARAP1-AS1 contributes to cell proliferation and migration in clear cell renal cell carcinoma via the miR-361-3p/placental growth factor axis. Bioengineered 13 34516333
2018 ARAP1 Bridges Actin Dynamics and AP-3-Dependent Membrane Traffic in Bone-Digesting Osteoclasts. iScience 12 30240610
2015 Joint effect of CENTD2 and KCNQ1 polymorphisms on the risk of type 2 diabetes mellitus among Chinese Han population. Molecular and cellular endocrinology 12 25749274
2020 Low expression of long non-coding RNA ARAP1-AS1 can inhibit lung cancer proliferation by inducing G0/G1 cell cycle organization. Journal of thoracic disease 11 33447422
2022 LncRNA ARAP1-AS1 Promotes Bladder Cancer Development by Regulating the miR-3918/KIF20A Axis. Molecular biotechnology 10 35556220
2021 LncRNA ARAP1-AS1 aggravates the malignant phenotypes of ovarian cancer cells through sponging miR-4735-3p to enhance PLAGL2 expression. Cytotechnology 9 34149172
2018 Biochemical and Structural Studies of the Interaction between ARAP1 and CIN85. Biochemistry 9 29589748
2017 Arap1 Deficiency Causes Photoreceptor Degeneration in Mice. Investigative ophthalmology & visual science 8 28324111
2022 Deep Resequencing of 9 Candidate Genes Identifies a Role for ARAP1 and IGF2BP2 in Modulating Insulin Secretion Adjusted for Insulin Resistance in Obese Southern Europeans. International journal of molecular sciences 7 35163144
2022 Arap1 loss causes retinal pigment epithelium phagocytic dysfunction and subsequent photoreceptor death. Disease models & mechanisms 6 35758026
2022 LncRNA ARAP1-AS1 targets miR-516b-5p/PDE5A axis to facilitate the progression of thyroid cancer. Anti-cancer drugs 6 36730555
2023 LncRNA ARAP1-AS1 contributes to lung adenocarcinoma development by targeting miR-8068 to upregulate CEACAM5. Cancer biomarkers : section A of Disease markers 4 37545214
2023 ARAP1 negatively regulates stress fibers formation and metastasis in lung adenocarcinoma via controlling Rho signaling. Discover oncology 4 38008882
2021 Correction to: LncRNA ARAP1-AS1 aggravates the malignant phenotypes of ovarian cancer cells through sponging miR-4735-3p to enhance PLAGL2 expression. Cytotechnology 4 35185295
2023 lncRNA ARAP1-AS1 enhances proliferation and impairs apoptosis of lymphoma cells by sponging miR-6867-5p. Cancer biomarkers : section A of Disease markers 3 37599524
2025 Aberrant expression of GTPase-activating protein ARAP1 triggers circular dorsal ruffles associated with malignancy in hepatocellular carcinoma Hep3B cells. Cell communication and signaling : CCS 2 39934854
2024 ARAP1-AS1: a novel long non-coding RNA with a vital regulatory role in human cancer development. Cancer cell international 2 39090630
2025 ARAP1-AS1 Overexpression Increases Diffuse Large B Cell Lymphoma Progression by Sponging miR-508-5p to Activate the EMP1-PI3K/AKT Pathway. Hematological oncology 1 40227114
2025 Association of MIF rs1007888 and ARAP1 rs1552224 genetic variants with the risk of gestational diabetes mellitus in a chinese population; case study and meta-analysis. Frontiers in endocrinology 0 41036138
2025 ARAP1 fine-tunes F-actin polymerization level in lymphocytes through RhoA inhibition. Frontiers in immunology 0 41488654
2024 GTPase-activating protein ARAP1 regulates circular dorsal ruffles as a nutrient uptake mechanism in the Hep3B hepatocellular carcinoma cell line. bioRxiv : the preprint server for biology 0 38260345

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