Affinage

VMP1

Vacuole membrane protein 1 · UniProt Q96GC9

Length
406 aa
Mass
46.2 kDa
Annotated
2026-06-11
73 papers in source corpus 31 papers cited in narrative 31 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VMP1 is an endoplasmic reticulum-resident multi-spanning membrane protein that governs the formation and disengagement of ER-derived membranes underlying autophagy, lipid trafficking, and inter-organelle contact sites (PMID:11785947, PMID:20009561, PMID:28890335). Through a DedA/VTT domain bearing a conserved glycine and reentrant loops, VMP1 acts as a lipid scramblase that controls transbilayer phospholipid distribution in the ER membrane (PMID:30785211, PMID:35044051). It nucleates autophagosome formation by binding the BH3 motif of Beclin 1 via its C-terminal hydrophilic domain, displacing Bcl-2 and recruiting the Class III PI3K (Beclin1/hVps34) complex to generate PtdIns3P and enable ATG16L1 and LC3 loading at the phagophore (PMID:23316280, PMID:23558782). A central function is the activation of the ER Ca2+ pump SERCA: VMP1 physically engages SERCA and prevents its inhibitory association with PLN/SLN, lowering local ER Ca2+ to drive dissociation of ER contacts with the isolation membrane, lipid droplets, mitochondria, and endolysosomes, with calmodulin acting as a downstream Ca2+ effector that tunes VPS34 activity (PMID:28890335, PMID:29494262); this Ca2+-regulatory activity depends on residue D272 and underlies VMP1's protection against ER and mitochondrial Ca2+ overload (PMID:36971758). Independent of autophagy, VMP1 maintains ER phospholipid composition (phosphatidylcholine and phosphatidylethanolamine) required for lipoprotein/VLDL release, such that its loss causes neutral lipid accumulation in the ER bilayer and hepatic steatosis (PMID:31526472, PMID:35452693). VMP1 also enables β-coronavirus double-membrane vesicle biogenesis by mediating the closure step of zippered ER, acting downstream of TMEM41B and dependent on phosphatidylserine distribution (PMID:35536318, PMID:35900889). Through these activities VMP1 mediates selective autophagy programs including zymophagy (with USP9x/p62) and a DRP1-Parkin-dependent mitophagy (PMID:21173155, PMID:33816487), and is transcriptionally induced by oncogenic KRAS via a PI3K-AKT1-GLI3-p300 axis (PMID:22535956). Loss of VMP1 produces pathological consequences including pancreatitis, dopaminergic neurodegeneration with α-synuclein accumulation, and NLRP3 inflammasome activation (PMID:33483473, PMID:34709991, PMID:38411635).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 Medium

    Establishing VMP1 as a transmembrane protein of the Golgi/ER compartment whose overexpression remodels intracellular membranes set the foundation for its role in membrane biogenesis.

    Evidence VMP1/EGFP fusion localization and overexpression-induced vacuole formation in cells

    PMID:11785947

    Open questions at the time
    • No molecular function assigned
    • Endogenous localization vs overexpression artifact not resolved
  2. 2010 Medium

    Genetic and biochemical work defined VMP1 as an ER protein essential for autophagosome formation and for selective clearance of damaged organelles, linking it mechanistically to ubiquitin-binding adaptors.

    Evidence Dictyostelium vmp1-null phenotypes with GFP-Atg8/TEM, and Co-IP of VMP1 with USP9x plus p62 in pancreatic acinar models

    PMID:20009561 PMID:21173155

    Open questions at the time
    • Direct molecular activity of VMP1 in membrane formation unknown
    • How VMP1 selects cargo not defined
  3. 2013 High

    Identifying the C-terminal VMP1-AtgD domain that binds Beclin 1's BH3 motif explained how VMP1 recruits and activates the autophagy-specific Class III PI3K complex at phagophore assembly sites.

    Evidence Domain deletion/mutagenesis with reciprocal Co-IP of VMP1 with Beclin1, hVps34, Bcl-2 and immunofluorescence

    PMID:23316280 PMID:23558782

    Open questions at the time
    • Structural basis of the VMP1-AtgD/BH3 interface not solved
    • Does not address VMP1's transmembrane/scramblase contribution
  4. 2012 High

    Mapping the KRAS-PI3K-AKT1-GLI3-p300 axis onto the VMP1 promoter clarified how oncogenic signaling drives VMP1-dependent autophagy in cancer.

    Evidence RNAi epistasis, ChIP showing GLI3 promoter binding, and promoter activity assays in cancer models

    PMID:22535956

    Open questions at the time
    • Other transcriptional inputs not mapped here
    • Hedgehog-independent GLI3 recruitment mechanism unresolved
  5. 2016 Medium

    Showing VMP1 at ER micro-domains contacting lipid droplets, mitochondria, and endosomes, and that its depletion increases ER-mitochondria contacts, broadened its role beyond autophagy to membrane contact site regulation.

    Evidence Live-cell imaging and EM quantification of MCS in VMP1-depleted HeLa/Cos-7 cells

    PMID:27861594

    Open questions at the time
    • Molecular mechanism of contact-site control not yet identified
    • Causality vs correlation with autophagy defects unclear at this stage
  6. 2017 High

    Discovery that VMP1 activates SERCA by blocking the inhibitory SERCA/PLN/SLN complex provided the unifying Ca2+-based mechanism for ER contact dissociation during autophagosome formation and at other contact sites.

    Evidence VMP1 KO cells, Co-IP with SERCA/PLN/SLN, SERCA activity and thapsigargin assays, calmodulin studies, EM

    PMID:28890335 PMID:29494262

    Open questions at the time
    • How VMP1 physically displaces PLN/SLN not structurally defined
    • Link between scramblase activity and SERCA regulation unresolved
  7. 2019 High

    Defining an autophagy-independent requirement for VMP1 in lipoprotein release, plus the DedA-domain glycine and TMEM41B association, recast VMP1 as a lipid-handling membrane protein.

    Evidence Zebrafish and mouse Vmp1 KO with ER lipid staining/EM and rescue comparisons; DedA glycine mutagenesis; CRISPR screen and Co-IP linking TMEM41B

    PMID:30773971 PMID:30785211 PMID:31526472

    Open questions at the time
    • Direct demonstration of scramblase catalysis in VMP1 not yet shown at this point
    • Substrate lipid specificity undefined
  8. 2021 High

    In vivo loss-of-function across flies, mice, and pancreatitis models tied VMP1 to mitochondria-ER contact regulation, selective mitophagy, neurodegeneration, and downstream NFE2L2 stress signaling.

    Evidence Drosophila vmp1/vps13d epistasis with patient fibroblasts; DRP1-Parkin1-VMP1 mitophagy in rat pancreatitis; conditional neuronal and acinar KO mice with NFE2L2 double KO rescue

    PMID:33483473 PMID:33816487 PMID:34019822 PMID:34709991

    Open questions at the time
    • Hierarchy of VMP1 within VPS13D/MFN2 pathway not fully ordered
    • Whether neurodegeneration is purely autophagic or also Ca2+/contact-driven unresolved
  9. 2022 High

    Demonstrating VMP1's role in ER closure for coronavirus DMV biogenesis and its scramblase-driven phospholipid control of VLDL secretion consolidated a lipid-distribution mechanism shared with TMEM41B.

    Evidence VMP1 vs TMEM41B KO cells with EM and PS-synthesis rescue; liver-specific Vmp1 KO with lipidomics and VLDL assays; DedA scramblase domain analysis

    PMID:35044051 PMID:35452693 PMID:35536318 PMID:35900889

    Open questions at the time
    • In vitro reconstitution of VMP1 scramblase activity from purified protein not established
    • Lipid headgroup selectivity of scrambling not fully resolved
  10. 2023 High

    Pinpointing residue D272 as essential for VMP1's ER Ca2+-releasing activity, and showing UPR-arm-specific modulation and CRL4/Cdt2-mediated ubiquitination, defined the regulatory machinery controlling VMP1 function.

    Evidence D272N knockin and T-cell conditional KO mice with Ca2+/ER-stress/apoptosis readouts; UPR reporter dissection; Co-IP/MS of Cdt2 with MLN4924 validation

    PMID:36870060 PMID:36971758 PMID:37629161

    Open questions at the time
    • How D272 mediates Ca2+ flux mechanistically (direct vs SERCA-coupled) not resolved
    • Functional consequence of VMP1 ubiquitination beyond recruitment unclear
  11. 2024 Medium

    Newer work extended VMP1 to developmental WNT-receptor surface delivery, Retromer-mediated tight-junction protein recycling, and secretory autophagy via extracellular vesicles.

    Evidence Vmp1/Tmem41b ESC mutants with Fzd2 rescue; VMP1 KO intestinal cells with CORO1C/Occludin trafficking assays; EV immunoisolation with mTOR/Atg5 dependence (preprint)

    PMID:37748280 PMID:39695329 PMID:41757559

    Open questions at the time
    • Whether these phenotypes are direct or downstream of altered ER lipid/contact biology unclear
    • Mechanistic link between scramblase activity and endosomal recycling undefined

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how VMP1's lipid scramblase activity, its SERCA/Ca2+ regulatory role, and its Beclin1-mediated PI3K recruitment are mechanistically integrated at the single-protein level.
  • No high-resolution structure of human VMP1 in the timeline
  • In vitro reconstitution coupling scramblase and Ca2+ activities not reported
  • Whether one domain underlies all functions or activities are separable is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 4 GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 2
Localization
GO:0005783 endoplasmic reticulum 5 GO:0005739 mitochondrion 2 GO:0005768 endosome 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-9612973 Autophagy 5 R-HSA-1430728 Metabolism 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-9709957 Sensory Perception 2
Partners
BECN1CDT2CORO1CPLNSERCA/ATP2ASLNTMEM41BUSP9X

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 VMP1 is a transmembrane protein with six hydrophobic regions that localizes to the Golgi apparatus and endoplasmic reticulum area; overexpression promotes formation of intracytoplasmic vacuoles and is located to the membranes of these vacuoles. VMP1/EGFP fusion protein localization by fluorescence microscopy; overexpression in cells Biochemical and biophysical research communications Medium 11785947
2010 VMP1 interacts with USP9x (a ubiquitin-protease) to mediate selective autophagy of activated zymogen granules (zymophagy) together with the ubiquitin-binding protein p62, preventing pancreatic cell death during pancreatitis. Co-immunoprecipitation of VMP1 with USP9x; biochemical and cellular characterization; genetic models (engineered mice and cultured acinar cells) The Journal of biological chemistry Medium 21173155
2010 VMP1 (Vmp1) is an ER-resident protein required for autophagosome formation in Dictyostelium; vmp1-null cells cannot survive starvation, show defects in autophagosome formation (confirmed by Atg8 colocalization), and accumulate ubiquitin-positive protein aggregates containing Atg8 and a p62 homologue. Dictyostelium vmp1 null mutant; confocal microscopy with GFP-Atg8; transmission electron microscopy; starvation survival assays Autophagy Medium 20009561
2013 VMP1 induces autophagosome formation through its C-terminal 20-amino-acid hydrophilic domain (VMP1-AtgD), which directly binds the BH3 motif of Beclin 1, promotes formation of the Beclin1/hVps34 Class III PI3K complex at autophagosome formation sites, displaces the autophagy inhibitor Bcl-2 from Beclin 1, and facilitates recruitment of Atg16L1 and LC3 to autophagosomal membranes. Domain deletion/mutagenesis of VMP1-AtgD; Co-immunoprecipitation of VMP1 with Beclin1, hVps34, and Bcl-2; immunofluorescence colocalization; siRNA knockdown Scientific reports High 23316280
2013 VMP1 recruits and activates the autophagy-specific Class III PI3K complex at the phagophore assembly site via its VMP1-AtgD domain binding to the BH3 domain of Beclin1, generating PtdIns3P and enabling ATG16L1 association with phagophore membranes. Co-immunoprecipitation; domain mutagenesis; immunofluorescence Autophagy Medium 23558782
2012 KRAS oncogene induces VMP1 expression through a PI3K-AKT1-GLI3-p300 signaling axis: GLI3 binds the VMP1 promoter and complexes with histone acetyltransferase p300 in a Hedgehog-independent manner to drive VMP1 transcription and autophagy; VMP1 is required for KRAS-induced autophagy. RNAi knockdown of KRAS and VMP1; chromatin immunoprecipitation (ChIP) assay showing GLI3 binding to VMP1 promoter; promoter activity assays; p300 knockdown; in vitro and in vivo models The Journal of biological chemistry High 22535956
2014 In Dictyostelium, Vmp1 is not strictly required for PtdIns3P generation but regulates its correct turnover/modulation on the ER; vmp1 null cells show elevated and aberrant PtdIns3P signaling on the ER with persistent recruitment of Atg18. Atg1 functions upstream of Vmp1 in this pathway (loss of Atg1 suppresses the aberrant PtdIns3P distribution and macropinocytosis defects of vmp1 mutants). Dictyostelium vmp1 null and double mutants (vmp1/atg1); lipid reporters for PtdIns3P; confocal microscopy; epistasis analysis Traffic Medium 25131297
2016 VMP1 localizes to ER micro-domains that are in close proximity to lipid droplets, mitochondria, and endosomes; VMP1-depleted cells display increased ER-mitochondria membrane contact sites and altered mitochondria morphology, demonstrating VMP1 regulates MCS formation. Live-cell fluorescence imaging in HeLa and Cos-7 cells; VMP1 depletion by siRNA; electron microscopy for MCS quantification PloS one Medium 27861594
2017 EPG-3/VMP1 is an ER-localized protein that controls ER-isolation membrane (IM) contacts during autophagosome formation by promoting SERCA (sarco/endoplasmic reticulum Ca2+ ATPase) activity. VMP1 physically interacts with SERCA and prevents formation of the inhibitory SERCA/PLN/SLN complex. Loss of VMP1 causes stable ER-IM association blocking autophagosome formation. Calmodulin acts as a downstream Ca2+ sensor/effector of VMP1/SERCA-mediated ER contacts. VMP1 similarly modulates ER contacts with lipid droplets, mitochondria, and endosomes. VMP1 KO cells; Co-immunoprecipitation of VMP1 with SERCA, PLN, SLN; SERCA activity assays; thapsigargin inhibitor experiments; calmodulin functional studies; electron microscopy; immunofluorescence Molecular cell High 28890335
2018 VMP1/EPG-3 activates SERCA (ATP2A) to control dissociation of ER contacts with the phagophore, lipid droplets, mitochondria, and endolysosomes; calmodulin acts as a downstream Ca2+ effector that modulates PIK3C3/VPS34 PI3-kinase activity to maintain these ER contacts. VMP1 loss-of-function studies; SERCA activity assays; calmodulin functional experiments; PI3K activity measurements Autophagy Medium 29494262
2019 VMP1 is required for lipoprotein release from the ER membrane; loss of vmp1 in zebrafish causes lipoprotein accumulation in the intestine and liver, and VMP1 deficiency in mice causes neutral lipid accumulation within the lipid bilayers of the ER membrane, impairing lipoprotein secretion. Other autophagy-related genes do not phenocopy this defect. Zebrafish vmp1 knockout; mouse Vmp1 knockout; lipid staining and electron microscopy of ER membrane; genetic rescue experiments comparing vmp1 to other ATG genes eLife High 31526472
2019 TMEM41B and VMP1 are physically and functionally associated; both are ER-localized multi-spanning membrane proteins that share a VTT domain, and TMEM41B functions together with VMP1 in autophagosome formation. Forward genetic CRISPR-Cas9 screen; Co-immunoprecipitation of TMEM41B and VMP1; autophagic flux reporter assay (GFP-LC3-RFP) Autophagy Medium 30773971
2019 The conserved glycine residue in the DedA/PF09335 domain of Vmp1 is essential for its function; substitution to leucine, glutamate, or arginine inactivates the protein, demonstrating functional relationship between VMP1 and bacterial DedA proteins. Site-directed mutagenesis of conserved glycine in Dictyostelium Vmp1; phenotypic rescue assays for development and lipid homeostasis The International journal of developmental biology Medium 30785211
2020 E2F1 transcription factor binds the VMP1 promoter and, together with the histone acetyltransferase EP300, regulates VMP1 expression and promoter activity in response to gemcitabine in KRAS-mutant pancreatic cancer cells. Chromatin immunoprecipitation (ChIP) demonstrating E2F1 binding to VMP1 promoter; promoter activity assays; siRNA knockdown of E2F1 and EP300 Frontiers in endocrinology Medium 32655498
2021 In Drosophila, Vmp1 functions upstream of Vps13D and upstream of Marf/Mfn2 in a conserved pathway regulating mitochondria-ER contact sites, mitochondrial size, and clearance by autophagy; loss of marf/MFN2 suppresses vps13d mutant phenotypes including mitochondria-ER contact. Drosophila vmp1 and vps13d loss-of-function mutants; genetic epistasis (double mutants); human patient fibroblasts with VPS13D mutations; mitochondria-ER contact quantification Current biology High 34019822
2021 VMP1 is required for mitophagy during acute pancreatitis; VMP1 redistributes around specific damaged mitochondrial populations, mitochondria are detected in autophagosomes isolated with anti-VMP1 antibodies, and VMP1 downregulation prevents mitochondrial degradation. A DRP1-Parkin1-VMP1 pathway mediates selective mitophagy. Co-localization studies in rat pancreatitis model; immunoisolation of VMP1-containing autophagosomes; pMITO-RFP-GFP mitophagy reporter; VMP1 knockdown; confocal microscopy Frontiers in cell and developmental biology Medium 33816487
2021 VMP1 deficiency in dopaminergic neurons in vivo leads to impaired autophagic flux (increased LC3 puncta and p62 aggregates), large vacuolar-like structures, damaged mitochondria, swollen ER, and ubiquitin-positive aggregates, resulting in progressive loss of dopaminergic neurons and α-synuclein accumulation. Conditional neuronal VMP1 knockout mice (VMP1fl/fl/DATCreERT2); immunofluorescence; electron microscopy; behavioral assays Cell death & disease Medium 33483473
2021 Loss of VMP1 in pancreatic acinar cells leads to defective autophagic degradation, ER stress, and activation of the NFE2L2/Nrf2 pathway; genetic ablation of NFE2L2 attenuates pancreatitis in VMP1-deficient mice, placing NFE2L2 downstream of VMP1 loss. Pancreatic acinar cell-specific Vmp1 knockout mice; NFE2L2/VMP1 double knockout mice (epistasis); histological and biochemical analysis Autophagy High 34709991
2022 VMP1 is required for DMV (double-membrane vesicle) biogenesis during β-coronavirus infection; in VMP1 KO cells, the nsp3/nsp4 complex forms normally but the zippered ER fails to close into DMVs. VMP1 regulates cross-membrane phosphatidylserine (PS) distribution, and inhibiting PS synthesis partially rescues DMV defects in VMP1 KO cells. VMP1 KO cells infected with β-coronavirus or expressing viral nsp3/nsp4; electron microscopy of DMVs; PS synthesis inhibition; comparison with TMEM41B KO cells The Journal of cell biology High 35536318
2022 VMP1 and TMEM41B possess a DedA domain with two predicted reentrant loops and have lipid scrambling activity; both proteins regulate the formation of ER-derived structures including autophagosomes, lipid droplets, lipoproteins, and DMVs for SARS-CoV-2 replication. Review and analysis of recent studies; scramblase activity data cited from the literature EMBO reports Medium 35044051
2022 Loss of hepatic VMP1 impairs VLDL secretion through decreased phosphatidylcholine and phosphatidylethanolamine levels and altered phospholipid composition, causing neutral lipid accumulation in the ER bilayer and reduced pre-VLDL assembly, leading to hepatic steatosis and NASH. Liver-specific Vmp1 knockout mice; metabolomic and transcriptome analyses; lipidomics; VLDL secretion assays; electron microscopy of ER Journal of hepatology High 35452693
2022 VMP1 deficiency leads to decreased SERCA activity, increased intracellular Ca2+, mitochondrial calcium overload, mitochondrial dysfunction, and release of mitochondrial DNA, resulting in increased NLRP3 inflammasome activation and release of proinflammatory molecules. CRISPR-Cas9 deletion of VMP1 in monocytic cell line; SERCA activity assay; Ca2+ fluorescence imaging; NLRP3 inflammasome FLICA assay and biosensor; ELISA; RNA sequencing; mitochondrial function assays Inflammation research High 38411635
2022 TMEM41B facilitates nsp3-nsp4 interaction and ER zippering during β-coronavirus DMV biogenesis (step 1), while VMP1 is required for the subsequent closing of the paired ER into DMVs (step 2), demonstrating the two proteins act at distinct steps. VMP1 KO and TMEM41B KO cells; electron microscopy; siRNA for PS synthesis (PTDSS1); rescue experiments Autophagy Medium 35900889
2023 VMP1 D272 (aspartic acid 272) is critical for its ER Ca2+ releasing activity; a D272N knockin mouse demonstrates that all VMP1 functions in T cells (preventing ER Ca2+ overload, ER stress, mitochondrial Ca2+ overload, and naive T cell apoptosis) depend on this Ca2+ regulatory function. VMP1 conditional KO in T cells; D272N knockin mouse; ER Ca2+ measurements; ER stress assays; mitochondrial Ca2+ measurements; apoptosis assays; in vivo T cell response The Journal of experimental medicine High 36971758
2023 VMP1 differentially modulates the three UPR arms: under basal conditions, Ca2+ binding specifically activates PERK; under ER stress, ER-mitochondria interaction-induced mitochondrial stress cooperates with PERK to suppress IRE1α and ATF6 by decelerating global protein synthesis, protecting cells from chronic ER stress. VMP1-deficient cells; UPR pathway reporter assays; Ca2+ chelation experiments; ER-mitochondria interaction manipulation; protein synthesis rate measurements Cell reports Medium 36870060
2023 VMP1 undergoes ubiquitination as a post-translational modification throughout autophagosome biogenesis until autolysosome formation, but VMP1 itself is not degraded by autophagy or the proteasome. The E3 ligase complex subunit Cdt2 (substrate recognition subunit of CRL4) is a novel VMP1 interactor mediating VMP1 ubiquitination; CRL4 inhibition decreases VMP1 ubiquitination and impairs VMP1 recruitment and autophagosome formation. Co-immunoprecipitation; mass spectrometry identification of Cdt2-VMP1 interaction; CRL4 inhibitor MLN4924; Cdt2 overexpression; biochemical ubiquitination assays International journal of molecular sciences Medium 37629161
2024 VMP1 and TMEM41B (functioning as lipid scramblases via their DedA domain) are required for primitive endoderm specification; their loss reduces FZD2 (WNT receptor) at the plasma membrane, impairing WNT signaling and XEN cell differentiation; transgenic Fzd2 expression rescues XEN differentiation. Vmp1/Tmem41b mutant mouse ESCs; WNT signaling gene expression analysis; cell surface proteome profiling; Fzd2 transgenic rescue; XEN differentiation assays Cell death and differentiation Medium 39695329
2025 VMP1 localizes at the mitochondrial-associated membrane (MAM); loss of hepatic VMP1 or TMEM41B reduces mitochondria-ER contact, decreases phosphatidylcholine and phosphatidylethanolamine, accumulates neutral lipids in the ER bilayer, and impairs VLDL secretion more severely than TMEM41B loss alone. Restoring TMEM41B in VMP1 KO mice rescues both VLDL secretion and autophagy, while restoring VMP1 in TMEM41B KO mice does not fully correct hepatic autophagy. Single and double conditional KO mice for Vmp1 and Tmem41b; lipidomic and metabolomic analyses; VLDL secretion assays; electron microscopy; knockin overexpression mice bioRxivpreprint Medium 40291711
2024 VMP1 is secreted into the extracellular medium and incorporated into extracellular vesicle (EV) membranes (~150 nm); VMP1-EV secretion decreases with mTOR inhibition and in Atg5-deficient cells; LC3-II is detected in VMP1-EVs; VMP1 downregulation reduces LC3 and p62 secretion, demonstrating that VMP1 drives a secretory autophagy pathway. Ultracentrifugation and immunoisolation of EVs; TEM and DLS; mTOR inhibitor treatment; Atg5-deficient cells; VMP1 knockdown; rat pancreatitis model bioRxivpreprint Medium bio_10.1101_2024.10.31.615473
2021 WHSC1L1 suppresses VMP1 transcription through H3K36me2-recruited DNMT3A-mediated epigenetic silencing following HSV-1 infection; VMP1 overexpression enhances mitophagy and suppresses microglial inflammatory activation, effects blocked by autophagy inhibitor 3-methyladenine. HSV-1 infection model in BV2 microglia and C57BL/6J mice; GSE35943 dataset screening; VMP1 overexpression; WHSC1L1 knockdown; autophagy inhibition; DNMT3A/H3K36me2 ChIP-based mechanistic studies Molecular immunology Medium 37748280
2026 VMP1 facilitates the recruitment of CORO1C to late endosomes, promoting Retromer-mediated recycling of the tight junction protein Occludin to the plasma membrane; VMP1 deficiency impairs this recycling, shifting Occludin trafficking toward ESCRT-dependent microautophagic degradation and resulting in tight junction loss and increased epithelial permeability. VMP1 KO in intestinal epithelial cells; Retromer recycling assays; ESCRT pathway analysis; Co-localization and trafficking studies of CORO1C and Occludin; permeability assays Advanced science Medium 41757559

Source papers

Stage 0 corpus · 73 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates SERCA Activity to Control ER-Isolation Membrane Contacts for Autophagosome Formation. Molecular cell 186 28890335
2010 Zymophagy, a novel selective autophagy pathway mediated by VMP1-USP9x-p62, prevents pancreatic cell death. The Journal of biological chemistry 156 21173155
2013 The VMP1-Beclin 1 interaction regulates autophagy induction. Scientific reports 144 23316280
2012 A novel source for miR-21 expression through the alternative polyadenylation of VMP1 gene transcripts. Nucleic acids research 89 22505577
2010 Gemcitabine induces the VMP1-mediated autophagy pathway to promote apoptotic death in human pancreatic cancer cells. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 86 20299819
2002 Cloning and expression of the rat vacuole membrane protein 1 (VMP1), a new gene activated in pancreas with acute pancreatitis, which promotes vacuole formation. Biochemical and biophysical research communications 84 11785947
2016 VMP1 Establishes ER-Microdomains that Regulate Membrane Contact Sites and Autophagy. PloS one 80 27861594
2014 Two-stage genome-wide methylation profiling in childhood-onset Crohn's Disease implicates epigenetic alterations at the VMP1/MIR21 and HLA loci. Inflammatory bowel diseases 73 25144570
2022 VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection. The Journal of cell biology 69 35536318
2019 A critical role of VMP1 in lipoprotein secretion. eLife 61 31526472
2022 Lack of VMP1 impairs hepatic lipoprotein secretion and promotes non-alcoholic steatohepatitis. Journal of hepatology 60 35452693
2012 Novel AKT1-GLI3-VMP1 pathway mediates KRAS oncogene-induced autophagy in cancer cells. The Journal of biological chemistry 60 22535956
2010 Autophagy dysfunction and ubiquitin-positive protein aggregates in Dictyostelium cells lacking Vmp1. Autophagy 59 20009561
2017 A novel HIF-1α/VMP1-autophagic pathway induces resistance to photodynamic therapy in colon cancer cells. Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology 50 28936522
2009 Striking diversity of vmp1, a variable gene encoding a putative membrane protein of the stolbur phytoplasma. Applied and environmental microbiology 49 19270150
2019 TMEM41B functions with VMP1 in autophagosome formation. Autophagy 44 30773971
2014 Vmp1 regulates PtdIns3P signaling during autophagosome formation in Dictyostelium discoideum. Traffic (Copenhagen, Denmark) 43 25131297
2022 TMEM41B and VMP1 modulate cellular lipid and energy metabolism for facilitating dengue virus infection. PLoS pathogens 38 35939522
2020 Roles of VMP1 in Autophagy and ER-Membrane Contact: Potential Implications in Neurodegenerative Disorders. Frontiers in molecular neuroscience 37 32296305
2019 Elevated VMP1 expression in acute myeloid leukemia amplifies autophagy and is protective against venetoclax-induced apoptosis. Cell death & disease 36 31142733
2013 VMP1 is a new player in the regulation of the autophagy-specific phosphatidylinositol 3-kinase complex activation. Autophagy 36 23558782
2022 Regulation of ER-derived membrane dynamics by the DedA domain-containing proteins VMP1 and TMEM41B. EMBO reports 35 35044051
2020 An autoregulatory feedback loop of miR-21/VMP1 is responsible for the abnormal expression of miR-21 in colorectal cancer cells. Cell death & disease 35 33318473
2021 PVT1 Knockdown Inhibits Autophagy and Improves Gemcitabine Sensitivity by Regulating the MiR-143/HIF-1α/VMP1 Axis in Pancreatic Cancer. Pancreas 32 33565800
2021 Loss of acinar cell VMP1 triggers spontaneous pancreatitis in mice. Autophagy 32 34709991
2016 The pancreatitis-associated protein VMP1, a key regulator of inducible autophagy, promotes Kras(G12D)-mediated pancreatic cancer initiation. Cell death & disease 32 27415425
2021 Vmp1, Vps13D, and Marf/Mfn2 function in a conserved pathway to regulate mitochondria and ER contact in development and disease. Current biology : CB 31 34019822
2003 VMP1 expression correlates with acinar cell cytoplasmic vacuolization in arginine-induced acute pancreatitis. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 31 12649568
2023 VMP1 affects endoplasmic reticulum stress sensitivity via differential modulation of the three unfolded protein response arms. Cell reports 29 36870060
2021 Essential role for autophagy protein VMP1 in maintaining neuronal homeostasis and preventing axonal degeneration. Cell death & disease 28 33483473
2014 Inactivation of von Hippel-Lindau increases ovarian cancer cell aggressiveness through the HIF1α/miR-210/VMP1 signaling pathway. International journal of molecular medicine 28 24549370
2023 VMP1 prevents Ca2+ overload in endoplasmic reticulum and maintains naive T cell survival. The Journal of experimental medicine 26 36971758
2021 Mitochondrial Dynamics and VMP1-Related Selective Mitophagy in Experimental Acute Pancreatitis. Frontiers in cell and developmental biology 26 33816487
2012 Novel roles of Vmp1: inhibition metastasis and proliferation of hepatocellular carcinoma. Cancer science 26 22971212
2015 Downregulation of VMP1 confers aggressive properties to colorectal cancer. Oncology reports 22 26328607
2013 VMP1 related autophagy and apoptosis in colorectal cancer cells: VMP1 regulates cell death. Biochemical and biophysical research communications 22 24365149
2008 Autophagy and VMP1 expression are early cellular events in experimental diabetes. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 21 19077458
2020 A Novel E2F1-EP300-VMP1 Pathway Mediates Gemcitabine-Induced Autophagy in Pancreatic Cancer Cells Carrying Oncogenic KRAS. Frontiers in endocrinology 19 32655498
2014 VMP1-deficient Chlamydomonas exhibits severely aberrant cell morphology and disrupted cytokinesis. BMC plant biology 19 24885763
2016 TMEM49-related apoptosis and metastasis in ovarian cancer and regulated cell death. Molecular and cellular biochemistry 16 27023910
2022 DMV biogenesis during β-coronavirus infection requires autophagy proteins VMP1 and TMEM41B. Autophagy 15 35900889
2010 Genetic variability of the stolbur phytoplasma vmp1 gene in grapevines, bindweeds and vegetables. Journal of applied microbiology 15 20846330
2004 Expression of vacuole membrane protein 1 (VMP1) in spontaneous chronic pancreatitis in the WBN/Kob rat. Pancreas 15 15367889
2018 The ER-localized autophagy protein EPG-3/VMP1 regulates ER contacts with other organelles by modulating ATP2A/SERCA activity. Autophagy 14 29494262
2021 A Dictyostelium model for BPAN disease reveals a functional relationship between the WDR45/WIPI4 homolog Wdr45l and Vmp1 in the regulation of autophagy-associated PtdIns3P and ER stress. Autophagy 13 34328055
2019 Evidence for an evolutionary relationship between Vmp1 and bacterial DedA proteins. The International journal of developmental biology 12 30785211
2022 The lncRNA TCONS_00021785/miR-21-5p/Trim33 axis regulates VMP1-mediated zymophagy, reduces the activation of trypsinogen, and promotes acinar cell recovery. Cell death discovery 11 35169128
2022 VMP1 Regulated by chi-miR-124a Effects Goat Myoblast Proliferation, Autophagy, and Apoptosis through the PI3K/ULK1/mTOR Signaling Pathway. Cells 11 35883670
2013 Novel role of VMP1 as modifier of the pancreatic tumor cell response to chemotherapeutic drugs. Journal of cellular physiology 11 23460482
2024 Altered vacuole membrane protein 1 (VMP1) expression is associated with increased NLRP3 inflammasome activation and mitochondrial dysfunction. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 9 38411635
2023 Ubiquitination Is a Novel Post-Translational Modification of VMP1 in Autophagy of Human Tumor Cells. International journal of molecular sciences 9 37629161
2022 VMP1 regulates hepatic lipoprotein secretion and NASH independent of autophagy. Autophagy 9 35617134
2024 VMP1: a multifaceted regulator of cellular homeostasis with implications in disease pathology. Frontiers in cell and developmental biology 8 39100095
2017 VMP1-related autophagy induced by a fructose-rich diet in β-cells: its prevention by incretins. Clinical science (London, England : 1979) 8 28188238
2024 Decoding the Versatile Landscape of Autophagic Protein VMP1 in Cancer: A Comprehensive Review across Tissue Types and Regulatory Mechanisms. International journal of molecular sciences 7 38612567
2024 The scramblases VMP1 and TMEM41B are required for primitive endoderm specification by targeting WNT signaling. Cell death and differentiation 6 39695329
2022 VMP1 promotes exosome secretion and enhances 5-FU resistance in colon cancer cells. Tissue & cell 6 35696974
2025 VMP1 attenuates ferroptosis and mitochondrial dysfunction in nucleus pulposus cells through the PINK1/Parkin-mediated mitophagy pathway. Journal of orthopaedic surgery and research 5 40629421
2025 Renal tubular VMP1 protects against acute kidney injury via modulating autophagy and autophagy-independent pathway. Autophagy 5 40660473
2022 Isolation and genomic characterization of Vmp-1 using Vibrio mimicus as the host: A novel virulent bacteriophage capable of cross-species lysis against three Vibrio spp. Microbial pathogenesis 5 36526034
2023 WHSC1L1-mediated epigenetic downregulation of VMP1 participates in herpes simplex virus 1 infection-induced mitophagy impairment and neuroinflammation. Molecular immunology 4 37748280
2023 Vacuole Membrane Protein 1 (VMP1) Restricts NLRP3 Inflammasome Activation by Modulating SERCA Activity and Autophagy. Research square 3 36747822
2025 m6A reader YTHDC1 mediates MAFF nuclear export to induce VMP1 transcription and alleviate I/R-induced oxidative stress injury in hepatocytes. Cellular signalling 2 40054588
2025 Overlapping yet Distinct Functions of VMP1 and TMEM41B in Modulating Hepatic Lipoprotein Secretion and Autophagy. bioRxiv : the preprint server for biology 2 40291711
2024 The contribution of the novel CLTC-VMP1 fusion gene to autophagy regulation and energy metabolism in cisplatin-resistant osteosarcoma. American journal of physiology. Cell physiology 2 39466176
2023 New insights into the effect of VMP1 on the treatment of pressure overload-induced pathological cardiac hypertrophy: Involving SERCA-regulated autophagic flux. Microvascular research 2 37353069
2022 The Expression and Function of lincRNA-154324 and the Adjoining Protein-Coding Gene vmp1 in the Caudal Fin Regeneration of Zebrafish. International journal of molecular sciences 2 36012210
2025 VMP1 enhances autophagy to mitigate cardiac fibroblast activation and reduce post-ischemia-reperfusion fibrosis. Cellular signalling 1 40886926
2025 Liraglutide Mitigates Renal Injury in Diabetic Kidney Disease by Suppressing Podocyte Cholesterol Accumulation Through mTOR/VMP1-Regulated Autophagy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 41246995
2026 VMP1 inhibits the progression of breast cancer via regulating PI3K/AKT and MEK/ERK signaling pathway. Cancer cell international 0 41484871
2026 Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 0 41757559
2025 Scrambling stem cell development: VMP1 and TMEM41B regulate FZD2/FRIZZLED2 secretion during primitive endoderm specification. Autophagy 0 39968886
2025 VMP1 Constitutive Expression in Mice Dampens Pancreatic and Systemic Histopathological Damage in an Experimental Model of Severe Acute Pancreatitis. International journal of molecular sciences 0 40243995

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