Affinage

IQSEC1

IQ motif and SEC7 domain-containing protein 1 · UniProt Q6DN90

Length
963 aa
Mass
108.3 kDa
Annotated
2026-06-10
34 papers in source corpus 19 papers cited in narrative 19 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

IQSEC1 (BRAG2/GEP100) is a guanine nucleotide exchange factor that activates ADP-ribosylation factor GTPases (Arf6 and the class II Arf5) on negatively charged membranes to drive receptor and adhesion-molecule trafficking across diverse cellular contexts (PMID:16461286, PMID:22815487, PMID:24058294). Its catalytic Sec7 domain is constitutively coupled to an atypical PH domain that potentiates nucleotide exchange ~2,000-fold; PI(4,5)P2 binding to the PH domain lowers Km and raises kcat, restricting activity to phosphoinositide-rich membranes (PMID:24058294, PMID:22613714). This PH module is the principal regulatory hub: it docks onto phosphotyrosine residues of activated receptor tyrosine kinases — EGFR, Her2, and VEGFR2 — to trigger Arf6 activation and downstream invasion, angiogenic migration, and cadherin endocytosis (PMID:18084281, PMID:21966491, PMID:21858086), and it is engaged by Plexin-D1-generated PI(4,5)P2 to disassemble focal adhesions in endothelial cells (PMID:21795701). IQSEC1 controls integrin trafficking by binding clathrin and the AP-2 adaptor at coated pits, where it activates Arf5 to internalize β1 integrin and where it interacts with α-catenin to modulate E-cadherin and F-actin (PMID:22815487, PMID:16807291). A Ca2+-dependent complex with the lipid transfer protein ORP3 translocates to ER–plasma membrane contact sites near focal adhesions, where ORP3 allosterically activates IQSEC1 toward Arf5 to drive focal adhesion disassembly during migration (PMID:32234213). At synapses, IQSEC1 directly binds the GluA2 subunit of AMPA receptors and, downstream of NMDA receptor activation, provides the Arf6 activation required for clathrin-mediated AMPA receptor internalization and long-term depression (PMID:20547133, PMID:26884337). Biallelic loss-of-function variants in IQSEC1 cause intellectual disability and developmental delay (PMID:31607425), and whole-animal knockout is embryonic lethal owing to defective membrane trafficking in visceral endoderm (PMID:39561249).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2006 High

    Establishing that IQSEC1/BRAG2 is a physiological Arf6 GEF answered whether this protein actively controls membrane traffic, by linking it to β1 integrin surface levels and cell adhesion.

    Evidence siRNA depletion with surface integrin flow cytometry and fibronectin spreading assays

    PMID:16461286

    Open questions at the time
    • Did not define the membrane compartment or upstream receptor triggering Arf6 activation
    • Did not distinguish Arf6 from other Arf isoforms
  2. 2006 High

    Identification of α-catenin as a binding partner and stimulator of GEP100 GEF activity connected Arf6 activation to cadherin-based adhesion and the actin cytoskeleton.

    Evidence Yeast two-hybrid, co-IP of endogenous proteins, in vitro GTPγS binding, and siRNA with GEF-inactive mutants

    PMID:16807291

    Open questions at the time
    • Mechanism by which α-catenin enhances exchange not structurally defined
    • Did not establish whether E-cadherin effects are direct or downstream of Arf6
  3. 2007 High

    Demonstrating that the PH domain binds phosphotyrosine-EGFR established the direct mechanism coupling receptor tyrosine kinase signaling to Arf6 activation and cancer invasion.

    Evidence Co-IP, siRNA, overexpression in MCF7 cells, and in vivo metastasis assay

    PMID:18084281

    Open questions at the time
    • Did not resolve how phosphotyrosine binding by an atypical PH domain coexists with lipid binding
    • Generality across other RTKs not yet tested
  4. 2007 Medium

    Discovery of CRM1-dependent nucleocytoplasmic shuttling and effects on Cajal body/nucleolar architecture raised the possibility of a nuclear function distinct from membrane trafficking.

    Evidence RNAi, leptomycin B inhibition, immunofluorescence, and catalytically inactive mutant overexpression

    PMID:17461797

    Open questions at the time
    • No molecular mechanism linking BRAG2 to nucleolar/Cajal body structure
    • GEF activity dispensable, so the relevant biochemical activity is unknown
  5. 2010 High

    Identifying a direct GluA2-BRAG2 interaction and a conditional-KO LTD deficit defined IQSEC1 as the convergent Arf6 activator required for synaptic AMPA receptor internalization.

    Evidence Reciprocal co-IP, CA1-specific conditional knockout, LTD electrophysiology, and pharmacological interaction blockade

    PMID:20547133

    Open questions at the time
    • Did not identify the upstream receptor coupling synaptic activity to BRAG2
    • Did not address whether class II Arfs also contribute at synapses
  6. 2010 Medium

    Linking GEP100 to Fcγ-mediated phagocytosis extended its Arf6-GEF role into innate immune membrane internalization.

    Evidence siRNA/shRNA depletion, rescue with ARF6 mutants, immunofluorescence, and F-actin staining in macrophages

    PMID:20601426

    Open questions at the time
    • Upstream signal recruiting GEP100 to phagocytic cups unknown
    • Single-lab study without structural detail
  7. 2011 Medium

    Showing Her2 and VEGFR2 also recruit GEP100 via the PH domain generalized the phosphotyrosine-PH coupling mechanism beyond EGFR to other RTK-driven invasion and angiogenesis programs.

    Evidence Co-IP, PH domain deletion mutants, siRNA, invasion and tube formation assays, in vivo angiogenesis models

    PMID:21858086 PMID:21966491

    Open questions at the time
    • Single-lab studies for each receptor
    • Did not quantify relative affinities across receptors
  8. 2011 Medium

    Demonstrating Plexin-D1-generated PI(4,5)P2 binding to the PH domain identified a lipid-driven route to GEF activation and focal adhesion disassembly distinct from phosphotyrosine docking.

    Evidence siRNA, GEF activity assays, PI(4,5)P2 lipid-binding and cell collapse assays in endothelial cells

    PMID:21795701

    Open questions at the time
    • Single-lab biochemical study
    • Did not reconcile lipid versus phosphotyrosine engagement of the same PH domain
  9. 2012 High

    Defining the biochemical basis of PH-domain allostery showed that PIP2 binding lowers Km and raises kcat through contributions requiring the Arf N-terminus and the interdomain linker.

    Evidence In vitro single-turnover and substrate-saturation kinetics with myristoylated Arf1, PH deletion mutants, and NMR

    PMID:22613714

    Open questions at the time
    • Did not capture the full membrane-bound enzyme-substrate complex
    • Phosphoinositide specificity not fully resolved
  10. 2012 High

    Discovering that BRAG2 activates Arf5 at clathrin-coated pits and binds clathrin/AP-2 revealed that β1 integrin internalization is mediated by a class II Arf rather than Arf6.

    Evidence siRNA, co-IP with clathrin/AP-2, Arf activity assays, rapid-cycling Arf5 rescue, and coated-pit microscopy

    PMID:22815487

    Open questions at the time
    • Determinants selecting Arf5 versus Arf6 in different contexts unclear
    • Did not map the clathrin/AP-2 binding interface
  11. 2013 High

    The Arf1-BRAG2 crystal structure explained the ~2,000-fold catalytic enhancement, showing an atypical PH domain constitutively anchored to Sec7 that targets activity to negatively charged membranes.

    Evidence X-ray crystallography with reconstituted quantitative exchange kinetics and mutagenesis

    PMID:24058294

    Open questions at the time
    • Structure lacked the bound phosphoinositide that confers regulation in cells
    • Did not include receptor or partner proteins
  12. 2013 Medium

    Immunoelectron localization to postsynaptic bipolar dyad processes with PSD-95 and AMPARs confirmed a defined synaptic localization for BRAG2 distinct from BRAG3.

    Evidence Immunohistochemistry, immunoelectron microscopy, and double immunofluorescence in mouse retina

    PMID:22886754

    Open questions at the time
    • Did not establish functional consequences at retinal synapses
    • Localization descriptive only
  13. 2016 Medium

    Mapping NMDA receptor subtype-specific recruitment showed GluN2A-NMDARs engage BRAG2 to activate Arf6, defining the upstream synaptic trigger and a developmental switch from a BRAG1 pathway.

    Evidence Arf6 activity assays in cortical cultures, shRNA knockdown, and patch-clamp electrophysiology in slices

    PMID:26884337

    Open questions at the time
    • Molecular link between NMDAR activation and BRAG2 recruitment not defined
    • Single-lab electrophysiology
  14. 2019 High

    The Bragsin inhibitor and its co-crystal structure provided proof that targeting the PH-domain/membrane interface blocks activation of lipidated Arf, validating the membrane-coupled mechanism pharmacologically.

    Evidence In vitro membrane GEF assays, BRAG2-Bragsin crystallography, SAR, and cellular TGN disruption assays

    PMID:30742123

    Open questions at the time
    • Cellular TGN role of BRAG2 not mechanistically detailed
    • Selectivity over other Arf GEFs not fully characterized
  15. 2019 Medium

    Identifying biallelic loss-of-function IQSEC1 variants in patients, validated by Drosophila rescue failure and mouse cortical KO spine phenotypes, established IQSEC1 as a cause of intellectual disability and developmental delay.

    Evidence Drosophila genetic complementation, mouse conditional knockout, and dendritic spine morphology analysis

    PMID:31607425

    Open questions at the time
    • Did not connect human variants directly to a specific Arf-GEF deficit
    • Immature spine phenotype mechanism not resolved
  16. 2020 High

    Discovery of the Ca2+-triggered IQSec1-ORP3 complex at ER-PM contact sites defined a lipid-transfer-coupled mode of Arf5 activation driving focal adhesion disassembly.

    Evidence Co-IP, siRNA, live-cell calcium imaging, Arf5 activity and lipid transfer assays, and FA disassembly quantification

    PMID:32234213

    Open questions at the time
    • How ORP3 allosterically activates IQSec1 structurally undefined
    • Single-lab study
  17. 2024 Medium

    CRISPR knockout demonstrating embryonic lethality with absent apical vacuoles in visceral endoderm established an essential developmental role in membrane trafficking.

    Evidence CRISPR/Cas9 knockout and electron microscopy of embryonic visceral endoderm

    PMID:39561249

    Open questions at the time
    • Which Arf and cargo pathway underlies the visceral endoderm defect not defined
    • Single-lab ultrastructural study

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the single PH domain integrates competing inputs — receptor phosphotyrosine, phosphoinositides, and partner proteins like α-catenin and ORP3 — to select between Arf5 and Arf6 in a context-specific manner.
  • No structure of the membrane-bound enzyme with a phosphotyrosine receptor
  • Determinants of Arf5 versus Arf6 substrate selection unknown
  • Mechanism linking nuclear shuttling and Sec7-independent apoptosis to canonical GEF function 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
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-112316 Neuronal System 2
Partners
ARF5ARF6CTNNA1EGFRERBB2GRIA2ORP3VEGFR2
Complex memberships
AP-2 adaptor / clathrin coatIQSEC1-ORP3 complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 GEP100/BRAG2, via its pleckstrin homology (PH) domain, directly binds to Tyr1068/1086-phosphorylated EGFR and thereby activates Arf6 to induce breast cancer cell invasion. Co-immunoprecipitation, siRNA knockdown, overexpression in MCF7 cells, in vivo metastasis assay Nature cell biology High 18084281
2006 BRAG2 (GEP100) activates Arf6 in vivo and controls endocytosis of β1 integrins; siRNA depletion of BRAG2 causes accumulation of β1 integrin on the cell surface and enhanced cell adhesion/spreading on fibronectin. siRNA knockdown, flow cytometry for surface integrin, cell spreading assay on fibronectin Current biology : CB High 16461286
2006 GEP100/BRAG2 interacts with α-catenin (identified by yeast two-hybrid and confirmed by co-immunoprecipitation of endogenous proteins), and α-catenin enhances GEP100-stimulated GTPγS binding by ARF6 in vitro. Depletion of GEP100 by siRNA increases E-cadherin levels ~3-fold and blocks HGF-induced E-cadherin redistribution. Overexpression of GEP100 (but not its GEF-inactive mutants) markedly reduces F-actin. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, in vitro GTPγS binding assay, overexpression with GEF-inactive mutants Proceedings of the National Academy of Sciences of the United States of America High 16807291
2010 BRAG2 directly interacts with the GluA2 subunit of AMPA receptors; BRAG2-mediated Arf6 activation is controlled by ligand-binding and tyrosine phosphorylation of GluA2 and is required for clathrin-mediated endocytosis of synaptic AMPA receptors during LTD. Targeted deletion of BRAG2 in CA1 pyramidal neurons prevents LTD. Co-immunoprecipitation (direct GluA2-BRAG2 interaction), conditional neuron-specific knockout, electrophysiology (LTD recordings), pharmacological blockade of GluA2-BRAG2 interaction Neuron High 20547133
2012 In addition to Arf6, endogenous BRAG2 also activates class II Arfs, specifically Arf5, at clathrin-coated pits; it is Arf5 (not Arf6) that mediates β1 integrin internalization via clathrin-mediated endocytosis. BRAG2 binds clathrin and the AP-2 adaptor complex. siRNA knockdown, co-immunoprecipitation of BRAG2 with clathrin/AP-2, Arf activity assays, rapid-cycling Arf5 rescue, fluorescence microscopy of clathrin-coated pits The Journal of biological chemistry High 22815487
2013 Crystal structure of Arf1-BRAG2 complex reveals an atypical PH domain constitutively anchored to the Sec7 domain; the PH domain potentiates nucleotide exchange ~2,000-fold by cumulative conformational and membrane-targeting contributions, and restricts BRAG2 activity to negatively charged membranes without phosphoinositide specificity via a positively charged surface peripheral to the canonical lipid-binding pocket. X-ray crystallography, quantitative exchange activity reconstituted on membranes, mutagenesis PLoS biology High 24058294
2012 Brag2 PH domain allosterically stimulates nucleotide exchange: PIP2 binding to the PH domain decreases Km and increases kcat; this effect requires the PH domain and the N-terminus of Arf and is largely independent of Arf myristoylation. The interdomain linker between Sec7 and PH domains contributes to activity. In vitro single-turnover and substrate-saturation kinetics with myristoylated Arf1·GDP, PH domain deletion mutants, NMR structural analysis The Journal of biological chemistry High 22613714
2011 Overexpressed Her2, when autonomously phosphorylated at Tyr1139/Tyr1196, recruits GEP100 via the GEP100 PH domain to activate Arf6 and induce invasion independently of external ligands, analogous to the EGFR-GEP100 mechanism. Co-immunoprecipitation, PH domain deletion mutants, siRNA knockdown, invasion assays PloS one Medium 21966491
2011 Upon Sema3E activation, Plexin-D1 recruits phosphatidylinositol-4-phosphate 5-kinase; the resulting PI(4,5)P2 binds the PH domain of GEP100/BRAG2, enhancing its GEF activity toward Arf6 to disassemble integrin-mediated focal adhesions in endothelial cells. siRNA knockdown, GEF activity assays, PI(4,5)P2 lipid-binding assays, cell adhesion/collapse assays The Journal of biological chemistry Medium 21795701
2011 VEGFR2, like EGFR, recruits GEP100 to activate Arf6 in HUVECs, and the GEP100-Arf6-AMAP1-cortactin pathway is essential for VEGF-induced angiogenic cell migration, tubular formation, VE-cadherin endocytosis, and increased permeability. siRNA knockdown, Co-immunoprecipitation of VEGFR2-GEP100, cell migration/tube formation assays, in vivo angiogenesis models PloS one Medium 21858086
2010 GEP100 regulates phagocytosis of IgG-coated beads and serum-treated zymosan in monocyte-macrophage cells in an ARF6-dependent manner, requiring its Sec7 (ARF-activating) domain; GEP100 and ARF6 co-localize around internalized particles, and constitutively active ARF6Q67N rescues phagocytosis in GEP100-depleted cells. siRNA/shRNA depletion, rescue with ARF6 constitutively active/dominant-negative mutants, immunofluorescence microscopy, F-actin staining The Journal of biological chemistry Medium 20601426
2020 IQSec1 forms a complex with the lipid transfer protein ORP3; Ca2+ influx via STIM1/Orai1 channels near focal adhesions triggers PKC-dependent translocation of this IQSec1-ORP3 complex to ER/plasma membrane contact sites adjacent to focal adhesions, where IQSec1 is allosterically activated by ORP3 to activate Arf5 (not Arf6), driving focal adhesion disassembly. ORP3-mediated PI4P extraction from the PM is also required for FA turnover. Co-immunoprecipitation, siRNA knockdown, live-cell calcium imaging, immunofluorescence, Arf5 activity assays, lipid transfer assays, FA disassembly quantification eLife High 32234213
2019 Small molecule Bragsin inhibits BRAG2-mediated Arf GTPase activation in vitro in a membrane-dependent, non-competitive manner; crystal structure reveals Bragsin binds at the interface between the BRAG2 PH domain and the lipid bilayer, preventing BRAG2 from activating lipidated Arf. In cells, Bragsin affects the trans-Golgi network in a BRAG2- and Arf-dependent manner. In vitro Arf GEF activity assays with membranes, X-ray crystallography of BRAG2-Bragsin complex, structure-activity relationship, cellular TGN disruption assays Nature chemical biology High 30742123
2016 In mature hippocampal cultures, GluN2A-containing NMDARs recruit BRAG2 to activate Arf6 upon NMDA stimulation; in young cultures, tonic Arf6 activation is mediated by GluN2B-BRAG1 instead. Knockdown of BRAG2 during postnatal weeks 4–5 reduces AMPAR miniature event frequency and quantal sizes of both AMPAR and NMDAR currents at Schaffer collateral synapses. Biochemical Arf6 activity assays in cortical cultures, shRNA knockdown, patch-clamp electrophysiology in acute hippocampal slices The Journal of biological chemistry Medium 26884337
2007 BRAG2 cycles between the cytoplasm and nucleus in a CRM1/exportin1-dependent manner. Depletion of BRAG2 by RNAi increases the number of Cajal bodies and alters nucleolar structure (less focal fibrillarin staining). Ectopic expression of nuclear GTPase PIKE/AGAP2 causes both BRAG2 and coilin to accumulate in nucleoli, resulting in fibrillarin redistribution to the nucleolar periphery; neither PIKE GTPase activity nor BRAG2 nucleotide exchange activity is required for this nucleolar concentration. RNAi knockdown, CRM1 inhibition (leptomycin B), immunofluorescence microscopy, overexpression with catalytically inactive mutants Traffic (Copenhagen, Denmark) Medium 17461797
2006 Overexpression of GEP100/BRAG2a in macrophage-like cells induces apoptosis (chromatin condensation, annexin V staining, TUNEL); a Sec7-domain deletion mutant lacking ARF-activating ability still induces apoptosis to the same level, suggesting the pro-apoptotic function is independent of ARF activation. GEP100 silencing suppresses TNF-α-induced apoptosis. Overexpression with Sec7 deletion mutant, Annexin V staining, TUNEL assay, morphological analysis, siRNA knockdown Journal of leukocyte biology Low 16877676
2019 Biallelic loss-of-function variants in IQSEC1 (p.Thr343Met and p.Arg321Gln) cause intellectual disability and developmental delay; in Drosophila, these variants fail to rescue embryonic lethality caused by loss of the IQSEC1 ortholog schizo, while the reference cDNA does rescue, confirming loss-of-function. Conditional deletion of Iqsec1 in mouse cortical neurons leads to increased density of immature dendritic spines. Drosophila genetic complementation/rescue assay, mouse conditional knockout (cortical neurons), dendritic spine morphology analysis American journal of human genetics Medium 31607425
2024 Iqsec1 knockout mice (CRISPR/Cas9) exhibit embryonic lethality (~99%); electron microscopy shows that Iqsec1-/- embryos at E8.5 lack large apical vacuoles in visceral endoderm cells of the yolk sac, indicating a critical role for IQSEC1 in membrane trafficking in visceral endoderm during embryogenesis. CRISPR/Cas9 knockout, electron microscopy of embryonic visceral endoderm FEBS letters Medium 39561249
2013 BRAG2 localizes to postsynaptic processes of bipolar dyads in the inner plexiform layer of the mouse retina and co-localizes preferentially with PSD-95 and AMPARs, as demonstrated by immunoelectron microscopy and double immunostaining; distinct from BRAG3 which localizes to inhibitory synapses. Immunohistochemistry, immunoelectron microscopy, double immunofluorescence The Journal of comparative neurology Medium 22886754

Source papers

Stage 0 corpus · 34 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 GEP100 links epidermal growth factor receptor signalling to Arf6 activation to induce breast cancer invasion. Nature cell biology 189 18084281
2010 AMPA receptor signaling through BRAG2 and Arf6 critical for long-term synaptic depression. Neuron 132 20547133
2006 The Arf6 GEF GEP100/BRAG2 regulates cell adhesion by controlling endocytosis of beta1 integrins. Current biology : CB 101 16461286
2009 The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis. Traffic (Copenhagen, Denmark) 98 19416474
2006 GEP100/BRAG2: activator of ADP-ribosylation factor 6 for regulation of cell adhesion and actin cytoskeleton via E-cadherin and alpha-catenin. Proceedings of the National Academy of Sciences of the United States of America 64 16807291
2020 Calcium-stimulated disassembly of focal adhesions mediated by an ORP3/IQSec1 complex. eLife 60 32234213
2011 GEP100-Arf6-AMAP1-cortactin pathway frequently used in cancer invasion is activated by VEGFR2 to promote angiogenesis. PloS one 57 21858086
2012 BRAG2/GEP100/IQSec1 interacts with clathrin and regulates α5β1 integrin endocytosis through activation of ADP ribosylation factor 5 (Arf5). The Journal of biological chemistry 47 22815487
2013 Integrated conformational and lipid-sensing regulation of endosomal ArfGEF BRAG2. PLoS biology 44 24058294
2011 Phosphatidylinositol-4-phosphate 5-kinase and GEP100/Brag2 protein mediate antiangiogenic signaling by semaphorin 3E-plexin-D1 through Arf6 protein. The Journal of biological chemistry 43 21795701
2011 Engagement of overexpressed Her2 with GEP100 induces autonomous invasive activities and provides a biomarker for metastases of lung adenocarcinoma. PloS one 43 21966491
2019 PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling. Nature chemical biology 35 30742123
2012 The pleckstrin homology (PH) domain of the Arf exchange factor Brag2 is an allosteric binding site. The Journal of biological chemistry 35 22613714
2019 Bi-allelic Variants in IQSEC1 Cause Intellectual Disability, Developmental Delay, and Short Stature. American journal of human genetics 31 31607425
2016 Subunit-selective N-Methyl-d-aspartate (NMDA) Receptor Signaling through Brefeldin A-resistant Arf Guanine Nucleotide Exchange Factors BRAG1 and BRAG2 during Synapse Maturation. The Journal of biological chemistry 30 26884337
2012 GEP100/Arf6 is required for epidermal growth factor-induced ERK/Rac1 signaling and cell migration in human hepatoma HepG2 cells. PloS one 28 22701712
2013 Distinct synaptic localization patterns of brefeldin A-resistant guanine nucleotide exchange factors BRAG2 and BRAG3 in the mouse retina. The Journal of comparative neurology 26 22886754
2013 GEP100 regulates epidermal growth factor-induced MDA-MB-231 breast cancer cell invasion through the activation of Arf6/ERK/uPAR signaling pathway. Experimental cell research 23 23747719
2014 Brag2 differentially regulates β1- and β3-integrin-dependent adhesion in endothelial cells and is involved in developmental and pathological angiogenesis. Basic research in cardiology 21 24522833
2013 Co-overexpression of GEP100 and AMAP1 proteins correlates with rapid local recurrence after breast conservative therapy. PloS one 18 24116160
2010 The guanine nucleotide exchange protein for ADP-ribosylation factor 6, ARF-GEP100/BRAG2, regulates phagocytosis of monocytic phagocytes in an ARF6-dependent process. The Journal of biological chemistry 18 20601426
2012 Down-regulation of GEP100 causes increase in E-cadherin levels and inhibits pancreatic cancer cell invasion. PloS one 17 22662237
2016 Inhibition of epithelial-mesenchymal transition by cetuximab via the EGFR-GEP100-Arf6-AMAP1 pathway in head and neck cancer. Head & neck 16 27880014
2018 GEP100/ARF6 regulates VEGFR2 signaling to facilitate high-glucose-induced epithelial-mesenchymal transition and cell permeability in retinal pigment epithelial cells. American journal of physiology. Cell physiology 15 30540496
2008 The EGFR-GEP100-Arf6 pathway in breast cancer: Full invasiveness is not from the inside. Cell adhesion & migration 15 19262097
2013 Aging-induced proteostatic changes in the rat hippocampus identify ARP3, NEB2 and BRAG2 as a molecular circuitry for cognitive impairment. PloS one 13 24069387
2007 Nuclear functions of the Arf guanine nucleotide exchange factor BRAG2. Traffic (Copenhagen, Denmark) 11 17461797
2022 circ-Iqsec1 induces bone marrow-derived mesenchymal stem cell (BMSC) osteogenic differentiation through the miR-187-3p/Satb2 signaling pathway. Arthritis research & therapy 10 36517907
2006 Involvement of a guanine nucleotide-exchange protein, ARF-GEP100/BRAG2a, in the apoptotic cell death of monocytic phagocytes. Journal of leukocyte biology 6 16877676
2020 Discrete localization patterns of Arf6, and its activators EFA6A and BRAG2, and its effector PIP5kinaseγ on myofibrils of myotubes and plasma membranes of myoblasts in developing skeletal muscles of mice. Acta histochemica 4 32059926
2024 The Abl-interactor Abi suppresses the function of the BRAG2 GEF family member Schizo. Biology open 1 34897417
2024 Disruption of Iqsec1 in mice leads to embryonic lethality with reduced large apical vacuoles in the visceral endoderm. FEBS letters 1 39561249
2018 Downregulation of GEP100 Improved the Growth Inhibition Effect of Erlotinib Through Modulating Mesenchymal Epithelial Transition Process in Pancreatic Cancer. Pancreas 1 29851753
2026 Novel Biallelic Variants in IQSEC1 in a Patient With Intellectual Developmental Disorder With Short Stature and Behavioral Abnormalities (IDDSSBA) and Corpus Callosum Dysgenesis. American journal of medical genetics. Part A 0 41738068

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