Affinage

VAC14

Protein VAC14 homolog · UniProt Q08AM6

Length
782 aa
Mass
88.0 kDa
Annotated
2026-06-11
43 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

VAC14 is a HEAT-repeat scaffold protein that organizes the synthesis and turnover of the signaling lipid PI(3,5)P2 on endosomal/vacuolar membranes by assembling the PIKfyve(Fab1) lipid kinase and the FIG4/Sac3 phosphatase into a single ternary complex, thereby governing endolysosomal membrane trafficking (PMID:19037259, PMID:17556371). VAC14 self-associates into a star-shaped pentameric scaffold, and this oligomerization is the prerequisite first molecular event for assembly of the kinase–phosphatase complex; monomeric or oligomerization-defective mutants fail to bind Fab1/FIG4, mislocalize, and cannot generate PI(3,5)P2 (PMID:23389034, PMID:40305106). Within the assembled complex VAC14 positively regulates PIKfyve/Fab1 kinase activity and PI(3,5)P2 production (PMID:12062051, PMID:15542851, PMID:18950639), directs FIG4/Sac3 to the vacuole/endosome, and stabilizes Sac3 against proteasomal degradation (PMID:14528018, PMID:20630877). Loss of VAC14 collapses cellular PI(3,5)P2 and disrupts endosome-to-TGN retrograde trafficking and vacuolar homeostasis (PMID:17956977). Through this lipid output VAC14 controls multiple physiological processes: regulated endocytosis of AMPA receptors at synapses (PMID:22842785), insulin-stimulated GLUT4 translocation in adipocytes (PMID:17475247), and lysosomal size and acidification via PI(3,5)P2-dependent inhibition of the chloride transporter ClC-7 (PMID:37363915). Biallelic and dimerization-domain mutations in VAC14 cause a pediatric neurological disease characterized by PI(3,5)P2 deficiency and cellular vacuolization that is rescued by wild-type VAC14 (PMID:27292112).

Mechanistic history

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

    Established that VAC14 acts genetically upstream of the Fab1 kinase, answering whether VAC14 is a regulator rather than a catalytic component of PI(3,5)P2 synthesis.

    Evidence Yeast deletion/overexpression genetics with phosphoinositide measurement and hyperosmotic shock, where FAB1 overexpression rescues vac14Δ

    PMID:12062051

    Open questions at the time
    • Molecular basis of activation not defined
    • Did not resolve whether VAC14 acts on the kinase directly or through other partners
  2. 2003 High

    Showed VAC14 dually controls PI(3,5)P2 metabolism by directing the phosphatase Fig4 to the vacuole while also activating the Fab1 kinase, revealing coordination of synthesis and turnover.

    Evidence GFP localization, co-IP, in vitro phosphatase assay and deletion genetics in yeast

    PMID:14528018

    Open questions at the time
    • Stoichiometry of the membrane complex unknown
    • Mechanism of Fig4 recruitment not defined at residue level
  3. 2004 High

    Extended the model to mammals, showing human VAC14 physically binds and activates PIKfyve, establishing functional conservation of the scaffold-kinase relationship.

    Evidence Reciprocal co-IP, co-fractionation, siRNA knockdown and in vitro lipid kinase assay; plus adipocyte hyperosmotic PI(3,5)P2 measurements

    PMID:15542851 PMID:15546865

    Open questions at the time
    • Did not yet define the phosphatase arm in mammals
    • Domains mediating binding not mapped
  4. 2007 High

    Defined the in vivo requirement for VAC14 and the full mammalian ternary (PAS) complex, demonstrating that VAC14 couples PI(3,5)P2 synthesis (PIKfyve) with turnover (Sac3) to drive endosomal dynamics.

    Evidence Vac14 knockout mouse with lipid and retrograde-trafficking phenotypes; endogenous co-IP, fractionation, in vitro phosphatase and endosome reconstitution assays

    PMID:17475247 PMID:17556371 PMID:17956977

    Open questions at the time
    • Structural architecture of the complex unknown
    • How synthesis and turnover are temporally balanced not resolved
  5. 2008 High

    Identified VAC14 as the central organizer of the PAS complex via homomeric and heteromeric contacts, answering which subunit nucleates assembly and showing its C-terminus is required for kinase activation.

    Evidence HEAT-repeat scaffold characterization with ingls mouse mutant; systematic co-IP with truncation mutants, in vitro kinase assay, dominant-negative peptide competition and GLUT4 readout

    PMID:18950639 PMID:19037259

    Open questions at the time
    • Oligomeric state not quantified
    • Atomic structure of interfaces not available
  6. 2009 High

    Mapped the PIKfyve Cpn60_TCP1 domain as the docking site for the VAC14-Sac3 subcomplex and confirmed that Sac3 phosphatase activity within the complex drives PI(3,5)P2 turnover.

    Evidence Domain mapping with truncation/point mutants and vacuole morphology readout using catalytic-dead Sac3 and PIKfyve mutants

    PMID:19840946

    Open questions at the time
    • Spatial relationship of kinase and phosphatase active sites unresolved
    • Regulatory switching between synthesis and turnover not addressed
  7. 2010 High

    Revealed a protein-stability function for VAC14, showing it protects Sac3 from proteasomal degradation, and linked failure of this mechanism to CMT4J disease via an unstabilizable Sac3 mutant.

    Evidence Cycloheximide chase with proteasome inhibitors, siRNA/overexpression and co-IP with the Sac3(I41T) disease mutant

    PMID:20630877

    Open questions at the time
    • Degradation pathway/E3 ligase not identified
    • Whether stabilization requires full complex assembly not tested
  8. 2012 High

    Connected VAC14 to neuronal physiology, demonstrating it controls AMPA receptor surface levels through regulated endocytosis at synapses.

    Evidence Endogenous localization, mEPSC electrophysiology in Vac14-/- neurons, AMPA receptor surface biotinylation and postsynaptic rescue

    PMID:22842785

    Open questions at the time
    • Direct lipid-to-receptor-trafficking link not mechanistically dissected
    • Identity of relevant endocytic machinery not defined
  9. 2013 High

    Ordered complex assembly by showing VAC14 self-multimerization is the obligatory first step that precedes recruitment of Fab1 and Fig4.

    Evidence Co-IP with C-terminal Vac14 mutants, two-hybrid, vacuole morphology and hyperosmotic PI(3,5)P2 assays in yeast

    PMID:23389034

    Open questions at the time
    • Exact oligomer number not determined
    • Trigger initiating multimerization unknown
  10. 2016 Medium

    Provided human disease causation, showing dimerization-domain VAC14 variants produce PI(3,5)P2 deficiency and cellular vacuolization rescuable by wild-type VAC14.

    Evidence Exome sequencing in two families with patient fibroblast vacuole rescue

    PMID:27292112

    Open questions at the time
    • Single cellular phenotype assayed
    • Tissue-specific basis of neurological presentation not established
  11. 2023 High

    Placed VAC14/FIG4-derived PI(3,5)P2 upstream of the lysosomal chloride transporter ClC-7, defining a downstream effector for lysosomal size and pH control.

    Evidence CLCN7 knockout in FIG4-null cells and dominant-negative CLCN7 in Fig4-null mice with lysosomal and in vivo phenotyping

    PMID:37363915

    Open questions at the time
    • Whether PI(3,5)P2 inhibits ClC-7 directly or via intermediaries not resolved
    • Generalizability beyond FIG4-null context untested for VAC14 alone
  12. 2025 High

    Delivered structural understanding, showing VAC14 forms a star-shaped pentameric scaffold whose interface mutations disrupt oligomerization, complex formation, localization and PI(3,5)P2 generation, unifying the assembly and disease models.

    Evidence Cryo-EM, AlphaFold2 modeling, oligomerization-interface mutagenesis in yeast and human KO cells, lipid analysis, pull-down, FSEC and VPS35-endosome colocalization

    PMID:40305106

    Open questions at the time
    • High-resolution structure of full kinase-phosphatase-loaded complex not solved
    • Dynamics of assembly/disassembly during signaling not captured

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VAC14 complex assembly and PI(3,5)P2 output are dynamically regulated by upstream signals and connected to its peripheral partners (nNOS, Rab9/TBC1D15, Synphilin-1, COPI/Arf1, cholesterol homeostasis) remains unresolved.
  • Functional significance of non-core partners largely untested
  • No mechanism linking VAC14 to plasma-membrane cholesterol established at molecular level
  • Signal-dependent regulation of pentamer assembly unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 4 GO:0005198 structural molecule activity 2
Localization
GO:0005768 endosome 4 GO:0005773 vacuole 3 GO:0005764 lysosome 1
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-9609507 Protein localization 2
Partners
ATG18FIG4NOS1PIKFYVERAB9ASNCAIPTBC1D15VAC7
Complex memberships
Fab1 PI(3,5)P2 regulatory complexPIKfyve-VAC14-FIG4/Sac3 (PAS) complex

Evidence

Reading pass · 24 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, making direct contact with Fig4, Fab1, Vac7, and Atg18. A missense mutation (ingls mouse) in Vac14 prevents association with Fab1, generating a partial complex. Vac14 mediates three distinct mechanisms for the rapid interconversion of PI3P and PI(3,5)P2. Yeast and mouse genetic analysis, co-immunoprecipitation, structural prediction, analysis of ingls mouse mutant with biochemical characterization The EMBO journal High 19037259
2003 In yeast, Vac14 is required for the vacuolar localization of the PI(3,5)P2 phosphatase Fig4; in the absence of Vac14, Fig4-GFP no longer localizes to the vacuole. Fig4 physically associates with Vac14 in a common membrane-associated complex. Vac14 both positively regulates Fab1 kinase activity and directs the localization/activation of Fig4. GFP localization microscopy, co-immunoprecipitation, in vitro phosphatase assay, yeast genetics (deletion mutants) Molecular biology of the cell High 14528018
2007 Loss of Vac14 in mice results in near-complete loss of PI(3,5)P2 and defects in endosome-to-TGN retrograde trafficking, establishing Vac14 as an essential regulator of PI(3,5)P2 synthesis required for membrane trafficking in vivo. Vac14 knockout mouse, lipid analysis, membrane trafficking assays, vacuole morphology Proceedings of the National Academy of Sciences of the United States of America High 17956977
2002 Vac14 is an upstream activator of Fab1-catalysed PI(3,5)P2 synthesis; vac14Δ cells make very little PI(3,5)P2 and fail to respond to hyperosmotic shock. FAB1 overexpression corrects vac14Δ defects. Vac14 is essential for regulated PI(3,5)P2 synthesis and for sorting of proteins to the vacuole lumen via multivesicular bodies. Yeast genetics (deletion mutants, overexpression), phosphoinositide lipid analysis, GFP trafficking assays, hyperosmotic shock Current biology : CB High 12062051
2004 Human VAC14 (ArPIKfyve) physically associates with PIKfyve, co-fractionates and co-localizes with it on intracellular membranes, and positively regulates PIKfyve lipid kinase activity. siRNA knockdown of hVac14 decreases PIKfyve kinase activity and PI(3,5)P2 levels; ectopic expression increases PIKfyve kinase activity and PI(3,5)P2. Co-immunoprecipitation, co-fractionation, siRNA knockdown, in vitro lipid kinase assay, intracellular lipid labeling Molecular and cellular biology High 15542851
2007 Mammalian VAC14 (ArPIKfyve) is part of a stable ternary complex with PIKfyve and Sac3 (the mammalian Fig4 ortholog). Sac3 co-fractionates and co-localizes with ArPIKfyve and PIKfyve. The ternary complex couples PI(3,5)P2 synthesis (PIKfyve) with turnover (Sac3) and regulates early endosome dynamics. Co-immunoprecipitation of endogenous proteins, subcellular fractionation, co-localization, in vitro phosphatase assay, siRNA knockdown with lipid measurements, in vitro endosome reconstitution assay The Journal of biological chemistry High 17556371
2008 ArPIKfyve (VAC14) organizes the PIKfyve-ArPIKfyve-Sac3 (PAS) complex through both homomeric (self-interaction via conserved C-terminal domain) and heteromeric interactions. ArPIKfyve is the principal organizer, interacting with both Sac3 and PIKfyve; Sac3 is permissive for maximal PIKfyve-ArPIKfyve association. Introduction of C-terminal ArPIKfyve peptide disassembles the PAS complex and reduces PIKfyve lipid kinase activity in vitro. Co-immunoprecipitation in transfected cells with single/double/triple combinations, in vitro PIKfyve lipid kinase assay, dominant-negative peptide competition, GLUT4 translocation assay Journal of molecular biology High 18950639
2009 Within the PAS complex, the Cpn60_TCP1 domain of PIKfyve is a major determinant for associating the ArPIKfyve-Sac3 subcomplex. Sac3 assembled in the PAS complex remains an active PI(3,5)P2 phosphatase; phosphatase-deficient Sac3(D488A) eliminates the vacuolar phenotype caused by kinase-deficient PIKfyve, demonstrating that Sac3 activity within the complex drives PI(3,5)P2 turnover. Biochemical domain mapping with truncation/point mutants, vacuole morphology assay as functional readout, co-expression of catalytic mutants The Journal of biological chemistry High 19840946
2010 ArPIKfyve (VAC14) stabilizes Sac3 protein by protecting it from rapid proteasome-dependent degradation. Knockdown of ArPIKfyve reduces Sac3 steady-state levels; overexpression of ArPIKfyve extends Sac3 half-life (from ~18.8 min). The pathogenic CMT4J mutation Sac3(I41T) cannot be stabilized by ArPIKfyve, suggesting failure of this stability mechanism underlies CMT4J pathogenesis. Cycloheximide chase assay, proteasome inhibitor experiments, siRNA knockdown, overexpression, co-immunoprecipitation The Journal of biological chemistry High 20630877
2007 ArPIKfyve (VAC14) physically associates with PIKfyve in 3T3-L1 adipocytes in an insulin-independent manner. Loss of either ArPIKfyve or PIKfyve by siRNA depletes PI(3,5)P2 and reduces insulin-stimulated glucose uptake, GLUT4 surface accumulation, and Akt phosphorylation, establishing the ArPIKfyve-PIKfyve-PI(3,5)P2 axis as required for insulin-regulated GLUT4 translocation. siRNA knockdown, co-immunoprecipitation, in vitro lipid kinase assay on isolated membranes, glucose uptake assay, GLUT4 surface quantification Experimental cell research High 17475247
2012 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 levels of AMPA receptor subunit GluA2, due to diminished regulated endocytosis of AMPA receptors. Re-introduction of VAC14 in postsynaptic cells reverses these effects. Immunofluorescence localization, electrophysiology (mEPSC recording) in Vac14-/- neurons, surface biotinylation of AMPA receptors, rescue by postsynaptic VAC14 re-expression The EMBO journal High 22842785
2013 Vac14 forms a homodimer/multimer, and Vac14 multimerization is prerequisite for Fab1 complex assembly. Monomeric Vac14 mutants (with mutations in conserved C-terminal motifs) fail to interact with Fab1 or Fig4, have enlarged vacuoles, and cannot generate PI(3,5)P2 in response to hyperosmotic shock, demonstrating that Vac14 self-interaction is the first molecular event in Fab1 complex assembly. Co-immunoprecipitation with Vac14 mutants, yeast vacuole morphology, hyperosmotic shock PI(3,5)P2 synthesis assay, two-hybrid analysis The Journal of biological chemistry High 23389034
2006 VAC14 interacts with the PDZ domain of neuronal nitric oxide synthase (nNOS) through a novel internal PDZ-recognition motif that is beta-finger independent. Deletion mapping and mutational analysis of Vac14 defined the essential residues of this internal motif. In vitro binding assays with Vac14 deletion constructs, mutational analysis of PDZ interaction motif FEBS letters Medium 17161399
2004 In 3T3-L1 adipocytes, hyperosmotic stress induces a marked PI(3,5)P2 increase that is fully dependent on the ArPIKfyve-PIKfyve axis; siRNA depletion of either ArPIKfyve or PIKfyve abolishes the hyperosmotically activated PI(3,5)P2 rise. siRNA knockdown of ArPIKfyve and PIKfyve, 32P lipid labeling and measurement in 3T3-L1 adipocytes The Journal of biological chemistry Medium 15546865
2017 Decreased VAC14 expression increases plasma membrane cholesterol, which facilitates Salmonella docking and invasion. The mechanism linking VAC14 to cholesterol homeostasis at the plasma membrane was established through siRNA knockdown and cholesterol measurement experiments. siRNA knockdown of VAC14, plasma membrane cholesterol quantification, Salmonella invasion assay, zebrafish infection model Proceedings of the National Academy of Sciences of the United States of America Medium 28827342
2014 VAC14 interacts with Rab9 and the Rab7 GAP TBC1D15, linking the VAC14 complex to endolysosomal vesicular transport regulation. These interactions were validated by reciprocal co-immunoprecipitation and proximity ligation assay. Protein affinity purification combined with MudPIT mass spectrometry, reciprocal co-immunoprecipitation, proximity ligation assay Molecular & cellular proteomics : MCP Medium 24578385
2015 The ArPIKfyve-Sac3 heterodimer (VAC14-Sac3 binary complex) interacts with Synphilin-1 (Sph1) in brain, as identified by mass spectrometry. Modulation of ArPIKfyve/Sac3 levels alters aggregation properties of Sph1-GFP through mechanisms involving increased cytosolic partitioning and basal autophagy-mediated clearance. Mass spectrometry of brain-derived ArPIKfyve-Sac3 interactors, RNA silencing and overexpression in mammalian cell lines including primary neurons, GFP aggregation assays The Journal of biological chemistry Medium 26405034
2021 BioID proximity labeling of Vac14 identified COPI subunit COPB1 and the GTPase Arf1 (required for COPI assembly) as proximal interactors of Vac14, validated by proximity ligation assay, suggesting a functional link between Vac14 and Golgi-associated COPI complex in endosomal dynamics. BioID proximity-dependent biotin labeling, mass spectrometry, proximity ligation assay Journal of proteome research Low 34554760
2025 VAC14 forms a star-shaped pentameric scaffold (medium-resolution structure). Atomic-resolution AlphaFold2 prediction combined with cryo-EM maps revealed that disease-linked mutations reside at VAC14-VAC14 interfaces. Mutations disrupting VAC14 oligomerization cause defects in PI(3,5)P2 generation, VAC14 localization, and Fab1/PIKfyve activity. In human VAC14 KO cells, patient mutations are defective in PIKfyve-VAC14-FIG4 complex formation (pull-down), VAC14 oligomerization (fluorescence-detection size-exclusion chromatography), and colocalization with VPS35-positive endosomes. CryoEM structure, AlphaFold2 modeling, yeast genetics with oligomerization interface mutants, lipid analysis, pull-down assay in human KO cells, fluorescence-detection size-exclusion chromatography, colocalization microscopy Molecular biology of the cell High 40305106
2016 VAC14 variants in the dimerization domain (p.Ala582Ser/p.Ser583Leu) cause pediatric neurological disease with PI(3,5)P2 deficiency. Vacuolization of patient fibroblasts was rescued by transfection of wild-type VAC14 cDNA, establishing that the patient variants are loss-of-function. Exome sequencing, patient fibroblast vacuole assay, rescue by wild-type VAC14 transfection American journal of human genetics Medium 27292112
2023 PI(3,5)P2 synthesized by the FIG4-VAC14 pathway inhibits the lysosomal chloride transporter ClC-7. Knockout of CLCN7 corrects lysosomal swelling and partially corrects lysosomal hyperacidification in FIG4 null cells, and dominant-negative CLCN7 in Fig4 null mice improved growth, neurological function, and lifespan by 20%, placing VAC14/FIG4-dependent PI(3,5)P2 upstream of ClC-7 in lysosomal regulation. CLCN7/CLCN6 knockout in FIG4 null cells, dominant-negative CLCN7 in Fig4 null mouse, lysosomal morphology and pH assays, in vivo phenotyping PLoS genetics High 37363915
2020 VAC14 homodimerization can be altered by missense mutations at the C-terminal dimerization domain; p.Leu648Phe and p.Ala562Val mutations enhance VAC14 homodimer formation compared to wildtype, while p.Arg623His does not, as measured in stably transfected SH-SY5Y cells. Stable overexpression in SH-SY5Y cells, co-immunoprecipitation to assess homodimer formation, patient fibroblast analysis Parkinsonism & related disorders Low 32949958
2016 siRNA knockdown of VAC14 in stem cell-derived peripheral neuronal cells increased docetaxel sensitivity, measured by decreased neurite processes and branches, indicating VAC14 is required for peripheral neuronal resilience to taxane-induced damage. siRNA knockdown in stem cell-derived peripheral neurons, neurite morphology quantification after docetaxel treatment Clinical cancer research Low 27143689
2024 Under ethanol stress in yeast, Vac14 dissociates from Atg18, its interaction partner in the Fab1 complex; this dissociation is linked to reduced PI(3,5)P2 levels caused by Fab1 downregulation, resulting in Atg18 membrane detachment and vacuole fusion. Fluorescence microscopy with PI(3,5)P2 sensor, genetic analysis with hyperactive Fab1 mutant, co-localization of Vac14 and Atg18 bioRxivpreprint Low

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 194 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 163 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 160 17556371
2002 Vac14 controls PtdIns(3,5)P(2) synthesis and Fab1-dependent protein trafficking to the multivesicular body. Current biology : CB 118 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
2014 The Vac14-interaction network is linked to regulators of the endolysosomal and autophagic pathway. Molecular & cellular proteomics : MCP 53 24578385
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
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
2019 Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes. Frontiers in neuroscience 48 30930738
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
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 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 3 39881544
2025 VAC14 oligomerization is essential for the function of the FAB1/PIKfyve-VAC14-FIG4 complex. Molecular biology of the cell 3 40305106
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

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