Affinage

VAPA

Vesicle-associated membrane protein-associated protein A · UniProt Q9P0L0

Length
249 aa
Mass
27.9 kDa
Annotated
2026-06-11
89 papers in source corpus 29 papers cited in narrative 28 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

VAPA is an ER-resident protein whose cytoplasmic MSP domain functions as a universal scaffold that recognizes FFAT and FFAT-like motifs in a broad range of cytoplasmic partners, tethering the ER to other organelles at membrane contact sites to support non-vesicular lipid transfer and phosphoinositide homeostasis (PMID:34312846, PMID:34103503, PMID:36693319). NMR mapping established that the MSP domain accommodates a diversity of FFAT-like peptides with defined sequence requirements (PMID:34312846), and cryo-tomography of reconstituted contacts showed that flexible disordered linkers allow VAPA to bridge membranes of variable intermembrane distance (PMID:34103503); its intrinsically disordered regions are required for correct distribution across distinct contact-site types without altering partner preference (PMID:36693319). Through these interactions VAPA anchors the lipid-transfer proteins OSBP, ORP2/ORP4L and CERT, which sense sterol and deliver lipids at ER–Golgi and ER–mitochondria contacts, contributing to ceramide and cardiolipin handling and to ER-to-Golgi cargo export (PMID:12023275, PMID:25681634, PMID:36693319). VAPA further organizes ER–plasma membrane junctions: it recruits to Kv2.1/Kv2.2 channels via a phosphorylation-dependent FFAT motif to drive channel clustering (PMID:29941597, PMID:30012696), and it maintains plasma-membrane PI(4)P and PI(4,5)P2 levels while coupling ventral ER–PM contacts to focal adhesions during cell migration (PMID:38446032). VAPA participates in autophagosome biogenesis by tethering the ER to isolation membranes through FFAT-dependent interactions with FIP200, ULK1 and WIPI2 (PMID:29628370), in ER-to-lysosome-associated degradation of misfolded ATZ via a VAPA:ORP1L:RAB7 complex (PMID:41179805), and in RNA-enriched extracellular vesicle biogenesis through its CERT-dependent control of multivesicular body ceramide and luminal filling (PMID:35421371). Beyond canonical lipid-transfer roles, VAPA suppresses type I interferon signaling by promoting NEDD4-mediated ubiquitination and proteasomal degradation of JAK1 (PMID:40080976). VAPA is co-opted by multiple pathogens whose proteins bind the MSP domain through FFAT mimics, including HCV NS5A/NS5B, norovirus NS1/2, Aichi virus nonstructural proteins, and HIV-1, to build replication organelles or remodel host membranes (PMID:15016871, PMID:28698274, PMID:29367253, PMID:37563144).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2002 High

    Establishing VAPA's first defined molecular partnership answered whether it acts as an ER anchor for lipid-handling machinery, by showing it binds OSBP and is required for OSBP ER targeting and ER-to-Golgi cargo and ceramide export.

    Evidence Yeast two-hybrid, GST pull-down, co-IP and live-cell VSVG-GFP trafficking in mammalian cells

    PMID:12023275

    Open questions at the time
    • Did not define the FFAT motif consensus on OSBP
    • Did not establish whether ER anchoring functions at discrete contact sites
  2. 2003 Medium

    Identifying VAPA as a target of norovirus p48 introduced the theme that pathogens hijack VAPA to disrupt host trafficking.

    Evidence Yeast two-hybrid, co-IP and VSV-G surface expression assay in transfected cells

    PMID:14557663

    Open questions at the time
    • Binding interface on VAPA not mapped
    • Mechanism of trafficking disruption not resolved
  3. 2004 High

    Showing VAPA binds HCV NS5A and NS5B and is required for the lipid-raft replication complex established VAPA as an essential host factor for a viral RNA replication organelle.

    Evidence Co-IP, siRNA knockdown, dominant-negative expression and membrane fractionation in HCV replicon hepatocytes

    PMID:15016871

    Open questions at the time
    • Direct binding domain on VAPA not mapped at the time
    • Did not address how host FFAT partners are displaced
  4. 2008 High

    Demonstrating that VAPA overexpression inhibits ER-to-Golgi transport, reversible by an FFAT peptide and linked to microtubule association, showed VAPA function is dose-sensitive and FFAT-dependent.

    Evidence Live-cell VSVG-GFP imaging, in vitro ER vesicle budding, FRAP, microtubule co-sedimentation and FFAT peptide rescue

    PMID:18713837

    Open questions at the time
    • Physiological consequence of VAPA-microtubule binding unresolved
    • Did not identify the relevant endogenous FFAT partners
  5. 2010 Medium

    Mutagenesis showing that proline content protects VAPA from the ALS-associated P56S-equivalent aggregation explained why VAPA, unlike VAPB, resists this misfolding fate.

    Evidence Site-directed mutagenesis of VAPA prolines and fluorescence microscopy in mammalian cells

    PMID:21144830

    Open questions at the time
    • No disease link for VAPA itself
    • Aggregation consequences for contact-site function not tested
  6. 2015 Medium

    Visualizing ORP-VAPA complexes redistributing with sterol levels established VAPA as the static ER anchor enabling sterol-sensing lipid-transfer proteins to respond to cellular cholesterol.

    Evidence BiFC of ORP-VAPA complexes with pharmacological sterol manipulation and sterol-binding mutants in HuH7 cells

    PMID:25681634

    Open questions at the time
    • Did not quantify lipid transfer flux
    • Did not resolve the contact-site geometry
  7. 2017 High

    Structural identification of a norovirus FFAT mimic binding the VAPA MSP domain explained mechanistically how viral proteins exploit the same binding pocket as host FFAT partners.

    Evidence Structural analysis of NS1 FFAT mimic, direct MSP-domain binding, VAPA/VAPB-deficient replication assays and mutagenesis

    PMID:28698274

    Open questions at the time
    • Precise replication step requiring VAPA not fully defined
    • Host partner competition not directly measured
  8. 2018 High

    Defining VAPA's roles in Kv2 channel clustering, autophagosome biogenesis, and Aichi virus replication organelles broadened VAPA from a lipid-transfer anchor to a general organizer of ER contact sites with diverse partners.

    Evidence BioID/FRET/KO for Kv2 clustering, co-IP and autophagy marker imaging for FIP200/ULK1/WIPI2, and siRNA plus co-IP for AiV nonstructural proteins

    PMID:29367253 PMID:29628370 PMID:29941597 PMID:30012696

    Open questions at the time
    • Stoichiometry and selectivity among competing FFAT partners not resolved
    • How VAPA prioritizes among simultaneous contact-site demands unknown
  9. 2020 Medium

    Showing that a peptide disrupting the Kv2.1-VAPA interaction is neuroprotective in stroke established functional and potentially therapeutic relevance of a specific VAPA contact-site interaction.

    Evidence TAT-DP-2 peptide disruption, electrophysiology, neuronal death assay and murine MCAO stroke model

    PMID:32937450

    Open questions at the time
    • Whether other VAPA functions are affected by the peptide not excluded
    • Long-term consequences not assessed
  10. 2021 High

    Structural and biophysical characterization of the MSP domain's FFAT-recognition breadth and the flexible VAPA-OSBP tethering architecture explained how one scaffold accommodates many partners and variable contact-site geometries.

    Evidence Solution NMR of MSP with FFAT-like peptides, cryo-ET of reconstituted MCS, plus co-IP/cell-death assays for CDIP1 FFAT-like binding

    PMID:33503978 PMID:34103503 PMID:34312846

    Open questions at the time
    • In vitro geometry not validated in vivo for all partners
    • Determinants of partner selectivity at endogenous contacts unresolved
  11. 2022 High

    Linking VAPA-CERT contacts to multivesicular body ceramide and RNA-enriched extracellular vesicle biogenesis extended VAPA's lipid-transfer role into intercellular RNA communication.

    Evidence siRNA knockdown, lipidomics, EV RNA quantification, PLA, live-cell imaging and in vivo tumor assay

    PMID:35421371

    Open questions at the time
    • Mechanism coupling ceramide transfer to RNA loading not resolved
    • Selectivity for the EV subpopulation not fully defined
  12. 2023 High

    Identifying that VAPA's disordered regions govern contact-site distribution, and that VAPA acts at the outer nuclear membrane in HIV-1 nuclear transfer, refined how VAPA partitions among contacts and revealed a role at the nuclear envelope.

    Evidence IDR deletion mutagenesis with lipid/morphology readouts for ER-mitochondria/ER-Golgi, and siRNA/co-IP/HIV-1 infection for the VOR (VAPA-ORP3-RAB7) complex

    PMID:36693319 PMID:37563144

    Open questions at the time
    • How IDRs encode contact-site targeting without altering partner choice unresolved
    • Direct membrane-fusion mechanism in HIV-1 transfer not defined
  13. 2024 High

    Demonstrating that VAPA maintains plasma-membrane phosphoinositides and couples ER-PM contacts to focal adhesions during migration assigned VAPA a direct role in cytoskeletal and adhesion dynamics.

    Evidence siRNA/shRNA knockdown, live migration assays, PI biosensors, TIRF of focal adhesions and microtubule depolymerization in CaCo2 cells

    PMID:38446032

    Open questions at the time
    • FFAT partner mediating focal-adhesion coupling not identified
    • Link between PI homeostasis and adhesion disassembly mechanistically incomplete
  14. 2025 Medium

    Defining VAPA roles in ERLAD of misfolded ATZ, JAK1 degradation suppressing IFN-I signaling, Leishmania vacuole lipid exchange, and inner nuclear membrane architecture established VAPA as a multifunctional regulator beyond canonical lipid transfer.

    Evidence Co-IP/PLA/ERLAD assay for VAPA:ORP1L:RAB7, ternary complex co-IP and NEDD4-KO ubiquitination for JAK1, siRNA/lipid transport/PLA for Leishmania PVs, and RAPIDS proximity proteomics with morphology readouts for INM

    PMID:40080976 PMID:40163521 PMID:41179805 PMID:41537431

    Open questions at the time
    • Mechanism by which VAPA promotes NEDD4-JAK1 association unresolved
    • Inner nuclear membrane targeting route for an ER protein unclear
    • Direct versus scaffolding contributions in each role not fully separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how VAPA selects and prioritizes among its many competing FFAT/FFAT-like partners to deploy the correct contact-site function in a given cellular context.
  • No quantitative model of partner competition at endogenous VAPA
  • Regulation of VAPA partitioning between organelle contacts not defined
  • Phosphoregulation of partner FFAT motifs not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0001618 virus receptor activity 4 GO:0008289 lipid binding 3
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005886 plasma membrane 3 GO:0005635 nuclear envelope 2 GO:0005794 Golgi apparatus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1643685 Disease 4 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9612973 Autophagy 2 R-HSA-168256 Immune System 1
Partners
CERTFIP200KCNB1ORP1LORP3OSBPPTPIP51ULK1
Complex memberships
VAPA-OSBP MCS tethering complexVAPA:ORP1L:RAB7 ERLAD complexVAPA:ORP3:RAB7 (VOR) complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 VAPA (VAP-A) physically interacts with oxysterol-binding protein (OSBP) through a region in OSBP spanning amino acids 351-442, and this interaction is required for OSBP targeting to the ER; VAP-A/OSBP complexes at the ER regulate export of membrane cargo (VSVG-GFP) and ceramide from the ER to the Golgi. Yeast two-hybrid screen, GST pull-down, co-immunoprecipitation, live-cell imaging with ts045-VSVG-GFP cargo trafficking assay The Journal of biological chemistry High 12023275
2001 VAPA is a resident ER/Golgi intermediate compartment protein that binds promiscuously to both v- and t-SNAREs, including VAMP, syntaxin 1A, rbet1, rsec22, alphaSNAP, and NSF; both N- and C-terminal domains of VAPA are required for SNARE binding and VAP dimerization. Subcellular fractionation, immunofluorescence, in vitro binding/pull-down, domain deletion mutagenesis in COS-7 cells Biochemical and biophysical research communications Medium 11511104
2004 VAPA (hVAP-33) binds directly to both HCV NS5A and NS5B nonstructural proteins and is required for formation of the HCV RNA replication complex on lipid raft (detergent-resistant membranes); dominant-negative VAPA mutants and siRNA knockdown of VAPA redistributed NS5B from detergent-resistant to detergent-sensitive membranes and reduced HCV RNA and protein levels. Co-immunoprecipitation, siRNA knockdown, dominant-negative expression, membrane fractionation in HCV replicon hepatocyte cell lines Journal of virology High 15016871
2003 VAPA interacts with Norwalk virus nonstructural protein p48 and forms a stable complex in mammalian cells; expression of p48 inhibits cell-surface expression of VSV-G glycoprotein, indicating that p48 disrupts intracellular protein trafficking by co-opting VAPA. Yeast two-hybrid screen, co-immunoprecipitation, fluorescence microscopy, VSV-G surface expression assay in transfected mammalian cells Journal of virology Medium 14557663
2008 Overexpression of VAPA (but not VAPB) inhibits ER-to-Golgi transport of membrane cargo by reducing segregation into ER vesicles and impeding lateral diffusion of membrane proteins, likely through stable association with microtubules; this inhibitory effect is reversed by expression of an FFAT motif peptide, which also restores in vitro ER vesicle budding and disrupts VAPA-microtubule association. Live-cell imaging of VSVG-GFP transport, in vitro ER vesicle budding assay, FRAP, microtubule co-sedimentation, FFAT peptide rescue experiments Journal of cell science High 18713837
2009 The glycolipid transfer protein (GLTP) contains a FFAT-like motif that mediates direct interaction with VAPA; disruption of specific amino acids in the FFAT-like motif abolishes this interaction. GST pull-down assay with FFAT-like motif mutagenesis Biochemical and biophysical research communications Medium 19665998
2010 VAPA and prestin (the OHC motor protein) interact; VAPA expression correlates with prestin presence in outer hair cells, and co-expression of VAPA with prestin increases prestin abundance at the plasma membrane, suggesting VAPA facilitates prestin transport to the cell surface. Membrane-based yeast two-hybrid, co-immunoprecipitation, immunofluorescence in prestin-KO vs wild-type OHCs Biochimica et biophysica acta Low 20359505
2010 Three conserved proline residues in VAPA (compared to two in VAPB) confer resistance to the ALS-associated P56S-equivalent mutation; when VAPA is mutated to match the proline distribution of VAPB-P56S (reducing proline count in the conserved region), VAPA forms ER membrane aggregates indistinguishable from those induced by VAPB-P56S. Site-directed mutagenesis of VAPA proline residues, fluorescence microscopy of mutant VAPA localization in mammalian cells Biochemical and biophysical research communications Medium 21144830
2011 Viperin inhibits HCV replication by binding to VAPA (hVAP-33) through its C-terminus, competitively interfering with the VAPA-NS5A interaction and thereby disrupting the HCV replication complex. Co-immunoprecipitation, competitive co-immunoprecipitation, laser confocal microscopy, C-terminal viperin mutagenesis, HCV replicon and HCVcc replication assays The Journal of general virology Medium 21957124
2013 GPS2 acts as a bridge between HCV NS5A and VAPA: GPS2 directly interacts with NS5A (via Domain I of NS5A and the coiled-coil domain of GPS2), overexpression of GPS2 enhances NS5A-VAPA association, and GPS2 knockdown disrupts the NS5A-VAPA interaction and suppresses HCV RNA replication. Co-immunoprecipitation in mammalian cells, siRNA knockdown with rescue, domain mutagenesis PloS one Medium 24223774
2015 Sterol ligand binding by OSBP, ORP2, and ORP4L regulates the subcellular distribution of their complexes with VAPA; depletion of cholesterol causes juxtanuclear concentration of OSBP-VAPA complexes reversible by LDL addition, while sterol-binding deficient ORP mutants fail to redistribute, demonstrating that VAPA serves as the ER anchor for ORP proteins during lipid-sensing responses. Bimolecular Fluorescence Complementation (BiFC) to visualize ORP-VAPA complexes in living HuH7 cells, combined with pharmacological sterol manipulation and sterol-binding mutants Steroids Medium 25681634
2017 Norovirus NS1/2 protein contains a mimic of the host FFAT motif that directly binds to the MSP domain of VAPA; this interaction is required for an early step in norovirus replication (after cytoplasmic RNA entry but before minus-sense RNA synthesis); mutations in the FFAT mimic abolish both VAPA binding and viral replication. Structural analysis of NS1 FFAT mimic, direct binding assay of NS1/2 to VAPA-MSP domain, VAPA/VAPB-deficient cell replication assays, site-directed mutagenesis of FFAT mimic residues mBio High 28698274
2018 VAPA and VAPB interact with Kv2.1 and Kv2.2 potassium channels through a noncanonical FFAT-binding domain on VAPA and a phosphorylation-dependent FFAT motif in the Kv2 C-terminus (PRC/clustering motif); this interaction recruits VAPs to ER-PM junctions and is required for Kv2.1 clustering, as VAPA knockout reduces Kv2.1 cluster formation. Proximity-based biotinylation (BioID), FRET assays, siRNA knockdown, colocalization/redistribution, CD4 chimera domain mapping, affinity immunopurification/mass spectrometry from brain tissue, VAPA knockout in mammalian cells Proceedings of the National Academy of Sciences / The Journal of Neuroscience High 29941597 30012696
2018 VAPA and VAPB are required for autophagosome biogenesis by tethering the ER to isolation membranes: VAPs directly interact with FIP200 and ULK1 via FFAT motifs, stabilize the ULK1/FIP200 complex at autophagosome formation sites, and interact with WIPI2 to enhance WIPI2/FIP200 ER-IM tethering; VAP depletion reduces ULK1 puncta formation and impairs isolation membrane progression. Co-immunoprecipitation, siRNA knockdown, fluorescence microscopy of autophagy markers, VAPB P56S mutant analysis Current biology : CB High 29628370
2018 VAPA and VAPB are required for Aichi virus (AiV) RNA replication and are present at viral RNA replication organelles; various AiV nonstructural proteins (2B, 2BC, 2C, 3A, 3AB) interact with VAP-A/B and with OSBP and SAC1, forming a protein-protein interaction network that recruits the cholesterol transport machinery to replication sites. siRNA knockdown of VAPA/B with replication assays, co-immunoprecipitation, immunofluorescence colocalization, cholesterol accumulation assay, electron microscopy Journal of virology Medium 29367253
2020 Disruption of the Kv2.1-VAPA interaction by a membrane-permeable peptide (TAT-DP-2) disperses Kv2.1 surface clusters, prevents pro-apoptotic potassium current enhancement after injury, and is neuroprotective both in vitro and in a murine ischemia-reperfusion model, reducing infarct size. Peptide-based disruption of Kv2.1-VAPA interaction, electrophysiology, in vitro neuronal death assay, murine middle cerebral artery occlusion stroke model Science advances Medium 32937450
2021 VAPA forms a tethering complex with OSBP at membrane contact sites; cryo-tomography reveals that VAPA is highly flexible due to disordered linkers, enabling formation of MCS of variable intermembrane distance, while the OSBP dimer has a T-shaped helical architecture that facilitates lipid transfer domain movement between membranes. In vitro reconstituted MCS with two membranes, cryo-electron tomography, structural modeling Nature communications High 34103503
2021 CDIP1 (a pro-apoptotic protein) binds VAPA and VAPB through a FFAT-like motif in CDIP1's C-terminal region; mutations in this FFAT-like motif reduce CDIP1-induced cell death, implicating the VAPA-CDIP1 interaction in apoptosis signaling. Co-immunoprecipitation of GFP-CDIP1 with VAPA/VAPB, FFAT-like motif mutagenesis, caspase-3/7 cell death assay International journal of molecular sciences Medium 33503978
2021 The VAP-A MSP domain binds a diversity of FFAT-like motif peptides with defined sequence requirements; NMR mapping revealed that 6 of 8 tested FFAT-like peptides specifically bind the VAPA MSP domain, and the SARS-CoV-2 RNA-dependent RNA polymerase contains an FFAT-like motif that also specifically binds VAPA-MSP. Solution NMR chemical shift perturbation mapping of VAP-A MSP domain with synthetic FFAT-like peptides FEBS letters High 34312846
2022 VAPA regulates biogenesis of a subpopulation of RNA-enriched small extracellular vesicles (EVs) through its interaction with the ceramide transfer protein CERT at ER membrane contact sites; VAPA knockdown reduces EV RNA content and ceramide levels in EVs; VAPA promotes luminal filling of multivesicular bodies and colocalizes with neutral sphingomyelinase 2; VAPA-regulated EVs mediate miR-100 transfer between cells. siRNA knockdown, lipid analysis (lipidomics), RNA quantification in EVs, live-cell imaging, proximity-ligation assay, in vivo tumor formation assay Developmental cell High 35421371
2023 VAPA forms a VOR complex with hyperphosphorylated ORP3 and Rab7 at the outer nuclear membrane; HIV-1 endosomes containing endocytosed virus promote nuclear envelope invaginations via this complex; silencing VAPA or ORP3 inhibits nuclear transfer of HIV-1 components and productive infection. siRNA knockdown, co-immunoprecipitation, fluorescence microscopy, HIV-1 infection assays in HeLa and activated CD4+ T cells Nature communications Medium 37563144
2023 VAPA intrinsically disordered regions (IDRs) are required for its localization to diverse MCS types (ER-mitochondria, ER-Golgi) but do not alter partner preference; removing IDRs restricts VAPA to ER-mitochondria MCS; at ER-mitochondria MCS, VAPA interaction with PTPIP51 and VPS13A promotes lipid transfer and cardiolipin accumulation supporting mitochondria fusion; at ER-Golgi MCS, VAPA interacts with OSBP and CERT for lipid exchange. IDR deletion mutagenesis, fluorescence microscopy in human cells, lipid analysis (cardiolipin), mitochondria morphology assay, co-immunoprecipitation Developmental cell High 36693319
2024 VAPA is required for cell motility: VAPA-depleted CaCo2 cells show collective and individual migration defects, disorganized actin cytoskeleton, and altered protrusive activity; VAPA maintains PI(4)P and PI(4,5)P2 levels at the plasma membrane during migration; VAPA MSP domain regulates focal adhesion dynamics, stabilizes and anchors ventral ER-PM contact sites to focal adhesions, and mediates microtubule-dependent focal adhesion disassembly. siRNA/shRNA knockdown, live-cell migration assays, phosphoinositide biosensors, TIRF microscopy of focal adhesions, immunofluorescence, microtubule depolymerization experiments eLife High 38446032
2025 VAPA negatively regulates IFN-I (JAK-STAT) signaling during viral infection by facilitating NEDD4 E3 ubiquitin ligase-mediated ubiquitination and proteasomal degradation of JAK1; VAPA promotes the physical interaction between NEDD4 and JAK1; in NEDD4-deficient cells, the pro-viral effect of VAPA is abrogated. Co-immunoprecipitation of VAPA-NEDD4-JAK1 complex, ubiquitination assay, siRNA knockdown, viral replication assays (BEFV and VSV), NEDD4 knockout cells Veterinary microbiology Medium 40080976
2025 VAPA forms a VAPA:ORP1L:RAB7 multi-protein complex at ER-endolysosome membrane contact sites that is required for ER-to-lysosome-associated degradation (ERLAD) of misfolded ATZ polymers; this complex engages calnexin/FAM134B/LC3 in a client-driven manner to facilitate STX17/VAMP8 SNARE-mediated membrane fusion for ATZ delivery to endolysosomes. Co-immunoprecipitation, proximity ligation, fluorescence microscopy, functional ERLAD assay with ATZ polymers as substrate Autophagy reports Medium 41179805
2026 VAPA localizes to the inner nuclear membrane (INM) in proximity to nuclear lamins, emerin, LAP2 isoforms, and Nup153; depletion of VAPA reduces nuclear lamin levels and causes aberrant nuclear morphology including membrane invaginations/tunnels and altered histone acetylation levels. RAPIDS proximity proteomics (rapamycin- and APEX-dependent SILAC), immunofluorescence, VAPA depletion with nuclear morphology and lamin quantification Journal of cell science Medium 41537431
2025 VAPA mediates lipid exchange between Leishmania amazonensis-containing parasitophorous vacuoles (PVs) and host macrophage ER: VAPA associates with communal PVs after infection; VAPA knockdown prevents parasite replication and PV expansion; VAPA is required for sphingolipid (ceramide) transport to PVs; VAPA normally interacts with CERT and ORP1L, but Leishmania disrupts these interactions; VAPA also mediates retrograde transfer of the Leishmania virulence glycolipid lipophosphoglycan from PVs to the host ER. siRNA knockdown, fluorescent ceramide transport assay, proximity-ligation assay for VAPA-CERT and VAPA-ORP1L interactions, intracellular parasite growth quantification in bone marrow-derived macrophages PLoS pathogens High 40163521
2025 ORP3 lipid transfer from the plasma membrane to the ER at ER-PM contacts during mitosis depends on VAPA; ORP3 phosphorylation on its VAPA-binding motif strongly recruits ORP3 to the ER for PI4P transfer; VAPA is required for ORP3-mediated regulation of PI4P and PI(4,5)P2 levels at the plasma membrane during cell division. siRNA knockdown, phosphoinositide biosensors, mutagenesis of ORP3 VAPA-binding motif, mitosis assays bioRxivpreprint Low bio_10.1101_2025.10.22.684039

Source papers

Stage 0 corpus · 89 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Interactions between viral nonstructural proteins and host protein hVAP-33 mediate the formation of hepatitis C virus RNA replication complex on lipid raft. Journal of virology 270 15016871
2016 VAP, a Versatile Access Point for the Endoplasmic Reticulum: Review and analysis of FFAT-like motifs in the VAPome. Biochimica et biophysica acta 259 26898182
2002 Vesicle-associated membrane protein-associated protein-A (VAP-A) interacts with the oxysterol-binding protein to modify export from the endoplasmic reticulum. The Journal of biological chemistry 212 12023275
2018 The ER Contact Proteins VAPA/B Interact with Multiple Autophagy Proteins to Modulate Autophagosome Biogenesis. Current biology : CB 152 29628370
2018 Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB. Proceedings of the National Academy of Sciences of the United States of America 141 29941597
2003 Deletion of vapA encoding Virulence Associated Protein A attenuates the intracellular actinomycete Rhodococcus equi. Molecular microbiology 112 14507368
2018 Identification of VAPA and VAPB as Kv2 Channel-Interacting Proteins Defining Endoplasmic Reticulum-Plasma Membrane Junctions in Mammalian Brain Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 30012696
2022 VAP-A and its binding partner CERT drive biogenesis of RNA-containing extracellular vesicles at ER membrane contact sites. Developmental cell 105 35421371
2011 Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33. The Journal of general virology 95 21957124
2008 Evolution of the Rhodococcus equi vap pathogenicity island seen through comparison of host-associated vapA and vapB virulence plasmids. Journal of bacteriology 79 18606735
2003 Norwalk virus nonstructural protein p48 forms a complex with the SNARE regulator VAP-A and prevents cell surface expression of vesicular stomatitis virus G protein. Journal of virology 78 14557663
2001 VAP-A binds promiscuously to both v- and tSNAREs. Biochemical and biophysical research communications 77 11511104
2007 Molecular epidemiology of Rhodococcus equi based on traA, vapA, and vapB virulence plasmid markers. The Journal of infectious diseases 68 17674320
2008 FFAT rescues VAPA-mediated inhibition of ER-to-Golgi transport and VAPB-mediated ER aggregation. Journal of cell science 62 18713837
2014 Membrane-bound methyltransferase complex VapA-VipC-VapB guides epigenetic control of fungal development. Developmental cell 60 24871947
2004 The LysR-type transcriptional regulator VirR is required for expression of the virulence gene vapA of Rhodococcus equi ATCC 33701. Journal of bacteriology 60 15317761
2017 Noroviruses Co-opt the Function of Host Proteins VAPA and VAPB for Replication via a Phenylalanine-Phenylalanine-Acidic-Tract-Motif Mimic in Nonstructural Viral Protein NS1/2. mBio 55 28698274
2018 Model of OSBP-Mediated Cholesterol Supply to Aichi Virus RNA Replication Sites Involving Protein-Protein Interactions among Viral Proteins, ACBD3, OSBP, VAP-A/B, and SAC1. Journal of virology 51 29367253
2021 Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites. Nature communications 45 34103503
2003 Analysis of anamnestic immune responses in adult horses and priming in neonates induced by a DNA vaccine expressing the vapA gene of Rhodococcus equi. Vaccine 43 12922115
2004 Foal IgG and opsonizing anti-Rhodococcus equi antibodies after immunization of pregnant mares with a protective VapA candidate vaccine. Veterinary microbiology 42 15530741
2015 vapA (A-layer) typing differentiates Aeromonas salmonicida subspecies and identifies a number of previously undescribed subtypes. Journal of fish diseases 41 25846742
2022 Large Oncosome-Loaded VAPA Promotes Bone-Tropic Metastasis of Hepatocellular Carcinoma Via Formation of Osteoclastic Pre-Metastatic Niche. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 37 36169100
2020 Targeted disruption of Kv2.1-VAPA association provides neuroprotection against ischemic stroke in mice by declustering Kv2.1 channels. Science advances 37 32937450
2006 Internally controlled real-time PCR method for quantitative species-specific detection and vapA genotyping of Rhodococcus equi. Applied and environmental microbiology 34 16751540
1997 Assessment of the immunogenic potential of Rhodococcus equi virulence associated protein (VapA) in mice. Veterinary microbiology 33 9226836
2023 VAP-A intrinsically disordered regions enable versatile tethering at membrane contact sites. Developmental cell 32 36693319
2005 Evaluation of a multiplex polymerase chain reaction assay for simultaneous detection of Rhodococcus equi and the vapA gene. American journal of veterinary research 30 16173481
2009 The glycolipid transfer protein interacts with the vesicle-associated membrane protein-associated protein VAP-A. Biochemical and biophysical research communications 28 19665998
1997 Restriction enzyme analysis of the virulence plasmids of VapA-positive Rhodococcus equi strains isolated from humans and horses. Journal of clinical microbiology 25 9041424
2011 Mucosal co-immunization of mice with recombinant lactococci secreting VapA antigen and leptin elicits a protective immune response against Rhodococcus equi infection. Vaccine 23 22019740
1997 Protective effect against Rhodococcus equi infection in mice of IgG purified from horses vaccinated with virulence associated protein (VapA)-enriched antigens. Veterinary microbiology 23 9226833
1993 Transcriptional analysis of the Aeromonas salmonicida S-layer protein gene vapA. Journal of bacteriology 23 7504668
2010 Vaccination of mice with salmonella expressing VapA: mucosal and systemic Th1 responses provide protection against Rhodococcus equi infection. PloS one 22 20072623
2007 Genotypic characterization of VapA positive Rhodococcus equi in foals with pulmonary affection and their soil environment on a warmblood horse breeding farm in Germany. Research in veterinary science 22 17360011
2001 B-Cell epitope mapping of the VapA protein of Rhodococcus equi: implications for early detection of R. equi disease in foals. Journal of clinical microbiology 21 11283104
2015 Sterol liganding of OSBP-related proteins (ORPs) regulates the subcellular distribution of ORP-VAPA complexes and their impacts on organelle structure. Steroids 19 25681634
2005 Assessment in mice of vapA-DNA vaccination against Rhodococcus equi infection. Veterinary immunology and immunopathology 18 15734542
2017 VapA of Rhodococcus equi binds phosphatidic acid. Molecular microbiology 17 29205554
2016 The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis. MicrobiologyOpen 17 27762083
2007 Oral administration of a live attenuated Salmonella vaccine strain expressing the VapA protein induces protection against infection by Rhodococcus equi. Microbes and infection 17 17307012
2024 The ER tether VAPA is required for proper cell motility and anchors ER-PM contact sites to focal adhesions. eLife 16 38446032
2023 HIV-1-induced nuclear invaginations mediated by VAP-A, ORP3, and Rab7 complex explain infection of activated T cells. Nature communications 15 37563144
2021 The Novel ALG-2 Target Protein CDIP1 Promotes Cell Death by Interacting with ESCRT-I and VAPA/B. International journal of molecular sciences 15 33503978
2011 The vapA co-expressed virulence plasmid gene vcgB (orf10) of the intracellular actinomycete Rhodococcus equi. Microbiology (Reading, England) 14 21565932
2004 Immunogenecity of synthetic peptides representing linear B-cell epitopes of VapA of Rhodococcus equi. Vaccine 14 15003638
2021 Sequence requirements of the FFAT-like motif for specific binding to VAP-A are revealed by NMR. FEBS letters 13 34312846
2019 Oncogenic Effect of the Novel Fusion Gene VAPA-Rab31 in Lung Adenocarcinoma. International journal of molecular sciences 13 31083279
2016 Use of Serial Quantitative PCR of the vapA Gene of Rhodococcus equi in Feces for Early Detection of R. equi Pneumonia in Foals. Journal of veterinary internal medicine 13 26806422
1995 The leucine zipper of Aeromonas salmonicida AbcA is required for the transcriptional activation of the P2 promoter of the surface-layer structural gene, vapA, in Escherichia coli. Molecular microbiology 13 7494486
2019 Biogeography of the fish pathogen Aeromonas salmonicida inferred by vapA genotyping. FEMS microbiology letters 12 30977802
2008 Chimeric vapA/groEL2 DNA vaccines enhance clearance of Rhodococcus equi in aerosol challenged C3H/He mice. Vaccine 12 18423949
2002 Serum and mucosal antibodies of infected foals recognized two distinct epitopes of VapA of Rhodococcus equi. FEMS immunology and medical microbiology 12 12443830
2024 Cancer-associated fibroblasts derived exosomal LINC01833 promotes the occurrence of non-small cell lung cancer through miR-335-5p -VAPA axis. Journal of biochemical and molecular toxicology 11 39152098
2006 Molecular typing of VapA-positive Rhodococcus equi isolates from Jeju native horses, Korea. The Journal of veterinary medical science 11 16598168
2010 Human VAPA and the yeast VAP Scs2p with an altered proline distribution can phenocopy amyotrophic lateral sclerosis-associated VAPB(P56S). Biochemical and biophysical research communications 10 21144830
2008 Association between polymorphisms in the vesicle-associated membrane protein-associated protein A (VAPA) gene on chromosome 18p and bipolar disorder. Journal of neural transmission (Vienna, Austria : 1996) 10 18665321
2013 Failure of a VapA/CpG oligodeoxynucleotide vaccine to protect foals against experimental Rhocococcus equi pneumonia despite induction of VapA-specific antibody and interferon-γ response. Canadian journal of veterinary research = Revue canadienne de recherche veterinaire 9 24101791
2011 Development of a live, attenuated, potential vaccine strain of R. equi expressing vapA and the virR operon, and virulence assessment in the mouse. Veterinary immunology and immunopathology 9 22088674
2010 Interaction between the motor protein prestin and the transporter protein VAPA. Biochimica et biophysica acta 9 20359505
2004 Rapid determination of vapA/vapB genotype in Rhodococcus equi using a differential polymerase chain reaction method. Antonie van Leeuwenhoek 9 15031644
2015 Validation and evaluation of VapA-specific IgG and IgG subclass enzyme-linked immunosorbent assays (ELISAs) to identify foals with Rhodococcus equi pneumonia. Equine veterinary journal 8 25257622
2002 Molecular epidemiology of VapA-positive Rhodococcus equi in thoroughbred horses in Kagoshima, Japan. The Journal of veterinary medical science 8 12237518
2005 Immune response to vaccines based upon the VapA protein of the horse pathogen, Rhodococcus equi, in a murine model. International journal of medical microbiology : IJMM 7 15715172
2005 Recognition of a B-cell epitope of the VapA protein of Rhodococcus equi in newborn and experimentally infected foals. Journal of veterinary medicine. B, Infectious diseases and veterinary public health 7 16219093
2025 VAPA suppresses BEFV and VSV-induced type I IFNs signaling response by targeting JAK1 for NEDD4-mediated ubiquitin-proteasome degradation. Veterinary microbiology 6 40080976
2024 The mechanistic basis of the membrane-permeabilizing activities of the virulence-associated protein A (VapA) from Rhodococcus equi. Molecular microbiology 6 38308564
2023 Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A. Proteomics 6 37926697
2023 Isolation and identification of vapA-absent Aeromonas salmonicida in diseased snakehead Channa argus in China. International microbiology : the official journal of the Spanish Society for Microbiology 6 38062211
2018 Identification of a VapA virulence factor functional homolog in Rhodococcus equi isolates housing the pVAPB plasmid. PloS one 6 30286098
2021 Role of Vesicle-Associated Membrane Protein-Associated Proteins (VAP) A and VAPB in Nuclear Egress of the Alphaherpesvirus Pseudorabies Virus. Viruses 5 34200728
2013 Nasal vaccination with attenuated Salmonella expressing VapA: TLR2 activation is not essential for protection against R. equi infection. Vaccine 5 23933366
2013 GPS2 is required for the association of NS5A with VAP-A and hepatitis C virus replication. PloS one 5 24223774
2006 Clinical evaluation of a peptide-ELISA based upon N-terminal B-cell epitope of the VapA protein for diagnosis of Rhodococcus equi pneumonia in foals. Journal of veterinary medicine. B, Infectious diseases and veterinary public health 5 16629724
2024 Synthesis and Evaluation of [18F]AlF-NOTA-c-DVAP: A Novel PET Probe for Imaging GRP78 in Cancer. Molecular pharmaceutics 4 38554143
2024 Coordination of oxysterol binding protein 1 and VAP-A/B modulates the generation of cholesterol and viral inclusion bodies to promote grass carp reovirus replication. Frontiers in immunology 4 39081319
2023 High immunogenicity of virus-like particles (VLPs) decorated with Aeromonas salmonicida VapA antigen in rainbow trout. Frontiers in immunology 3 37283749
2025 VAPA mediates lipid exchange between Leishmania amazonensis and host macrophages. PLoS pathogens 2 40163521
2025 Isolation of vapA-positive Rhodococcus equi from soil and fecal samples in Mongolia. The Journal of veterinary medical science 2 40754416
2024 The N-terminal domain is required for cell surface localisation of VapA, a member of the Vap family of Rhodococcus equi virulence proteins. PloS one 2 38421980
2021 Development of diagnostic assays for differentiation of atypical Aeromonas salmonicida vapA type V and type VI in ballan wrasse (Labrus bergylta, Ascanius). Journal of fish diseases 2 33493378
2018 Molecular analysis of the chromosomal 16S rRNA gene and vapA plasmid gene of Polish field strains of R. equi. PloS one 2 30252885
2026 VapA/Scs2 sustains polarized growth in Aspergillus nidulans by maintaining AP-2-mediated apical endocytosis. Microbial cell (Graz, Austria) 1 41732678
2023 Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A. bioRxiv : the preprint server for biology 1 37502906
2026 VAPA at the inner nuclear membrane affects nuclear lamins and nuclear morphology. Journal of cell science 0 41537431
2026 Endothelial cell-derived IGFBP7 suppresses angiogenesis and tumor progression in colorectal cancer via the VAPA-TGF-β1 pathway. Journal of experimental & clinical cancer research : CR 0 41692778
2025 CNX:FAM134B-driven ERLAD of ATZ polymers proceeds via enhanced formation of VAPA:ORP1L:RAB7 contact sites between ER and endolysosomes. Autophagy reports 0 41179805
2025 Update on VAP, a ubiquitous signpost for the ER. Biological chemistry 0 41261728
2012 [siRNAs targeting La, hVAP-33, eIF2Bgamma, and HCV IRES inhibit the replication and expression of HCV in Huh7 cells]. Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 0 23207339

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