Affinage

YKT6

Synaptobrevin homolog YKT6 · UniProt O15498

Length
198 aa
Mass
22.4 kDa
Annotated
2026-06-11
58 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

YKT6 is an evolutionarily conserved R-SNARE that, uniquely among SNAREs, lacks a transmembrane domain and instead cycles between an autoinhibited cytosolic pool and an active membrane-bound pool to drive fusion at multiple steps of the secretory and degradative pathways (PMID:11323436, PMID:12589064, PMID:15044687). Membrane recruitment is governed by C-terminal lipidation: farnesylation of the CAAX cysteine is a prerequisite for palmitoylation of the upstream cysteine, and this double lipid modification, together with a longin domain–SNARE motif intramolecular interaction that maintains a closed conformation, controls stable membrane association and activity (PMID:15044687, PMID:18329045). Efficient targeting further requires double prenylation, in which the singly farnesylated protein is geranylgeranylated by a GGTase-III (PTAR1/Bet2 in mammals; Ecm9/Bet2 in yeast), a step needed for lysosomal hydrolase trafficking from the TGN and for organelle membrane localization including autophagosomes (PMID:33035318, PMID:40049413). The closed–open conformational switch is additionally driven by phosphorylation of SNARE-domain serines, including a Ca2+-regulated site, which redistributes YKT6 to membranes and reshapes its interactome (PMID:33207719, PMID:33723042). In its open form YKT6 assembles into distinct SNARE complexes mediating late ER-to-Golgi and intra-Golgi transport (with syntaxin 5, GS28, Bet1 or GS15), endosome-to-TGN recycling, and constitutive secretory carrier fusion at the plasma membrane (PMID:11323436, PMID:12388752, PMID:15215310, PMID:28403141). At the autophagosome, YKT6 forms a priming complex with STX17 and SNAP29 that is subsequently displaced by VAMP8 for the fusogenic step, and it can also act in a STX17-independent complex with SNAP29 and STX7, with its activity gated by ULK1/Atg1 phosphorylation that prevents premature complex assembly (PMID:29789439, PMID:36644903, PMID:38340317). Beyond fusion, the yeast longin domain presents palmitoyl-CoA to the vacuolar factor Vac8, conferring a non-enzymatic acyltransferase-like activity (PMID:14685280, PMID:15479160). YKT6 also supports exosome secretion and hippocampal AMPA receptor insertion during LTP (PMID:40840626, PMID:39794126), and pathological α-synuclein binds and deactivates YKT6 to block YKT6–SNAP29 complex formation and impair autophagosome-lysosome fusion in Parkinson's disease neuron models, a defect reversible by farnesyltransferase inhibitors (PMID:31648898, PMID:36788031).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2001 High

    Established YKT6 as a functional SNARE in the early secretory pathway, answering where this R-SNARE acts and with which partners.

    Evidence Co-IP and in vitro ER-Golgi transport assay with antibody inhibition in mammalian cells, plus genetic suppressor analysis in yeast

    PMID:11323436 PMID:11445562

    Open questions at the time
    • Did not resolve how YKT6 associates with membranes without a transmembrane domain
    • Mechanism of cycling between compartments unaddressed
  2. 2002 High

    Defined a distinct GS15-containing SNARE complex, showing YKT6 participates in more than one Golgi fusion complex.

    Evidence Reciprocal Co-IP, immuno-EM, and siRNA knockdown in Golgi extracts

    PMID:12388752

    Open questions at the time
    • Functional discrimination between GS15 and Bet1 complexes not fully resolved
  3. 2003 High

    Revealed a non-fusion biochemical activity, with the longin domain presenting palmitoyl-CoA to Vac8, broadening YKT6's molecular repertoire.

    Evidence In vitro vacuole fusion and palmitoylation assays with domain mutagenesis in yeast

    PMID:14685280

    Open questions at the time
    • Whether this acyltransferase-like activity operates on substrates beyond Vac8 unknown
    • Relevance in mammalian cells not established
  4. 2004 High

    Established the lipidation hierarchy and autoinhibition model, explaining how a TM-less SNARE achieves regulated membrane association.

    Evidence Metabolic labeling, in vitro intra-Golgi transport, recombinant self-palmitoylation assays, and longin-domain surface mutagenesis in mammalian/neuronal cells

    PMID:12589064 PMID:15044687 PMID:15331663 PMID:15479160

    Open questions at the time
    • Trigger for opening the closed conformation in vivo not identified
    • Identity of palmitoyltransferase in vivo unresolved
  5. 2005 High

    Demonstrated that depalmitoylation drives YKT6 cycling off membranes, linking lipid turnover to its trafficking life cycle.

    Evidence In vitro vacuole fusion, [3H]palmitate labeling, and lethal palmitoylation-site mutagenesis in yeast

    PMID:15723044

    Open questions at the time
    • Depalmitoylating enzyme not identified
    • Coupling of disassembly to depalmitoylation mechanistically incomplete
  6. 2008 High

    Provided structural and biophysical proof of the closed autoinhibited conformation, with the farnesyl group folding into the longin domain.

    Evidence X-ray crystallography of the yeast longin domain plus CD, SPR, limited proteolysis, and acyltransferase overexpression in yeast

    PMID:18329045 PMID:18541004

    Open questions at the time
    • No structure of the full-length open membrane-bound form
    • How conformational opening is triggered physiologically unresolved
  7. 2016 Medium

    Quantified the conformational dynamics of the longin–SNARE switch and showed lipid environment locks the closed state.

    Evidence Single-molecule FRET, FCCS, and MD simulation on rat YKT6

    PMID:27493064

    Open questions at the time
    • Dynamics measured in detergent/lipid mimics, not native membranes
    • Link between observed microsecond dynamics and SNARE engagement not directly demonstrated
  8. 2017 Medium

    Extended YKT6 function to constitutive secretory fusion at the plasma membrane, showing a conserved exocytic role.

    Evidence Quantitative secretion assays with combinatorial RNAi in Drosophila and mammalian cells

    PMID:28403141

    Open questions at the time
    • Direct demonstration of the proposed PM SNARE complexes biochemically incomplete
    • Regulation of YKT6 recruitment to secretory carriers unaddressed
  9. 2018 High

    Identified YKT6 as an autophagosomal SNARE acting independently of STX17, redefining the autophagosome-lysosome fusion machinery.

    Evidence siRNA SNARE screen, STX17 CRISPR KO epistasis, Co-IP, and autophagy flux assays in mammalian cells; genetics and in vitro fusion in Drosophila and yeast

    PMID:29694367 PMID:29789439 PMID:30097515

    Open questions at the time
    • Whether YKT6 acts fusogenically or regulatorily in autophagy not yet settled at this stage
    • Relationship between STX7- and STX17-containing complexes unclear
  10. 2019 High

    Linked YKT6 to a lysosomal stress response and to Parkinson's disease, showing α-synuclein deactivates YKT6 and FTase inhibitors rescue it.

    Evidence Membrane fractionation, Co-IP of α-synuclein, patient iPSC neurons, and FTase inhibitor treatment in neurons and mice

    PMID:31648898

    Open questions at the time
    • Structural basis of α-synuclein–YKT6 interaction not defined
    • How α-synuclein binding alters lipidation or conformation unresolved
  11. 2020 Medium

    Established phosphorylation as a conformational switch and identified the kinases and recruitment machinery controlling YKT6 activation.

    Evidence Phosphomimetic mutagenesis, BioID, in vitro Atg1 kinase assays, and genetic epistasis with Dsl1/COPII in yeast and Drosophila

    PMID:32611603 PMID:33025734 PMID:33207719

    Open questions at the time
    • Phosphatases reversing YKT6 phosphorylation not identified
    • Cross-talk between phosphorylation and lipidation states incompletely defined
  12. 2021 High

    Resolved the prenylation requirement and a Ca2+-regulated phosphosite, connecting double prenylation and signaling to YKT6's interactome and pathway choice.

    Evidence PTAR1 KO with prenylation assays, NMR structural analysis, mass spectrometry, and Ca2+ modulation in mammalian cells and PD models

    PMID:33035318 PMID:33723042

    Open questions at the time
    • Upstream signals controlling the Ca2+-dependent kinase unknown
    • How prenylation and phosphorylation are coordinated temporally unresolved
  13. 2023 High

    Defined ULK1-mediated phosphorylation as a conserved brake preventing premature autophagic SNARE assembly, and reinforced the α-synuclein/FTase axis in patient neurons.

    Evidence In vitro ULK1 kinase assays and phospho-mutant phenotypes across yeast, mammals, and C. elegans; Co-IP of YKT6-SNAP29 and FTase intervention in PD iPSC neurons and mice

    PMID:36644903 PMID:36788031

    Open questions at the time
    • Timing of dephosphorylation relative to fusion not precisely mapped
    • Whether ULK1 directly senses autophagosome maturation state unknown
  14. 2024 High

    Assigned YKT6 a priming rather than fusogenic role in autophagy and demonstrated functional redundancy with other R-SNAREs.

    Evidence Co-IP, VAMP8 displacement assays, in vitro lipid/content mixing reconstitution in mammalian cells; double-mutant genetics in yeast

    PMID:38340317 PMID:38588809

    Open questions at the time
    • Molecular trigger for VAMP8 displacement of YKT6 not defined
    • Physiological conditions selecting priming vs fusogenic complexes unclear
  15. 2025 Medium

    Expanded YKT6's roles to exosome secretion and synaptic plasticity, and identified Ecm9 as the yeast GGTase-III α subunit completing the prenylation pathway.

    Evidence In vitro Ecm9/Bet2 prenylation with MALDI MS and ecm9Δ phenotyping in yeast; EV nanoparticle tracking with FTase inhibition in neurons; AMPA receptor and mEPSC electrophysiology in hippocampal neurons

    PMID:39794126 PMID:40049413 PMID:40840626

    Open questions at the time
    • Mechanistic link between YKT6 and AMPA receptor insertion not defined
    • Which YKT6 SNARE complex mediates exosome release unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of the open, membrane-engaged YKT6 conformation and how lipidation, phosphorylation, and partner selection are integrated to direct YKT6 into one of its many distinct SNARE complexes remains unresolved.
  • No structure of full-length open/membrane-bound YKT6
  • Rules governing which SNARE complex YKT6 enters in a given compartment unknown
  • Phosphatases and depalmitoylases acting on YKT6 unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 5 GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005773 vacuole 4 GO:0005829 cytosol 4 GO:0005794 Golgi apparatus 3 GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9612973 Autophagy 4 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9609507 Protein localization 2
Partners
BET1GS15GS28SNAP29STX17STX5STX7VAMP8
Complex memberships
STX5-GS28-Bet1-YKT6 (ER-Golgi SNARE complex)STX5-GS28-GS15-YKT6 (Golgi/endosome-TGN SNARE complex)YKT6-SNAP29-STX7 (autophagosomal SNARE complex)YKT6-STX17-SNAP29 (autophagosome priming complex)

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Mammalian YKT6 forms a SNARE complex with syntaxin 5, GS28, and Bet1, localizes primarily to Golgi membranes, and functions at a late stage in ER-to-Golgi transport; antibodies against YKT6 inhibit in vitro ER-Golgi transport of VSVG before the EGTA-sensitive stage, and microinjection of YKT6 antibodies fragments the Golgi apparatus. Co-immunoprecipitation, in vitro ER-Golgi transport assay, antibody inhibition, microinjection, immunofluorescence microscopy The Journal of biological chemistry High 11323436
2001 In yeast, YKT6 (R-SNARE) acts as a multicopy and low-copy suppressor of vti1-2 defects, functionally interacting with VTI1 in transport to the prevacuole and vacuole; YKT6 participates in SNARE complexes containing Pep12p and Vam3p/Vam7p. Mutation of the zero ionic layer arginine (ykt6-R165Q) renders these complexes nonfunctional, establishing that arginine in the 0-layer is essential. Genetic suppressor screen, double-mutant analysis, in vivo transport assays, site-directed mutagenesis The Journal of biological chemistry High 11445562
2002 GS15 forms a distinct SNARE complex with syntaxin 5, GS28, and Ykt6 in the medial-cisternae of the Golgi; co-immunoprecipitation of COPI coat components with GS15 from Golgi extracts links this complex to early Golgi trafficking. Co-immunoprecipitation, immuno-electron microscopy, siRNA knockdown, dominant-negative overexpression Molecular biology of the cell High 12388752
2003 The yeast SNARE Ykt6 mediates palmitoylation of the vacuolar fusion factor Vac8 via its N-terminal longin domain, which presents palmitoyl-CoA (Pal-CoA) to Vac8; transfer to Vac8's SH4 domain occurs spontaneously rather than enzymatically. This acyltransferase activity operates during a Sec17-independent subreaction of vacuole fusion controlled by Sec18. In vitro vacuole fusion assay, palmitoylation assay, domain mutagenesis, biochemical reconstitution The EMBO journal High 14685280
2003 Rat neuronal Ykt6 localizes to a specialized punctate compartment distinct from conventional endomembrane markers; targeting to this compartment is directed by the profilin-like longin domain even in the absence of prenylation. Cytosolic Ykt6 is conformationally inactive for SNARE complex assembly, suggesting autoinhibition. Immunofluorescence microscopy, subcellular fractionation, domain deletion/mutagenesis, SNARE complex assembly assays Molecular biology of the cell Medium 12589064
2004 Both cytosolic and membrane-bound mammalian Ykt6 are farnesylated at the C-terminal CCAIM cysteine; farnesylation is a prerequisite for subsequent palmitoylation of the upstream cysteine, enabling stable membrane association. The double lipid modification (farnesyl + palmitoyl) is essential for intra-Golgi transport in vitro and cell survival in vivo. The N-terminal longin domain interacts with the SNARE motif, maintaining Ykt6 in an inactive closed conformation that controls membrane recruitment and palmitoylation. Metabolic labeling, in vitro intra-Golgi transport assay, site-directed mutagenesis of CAAX cysteines, cell viability assays Proceedings of the National Academy of Sciences of the United States of America High 15044687
2004 Human Ykt6 has intrinsic self-palmitoylating activity: incubation of recombinant hYkt6 with [3H]Pal-CoA leads to covalent attachment of palmitate to C-terminal cysteine residues. The N-terminal longin domain contains a Pal-CoA binding site and is required for the reaction. In vitro palmitoylation assay with [3H]palmitoyl-CoA and recombinant protein, domain deletion The Biochemical journal High 15479160
2004 In mammalian neuronal Ykt6, the longin domain controls conformation and subcellular targeting through intramolecular protein-protein interactions with the SNARE motif and protein-lipid interactions with C-terminal lipid groups. Two hydrophobic pockets on opposite faces of the longin domain participate; one suppresses palmitoylation-dependent mislocalization to the plasma membrane. Both protein-protein and protein-lipid intramolecular interactions are required for a tightly closed, autoinhibited conformation. Site-directed mutagenesis of longin domain surface residues, immunofluorescence localization, cell fractionation Journal of cell science Medium 15331663
2004 Syntaxin 5, GS28, Ykt6, and GS15 function as a SNARE complex mediating transport from the early/recycling endosome (EE/RE) to the trans-Golgi network (TGN); antibodies to each of these four SNAREs specifically inhibit STxB transport in vitro. GS15 and Ykt6 redistribute from the Golgi to endosomes when the recycling endosome is perturbed, indicating they cycle between these compartments. In vitro EE/RE-to-TGN transport assay with STxB, antibody inhibition, siRNA knockdown of GS15, overexpression of SNX3 to perturb recycling endosomes, immunofluorescence Molecular biology of the cell High 15215310
2005 Ykt6 is released from yeast vacuolar membranes during an early stage of homotypic vacuole fusion in a manner dependent on SNARE disassembly (priming by Sec18). Yeast Ykt6 undergoes palmitoylation at its C-terminal CAAX motif in vitro; mutagenesis of the palmitoylation site prevents stable membrane association and is lethal, indicating depalmitoylation drives Ykt6 cycling between membranes and cytosol. In vitro vacuole fusion assay, [3H]palmitate labeling, site-directed mutagenesis of palmitoylation site, cell viability assay EMBO reports High 15723044
2008 The Ykt6 longin domain–SNARE domain intramolecular interaction controls cycling between cytosol and membranes; a mutant deficient in this interaction accumulates on membranes and is not released from vacuoles. Ykt6 is a substrate of the DHHC acyltransferase network; overexpression of the vacuolar acyltransferase Pfa3 drives a constitutively membrane-associated Ykt6 mutant into the vacuolar lumen via the MVB pathway, showing that depalmitoylation and release are required to prevent entry into the MVB pathway. Site-directed mutagenesis of longin-SNARE interface, overexpression of Pfa3 acyltransferase, vacuole isolation and fractionation, fluorescence microscopy Traffic (Copenhagen, Denmark) Medium 18541004
2008 In vitro farnesylation of the C-terminal CAAX box of recombinant Ykt6 stabilizes the native protein, increases helical content, and promotes a more compact structure. The farnesyl moiety folds onto a hydrophobic groove in the longin domain, consistent with a closed autoinhibited conformation; the crystal structure of the yeast Ykt6 longin domain (residues 1–140) was determined at 2.5 Å resolution. In vitro farnesylation assay, size exclusion chromatography, limited proteolysis, circular dichroism spectroscopy, surface plasmon resonance, X-ray crystallography Journal of molecular biology High 18329045
2016 Single-molecule FRET and fluorescence cross-correlation spectroscopy reveal that rat Ykt6 undergoes intramolecular conformational dynamics between its longin domain and SNARE core at a timescale of ~200 μs. The presence of the lipid dodecylphosphocholine (DPC) regulates and can eliminate these dynamics, locking Ykt6 in a closed conformation; molecular dynamics simulations show that the SNARE core is flexible while the longin domain is relatively stable in the apo state. Single-molecule FRET, fluorescence cross-correlation spectroscopy (FCCS), molecular dynamics simulation Scientific reports Medium 27493064
2017 RNAi depletion of YKT6 in Drosophila cells blocks constitutive secretory carrier fusion with the plasma membrane; YKT6 participates in at least two SNARE complexes mediating Golgi-to-PM transport (STX1/SNAP24-29/YKT6 and STX4/SNAP24/Syb). RNAi depletion of YKT6 and VAMP3 in mammalian cells also blocks constitutive secretion, establishing an evolutionarily conserved role. Quantitative secretion assay, combinatorial RNAi in Drosophila cells, RNAi in mammalian cells PLoS genetics Medium 28403141
2018 In mammalian cells, YKT6 is an autophagosomal SNARE that mediates autophagosome-lysosome fusion independently of STX17. YKT6 forms a SNARE complex with SNAP29 and lysosomal STX7. Recruitment of YKT6 to autophagosomes requires its N-terminal longin domain but not C-terminal palmitoylation/farnesylation (which are required for Golgi localization). YKT6 depletion completely blocks autophagosome-lysosome fusion in STX17 KO cells, indicating two independent SNARE complexes mediate this fusion. SNARE screen by siRNA, STX17 CRISPR KO, YKT6 depletion, co-immunoprecipitation of SNARE complex (YKT6/SNAP29/STX7), domain mutant analysis, autophagy flux assays The Journal of cell biology High 29789439
2018 In Drosophila, Ykt6 is required for autophagosome-lysosome fusion and localizes to lysosomes and autolysosomes. Ykt6 forms a SNARE complex with Syx17 and Snap29 but can be outcompeted by Vamp7; Vamp7 overexpression rescues the fusion defect of ykt6 loss-of-function cells. A zero-ionic-layer mutation (R→Q) in Ykt6 does not impair autophagic activity, whereas palmitoylation/farnesylation site mutations do, supporting a non-canonical regulatory (non-fusogenic) role for Ykt6 in this complex. Drosophila genetics (loss-of-function mutants, transgenic rescue), Co-immunoprecipitation, immunofluorescence localization, Vamp7 overexpression rescue, site-directed mutagenesis PLoS genetics High 29694367
2018 In yeast, Ykt6 is the autophagosomal SNARE required for autophagosome-vacuole fusion. A novel in vitro fusion assay using intact autophagosomes and vacuoles demonstrated that Ykt6 localizes to the autophagosome side of the fusion machinery, and that this process requires ATP, physiological temperature, HOPS tethering complex, Ypt7 GTPase, and Mon1-Ccz1 GEF. Novel in vitro autophagosome-vacuole fusion assay, SNARE localization by biochemical fractionation The Journal of cell biology High 30097515
2019 During lysosomal stress, cytosolic ykt6 (normally autoinhibited by a farnesyl-mediated regulatory mechanism) activates and redistributes to membranes to promote lysosomal hydrolase trafficking and enhance cellular clearance. α-Synuclein aberrantly binds and deactivates ykt6 in patient-derived neurons, disabling this lysosomal stress response. Farnesyltransferase inhibitors restore ykt6 activity and reduce α-synuclein in patient-derived neurons and mice. Membrane fractionation, co-immunoprecipitation of α-synuclein with ykt6, patient-derived iPSC neurons, farnesyltransferase inhibitor treatment, lysosomal activity assays, mouse in vivo experiments Neuron High 31648898
2020 In yeast, Ykt6 is recruited to autophagosomes at an early stage of their formation via a mechanism dependent on the ER-resident Dsl1 complex and COPII-coated vesicles. The Atg1 kinase complex directly phosphorylates Ykt6 on autophagosomes to keep it inactive; dephosphorylation of Ykt6 allows its engagement in autophagosome-vacuole fusion. In vitro kinase assay (Atg1 phosphorylation of Ykt6), genetic epistasis with Dsl1 complex and COPII mutants, fluorescence microscopy, autophagy flux assays EMBO reports High 33025734
2020 In Drosophila wing epithelium, most Ykt6 is cytosolic but is recruited to de-acidified endosomal compartments where it recycles Wnt/Wingless to the plasma membrane via Rab4-positive recycling endosomes; this recycling is required for proper Wnt secretion. Proximity-dependent proteomics and biochemical analyses confirmed Ykt6 interactions within endosomal compartments. In vivo Drosophila genetics, proximity-dependent proteomics (BioID), immunofluorescence co-localization with Rab4, membrane fractionation, Wnt trafficking assays Development (Cambridge, England) Medium 32611603
2020 Phosphorylation of Ykt6 SNARE domain serine residues drives the conformational switch from a closed cytosolic form to an open membrane-bound form; phosphorylation mediates Ykt6 recruitment to several organelle membranes and functionally regulates Wnt protein trafficking and extracellular vesicle secretion. Phosphomimetic and phospho-dead mutagenesis, proximity-dependent labeling (BioID), membrane fractionation, Wnt trafficking assay, extracellular vesicle quantification Biomolecules Medium 33207719
2021 In mammalian cells, Ykt6 is phosphorylated at an evolutionarily conserved site regulated by Ca2+ signaling; this phosphorylation triggers a conformational change from a closed cytosolic to an open membrane-bound form. In the phosphorylated open form the spectrum of protein interactions changes, leading to defects in both the secretory and autophagy pathways and enhanced toxicity in Parkinson's disease models. Mass spectrometry identification of phosphorylation site, NMR structural analysis, phosphomimetic/phospho-dead mutagenesis, Ca2+ signaling modulation, Co-IP of interaction partners, autophagy and secretory pathway assays, PD model toxicity assays Proceedings of the National Academy of Sciences of the United States of America High 33723042
2021 Double prenylation of Ykt6 (farnesylation of Cys195 by farnesyltransferase followed by geranylgeranylation of Cys194 by a novel GGTase-III consisting of PTAR1/Bet2) is required for efficient trafficking of lysosomal hydrolases (cathepsin D and β-hexosaminidase) from the trans-Golgi network to lysosomes. In PTAR1 KO cells (singly farnesylated Ykt6), hydrolases are missorted and secreted extracellularly, their maturation is impaired, and LC3B accumulates indicating autophagic defects. PTAR1 knockout cells, lysosomal hydrolase secretion assay, hydrolase maturation analysis, LC3B accumulation by immunoblot, in vitro prenylation assays Journal of biochemistry High 33035318
2023 ULK1 (mammalian Atg1 ortholog) phosphorylates YKT6 on autophagosomes, preventing premature SNARE complex assembly with lysosomal SNAREs and inhibiting autophagosome-lysosome fusion; this regulation is conserved in yeast, mammalian cells, and C. elegans. Alterations in YKT6 phosphorylation status produce both early and late autophagy defects and reduce cellular survival. In vitro ULK1 kinase assay, phosphomimetic/phospho-dead YKT6 mutants, autophagy flux assays in mammalian cells and C. elegans, survival assays Journal of cell science High 36644903
2023 In Parkinson's disease patient iPSC-derived midbrain neurons, chronic endogenous α-synuclein accumulation directly impairs autophagosome-lysosome fusion by blocking ykt6-SNAP-29 complex formation. ykt6 depletion causes near-complete block of autophagic flux in human neurons. Increased farnesyltransferase activity in PD suppresses active (membrane-associated) ykt6; farnesyltransferase inhibitors restore autophagic flux by promoting active ykt6. iPSC-derived midbrain neuron culture from PD patients, Co-immunoprecipitation of ykt6-SNAP29 complex, autophagic flux assays, farnesyltransferase activity measurement, FTase inhibitor treatment in neurons and mice The Journal of neuroscience : the official journal of the Society for Neuroscience High 36788031
2024 YKT6 forms a priming SNARE complex with STX17 and SNAP29 on autophagosomes via its SNARE domain, enhancing autophagy flux. VAMP8 displaces YKT6 from this complex to form the fusogenic STX17-SNAP29-VAMP8 complex. The YKT6-SNAP29-STX17 complex facilitates both lipid and content mixing driven by STX17-SNAP29-VAMP8, indicating YKT6 plays a priming (not direct fusogenic) role for efficient autophagosome-lysosome fusion. Co-immunoprecipitation of YKT6/STX17/SNAP29 complex, VAMP8 displacement assay, in vitro lipid mixing and content mixing fusion assays, domain mutagenesis Cell reports High 38340317
2024 In yeast, Ykt6 and Nyv1 are functionally redundant R-SNAREs in homotypic vacuole fusion; a ykt6-104 nyv1Δ double mutant exhibits highly fragmented vacuoles while neither single mutant does. Ykt6 can also substitute for exocytic R-SNAREs Snc1/Snc2 when those lose the ability to assemble into exocytic SNARE complexes, indicating Ykt6 can function as a backup R-SNARE maintaining robustness of the vesicular transport network. Yeast genetic double-mutant analysis, vacuole morphology by fluorescence microscopy, SNARE complex assembly assays The Journal of biological chemistry Medium 38588809
2025 In budding yeast, the uncharacterized protein Ecm9 is the functional α subunit of yeast GGTase-III; Ecm9 forms a complex with Bet2 and transfers a geranylgeranyl group to mono-farnesylated Ykt6. MALDI-TOF/TOF mass spectrometry confirmed double prenylation (farnesyl + geranylgeranyl) of Ykt6 in wild-type but not ecm9Δ cells. Loss of Ecm9 impairs Ykt6 localization to organelle membranes including autophagosomes, reduces autophagic activity, and causes Golgi mannosyltransferase mislocalization and cell wall fragility. Structural prediction, in vitro prenylation assay with recombinant Ecm9/Bet2 complex, MALDI-TOF/TOF mass spectrometry of Ykt6 prenylation state, ecm9Δ yeast phenotyping, immunofluorescence of Ykt6 localization and mannosyltransferases, autophagy flux assay The Journal of biological chemistry High 40049413
2025 Ykt6 is highly expressed in the mammalian hippocampus, localizes to synaptic spines, and is required for LTP-dependent insertion of GluA1 and GluA2 AMPA receptor subunits at the postsynaptic membrane. Loss of Ykt6 function alters synaptic vesicle pool dynamics and the amplitude and frequency of miniature excitatory postsynaptic currents, modulates spine morphology, and impairs LTP. Immunofluorescence localization in hippocampal neurons, loss-of-function with defined synaptic phenotype, surface GluA1/GluA2 expression assay, mEPSC electrophysiology, spine morphology analysis The Journal of biological chemistry Medium 40840626
2025 Elevated α-synuclein reduces membrane-associated YKT6, impairing YKT6-mediated extracellular vesicle (exosome) secretion in H4 cells and iPSC-derived dopaminergic neurons. Pharmacological farnesyltransferase inhibition (FTI) decreases both membrane-associated YKT6 and EV secretion, establishing that farnesylation-dependent membrane association of YKT6 is required for EV secretion and that α-synuclein disrupts this by reducing membrane-associated YKT6. α-Synuclein-inducible H4 cells and iPSC-derived dopaminergic neurons, nanoparticle tracking analysis of EVs, membrane fractionation of YKT6, farnesyltransferase inhibitor treatment The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 39794126
2018 In mammalian prostate epithelial cells, Ykt6 acts as a negative regulator of cell migration and invasion by upregulating microRNA-145, which decreases Junctional Adhesion Molecule A (JAM-A) expression, thereby reducing Rap1 and Rac1 GTPase activity and attenuating cell spreading and motility. Ykt6 overexpression/knockdown in prostate epithelial cells, migration and invasion assays, miR-145 quantification, JAM-A protein level measurement, Rap1/Rac1 activity assays Cell cycle (Georgetown, Tex.) Low 30010460

Source papers

Stage 0 corpus · 58 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. The Journal of cell biology 194 29789439
2004 Participation of the syntaxin 5/Ykt6/GS28/GS15 SNARE complex in transport from the early/recycling endosome to the trans-Golgi network. Molecular biology of the cell 135 15215310
2004 Localization and activity of the SNARE Ykt6 determined by its regulatory domain and palmitoylation. Proceedings of the National Academy of Sciences of the United States of America 121 15044687
2001 Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a late stage in endoplasmic reticulum-Golgi transport. The Journal of biological chemistry 113 11323436
2016 YKT6 expression, exosome release, and survival in non-small cell lung cancer. Oncotarget 106 27285987
2002 GS15 forms a SNARE complex with syntaxin 5, GS28, and Ykt6 and is implicated in traffic in the early cisternae of the Golgi apparatus. Molecular biology of the cell 104 12388752
2018 Non-canonical role of the SNARE protein Ykt6 in autophagosome-lysosome fusion. PLoS genetics 81 29694367
2018 A novel in vitro assay reveals SNARE topology and the role of Ykt6 in autophagosome fusion with vacuoles. The Journal of cell biology 81 30097515
2001 Genetic interactions with the yeast Q-SNARE VTI1 reveal novel functions for the R-SNARE YKT6. The Journal of biological chemistry 81 11445562
2003 Mammalian ykt6 is a neuronal SNARE targeted to a specialized compartment by its profilin-like amino terminal domain. Molecular biology of the cell 71 12589064
2003 The SNARE Ykt6 mediates protein palmitoylation during an early stage of homotypic vacuole fusion. The EMBO journal 71 14685280
2020 LncRNA PVT1 promotes exosome secretion through YKT6, RAB7, and VAMP3 in pancreatic cancer. Aging 70 32499447
2006 Possible involvement of CCT5, RGS3, and YKT6 genes up-regulated in p53-mutated tumors in resistance to docetaxel in human breast cancers. Breast cancer research and treatment 69 16821082
2019 Stress-Induced Cellular Clearance Is Mediated by the SNARE Protein ykt6 and Disrupted by α-Synuclein. Neuron 61 31648898
2004 Intramolecular protein-protein and protein-lipid interactions control the conformation and subcellular targeting of neuronal Ykt6. Journal of cell science 48 15331663
2019 The multi-functional SNARE protein Ykt6 in autophagosomal fusion processes. Cell cycle (Georgetown, Tex.) 37 30836834
2008 Farnesylation of the SNARE protein Ykt6 increases its stability and helical folding. Journal of molecular biology 37 18329045
2017 VAMP3/Syb and YKT6 are required for the fusion of constitutive secretory carriers with the plasma membrane. PLoS genetics 35 28403141
2008 Depalmitoylation of Ykt6 prevents its entry into the multivesicular body pathway. Traffic (Copenhagen, Denmark) 34 18541004
2005 The SNARE Ykt6 is released from yeast vacuoles during an early stage of fusion. EMBO reports 34 15723044
2020 Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex. EMBO reports 32 33025734
2021 Tumor Suppressor miR-584-5p Inhibits Migration and Invasion in Smoking Related Non-Small Cell Lung Cancer Cells by Targeting YKT6. Cancers 27 33800298
2024 Human YKT6 forms priming complex with STX17 and SNAP29 to facilitate autophagosome-lysosome fusion. Cell reports 26 38340317
2004 The human SNARE protein Ykt6 mediates its own palmitoylation at C-terminal cysteine residues. The Biochemical journal 23 15479160
2021 A conformational switch driven by phosphorylation regulates the activity of the evolutionarily conserved SNARE Ykt6. Proceedings of the National Academy of Sciences of the United States of America 22 33723042
2020 Ykt6-dependent endosomal recycling is required for Wnt secretion in the Drosophila wing epithelium. Development (Cambridge, England) 22 32611603
2023 Impaired Autophagic-Lysosomal Fusion in Parkinson's Patient Midbrain Neurons Occurs through Loss of ykt6 and Is Rescued by Farnesyltransferase Inhibition. The Journal of neuroscience : the official journal of the Society for Neuroscience 21 36788031
2023 ULK1-mediated phosphorylation regulates the conserved role of YKT6 in autophagy. Journal of cell science 19 36644903
2021 Double prenylation of SNARE protein Ykt6 is required for lysosomal hydrolase trafficking. Journal of biochemistry 19 33035318
2018 YKT6 as a second SNARE protein of mammalian autophagosomes. Autophagy 19 30290708
2010 Evidence for prenylation-dependent targeting of a Ykt6 SNARE in Plasmodium falciparum. Molecular and biochemical parasitology 19 21075148
2023 A pan-cancer analysis of the oncogenic role of YKT6 in human tumors. Medicine 17 37058019
2018 Another longin SNARE for autophagosome-lysosome fusion-how does Ykt6 work? Autophagy 16 30290706
2020 Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity. Biomolecules 15 33207719
2016 Lipid Regulated Intramolecular Conformational Dynamics of SNARE-Protein Ykt6. Scientific reports 15 27493064
2022 Unbalanced Regulation of Sec22b and Ykt6 Blocks Autophagosome Axonal Retrograde Flux in Neuronal Ischemia-Reperfusion Injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 14 35654605
2018 A membrane fusion protein, Ykt6, regulates epithelial cell migration via microRNA-mediated suppression of Junctional Adhesion Molecule A. Cell cycle (Georgetown, Tex.) 11 30010460
2014 Lipid regulated conformational dynamics of the longin SNARE protein Ykt6 revealed by molecular dynamics simulations. The journal of physical chemistry. A 11 25268560
2012 R-SNARE ykt6 resides in membrane-associated protease-resistant protein particles and modulates cell cycle progression when over-expressed. Biology of the cell 11 22443861
2018 Ykt6 mediates autophagosome-vacuole fusion. Molecular & cellular oncology 9 30525099
2021 The R-SNARE Ykt6 is required for multiple events during oogenesis in Drosophila. Cells & development 8 34856414
2023 Different conformational dynamics of SNARE protein Ykt6 among yeast and mammals. The Journal of biological chemistry 7 37380075
2025 Double prenylation of budding yeast Ykt6 regulates cell wall integrity and autophagy. The Journal of biological chemistry 6 40049413
2017 Involvement of SNARE protein Ykt6 in glycosome biogenesis in Trypanosoma brucei. Molecular and biochemical parasitology 6 29107734
2025 Alpha-Synuclein Inhibits the Secretion of Extracellular Vesicles through Disruptions in YKT6 Lipidation. The Journal of neuroscience : the official journal of the Society for Neuroscience 5 39794126
2022 Regulation of the SNARE protein Ykt6 function by diprenylation and phosphorylation. Journal of biochemistry 5 36166826
1999 Characterization of the sequence and expression of a Ykt6 prenylated SNARE from rat. DNA and cell biology 5 10073573
2024 Ykt6 functionally overlaps with vacuolar and exocytic R-SNAREs in the yeast Saccharomyces cerevisiae. The Journal of biological chemistry 4 38588809
2024 miR-584-5p / Ykt6 - mediated autophagy - lysosome - exosome pathway as a critical route affecting the toxic effects of lead on HK-2 cells. Ecotoxicology and environmental safety 4 38636258
2024 Homozygous missense variants in YKT6 result in loss of function and are associated with developmental delay, with or without severe infantile liver disease and risk for hepatocellular carcinoma. Genetics in medicine : official journal of the American College of Medical Genetics 3 38522068
2025 Use of Biotin-Labeled Geranyl Pyrophosphate for Analysis of Ykt6 Geranylgeranylation. Methods in molecular biology (Clifton, N.J.) 2 39806148
2025 MACC1 drives metastasis in colorectal cancer by coordinating YKT6-dependent exosome biogenesis and c-Met cargo selection. Cellular signalling 2 40834974
2025 The SNARE protein Ykt6 drives insertion of the GluA1 and GluA2 glutamate receptors at synaptic spines during long-term potentiation. The Journal of biological chemistry 1 40840626
2025 YKT6 Promotes Bladder Cancer Progression by Stabilizing β-catenin Through USP7-Mediated Deubiquitination. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 1 41298248
2026 Artematrolide F suppresses communication between hepatocellular carcinoma cells and hepatic stellate cells to attenuate liver cancer progression through targeting YKT6. Cellular signalling 0 42177960
2025 Ykt6 SNARE protein drives GluA1 insertion at synaptic spines during LTP. bioRxiv : the preprint server for biology 0 40236018
2025 Expression of DKK1, HOXC6, and YKT6 Genes in Subjects With Oral Squamous Cell Carcinoma Residing in Central India: A Case-Control Study. Cureus 0 41477365
2023 Conserved regulation of autophagosome-lysosome fusion through YKT6 phosphorylation. Autophagy reports 0 40395297

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