Affinage

ASAP1

Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 1 · UniProt Q9ULH1

Length
1129 aa
Mass
125.5 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASAP1 is a multi-domain ArfGAP scaffold protein that integrates membrane remodeling, actin cytoskeletal dynamics, and vesicular trafficking through its enzymatic and structural activities. Its PH domain cooperatively binds PtdIns(4,5)P2 at two sites, allosterically positioning membrane-anchored Arf1-GTP for catalytic GTP hydrolysis via the arginine finger Arg-497, with the N-BAR domain exerting autoinhibitory control over GAP activity through intramolecular contacts (PMID:26365802, PMID:17112341, PMID:19017632, PMID:37989735). The N-BAR domain additionally binds and bundles F-actin directly, tubulates membranes, and serves as a binding platform for NM2A and GEFH1, while the C-terminal SH3 domain recruits FAK and CrkL to focal adhesions; Src-mediated tyrosine phosphorylation and these scaffolding interactions are required for podosome/invadopodium formation, cell spreading, and migration (PMID:32444496, PMID:17893324, PMID:12058076, PMID:26893376). ASAP1 also scaffolds an Arf4–Rab11–FIP3–Rabin8–Rab8 complex that targets rhodopsin and other sensory receptors to primary cilia, and its loss abolishes ciliary receptor trafficking (PMID:22983554, PMID:25673879).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Establishing ASAP1 as a PIP2-dependent ArfGAP with Src-family and Crk interactions defined its molecular identity and placed it at the intersection of Arf signaling, phosphoinositide regulation, and tyrosine-kinase pathways.

    Evidence In vitro GAP assay with purified protein, GST pulldown and co-IP for Src/Crk binding, tyrosine phosphorylation in activated-Src cells

    PMID:9819391

    Open questions at the time
    • Physiological substrates among Arf isoforms in cells not determined
    • Tyrosine phosphorylation site identity and functional consequence unknown
    • No structural information on multi-domain architecture
  2. 2001 High

    Demonstration that ASAP1 localizes to focal adhesions, regulates cell spreading and migration in a GAP-activity-dependent manner, and acts on Arf1 (not Arf6) in cells connected its enzymatic specificity to cytoskeletal remodeling phenotypes.

    Evidence Fluorescence microscopy, overexpression of WT and GAP-inactive mutants, cell-based ARF GAP assay, chemotaxis assays

    PMID:10725410 PMID:11773070

    Open questions at the time
    • Mechanism linking Arf1 GTP hydrolysis to focal adhesion dynamics unknown
    • Contribution of non-catalytic domains not dissected
  3. 2003 High

    Identification of direct FAK and CrkL interactions mapped how ASAP1 is recruited to focal adhesions and linked its scaffold function to focal adhesion assembly independent of catalysis.

    Evidence Yeast two-hybrid, reciprocal co-IP, GST pulldown, SH3/SH2-domain mutant analysis, cell spreading assays

    PMID:12058076 PMID:12522101

    Open questions at the time
    • Whether FAK phosphorylates ASAP1 and its consequence unknown
    • CrkL–ASAP1 interaction validated in a single lab
  4. 2004 High

    Defining the Arf1 N-terminal extension (residues 2–17) as a critical substrate-recognition determinant for ASAP1 resolved how ASAP1 discriminates among Arf family members.

    Evidence In vitro GAP assay with Arf1 deletion/point mutants, direct peptide binding

    PMID:15212764

    Open questions at the time
    • Structural basis of the N-terminus–ASAP1 interface not resolved at atomic level
    • How this recognition interface operates on membrane surfaces unknown
  5. 2006 High

    Discovery that the BAR domain dimerizes, tubulates membranes, and promotes EGFR recycling established ASAP1 as a membrane-bending protein linking Arf signaling to receptor trafficking.

    Evidence Recombinant BAR-PH biophysics, LUV tubulation with EM, EGFR trafficking assays in cells

    PMID:16431365

    Open questions at the time
    • Endogenous role in EGFR trafficking not confirmed by loss-of-function
    • How Arf1-GTP binding regulates BAR-mediated tubulation structurally unresolved
  6. 2007 High

    Kinetic characterization identified Arg-497 as the catalytic arginine finger and established a conformational-transition mechanism for GAP-catalyzed GTP hydrolysis, while siRNA experiments showed ASAP1 is required for podosome/invadopodium formation via Src phosphorylation and the BAR/SH3 domains rather than GAP activity alone.

    Evidence Steady-state and single-turnover kinetics with mutagenesis; siRNA knockdown and systematic domain-mutant rescue in podosome/invadopodium assays

    PMID:17112341 PMID:17893324

    Open questions at the time
    • Identity of the Src phosphorylation site critical for podosomes not mapped
    • How BAR and SH3 domains cooperate in podosome nucleation mechanistically unclear
  7. 2008 High

    NMR and kinetic analyses revealed that the BAR domain autoinhibits GAP activity via its N-terminal loop and that the PH domain allosterically communicates PIP2 binding to the ArfGAP domain, establishing a multi-layered intramolecular regulatory mechanism.

    Evidence NMR spectroscopy of PH–ArfGAP interdomain contacts, LUV-based kinetics with BAR-loop and PH-domain mutants

    PMID:18675341 PMID:19017632

    Open questions at the time
    • Full-length ASAP1 structure not available
    • How autoinhibition is relieved by physiological signals undefined
  8. 2011 Medium

    Identification of GEFH1 as a BAR-domain-binding negative regulator of podosomes through ASAP1 added a RhoA-GEF input to the ASAP1 signaling nexus at podosomes.

    Evidence Yeast two-hybrid, endogenous co-IP, overexpression and siRNA with podosome/GAP readouts

    PMID:21352810

    Open questions at the time
    • Whether GEFH1 activates RhoA locally at podosomes through ASAP1 not tested
    • GEFH1–ASAP1 interaction confirmed in single lab
  9. 2012 High

    Demonstrating that ASAP1 scaffolds an Arf4–Rab11–Rabin8–Rab8 complex for rhodopsin ciliary targeting revealed a non-cytoskeletal function: coordinating the Arf-to-Rab cascade at the base of primary cilia.

    Evidence siRNA/shRNA ablation with ciliary targeting readout, co-IP of multi-protein complex, FR motif mutagenesis

    PMID:22983554

    Open questions at the time
    • Whether ASAP1 GAP activity is required for ciliary targeting not resolved
    • Generalizability to other ciliary cargo beyond rhodopsin not established
  10. 2015 High

    Crystal structures of the PH domain with and without PtdIns(4,5)P2, combined with mutagenesis, established a cooperative two-site PIP2 binding mechanism enabling switch-like regulation of GAP activity, while FIP3 was shown to coordinate ASAP1 and Rab11a in ciliary transport.

    Evidence X-ray crystallography of apo and PIP2-bound PH domain, LUV binding/GAP assays with C/A-site mutants; co-IP and competition binding for FIP3

    PMID:25673879 PMID:26365802

    Open questions at the time
    • Full kinetic model of cooperativity with membrane-reconstituted protein lacking
    • FIP3 competition mechanism not structurally resolved
  11. 2016 High

    Direct binding of NM2A to the BAR-PH tandem and reciprocal knockdown phenocopy established ASAP1 as a positive regulator of actomyosin contractility at focal adhesions and circular dorsal ruffles.

    Evidence In vitro binding, reciprocal co-IP, siRNA KD phenocopy, NM2A rescue of ASAP1-KD CDR defect

    PMID:26893376

    Open questions at the time
    • Whether NM2A binding competes with actin bundling by the BAR domain not tested
    • Structural basis of BAR-PH–NM2A interaction unknown
  12. 2019 High

    Reconstitution showed the N-BAR domain directly binds and bundles F-actin and that PIP2-dependent PH domain interaction with the Arf1 N-terminal extension is a key determinant of GAP regulation, unifying the actin-remodeling and catalytic functions in a single mechanistic framework.

    Evidence Actin cosedimentation/bundling, TIRF, EM; GAP assays with N-terminally truncated Arf1 and PH-domain mutants

    PMID:31591270 PMID:31785555

    Open questions at the time
    • How simultaneous actin bundling and membrane tubulation are coordinated unclear
    • Relative contributions of actin bundling vs. GAP activity to cell migration not separated
  13. 2020 High

    Biophysical studies revealed that cooperative PIP2 binding orients the PH domain at the membrane surface, and the PH domain in turn locks membrane-anchored Arf1 in a conformation competent for GTP hydrolysis, completing a structural model of allosteric catalytic activation.

    Evidence NMR, neutron reflectometry, MD simulations of PH domain–membrane and Arf1–membrane complexes

    PMID:32998886 PMID:37989735

    Open questions at the time
    • Full-length ASAP1 on membranes not yet visualized structurally
    • How BAR-domain autoinhibition integrates with PH-domain membrane orientation unknown
  14. 2023 Medium

    A novel non-GAP function was described in which ASAP1 stabilizes IQGAP1 by inhibiting its ubiquitin-mediated degradation, thereby activating CDC42 and EGFR-MAPK signaling in cancer cells.

    Evidence Co-IP, ubiquitination assay, siRNA/overexpression, xenograft

    PMID:36792578

    Open questions at the time
    • Whether ASAP1 directly deubiquitinates IQGAP1 or prevents ubiquitin ligase access not distinguished
    • Single lab, not independently replicated
    • Relevance beyond gastric cancer unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length ASAP1 structure on membranes that explains how BAR-mediated autoinhibition, PIP2-driven allosteric activation, actin bundling, and scaffold interactions are coordinated spatiotemporally remains unresolved.
  • No full-length atomic structure of ASAP1
  • Mechanism by which Src phosphorylation relieves autoinhibition and promotes podosomes not structurally defined
  • How ASAP1 partitions between focal adhesion, podosome, and ciliary functions in a single cell unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 6 GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 2 GO:0005929 cilium 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1852241 Organelle biogenesis and maintenance 2
Partners
ARF1ARF4CRKLFAKFIP3GEFH1MYH9RAB11A

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ASAP1 is a PIP2-dependent Arf GTPase-activating protein (GAP) with activity on Arf1 and Arf5 (less on Arf6, none on Arl2) in vitro. It contains PH, zinc finger, and ANK repeat domains that together confer PIP2-dependent GAP activity. ASAP1 associates with SH3 domains of Src family members and the Crk adapter protein via a proline-rich class II Src SH3 binding site, and is phosphorylated on tyrosine residues in cells expressing activated Src. Protein purification, in vitro GAP assay, GST pulldown, co-immunoprecipitation, tyrosine phosphorylation in cells with activated Src Molecular and cellular biology High 9819391
2000 ASAP1 localizes to focal adhesions and cycles with focal adhesion proteins during cell migration. Overexpression of wild-type ASAP1 alters focal adhesion morphology and blocks cell spreading and dorsal ruffle formation induced by PDGF, while a GAP-inactive mutant has reduced effect on spreading and increases dorsal ruffle formation, indicating ASAP1 regulates cytoskeletal remodeling through its GAP activity. Fluorescence microscopy, overexpression of wild-type and GAP-inactive mutants, cell spreading and dorsal ruffle assays Proceedings of the National Academy of Sciences of the United States of America High 10725410
2001 DEF-1/ASAP1 functions as a GAP for ARF1 but not ARF6 in vivo (cell-based ARF GAP assay), distinguishing its substrate specificity from other ARF GAPs. Stable expression of DEF-1 enhances cell migration in a GAP-activity-dependent manner, while inhibition of cell spreading is GAP-activity-independent, indicating DEF-1 modulates motility and spreading through different pathways. Cell-based ARF GAP assay, stable cell line generation, chemotaxis/motility assays, GAP-domain deletion mutant analysis The Journal of biological chemistry High 11773070
2002 ASAP1 directly binds focal adhesion kinase (FAK) via an interaction between the C-terminal SH3 domain of ASAP1 and the second proline-rich motif in the C-terminal region of FAK. This interaction contributes to focal adhesion assembly: overexpression of wild-type ASAP1 inhibits cell spreading and prevents efficient organization of paxillin and FAK in focal adhesions, while a FAK-binding-deficient ASAP1 truncation or GAP-inactive variant has less pronounced effects. Affinity chromatography, yeast two-hybrid, GST pulldown, co-immunoprecipitation, cell spreading assays, fluorescence microscopy Molecular biology of the cell High 12058076
2003 CrkL binds ASAP1 and directs its localization to peripheral focal adhesions. In spreading platelets, endogenous ASAP1 localizes at peripheral focal adhesions. Co-expression of wild-type CrkL (but not an SH2-mutated CrkL that cannot localize at focal adhesions) recruits ASAP1 to CrkL-induced focal adhesions, indicating CrkL links ASAP1 to focal adhesions via CrkL's SH2 domain-dependent focal adhesion targeting. Pulldown with mass spectrometry identification, co-immunoprecipitation, overexpression in COS7 cells, fluorescence microscopy The Journal of biological chemistry Medium 12522101
2006 The N-terminal BAR domain of ASAP1, together with the PH domain, dimerizes to form an extended structure that binds large unilamellar vesicles containing acidic phospholipids and bends vesicle membranes to form tubular structures in vitro. This membrane-bending activity is regulated by Arf1-GTP binding to the ArfGAP domain. In cells, ASAP1 BAR domain-containing mutants induced tubular structures containing EGFR and Rab11, and ASAP1 colocalized with EGFR during receptor recycling; expression of ASAP1 accelerated EGFR trafficking and slowed cell spreading in a BAR-domain-dependent manner. Recombinant protein biophysics, large unilamellar vesicle (LUV) binding and tubulation assays, electron microscopy, live-cell fluorescence microscopy, EGFR trafficking assays Current biology : CB High 16431365
2007 Both ASAP1a and ASAP1b splice variants associate with invadopodia and podosomes. Reduction of ASAP1 by siRNA blocks formation of invadopodia and podosomes. Podosome formation requires ASAP1's BAR domain, SH3 domain, and Src phosphorylation site, but not the Src binding site or GAP activity per se. ASAP1 is thus a critical downstream target of tyrosine kinase signaling (Src) in podosome and invadopodium assembly, functioning as a potential coincidence detector of SH3-domain protein association and Src phosphorylation. siRNA knockdown, recombinant mutant rescue, fluorescence microscopy, live-cell FRAP Molecular and cellular biology High 17893324
2007 ASAP1 uses Arf1-GTP as a substrate with a kcat of ~57 s⁻¹ and Km of ~2.2 μM (steady-state), forming a binary Arf1-GTP–ASAP1 complex that is stabilized by AlF4⁻. Arg-497 is the catalytic arginine finger (mutations reduce kcat >> Km). Mutations in residues Trp-479, Ile-490, Arg-505, Leu-511, and Asp-512 also primarily affect kcat rather than Km, suggesting a conformational transition to the catalytically active state. ASAP1 mutants lacking activity in vitro also lack activity in a dorsal ruffle cell-based assay. Steady-state and single-turnover kinetics with LUVs, AlF4⁻ stabilization, site-directed mutagenesis, in vivo dorsal ruffle assay The Biochemical journal High 17112341
2008 The BAR domain of ASAP1 autoinhibits GAP activity through intraprotein interactions. The BAR-PZA protein has greater Km and smaller kcat than PZA (PH-ArfGAP-Ank) alone on LUV surfaces. This effect depends on the N-terminal loop of the BAR domain and is not due to differential membrane association or changes in vesicle curvature, suggesting the BAR domain modulates the catalytic mechanism of the adjacent PH and GAP domains. Recombinant protein LUV-based kinetic assays, BAR domain loop deletion mutants, analytical ultracentrifugation The Journal of biological chemistry High 19017632
2008 NMR spectroscopy and biochemical analysis reveal that the PH domain of ASAP1 dynamically interacts with the ArfGAP and ankyrin repeat domains. The PH-ArfGAP domain interaction partially occludes the PIP2 binding site in the soluble protein, but the PIP2 binding site is accessible when ASAP1 is membrane-bound. PIP2 binding alters PH domain conformation; mutations in the PH domain loop contacting the ArfGAP domain affect PIP2 binding and both Km and kcat for Arf1-GTP hydrolysis. NMR spectroscopy, analytical ultracentrifugation, PIP2 binding assay, GAP activity kinetics with point mutants Cellular signalling High 18675341
2011 GEFH1, a RhoA guanine nucleotide exchange factor, binds the BAR domain of ASAP1. Endogenous GEFH1 co-immunoprecipitates with ASAP1 and colocalizes with ASAP1 in podosomes. Overexpression of GEFH1 inhibits podosome assembly and ASAP1 GAP catalytic activity; a GEFH1 mutant lacking the BAR-domain binding region is less effective. siRNA knockdown of GEFH1 does not affect matrix degradation but increases the rate of podosome assembly. GEFH1 is therefore a negative regulator of podosomes acting via ASAP1. Yeast two-hybrid screening, co-immunoprecipitation, fluorescence microscopy, overexpression and siRNA knockdown, GAP activity assay Biochemical and biophysical research communications Medium 21352810
2012 The Arf GAP ASAP1 serves as a scaffold for ciliary receptor targeting of rhodopsin. ASAP1 brings together Arf4 (GTP-bound), Rab11, Rab8, and the Rab8-GEF Rabin8 into a complex. Ablation of ASAP1 abolishes ciliary targeting and causes formation of actin-rich periciliary membrane projections with mislocalized rhodopsin. ASAP1 recognizes the FR ciliary targeting signal of rhodopsin; the rhodopsin FR→AA mutant fails to interact with Rab8 and fails to cross the periciliary diffusion barrier. siRNA/shRNA ablation, co-immunoprecipitation, fluorescence and electron microscopy, ciliary targeting assays, ciliary signal mutant analysis The EMBO journal High 22983554
2015 The PH domain of ASAP1 binds PtdIns(4,5)P2 at two sites: a canonical (C) site and an atypical (A) site. Structures of unliganded and dibutyryl-PtdIns(4,5)P2-bound PH domain were solved. PtdIns(4,5)P2 dependence of LUV binding and GAP activity is sigmoidal (cooperative), and mutations in either the C or A site reduce both PIP2-dependent vesicle binding and GAP activity, supporting a cooperative two-site PIP2 binding mechanism that enables rapid switching of ASAP1 activity. X-ray crystallography, LUV binding assays, GAP activity assays, site-directed mutagenesis, comparison with PLC-δ1 PH domain Structure (London, England : 1993) High 26365802
2015 FIP3 (RAB11FIP3), an Arf and Rab11 effector, promotes the activity of Rab11a and ASAP1 in Arf4-dependent ciliary transport of rhodopsin. FIP3 competes with rhodopsin for binding to ASAP1 and displaces rhodopsin from the ternary Arf4-GTP–ASAP1 complex. FIP3 also coordinates ASAP1 and Rab11a interactions with Rabin8, facilitating the Rab11-Rabin8-Rab8 cascade assembly for ciliary receptor trafficking. Co-immunoprecipitation, competition binding assays, siRNA ablation with ciliary targeting readout, fluorescence microscopy Journal of cell science High 25673879
2015 ASAP1 knockdown in mouse mammary gland leads to a marked increase in repopulating activity in vivo, indicating ASAP1 acts as a negative regulator of mammary stem cell activity. Pooled shRNA screen in primary mammary cells, in vivo transplantation assay, RNA-seq expression profiling BMC cancer Medium 25879659
2015 ASAP1-depleted dendritic cells show impaired matrix degradation and migration, and rs10956514 is associated with the level of reduction of ASAP1 expression after M. tuberculosis infection. ASAP1 is highly expressed in dendritic cells and involved in podosome formation and actin/membrane remodeling; its depletion impairs DC migration in the context of TB susceptibility. siRNA knockdown of ASAP1 in DCs, matrix degradation assay, migration assay, eQTL analysis linking SNP to ASAP1 expression Nature genetics Medium 25774636
2016 ASAP1 directly binds nonmuscle myosin 2A (NM2A) through the BAR-PH tandem domain in vitro, and ASAP1 and NM2A co-immunoprecipitate and colocalize in cells. Knockdown of ASAP1 reduces colocalization of NM2A and F-actin. ASAP1 and NM2A knockdowns recapitulate each other's effects on focal adhesions, cell migration, cell spreading, and circular dorsal ruffles (CDRs). Exogenous NM2A rescues ASAP1 knockdown effects on CDRs but not vice versa, indicating ASAP1 is a positive regulator of NM2A. In vitro binding assay, co-immunoprecipitation, siRNA knockdown, fluorescence microscopy, functional assays (spreading, migration, CDRs) The Journal of biological chemistry High 26893376
2019 Loss of ASAP1 in mice leads to defects in adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Mechanistically, FAK/Src and PI3K/AKT signaling are compromised in Asap1GT/GT MEFs, leading to impaired adipogenic and osteogenic differentiation, while chondrogenic differentiation is accelerated. Gene-trap mouse model, in vivo histology, in vitro differentiation assays, kinase signaling analysis PLoS genetics Medium 31246957
2019 The N-BAR domain of ASAP1 directly controls actin stress fiber organization. ASAP1 depletion causes defects in stress fiber organization while overexpression enhances actin remodeling; the BAR-PH fragment is sufficient for this effect. The BAR-PH tandem of ASAP1 directly binds and bundles actin filaments in vitro; the ArfGAP and C-terminal SH3 domains reduce filament binding and bundling by the BAR-PH domain. siRNA knockdown, overexpression, actin cosedimentation/bundling assays, fluorescence microscopy iScience High 31785555
2019 PIP2 regulates binding of the ASAP1 PH domain to the N-terminal extension (residues 2–17) of ARF1, thereby contributing to GAP activity regulation. Without the ARF1 N-terminus, PIP2 has little effect on ASAP1 GAP activity. A peptide comprising residues 2–17 of ARF1 inhibits GAP activity and binds PIP2-dependently to the PH domain and a 17-amino-acid interdomain linker. Mutations reducing ARF1 N-terminal binding to the PH domain also reduce GAP activity and ASAP1-driven cellular actin remodeling. In vitro GAP assay with truncated ARF1 variants and peptides, PH domain binding assays, site-directed mutagenesis, actin remodeling cell assay The Journal of biological chemistry High 31591270
2020 The N-BAR domain of ASAP1 directly binds F-actin, promotes formation of predominantly unipolar actin bundles, and stabilizes them against depolymerization. ASAP1 homodimerization aligns F-actin in bundles. The ASAP1 N-BAR domain moderately reduces spontaneous G-actin polymerization. Overexpression of the BAR-PH tandem in fibroblasts induces actin-filled cellular projections more effectively than full-length ASAP1; an ASAP1 construct lacking the N-BAR domain fails to induce projections. Actin cosedimentation, polymerization and depolymerization assays, TIRF microscopy, confocal microscopy, electron microscopy, cell overexpression The Journal of biological chemistry High 32444496
2020 Binding of multiple PIP2 molecules to the ASAP1 PH domain triggers an allosteric conformational switch and maintains the PH domain in a well-defined orientation at the membrane, allowing critical contacts with Arf1 to occur. NMR, neutron reflectometry, and molecular dynamics simulations together define how PH domain membrane binding positions ASAP1 for optimal Arf1 interaction and GTP hydrolysis. Solution NMR, neutron reflectometry, molecular dynamics simulation, reconstituted membrane-binding assays Science advances High 32998886
2004 The N-terminal extension (amino acids 2–17) of Arf1 is a critical structural determinant for interaction with ASAP1, AGAP1, and Arf GAP1, though each GAP has a unique interface. Deletion of residues 2–17 reduces ASAP1 interaction by 200-fold and residues 2–17 bind directly to ASAP1. Lysines 15 and 16 contribute more to ASAP1/AGAP1 interaction than to Arf GAP1 interaction; Leu-8 distinguishes Arf GAP1 binding from ASAP1/AGAP1. GAP activity assay with Arf1 deletion and point mutants, antibody sequestration, direct peptide binding assay Cellular signalling High 15212764
2023 Myr-Arf1 (active, membrane-anchored GTP form) exists in dynamic equilibrium between membrane-associated and membrane-distal G-domain conformations on lipid bilayers. The PH domain of ASAP1 restricts Arf1 G-domain motions and locks it in a conformation that exposes functionally relevant regions for GAP-catalyzed GTP hydrolysis. NMR, neutron reflectometry, molecular dynamics simulation of membrane-anchored Arf1 in complex with ASAP1 PH domain Nature communications High 37989735
2023 ASAP1 inhibits ubiquitin-mediated proteasomal degradation of IQGAP1, thereby enhancing CDC42 activity. Activated CDC42 upregulates the EGFR-MAPK pathway, promoting chemotherapy resistance in gastric cancer cells. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown, overexpression in cell lines, in vivo xenograft Cell death & disease Medium 36792578

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Evidence for a SAL1-PAP chloroplast retrograde pathway that functions in drought and high light signaling in Arabidopsis. The Plant cell 412 22128124
1998 ASAP1, a phospholipid-dependent arf GTPase-activating protein that associates with and is phosphorylated by Src. Molecular and cellular biology 211 9819391
2000 The Arf GTPase-activating protein ASAP1 regulates the actin cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America 182 10725410
2021 EIF4A3-induced circular RNA ASAP1 promotes tumorigenesis and temozolomide resistance of glioblastoma via NRAS/MEK1/ERK1-2 signaling. Neuro-oncology 168 32926734
1990 Regulation of pap pilin phase variation by a mechanism involving differential dam methylation states. The EMBO journal 158 2147413
2002 The association of ASAP1, an ADP ribosylation factor-GTPase activating protein, with focal adhesion kinase contributes to the process of focal adhesion assembly. Molecular biology of the cell 142 12058076
2015 Susceptibility to tuberculosis is associated with variants in the ASAP1 gene encoding a regulator of dendritic cell migration. Nature genetics 136 25774636
1996 Epigenetic phase variation of the pap operon in Escherichia coli. Trends in microbiology 132 8824788
2005 DDEF1 is located in an amplified region of chromosome 8q and is overexpressed in uveal melanoma. Clinical cancer research : an official journal of the American Association for Cancer Research 108 15897555
2012 The Arf GAP ASAP1 provides a platform to regulate Arf4- and Rab11-Rab8-mediated ciliary receptor targeting. The EMBO journal 107 22983554
2008 PAP- and GLD-2-type poly(A) polymerases are required sequentially in cytoplasmic polyadenylation and oogenesis in Drosophila. Development (Cambridge, England) 101 18434412
1996 HIP/PAP is an adhesive protein expressed in hepatocarcinoma, normal Paneth, and pancreatic cells. The American journal of physiology 99 8997243
2010 DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer. Journal of immunotherapy (Hagerstown, Md. : 1997) 95 20551832
2007 Src-dependent phosphorylation of ASAP1 regulates podosomes. Molecular and cellular biology 88 17893324
2001 The regulation of pap and type 1 fimbriation in Escherichia coli. Advances in microbial physiology 83 11450107
2001 DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism. The Journal of biological chemistry 81 11773070
1997 A ubiquitous plant housekeeping gene, PAP, encodes a major protein component of bell pepper chromoplasts. Plant physiology 81 9390444
2006 A BAR domain in the N terminus of the Arf GAP ASAP1 affects membrane structure and trafficking of epidermal growth factor receptor. Current biology : CB 78 16431365
2007 YtqI from Bacillus subtilis has both oligoribonuclease and pAp-phosphatase activity. Nucleic acids research 77 17586819
2014 Automatic cervical cell segmentation and classification in Pap smears. Computer methods and programs in biomedicine 75 24433758
2004 Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Molecular cell 72 15546614
2007 Experimental acute pancreatitis in PAP/HIP knock-out mice. Gut 69 17409121
1999 pap, reg Ialpha and reg Ibeta mRNAs are concomitantly up-regulated during human colorectal carcinogenesis. International journal of cancer 69 10328217
2012 PARP1 represses PAP and inhibits polyadenylation during heat shock. Molecular cell 68 23219533
1991 Production of a pokeweed antiviral protein (PAP)-containing immunotoxin, B43-PAP, directed against the CD19 human B lineage lymphoid differentiation antigen in highly purified form for human clinical trials. Journal of immunological methods 67 1705571
2008 Autoinhibition of Arf GTPase-activating protein activity by the BAR domain in ASAP1. The Journal of biological chemistry 64 19017632
1990 Frequency and organization of pap homologous DNA in relation to clinical origin of uropathogenic Escherichia coli. The Journal of infectious diseases 64 1968935
2005 HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice. Hepatology (Baltimore, Md.) 58 16116631
2015 Molecular Basis for Cooperative Binding of Anionic Phospholipids to the PH Domain of the Arf GAP ASAP1. Structure (London, England : 1993) 56 26365802
2005 Psychological, behavioral, and interpersonal impact of human papillomavirus and Pap test results. Journal of women's health (2002) 56 16181021
2005 Safety and immunological efficacy of a prostate cancer plasmid DNA vaccine encoding prostatic acid phosphatase (PAP). Vaccine 55 16115700
2000 PAP-1, a novel target protein of phosphorylation by pim-1 kinase. European journal of biochemistry 54 10931201
2000 Pyrophosphorolysis-activated polymerization (PAP): application to allele-specific amplification. BioTechniques 54 11084870
2016 Long non-coding RNAs, ASAP1-IT1, FAM215A, and LINC00472, in epithelial ovarian cancer. Gynecologic oncology 52 27667152
2001 A novel nuclear human poly(A) polymerase (PAP), PAP gamma. The Journal of biological chemistry 52 11431479
2015 The Arf and Rab11 effector FIP3 acts synergistically with ASAP1 to direct Rabin8 in ciliary receptor targeting. Journal of cell science 49 25673879
2003 CrkL directs ASAP1 to peripheral focal adhesions. The Journal of biological chemistry 49 12522101
2005 Expression of Reg/PAP family members during motor nerve regeneration in rat. Biochemical and biophysical research communications 40 15896308
1998 Formation of DNA methylation patterns: nonmethylated GATC sequences in gut and pap operons. Journal of bacteriology 39 9811649
2007 Kinetic analysis of GTP hydrolysis catalysed by the Arf1-GTP-ASAP1 complex. The Biochemical journal 38 17112341
2008 Competitive Lrp and Dam assembly at the pap regulatory region: implications for mechanisms of epigenetic regulation. Journal of molecular biology 37 18706913
2003 Hemin binding, functional expression, and complementation analysis of Pap 31 from Bartonella henselae. Journal of bacteriology 37 12591895
1993 Identification and transcriptional analysis of the Escherichia coli htrE operon which is homologous to pap and related pilin operons. Journal of bacteriology 37 8102362
2019 Loss of ASAP1 in mice impairs adipogenic and osteogenic differentiation of mesenchymal progenitor cells through dysregulation of FAK/Src and AKT signaling. PLoS genetics 34 31246957
2019 PAP-1 ameliorates DSS-induced colitis with involvement of NLRP3 inflammasome pathway. International immunopharmacology 34 31351364
2019 A pap-smear analysis tool (PAT) for detection of cervical cancer from pap-smear images. Biomedical engineering online 33 30755214
1997 Presence of pap-, sfa-, and afa-related sequences in necrotoxigenic Escherichia coli isolates from cattle: evidence for new variants of the AFA family. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 33 9242999
2020 Novel ASAP1-USP6, FAT1-USP6, SAR1A-USP6, and TNC-USP6 fusions in primary aneurysmal bone cyst. Genes, chromosomes & cancer 32 32011035
2014 Neonatal screening for cystic fibrosis: comparing the performances of IRT/DNA and IRT/PAP. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 32 24513262
2016 The Arf GTPase-activating Protein, ASAP1, Binds Nonmuscle Myosin 2A to Control Remodeling of the Actomyosin Network. The Journal of biological chemistry 31 26893376
2014 Semi-automatic segmentation and classification of Pap smear cells. IEEE journal of biomedical and health informatics 31 24403407
2012 A SNP in ASAP1 gene is associated with meat quality and production traits in Nelore breed. Meat science 31 22682072
2001 Conformational changes of pancreatitis-associated protein (PAP) activated by trypsin lead to insoluble protein aggregates. Pancreas 31 11249074
2018 LncRNA ASAP1-IT1 positively modulates the development of cholangiocarcinoma via hedgehog signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 30 29653361
2018 RNA Polymerase II Read-Through Promotes Expression of Neighboring Genes in SAL1-PAP-XRN Retrograde Signaling. Plant physiology 30 30301775
2004 Differences between AGAP1, ASAP1 and Arf GAP1 in substrate recognition: interaction with the N-terminus of Arf1. Cellular signalling 30 15212764
2004 Immunocytochemical staining of p16INK4a protein from conventional Pap test and its association with human papillomavirus infection. Diagnostic cytopathology 29 15452898
2015 A pooled shRNA screen for regulators of primary mammary stem and progenitor cells identifies roles for Asap1 and Prox1. BMC cancer 28 25879659
2020 Membrane surface recognition by the ASAP1 PH domain and consequences for interactions with the small GTPase Arf1. Science advances 27 32998886
2019 The ArfGAP ASAP1 Controls Actin Stress Fiber Organization via Its N-BAR Domain. iScience 27 31785555
2002 Polyadenylate polymerase (PAP) and 3' end pre-mRNA processing: function, assays, and association with disease. Critical reviews in clinical laboratory sciences 27 12120781
1999 Expression of pancreatitis-associated protein (PAP) in rat spontaneous chronic pancreatitis: effect of herbal medicine Saiko-keishi-to (TJ-10). Pancreas 27 10505754
2020 The PAP/SAL1 retrograde signaling pathway is involved in iron homeostasis. Plant molecular biology 25 31900819
2019 Nerve Injury-Induced Neuronal PAP-I Maintains Neuropathic Pain by Activating Spinal Microglia. The Journal of neuroscience : the official journal of the Society for Neuroscience 25 31744864
2016 eIF5B increases ASAP1 expression to promote HCC proliferation and invasion. Oncotarget 25 27694689
2014 HIP/PAP prevents excitotoxic neuronal death and promotes plasticity. Annals of clinical and translational neurology 25 25493266
2020 The BAR domain of the Arf GTPase-activating protein ASAP1 directly binds actin filaments. The Journal of biological chemistry 24 32444496
2023 ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer. Cell death & disease 22 36792578
2020 A Thermosensitive, Phase-Variable Epigenetic Switch: pap Revisited. Microbiology and molecular biology reviews : MMBR 22 32727743
2018 PAP genes are tissue- and cell-specific markers of chloroplast development. Planta 22 29855700
1994 The pancreatitis-associated protein (PAP). A new candidate for neonatal screening of cystic fibrosis. Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie 22 7527291
2020 Expression of ASAP1 and FAK in gastric cancer and its clinicopathological significance. Oncology letters 21 32566028
2018 Lentiviral vector mediated-ASAP1 expression promotes epithelial to mesenchymal transition in ovarian cancer cells. Oncology letters 21 29541211
2008 Dynamic interaction between Arf GAP and PH domains of ASAP1 in the regulation of GAP activity. Cellular signalling 21 18675341
2018 Genome-wide analysis of purple acid phosphatase (PAP) family proteins in Jatropha curcas L. International journal of biological macromolecules 20 30414420
1998 Expression of pancreatitis-associated protein (PAP) mRNA in gastrointestinal cancers. International journal of pancreatology : official journal of the International Association of Pancreatology 20 9520086
2022 Analysis of Cytology Pap Smear Images Based on Ensemble Deep Learning Approach. Diagnostics (Basel, Switzerland) 19 36428816
2015 Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets. Nucleic acids research 19 26138484
2011 p16INK⁴a and p14ARF mRNA expression in Pap smears is age-related. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 19 22080060
2004 Pathogenicity of pap-negative avian Escherichia coli isolated from septicaemic lesions. Microbes and infection 19 15158770
2019 Characterization of TP53 mutations in Pap test DNA of women with and without serous ovarian carcinoma. Gynecologic oncology 18 31839337
1996 Regulation of pancreatitis-associated protein (HIP/PAP) mRNA levels in mouse pancreas and small intestine. Clinical science (London, England : 1979) 18 8795446
2023 Myr-Arf1 conformational flexibility at the membrane surface sheds light on the interactions with ArfGAP ASAP1. Nature communications 17 37989735
2013 Cytomorphology of unusual primary tumors in the Pap test. CytoJournal 17 24082913
2016 Loss of EGFR-ASAP1 signaling in metastatic and unresectable hepatoblastoma. Scientific reports 16 27910913
2011 GEFH1 binds ASAP1 and regulates podosome formation. Biochemical and biophysical research communications 16 21352810
2021 Long non‑coding RNA ASAP1‑IT1 suppresses ovarian cancer progression by regulating Hippo/YAP signaling. International journal of molecular medicine 15 33576454
2014 Anal Pap smears and anal cancer: what dermatologists should know. Journal of the American Academy of Dermatology 15 25088812
2009 Induction of pancreatitis-associated protein (PAP) family members in neurons after traumatic brain injury. Journal of neurotrauma 15 19351265
1999 The Bethesda system and evaluation of abnormal pap smears. Seminars in surgical oncology 15 10225298
2013 Star-PAP controls HPV E6 regulation of p53 and sensitizes cells to VP-16. Oncogene 14 23416977
2011 Pattern of epithelial cell abnormality in Pap smear: A clinicopathological and demographic correlation. CytoJournal 14 21713015
1996 Mechanism of PAP I gene induction during hepatocarcinogenesis: clinical implications. British journal of cancer 14 8956791
2019 Interaction of the N terminus of ADP-ribosylation factor with the PH domain of the GTPase-activating protein ASAP1 requires phosphatidylinositol 4,5-bisphosphate. The Journal of biological chemistry 13 31591270
2018 Glycerophosphatidylcholine PC(36:1) absence and 3'-phosphoadenylate (pAp) accumulation are hallmarks of the human glioma metabolome. Scientific reports 13 30283018
2016 No Significant Effect of ASAP1 Gene Variants on the Susceptibility to Tuberculosis in Chinese Population. Medicine 13 27227929
2012 Golgi-resident PAP-specific 3'-phosphatase-coupled sulfotransferase assays. Analytical biochemistry 13 22289690
2001 Pancreatitis-associated protein (PAP) in patients with pancreatic cancer. Anticancer research 13 11396234
2022 Pap Smear Collection and Preparation: Key Points. CytoJournal 12 35510105
2010 Ambulatory care visits for Pap tests, abnormal Pap test results, and cervical cancer procedures in the United States. The American journal of managed care 12 20536271