Affinage

VAC14

Protein VAC14 homolog · UniProt Q08AM6

Length
782 aa
Mass
88.0 kDa
Annotated
2026-04-28
43 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VAC14 is a HEAT-repeat scaffold protein that assembles a star-shaped pentameric complex with the lipid kinase PIKfyve/FAB1 and the PI(3,5)P₂ phosphatase FIG4/Sac3, thereby controlling the dynamic interconversion of PI3P and PI(3,5)P₂ on endolysosomal membranes essential for membrane trafficking and neuronal survival. VAC14 oligomerizes through conserved C-terminal motifs—a prerequisite for PIKfyve binding, FIG4 recruitment to vacuolar/endosomal membranes, and activation of PIKfyve kinase activity—and additionally stabilizes FIG4/Sac3 protein by protecting it from proteasomal degradation (PMID:19037259, PMID:23389034, PMID:20630877, PMID:40305106). Loss of VAC14 causes massive neuronal vacuolation and neurodegeneration in mice, defective endosome-to-TGN retrograde trafficking, impaired AMPA receptor endocytosis at synapses with elevated surface GluA2 and enhanced excitatory transmission, and reduced insulin-stimulated GLUT4 translocation (PMID:17956977, PMID:22842785, PMID:15546865). Biallelic VAC14 mutations that disrupt the dimerization domain cause PI(3,5)P₂ deficiency in human patients, establishing VAC14 loss-of-function as a cause of a neurodegenerative vacuolar disorder (PMID:27292112, PMID:40305106).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2002 High

    Establishing VAC14 as an upstream activator of PI(3,5)P₂ synthesis resolved how Fab1 kinase activity is regulated: Vac14 deletion nearly abolished PI(3,5)P₂ production in yeast, and FAB1 overexpression suppressed the phenotype, placing Vac14 genetically upstream.

    Evidence Yeast genetic deletion, lipid measurements, epistasis via FAB1 overexpression, and MVB sorting assays

    PMID:12062051

    Open questions at the time
    • Mechanism of Vac14-mediated Fab1 activation unknown at this stage
    • Whether the relationship is via direct physical interaction was not demonstrated
  2. 2003 High

    Demonstrating that Vac14 physically associates with Fig4 and recruits it to the vacuolar membrane revealed that the same scaffold protein controls both PI(3,5)P₂ synthesis and turnover, establishing the concept of a coordinated regulatory complex.

    Evidence Co-immunoprecipitation, GFP localization, in vitro phosphatase assay, and genetic deletion analysis in yeast

    PMID:14528018

    Open questions at the time
    • Stoichiometry of the complex unknown
    • Whether the interaction is conserved in mammals was not yet tested
  3. 2004 High

    Identification of human VAC14 (ArPIKfyve) as a direct PIKfyve-binding partner that positively regulates its kinase activity extended the yeast findings to mammals and linked the pathway to insulin-stimulated GLUT4 translocation and glucose uptake in adipocytes.

    Evidence Co-IP in mammalian cells and 3T3-L1 adipocytes, siRNA knockdown with in vitro kinase assay and lipid measurements, GLUT4 surface labeling

    PMID:15542851 PMID:15546865

    Open questions at the time
    • How VAC14 stimulates PIKfyve kinase activity mechanistically was not resolved
    • Whether the mammalian complex also includes a phosphatase subunit was not yet shown
  4. 2007 High

    Generation of Vac14 knockout mice revealed that VAC14 is essential for neuronal survival: loss causes massive neurodegeneration and cellular vacuolation, and the ternary PIKfyve-ArPIKfyve-Sac3 (PAS) complex was biochemically reconstituted in mammalian cells, confirming that kinase and phosphatase coexist on the same scaffold.

    Evidence Vac14 KO mouse phenotyping, membrane trafficking assays, co-IP/co-fractionation/co-localization of endogenous mammalian complex, in vitro phosphatase assay

    PMID:17556371 PMID:17956977

    Open questions at the time
    • Specific neuronal cell types and circuits affected were not defined
    • Whether Sac3/FIG4 stability depends on VAC14 was unknown
  5. 2008 High

    Mapping the HEAT-repeat architecture of VAC14 and demonstrating that C-terminal-mediated homomeric interaction is required for PAS complex assembly established VAC14 as the obligate scaffold organizing both enzymatic partners.

    Evidence Structural prediction, truncation/point mutant co-IP, in vitro kinase assay, GLUT4 translocation in adipocytes, yeast epistasis and mouse mutant analysis

    PMID:18950639 PMID:19037259

    Open questions at the time
    • Atomic-resolution structure of the multimer was lacking
    • Precise oligomeric state (dimer vs. higher order) was debated
  6. 2009 High

    Identifying the PIKfyve Cpn60_TCP1 domain as the determinant for docking with the ArPIKfyve-Sac3 subcomplex, and showing that enzymatic activities of neither partner affect complex stability, clarified that scaffold assembly precedes and is independent of catalysis.

    Evidence Domain truncation/point mutant co-IP in triple-transfected COS cells, vacuolation assay

    PMID:19840946

    Open questions at the time
    • Whether post-translational modifications regulate assembly was not tested
    • No structural data for the PIKfyve-VAC14 interface
  7. 2010 High

    Discovering that VAC14 stabilizes FIG4/Sac3 by attenuating its proteasomal degradation added a non-catalytic regulatory function to the scaffold and explained why the CMT4J-associated Sac3(I41T) mutation reduces Sac3 levels—it disrupts VAC14-mediated stabilization.

    Evidence Cycloheximide chase, proteasome inhibitor treatment, co-expression experiments, half-life measurements, siRNA knockdown

    PMID:20630877

    Open questions at the time
    • Whether VAC14 shields a specific Sac3 degron was not determined
    • Ubiquitin ligase responsible for Sac3 turnover was not identified
  8. 2012 High

    Demonstrating that VAC14 localizes to synapses and that its loss elevates surface AMPA receptors by impairing regulated endocytosis established a postsynaptic function for PI(3,5)P₂ signaling in excitatory neurotransmission.

    Evidence Immunofluorescence, mEPSC electrophysiology, surface GluA2 labeling, rescue by VAC14 re-expression in Vac14⁻/⁻ neurons

    PMID:22842785

    Open questions at the time
    • Whether PI(3,5)P₂ acts directly on endocytic machinery or via an effector at the synapse is unclear
    • Behavioral consequences of enhanced AMPA signaling not characterized
  9. 2013 High

    Precise mutagenesis in yeast confirmed that Vac14 multimerization through C-terminal motifs is an absolute prerequisite for Fab1 and Fig4 binding, resolving the order of assembly: self-association first, then partner recruitment.

    Evidence Yeast two-hybrid, co-IP, vacuole morphology and hyperosmotic shock assays, site-directed mutagenesis

    PMID:23389034

    Open questions at the time
    • Whether the multimer is a dimer, trimer, or higher-order oligomer remained unclear
  10. 2016 Medium

    Identification of biallelic VAC14 mutations in human patients with striatal neurodegeneration and vacuolar pathology, rescued by wild-type VAC14 cDNA, established VAC14 deficiency as a human Mendelian neurodegenerative disease.

    Evidence Exome sequencing, fibroblast vacuolation assay, wild-type VAC14 rescue transfection

    PMID:27292112

    Open questions at the time
    • Small number of families reported
    • Genotype–phenotype correlation across different VAC14 domains not established
  11. 2023 High

    Genetic epistasis placing the lysosomal chloride transporter CLCN7 downstream of PI(3,5)P₂ identified a key effector: CLCN7 knockout rescued the enlarged lysosome phenotype of FIG4/VAC14 loss and improved neurological function in Fig4-null mice.

    Evidence CLCN7 KO in FIG4-null cells, lysosome morphology and pH measurement, dominant-negative CLCN7 in Fig4-null mouse with neurological and lifespan readouts

    PMID:37363915

    Open questions at the time
    • Whether CLCN7 inhibition is a direct effect of PI(3,5)P₂ binding or indirect is not fully resolved
    • Therapeutic window for CLCN7 modulation unknown
  12. 2025 High

    A medium-resolution cryo-EM structure revealed VAC14 as a star-shaped pentamer, with two legs binding FIG4 and one additionally occupied by PIKfyve, and showed that patient mutations at VAC14–VAC14 interfaces disrupt oligomerization, complex assembly, and colocalization with retromer-positive endosomes.

    Evidence Cryo-EM, AlphaFold2 prediction, yeast interface mutants, PI(3,5)P₂ measurement, FSEC, human VAC14 KO cell complementation

    PMID:40305106

    Open questions at the time
    • High-resolution atomic model not yet available
    • How the pentameric architecture positions PIKfyve for catalysis on the membrane is not resolved
    • Structural basis for VAC14-mediated FIG4 stabilization remains unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major unresolved questions include how VAC14 pentamer geometry mechanistically activates PIKfyve kinase activity, which E3 ubiquitin ligase targets FIG4 for degradation in the absence of VAC14, and whether the VAC14 complex directly senses upstream signals to dynamically regulate PI(3,5)P₂ pools.
  • No reconstituted in vitro activation assay with defined stoichiometry
  • E3 ligase for FIG4 not identified
  • Signal-dependent regulation of complex assembly/disassembly not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005768 endosome 4 GO:0005764 lysosome 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-9609507 Protein localization 4 R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-112316 Neuronal System 2 R-HSA-162582 Signal Transduction 2
Partners
ATG18CLCN7FIG4PIKFYVERAB9ATBC1D15VAC7
Complex memberships
PIKfyve-ArPIKfyve-Sac3 (PAS) complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 VAC14/Vac14 is composed entirely of HEAT repeats and functions as a scaffold protein for the PI(3,5)P2 regulatory complex by directly contacting FIG4, FAB1/PIKfyve, VAC7, and ATG18; it mediates three distinct mechanisms for rapid interconversion of PI3P and PI(3,5)P2, and the ingls missense mutation in Vac14 prevents association with Fab1, generating a partial complex Structural prediction, yeast genetics, direct binding assays, mouse mutant analysis, epistasis The EMBO journal High 19037259
2003 In yeast, Vac14 both positively regulates Fab1 kinase activity and directs the vacuolar localization and activation of the Fig4 PI(3,5)P2 phosphatase; Fig4 physically associates with Vac14 in a common membrane-associated complex, and in the absence of Vac14, Fig4 no longer localizes to the vacuole GFP localization, co-immunoprecipitation, in vitro phosphatase assay, genetic deletion analysis Molecular biology of the cell High 14528018
2007 Loss of Vac14 in mice results in massive neurodegeneration, vacuolation of neurons and fibroblasts, and defective endosome-to-TGN retrograde trafficking, establishing VAC14 as essential for PI(3,5)P2-dependent membrane trafficking in neural cells Vac14 knockout mouse, cellular vacuolation assay, membrane trafficking assays Proceedings of the National Academy of Sciences of the United States of America High 17956977
2007 Human VAC14 (ArPIKfyve/hVac14) forms a stable ternary complex with PIKfyve and Sac3 (the mammalian FIG4 ortholog) on endosomal membranes; Sac3 preferentially hydrolyzes PI(3,5)P2 in vitro, and siRNA knockdown of Sac3 elevates PI(3,5)P2 levels, while depletion of ArPIKfyve or PIKfyve reduces PI(3,5)P2 Co-immunoprecipitation, co-fractionation, co-localization, in vitro phosphatase assay, siRNA knockdown with lipid measurements, in vitro carrier vesicle reconstitution The Journal of biological chemistry High 17556371
2004 Human VAC14 (hVac14/ArPIKfyve) physically associates with PIKfyve, co-fractionates with it on intracellular membranes, and positively regulates PIKfyve lipid kinase activity; siRNA depletion of hVac14 reduces in vitro PIKfyve kinase activity and intracellular PI(3,5)P2, while ectopic expression increases PIKfyve activity and PI(3,5)P2 production Co-immunoprecipitation, siRNA knockdown, in vitro kinase assay, intracellular lipid labeling Molecular and cellular biology High 15542851
2002 In yeast, Vac14 is an upstream activator of Fab1-catalyzed PI(3,5)P2 synthesis required for regulated PI(3,5)P2 production in response to hyperosmotic shock; vac14Δ cells make very little PI(3,5)P2 and fail to sort proteins to the multivesicular body; FAB1 overexpression suppresses vac14Δ phenotypes, placing Vac14 upstream of Fab1 Genetic deletion, lipid measurements, protein trafficking assays, FAB1 overexpression epistasis, visual screening Current biology : CB High 12062051
2008 ArPIKfyve (human VAC14) scaffolds the PIKfyve-ArPIKfyve-Sac3 (PAS) ternary complex through homomeric interactions mediated via its conserved C-terminal domain; ArPIKfyve is the principal organizer interacting with both Sac3 and PIKfyve; disruption of ArPIKfyve-ArPIKfyve contact sites with a C-terminal peptide disassembles the PAS complex, reduces PIKfyve lipid kinase activity in vitro, and inhibits insulin-stimulated GLUT4 translocation Co-immunoprecipitation in transfected mammalian cells with truncation/point mutants, in vitro lipid kinase assay, GLUT4 translocation assay in 3T3-L1 adipocytes Journal of molecular biology High 18950639
2009 Within the PAS (PIKfyve-ArPIKfyve-Sac3) complex, the Cpn60_TCP1 domain of PIKfyve is the major determinant for associating the ArPIKfyve-Sac3 subcomplex; Sac3 assembled in the PAS complex retains active PI(3,5)P2 phosphatase activity; neither Sac3 nor PIKfyve enzymatic activities affect PAS complex formation or stability Co-immunoprecipitation with domain truncation/point mutants in triple-transfected COS cells, vacuolation assay as functional readout The Journal of biological chemistry High 19840946
2010 ArPIKfyve stabilizes Sac3 protein by attenuating proteasome-dependent degradation; ArPIKfyve elevates Sac3 steady-state levels and extends its half-life through direct association, without altering Sac3 mRNA levels; the CMT4J pathogenic Sac3(I41T) mutation prevents ArPIKfyve from extending Sac3 half-life, identifying failure of this stabilization mechanism as a molecular defect in CMT4J Cycloheximide chase, proteasome inhibitor treatment, co-expression experiments, half-life measurements, siRNA knockdown The Journal of biological chemistry High 20630877
2013 Vac14 forms a dimer/multimer via conserved C-terminal motifs; multimerization is a prerequisite for Fab1 complex assembly, as monomeric Vac14 mutants cannot interact with Fab1 or Fig4; cells expressing monomeric Vac14 mutants have enlarged vacuoles that fail to fragment after hyperosmotic shock, indicating severely reduced PI(3,5)P2 levels Yeast two-hybrid, co-immunoprecipitation, vacuole morphology assay, hyperosmotic shock assay, site-directed mutagenesis The Journal of biological chemistry High 23389034
2012 Endogenous VAC14 localizes to endocytic organelles in fibroblasts and neurons, and shows pronounced synaptic localization in hippocampal neurons; loss of VAC14 enhances miniature excitatory postsynaptic current amplitude and increases surface AMPA receptor (GluA2) levels due to diminished regulated AMPA receptor endocytosis; re-introduction of VAC14 into postsynaptic Vac14-/- cells reverses these effects Immunofluorescence localization, electrophysiology (mEPSC recording), surface receptor labeling, rescue by VAC14 re-expression in Vac14-/- neurons The EMBO journal High 22842785
2006 VAC14 interacts with the PDZ domain of neuronal nitric oxide synthase (nNOS) via a novel internal PDZ-recognition motif that is beta-finger independent; mutagenesis defined essential residues within this motif Binding assays with Vac14 deletion constructs and nNOS PDZ domain, mutational analysis FEBS letters Medium 17161399
2014 VAC14 interacts with Rab9 and the Rab7 GAP TBC1D15 as part of its protein interaction network, linking the VAC14 complex to regulation of vesicular transport; overexpression of wild-type Vac14 or PIKfyve-binding deficient Vac14 L156R causes late endosomal/lysosomal vacuolation with late endosomal marker proteins on the vacuole membranes Protein affinity purification combined with MudPIT mass spectrometry, co-immunoprecipitation validation, immunofluorescence Molecular & cellular proteomics : MCP Medium 24578385
2004 ArPIKfyve (VAC14) and PIKfyve physically associate in 3T3-L1 adipocytes in an insulin-independent manner; the ArPIKfyve-PIKfyve-PI(3,5)P2 pathway is physiologically linked to insulin-activated GLUT4 translocation and glucose transport, with siRNA depletion of ArPIKfyve or PIKfyve reducing PI(3,5)P2, inhibiting insulin-stimulated Akt phosphorylation, and reducing GLUT4 surface accumulation Co-immunoprecipitation in 3T3-L1 adipocytes, siRNA knockdown, in vitro lipid labeling of membranes, glucose uptake assay, GLUT4 surface labeling The Journal of biological chemistry High 15546865
2017 Decreased VAC14 expression increases plasma membrane cholesterol, facilitating Salmonella docking and invasion; VAC14 therefore regulates susceptibility to Salmonella infection through modulation of cholesterol levels at the plasma membrane siRNA knockdown of VAC14, cholesterol measurement, Salmonella invasion assay, zebrafish infection model with ezetimibe treatment Proceedings of the National Academy of Sciences of the United States of America Medium 28827342
2015 The ArPIKfyve-Sac3 heterodimer interacts with synphilin-1 (Sph1) in brain tissue; the ArPIKfyve-Sac3 complex prevents Sph1 aggregation through mechanisms involving increased cytosolic partitioning and basal autophagy-dependent removal of Sph1 aggregates; this effect requires active Sac3 phosphatase activity Mass spectrometry of brain-derived interactors, co-immunoprecipitation, modulation of ArPIKfyve/Sac3 levels by RNA silencing or overexpression, GFP-tagged Sph1 aggregation assay in multiple cell lines including primary neurons The Journal of biological chemistry Medium 26405034
2021 BioID proximity labeling of Vac14 and Fig4 identified COPI subunit COPB1 and the GTPase Arf1 (required for COPI assembly) as proximity interactors of Vac14, validated by proximity ligation assays, suggesting a novel link between the VAC14-PIKfyve-FIG4 complex and COPI-dependent endosomal dynamics BioID proximity labeling, mass spectrometry, proximity ligation assay validation Journal of proteome research Low 34554760
2025 VAC14 forms a star-shaped pentamer scaffold (medium-resolution structure); two legs of VAC14 bind FIG4, with one leg also occupied by PIKfyve; VAC14 oligomerization is essential for Fab1/PIKfyve function, PI(3,5)P2 generation, VAC14 endosomal localization, and PIKfyve-VAC14-FIG4 complex formation; patient mutations in VAC14-VAC14 interfaces disrupt oligomerization, complex assembly, and colocalization with VPS35-containing endosomes CryoEM structure, AlphaFold2 prediction, yeast genetics with interface mutations, PI(3,5)P2 measurement, pull-down assays, fluorescence-detection size-exclusion chromatography (FSEC) of cell lysates, human VAC14 KO cell complementation Molecular biology of the cell High 40305106
2016 siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increases docetaxel sensitivity, measured by decreased neurite processes and branches; VAC14 heterozygous mice have greater nociceptive sensitivity prior to docetaxel treatment, demonstrating a neuroprotective role of VAC14 in peripheral neurons siRNA knockdown in neuronal cells, morphometric analysis of neurites, nociceptive behavioral testing in VAC14 heterozygous mice Clinical cancer research Medium 27143689
2016 Biallelic VAC14 mutations (splice-site and missense variants in the dimerization domain) cause PI(3,5)P2 deficiency in patient fibroblasts manifesting as vacuole accumulation, which is rescued by transfection of wild-type VAC14 cDNA, demonstrating that VAC14 dimerization domain integrity is essential for its function Exome sequencing, fibroblast vacuolation assay, wild-type VAC14 rescue transfection American journal of human genetics Medium 27292112
2023 PI(3,5)P2, produced by the VAC14-PIKfyve-FIG4 complex, inhibits the lysosomal chloride transporter ClC-7 (CLCN7); loss of FIG4 or VAC14 reduces PI(3,5)P2 and results in enlarged lysosomes that are rescued by CLCN7 knockout, and CLCN7 reduction improves neurological function in Fig4 null mice, placing CLCN7 downstream of VAC14/FIG4 signaling CLCN7 knockout in FIG4 null cells, lysosome morphology assay, lysosomal pH measurement, dominant-negative CLCN7 in Fig4 null mouse with neurological and lifespan readouts PLoS genetics High 37363915

Source papers

Stage 0 corpus · 43 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and mouse. The EMBO journal 198 19037259
2007 Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice. Proceedings of the National Academy of Sciences of the United States of America 193 17956977
2003 Vacuole size control: regulation of PtdIns(3,5)P2 levels by the vacuole-associated Vac14-Fig4 complex, a PtdIns(3,5)P2-specific phosphatase. Molecular biology of the cell 162 14528018
2007 Core protein machinery for mammalian phosphatidylinositol 3,5-bisphosphate synthesis and turnover that regulates the progression of endosomal transport. Novel Sac phosphatase joins the ArPIKfyve-PIKfyve complex. The Journal of biological chemistry 159 17556371
2002 Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking to the multivesicular body. Current biology : CB 117 12062051
2008 ArPIKfyve homomeric and heteromeric interactions scaffold PIKfyve and Sac3 in a complex to promote PIKfyve activity and functionality. Journal of molecular biology 62 18950639
2006 The retroviral oncoprotein Tax targets the coiled-coil centrosomal protein TAX1BP2 to induce centrosome overduplication. Nature cell biology 60 16767081
2009 PIKfyve-ArPIKfyve-Sac3 core complex: contact sites and their consequence for Sac3 phosphatase activity and endocytic membrane homeostasis. The Journal of biological chemistry 55 19840946
2004 A mammalian ortholog of Saccharomyces cerevisiae Vac14 that associates with and up-regulates PIKfyve phosphoinositide 5-kinase activity. Molecular and cellular biology 53 15542851
2016 Biallelic Mutations of VAC14 in Pediatric-Onset Neurological Disease. American journal of human genetics 52 27292112
2014 The Vac14-interaction network is linked to regulators of the endolysosomal and autophagic pathway. Molecular & cellular proteomics : MCP 52 24578385
2004 Acquisition of unprecedented phosphatidylinositol 3,5-bisphosphate rise in hyperosmotically stressed 3T3-L1 adipocytes, mediated by ArPIKfyve-PIKfyve pathway. The Journal of biological chemistry 50 15546865
2007 ArPIKfyve-PIKfyve interaction and role in insulin-regulated GLUT4 translocation and glucose transport in 3T3-L1 adipocytes. Experimental cell research 48 17475247
2016 Pharmacogenetic Discovery in CALGB (Alliance) 90401 and Mechanistic Validation of a VAC14 Polymorphism that Increases Risk of Docetaxel-Induced Neuropathy. Clinical cancer research : an official journal of the American Association for Cancer Research 47 27143689
2019 Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers in neuroscience 46 30930738
2012 Modulation of synaptic function by VAC14, a protein that regulates the phosphoinositides PI(3,5)P₂ and PI(5)P. The EMBO journal 46 22842785
2010 ArPIKfyve regulates Sac3 protein abundance and turnover: disruption of the mechanism by Sac3I41T mutation causing Charcot-Marie-Tooth 4J disorder. The Journal of biological chemistry 41 20630877
2017 Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol. Proceedings of the National Academy of Sciences of the United States of America 39 28827342
2017 Nbeal2 interacts with Dock7, Sec16a, and Vac14. Blood 32 29187380
2017 Yunis-Varón syndrome caused by biallelic VAC14 mutations. European journal of human genetics : EJHG 29 28635952
2007 Phase I study of a candidate vaccine based on recombinant HIV-1 gp160 (MN/LAI) administered by the mucosal route to HIV-seronegative volunteers: the ANRS VAC14 study. Vaccine 29 18068876
2006 Binding of Vac14 to neuronal nitric oxide synthase: Characterisation of a new internal PDZ-recognition motif. FEBS letters 27 17161399
2017 Neuropathology of childhood-onset basal ganglia degeneration caused by mutation of VAC14. Annals of clinical and translational neurology 22 29296614
2013 Vac14 protein multimerization is a prerequisite step for Fab1 protein complex assembly and function. The Journal of biological chemistry 21 23389034
2019 VAC14 syndrome in two siblings with retinitis pigmentosa and neurodegeneration with brain iron accumulation. Cold Spring Harbor molecular case studies 15 31387860
2023 The chloride antiporter CLCN7 is a modifier of lysosome dysfunction in FIG4 and VAC14 mutants. PLoS genetics 14 37363915
2019 Novel VAC14 variants identified in two Chinese siblings with childhood-onset striatonigral degeneration. Molecular genetics & genomic medicine 14 31876398
2017 Cellular vacuolization caused by overexpression of the PIKfyve-binding deficient Vac14L156R is rescued by starvation and inhibition of vacuolar-ATPase. Biochimica et biophysica acta. Molecular cell research 13 28216340
2013 The PIKfyve-ArPIKfyve-Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines. Biochemical and biophysical research communications 12 24070605
2020 Altered homodimer formation and increased iron accumulation in VAC14-related disease: Case report and review of the literature. Parkinsonism & related disorders 11 32949958
2020 Centrosomal protein TAX1BP2 inhibits centrosome-microtubules aberrations induced by hepatitis B virus X oncoprotein. Cancer letters 9 32827601
2015 The Protein Complex of Neurodegeneration-related Phosphoinositide Phosphatase Sac3 and ArPIKfyve Binds the Lewy Body-associated Synphilin-1, Preventing Its Aggregation. The Journal of biological chemistry 8 26405034
2021 Proximity Interactome Map of the Vac14-Fig4 Complex Using BioID. Journal of proteome research 6 34554760
2023 TIG1 Inhibits the mTOR Signaling Pathway in Malignant Melanoma Through the VAC14 Protein. Anticancer research 5 37247911
2025 VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex. Molecular biology of the cell 3 40305106
2025 Centrosome protein TAX1BP2 mediates STING-dependent immune response and potentiates anti-PD-1 efficacy in hepatocellular carcinoma. Molecular therapy : the journal of the American Society of Gene Therapy 2 39881544
2020 Downregulating VAC14 in Guard Cells Causes Drought Hypersensitivity by Inhibiting Stomatal Closure. Frontiers in plant science 2 33391314
2013 The tumor suppressor, TAX1BP2, is a novel substrate of ATM kinase. Oncogene 2 24240686
2025 Homeostatic Influence of Fig4 Outside of the Fab1-Vac14-Fig4 Complex in Saccharomyces cerevisiae. Molecular microbiology 1 40741910
2024 Impact of Fab1/Vac14 inhibition on β-1,3-glucanase localization at the tip in Saccharomyces cerevisiae. Biochemical and biophysical research communications 1 39536411
2018 Nephron-specific knockin of the PIKfyve-binding-deficient Vac14L156R mutant results in albuminuria and mesangial expansion. American journal of physiology. Renal physiology 1 30066585
2025 Conservative iron chelation for VAC14: Two-year clinical-radiological follow-up. Journal of Parkinson's disease 0 40221969
2022 The vacuolar morphology protein VAC14 plays an important role in sexual development in the filamentous ascomycete Sordaria macrospora. Current genetics 0 35776170