ATG14/Barkor is a regulatory and membrane-targeting subunit of human class III PI3K complex I (PI3KC3-C1). It recruits and organizes the VPS34–VPS15–BECN1 complex at ER-associated omegasome and phagophore membranes, supporting local PI3P production and autophagosome assembly. ATG14 controls BECN1 complex stability and phosphorylation, and its autophagic machinery participates in Parkin-mediated mitophagy. It also binds the STX17–SNAP29 fusion machinery to promote autophagosome–endolysosome fusion and interacts with Snapin to support late endosomal trafficking.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0035014 phosphatidylinositol 3-kinase regulator activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATG14 has a core PI3KC3-C1 regulatory role. Reason: Accept as a core molecular function. ATG14 targets and regulates the Beclin1/VPS34/VPS15 class III PI3K complex at ER/phagophore membranes for autophagosome biogenesis. The existing Falcon report corroborates this targeting/regulatory role; its ULK1-phosphorylation and disease-association findings do not establish new catalytic functions for ATG14. Supporting Evidence: PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 file:human/ATG14/ATG14-deep-research-falcon.md ATG14 is the autophagy-specific subunit of PI3KC3-C1 and helps activate VPS34 lipid kinase to generate PI3P needed for early autophagosome formation |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATG14 acts as a protein-membrane adaptor for PI3KC3-C1 and for autophagosome fusion machinery. Reason: Accept as a core molecular function. ATG14 couples PI3KC3-C1 to ER/omegasome/autophagic membranes through the BATS and ER-targeting regions and also couples mature autophagosomes to STX17-SNAP29/VAMP8 fusion machinery. Supporting Evidence: PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 the BATS domain directly binds to the membrane PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0016240 autophagosome membrane docking | IBA GO_REF:0000033 | ACCEPT | Summary: Autophagosome membrane docking is a core ATG14 late-autophagy function. Reason: Accept as core. ATG14 oligomerization, membrane tethering, and STX17-SNAP29 binding prime autophagosomes for VAMP8-dependent endolysosome fusion. Supporting Evidence: PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain PMID:25686604 autophagosomes still efficiently form but their fusion with endolysosomes is blocked file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IBA GO_REF:0000033 | MODIFY | Summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing PI3KC3-C1/type I autophagy complex. Cryo-EM of human PI3KC3-C1 (PDB 9MHF/9MHG/9MHH) resolves ATG14 as one of the four heterotetramer subunits alongside VPS34, VPS15, and BECN1. Reason: ATG14 defines the autophagy-associated class III PI3K complex I. The parent complex annotation is biologically correct; refinement to the established C1 term records the demonstrated complex composition. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001784663 · PTN001784663 SUPPORTS TRANSFER The ancestral ATG14 complex assertion is correct. The optional refinement names the supported complex I subtype; it does not indicate loss of ancestral complex membership. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 PMID:39913640 still no structures of the autophagy-specific PI3KC3-C1 have been resolved at a high enough resolution to place amino acid side chains. We determined the PI3KC3-C1 structure at a best local resolution of 3.26 Å PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Autophagosome assembly is a core ATG14 process. Reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome formation, ER-localized PI3P production, and autophagosome formation. Supporting Evidence: PMID:18843052 Silencing of human Atg14 in HeLa cells suppresses autophagosome formation PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation PMID:39913640 PI3KC3-C1 produces phosphatidylinositol (PI) 3-phosphate (PI3P) on the phagophore, which is the precursor to the autophagosome |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: ATG14 contributes directly to the autophagic machinery used in Parkin-mediated mitophagy. Reason: The full PMID:23878393 tests human HCT116 ATG14 knockout cells expressing Parkin: mitochondrial clearance after 24 h valinomycin is impaired while early Parkin recruitment is preserved (Fig. 1G/H). ATG14 organizes the PI3KC3-C1 membrane-building machinery that executes mitochondrial sequestration; it need not itself be a cargo receptor. This conditional mitophagy role is retained alongside its broader core autophagy function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN001784663 · PTN001784663 SUPPORTS TRANSFER The ATG14-node mitophagy assertion includes experimental evidence on human Q6ZNE5 itself (PMID:23878393). The direct target evidence supports participation; it is not a circular or unsupported family-only transfer. Supporting Evidence: PMID:23878393 mitochondrial clearance was greatly reduced in hAtg14 knockout cells |
| GO:0005776 autophagosome | IBA GO_REF:0000033 | ACCEPT | Summary: Autophagosome localization/activity context is supported. Reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during autophagy and to mature autophagosomes during STX17-dependent fusion. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0009267 cellular response to starvation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Starvation response is a supported induction context, but the core process is autophagy/autophagosome assembly. Reason: Keep as non-core. Starvation is a major experimental and physiological trigger for ATG14-dependent autophagy, while the direct ATG14 function is PI3KC3-C1 recruitment/regulation for autophagosome formation. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:23878393 phosphorylation at these sites is necessary for maximal autophagy file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0097629 extrinsic component of omegasome membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ATG14 is a peripheral component of the indicated autophagic membrane. Reason: The BATS amphipathic region binds curved lipid membranes and targets the complex to early autophagic structures (PMID:21518905). Live QuickGO on 2026-09-20 confirms GO:0097629 and GO:0097632 remain valid; their extrinsic-component topology accurately describes ATG14. Obsolescence of related terms does not invalidate these terms. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001784663 · PTN001784663 SUPPORTS TRANSFER The ancestral ATG14 localization assertion is grounded in human target evidence and agrees with direct membrane-binding experiments. No topology or compartment-transfer failure is established. Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0097632 extrinsic component of phagophore assembly site membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ATG14 is a peripheral component of the indicated autophagic membrane. Reason: The BATS amphipathic region binds curved lipid membranes and targets the complex to early autophagic structures (PMID:21518905). Live QuickGO on 2026-09-20 confirms GO:0097629 and GO:0097632 remain valid; their extrinsic-component topology accurately describes ATG14. Obsolescence of related terms does not invalidate these terms. Live QuickGO rechecked on 2026-09-22 retains GO:0097632 under the current name extrinsic component of phagophore membrane; GO:7770114 lists it as a part_of child. Its old phagophore-assembly-site wording is a related synonym. The ontology rewired this surviving term when GO:0034045 was obsoleted, so these two status statements are consistent. The machine-sourced GOA label is preserved. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001784663 · PTN001784663 SUPPORTS TRANSFER The ancestral ATG14 localization assertion is grounded in human target evidence and agrees with direct membrane-binding experiments. No topology or compartment-transfer failure is established. Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0000421 autophagosome membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Autophagosome membrane localization is supported. Reason: Accept as core location. ATG14 localizes to autophagosome membranes and binds autophagic SNARE machinery on mature autophagosomes. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: Cytoplasmic localization is supported as the broad ATG14 location. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to autophagic cytoplasmic foci after induction. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0032991 protein-containing complex | IEA GO_REF:0000117 | MODIFY | Summary: Protein-containing complex is true but too generic for ATG14. Reason: Modify to PI3KC3-C1/type I class III PI3K complex. ATG14 is specifically the autophagy-directed regulatory subunit of PI3KC3-C1 rather than merely part of an unspecified protein complex. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 |
| GO:0034045 phagophore assembly site membrane | IEA GO_REF:0000044 | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0005515 protein binding | IPI PMID:19050071 Identification of Barkor as a mammalian autophagy-specific f... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:22081109 Inhibition of autophagy by TAB2 and TAB3. | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:22493499 Receptor signaling lymphocyte-activation molecule family 1 (... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:23112296 Akt-mediated regulation of autophagy and tumorigenesis throu... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:23332761 Differential regulation of distinct Vps34 complexes by AMPK ... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:23954414 Beclin 2 functions in autophagy, degradation of G protein-co... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Interacts with BECN2 via the coiled-coil domain file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:24034250 EGFR-mediated Beclin 1 phosphorylation in autophagy suppress... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:24785657 NRBF2 regulates macroautophagy as a component of Vps34 Compl... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:25490155 Architecture and dynamics of the autophagic phosphatidylinos... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:25594178 A kinase-independent role for EGF receptor in autophagy init... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:33422265 ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-m... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005930 axoneme | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Axoneme localization is by similarity and is not the proteostasis-network core function. Reason: Keep as non-core. UniProt records ciliary axoneme localization by similarity, but the human ATG14 evidence reviewed here is dominated by autophagy-specific PI3KC3-C1 and autophagosome-fusion roles. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Also localizes to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme by similarity |
| GO:0006914 autophagy | IEA GO_REF:0000120 | ACCEPT | Summary: Autophagy is a core ATG14 process. Reason: Accept as core. ATG14/Barkor is repeatedly shown to be required for basal and inducible autophagy through PI3KC3-C1 recruitment and autophagosome formation. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19050071 Overexpression of Barkor leads to autophagy activation and increased number and enlarged volume of autophagosomes PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IEA GO_REF:0000107 | MODIFY | Summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing PI3KC3-C1/type I autophagy complex. Reason: ATG14 defines the autophagy-associated class III PI3K complex I. The parent complex annotation is biologically correct; refinement to the established C1 term records the demonstrated complex composition. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0042149 cellular response to glucose starvation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glucose starvation response is a valid induction context, not the primary ATG14 function. Reason: Keep as non-core. Nutrient/glucose starvation is an autophagy stimulus in ATG14 studies; the core annotatable role is autophagosome assembly and PI3KC3-C1 regulation. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondria-associated ER membrane contact-site localization is plausible but secondary. Reason: ER–mitochondria contact sites are a conditional platform for ATG14-containing autophagy initiation machinery. This location can coexist with ER, omegasome and autophagosome pools; its contextual classification does not imply exclusion from the contact site. Supporting Evidence: PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0045335 phagocytic vesicle | IEA GO_REF:0000107 | UNDECIDED | Summary: The mouse-to-human phagocytic-vesicle localization needs clarification. Reason: The Ensembl donor is mouse Atg14/Q8CDJ3, with an IDA annotation to PMID:22493499 confirmed in live QuickGO. Inspection of the full paper finds phagosomal SLAMF1/VPS34/BECN1/UVRAG experiments and negative SLAMF1–ATG14 coimmunoprecipitation, but no clear direct ATG14 localization assay was identified. Failure to bind this receptor complex does not exclude every phagosomal ATG14 pool; ordinary autophagosome localization also does not refute a conditional phagosome location. Propagation Review Root cause: UNRESOLVED Sources checked: UniProtKB:Q8CDJ3 UNRESOLVED Live QuickGO recovers mouse Atg14 IDA PMID:22493499. Full-text receptor-complex exclusion is not a direct negative localization experiment; the precise positive localization basis requires clarification. Supporting Evidence: PMID:22493499 Because Slamf1 did not interact with Atg14L or Rubicon |
| GO:0006622 protein targeting to lysosome | NAS PMID:16467569 Regulation of membrane traffic by phosphoinositide 3-kinases... | ACCEPT | Summary: ATG14 supports delivery of proteins to lysosomal degradation. Reason: The broad targeting annotation is compatible with ATG14-mediated cargo sequestration, endosomal maturation and autophagosome–endolysosome fusion. PMID:22797916 provides a direct Snapin-dependent mechanism and receptor-degradation rescue, so the role is not merely a perturbation phenotype or an inference from a specialized lysosomal targeting signal. Supporting Evidence: PMID:22797916 This phenotype was effectively complemented by wild-type Atg14L or Beclin 1-binding mutant, but not by its Snapin-binding mutant. |
| GO:0016236 macroautophagy | NAS PMID:40442316 Structure and activation of the human autophagy-initiating U... | ACCEPT | Summary: Macroautophagy is a core ATG14 process. Cryo-EM of human PI3KC3-C1 (PDB 9MHF) places ATG14 as the autophagy-specific subunit of the heterotetramer that produces PI3P on the phagophore during macroautophagy. Reason: Accept as core. ATG14 is the autophagy-specific PI3KC3-C1 subunit required for macroautophagy initiation and autophagosome formation. Supporting Evidence: PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0016241 regulation of macroautophagy | IDA PMID:10625637 Distinct classes of phosphatidylinositol 3'-kinases are invo... | ACCEPT | Summary: ATG14 positively regulates macroautophagy through PI3KC3-C1. Reason: Accept as core process regulation. Depletion impairs, and overexpression stimulates, autophagy/autophagosome formation; structurally ATG14 is part of the PI3KC3-C1 initiation complex. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19050071 Overexpression of Barkor leads to autophagy activation and increased number and enlarged volume of autophagosomes PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IPI PMID:25490155 Architecture and dynamics of the autophagic phosphatidylinos... | MODIFY | Summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing PI3KC3-C1/type I autophagy complex. Reason: ATG14 defines the autophagy-associated class III PI3K complex I. The parent complex annotation is biologically correct; refinement to the established C1 term records the demonstrated complex composition. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IPI PMID:40442316 Structure and activation of the human autophagy-initiating U... | MODIFY | Summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing PI3KC3-C1/type I autophagy complex. Reason: ATG14 defines the autophagy-associated class III PI3K complex I. The parent complex annotation is biologically correct; refinement to the established C1 term records the demonstrated complex composition. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process | IDA PMID:8999962 Characterization of p150, an adaptor protein for the human p... | ACCEPT | Summary: ATG14 supports PI3P biosynthesis as the targeting/regulatory PI3KC3-C1 subunit, not as the catalytic kinase. Reason: Accept as process contribution. ATG14 recruits PI3KC3-C1 to ER/phagophore membranes and is required for local PI3P production during autophagy initiation; PIK3C3/VPS34 remains the catalytic lipid kinase. Supporting Evidence: PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0045022 early endosome to late endosome transport | IDA PMID:14617358 Human VPS34 and p150 are Rab7 interacting partners. | UNDECIDED | Summary: ATG14 has an established endosomal role, but this early-to-late stage attribution is unresolved. Reason: PMID:14617358 now has cached full text, although this source-specific early-to-late transition assessment has not yet been re-adjudicated against that newly available text. Its title and abstract foreground VPS34/p150; that is not evidence that the curator misattributed ATG14. Full PMID:22797916 establishes a Snapin-dependent ATG14 function at the late stage of endocytic trafficking, which does not by itself settle participation in the earlier transition. Retain uncertainty about this specific source assertion rather than treating the two stages as interchangeable. Supporting Evidence: PMID:22797916 atg14l knockdown significantly delayed the late stage of endocytic trafficking |
| GO:0097352 autophagosome maturation | IDA PMID:10625637 Distinct classes of phosphatidylinositol 3'-kinases are invo... | ACCEPT | Summary: Autophagosome maturation is supported by ATG14 fusion/tethering biology. Reason: Accept as core late-autophagy process. ATG14 binds STX17-SNAP29 on mature autophagosomes and promotes VAMP8-dependent autophagosome-endolysosome fusion. Supporting Evidence: PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain PMID:25686604 autophagosomes still efficiently form but their fusion with endolysosomes is blocked file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0005737 cytoplasm | EXP PMID:19050071 Identification of Barkor as a mammalian autophagy-specific f... | ACCEPT | Summary: Cytoplasmic localization is supported as the broad ATG14 location. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to autophagic cytoplasmic foci after induction. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005737 cytoplasm | EXP PMID:37632749 MARCH7-mediated ubiquitination decreases the solubility of A... | ACCEPT | Summary: Cytoplasmic localization is supported as the broad ATG14 location. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to autophagic cytoplasmic foci after induction. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:20713597 Autophagy requires endoplasmic reticulum targeting of the PI... | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0034045 phagophore assembly site membrane | EXP PMID:18843052 Beclin 1 forms two distinct phosphatidylinositol 3-kinase co... | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0034045 phagophore assembly site membrane | EXP PMID:19050071 Identification of Barkor as a mammalian autophagy-specific f... | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0034045 phagophore assembly site membrane | EXP PMID:22314358 Imperfect interface of Beclin1 coiled-coil domain regulates ... | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0061635 regulation of protein complex stability | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | ACCEPT | Summary: ATG14 stabilizes the BECN1-containing autophagy complex. Reason: Full PMID:23878393 observes reduced BECN1 abundance in ATG14 knockout cells (Fig. 1B/D/E) and loss of nearly all residual endogenous BECN1 after additional UVRAG depletion (Fig. 2Cii). This supports complex stability in addition to the separately demonstrated control of BECN1 phosphorylation. Supporting Evidence: PMID:23878393 suggesting that these beclin-1 binding partners play a critical role in complex stability |
| GO:0043491 phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | MODIFY | Summary: The source directly supports class III PI3K-dependent PI3P production. Reason: The full PMID:21062745 tests ATG14 in Fig. 4C/D and shows stimulation of VPS34 lipid kinase activity. It does not test the PDK1/AKT endpoint required by GO:0043491. Refine this source-specific claim to PI3P biosynthesis, to which ATG14 contributes as a complex regulator; this does not assert that all AKT-related effects of ATG14 are biologically impossible. Proposed replacements: phosphatidylinositol-3-phosphate biosynthetic process Supporting Evidence: file:human/ATG14/ATG14-PMID21062745-primary-check.md Both Barkor/Atg14(L) and UVRAG stimulated hVps34 lipid kinase activity |
| GO:0141039 phosphatidylinositol 3-kinase inhibitor activity | IDA PMID:21062745 The RUN domain of rubicon is important for hVps34 binding, l... | REMOVE | Summary: The cited direct assay shows ATG14 stimulation, not PI3K inhibition. Reason: Full PMID:21062745 Fig. 4C/D explicitly includes ATG14/Barkor and shows increased VPS34 activity; inhibition is attributed to Rubicon. This is a verified mismatch of the inhibitory molecular function to the target in this experiment, rather than an inference from the paper title. The positive regulatory role is supported by the other ATG14 annotations. Supporting Evidence: file:human/ATG14/ATG14-PMID21062745-primary-check.md Both Barkor/Atg14(L) and UVRAG stimulated hVps34 lipid kinase activity |
| GO:0000045 autophagosome assembly | IDA PMID:20713597 Autophagy requires endoplasmic reticulum targeting of the PI... | ACCEPT | Summary: Autophagosome assembly is a core ATG14 process. Reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome formation, ER-localized PI3P production, and autophagosome formation. Supporting Evidence: PMID:18843052 Silencing of human Atg14 in HeLa cells suppresses autophagosome formation PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation PMID:39913640 PI3KC3-C1 produces phosphatidylinositol (PI) 3-phosphate (PI3P) on the phagophore, which is the precursor to the autophagosome |
| GO:0000407 phagophore assembly site | IDA PMID:20713597 Autophagy requires endoplasmic reticulum targeting of the PI... | ACCEPT | Summary: Phagophore assembly site localization/activity context is supported. Reason: Accept as core location/context. ATG14 localizes to and organizes the ER/phagophore assembly site where PI3KC3-C1 produces PI3P for autophagosome formation. Supporting Evidence: PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:20713597 Knockdown of Atg14L leads to the disappearance of the DFCP1-positive omegasome file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0043495 protein-membrane adaptor activity | IDA PMID:20713597 Autophagy requires endoplasmic reticulum targeting of the PI... | ACCEPT | Summary: ATG14 acts as a protein-membrane adaptor for PI3KC3-C1 and for autophagosome fusion machinery. Reason: Accept as a core molecular function. ATG14 couples PI3KC3-C1 to ER/omegasome/autophagic membranes through the BATS and ER-targeting regions and also couples mature autophagosomes to STX17-SNAP29/VAMP8 fusion machinery. Supporting Evidence: PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 the BATS domain directly binds to the membrane PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0005515 protein binding | IPI PMID:31806350 The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulat... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0034045 phagophore assembly site membrane | TAS Reactome:R-HSA-5682385 | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0051020 GTPase binding | IPI PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | KEEP AS NON CORE | Summary: GTPase binding is supported for IRGM interaction but is not the ATG14 core function. Reason: Keep as non-core. ATG14L physically interacts with the human immunity-related GTPase IRGM in antimicrobial autophagy context, but ATG14 core function is PI3KC3-C1 autophagy regulation/adaptor activity. Supporting Evidence: PMID:25891078 IRGM physically interacts with key autophagy regulators, ULK1, Beclin 1, ATG14L and ATG16L1 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0000423 mitophagy | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | KEEP AS NON CORE | Summary: ATG14 contributes directly to the autophagic machinery used in Parkin-mediated mitophagy. Reason: The full PMID:23878393 tests human HCT116 ATG14 knockout cells expressing Parkin: mitochondrial clearance after 24 h valinomycin is impaired while early Parkin recruitment is preserved (Fig. 1G/H). ATG14 organizes the PI3KC3-C1 membrane-building machinery that executes mitochondrial sequestration; it need not itself be a cargo receptor. This conditional mitophagy role is retained alongside its broader core autophagy function. Supporting Evidence: PMID:23878393 mitochondrial clearance was greatly reduced in hAtg14 knockout cells |
| GO:0098780 response to mitochondrial depolarisation | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | KEEP AS NON CORE | Summary: ATG14 contributes to autophagic clearance triggered by mitochondrial depolarization. Reason: The valinomycin experiment in full PMID:23878393 directly compares wild-type and ATG14-knockout human cells. ATG14 executes the autophagic response downstream of Parkin recruitment; stimulus specificity is a reason to record a conditional role, not to erase the demonstrated process. Supporting Evidence: PMID:23878393 mitochondrial clearance was greatly reduced in hAtg14 knockout cells |
| GO:0005515 protein binding | IPI PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosom... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0005776 autophagosome | IDA PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosom... | ACCEPT | Summary: Autophagosome localization/activity context is supported. Reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during autophagy and to mature autophagosomes during STX17-dependent fusion. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0016240 autophagosome membrane docking | IDA PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosom... | ACCEPT | Summary: Autophagosome membrane docking is a core ATG14 late-autophagy function. Reason: Accept as core. ATG14 oligomerization, membrane tethering, and STX17-SNAP29 binding prime autophagosomes for VAMP8-dependent endolysosome fusion. Supporting Evidence: PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes PMID:25686604 ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain PMID:25686604 autophagosomes still efficiently form but their fusion with endolysosomes is blocked file:human/ATG14/ATG14-uniprot.txt Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8 interaction |
| GO:0009267 cellular response to starvation | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | KEEP AS NON CORE | Summary: Starvation response is a supported induction context, but the core process is autophagy/autophagosome assembly. Reason: Keep as non-core. Starvation is a major experimental and physiological trigger for ATG14-dependent autophagy, while the direct ATG14 function is PI3KC3-C1 recruitment/regulation for autophagosome formation. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:23878393 phosphorylation at these sites is necessary for maximal autophagy file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0010608 post-transcriptional regulation of gene expression | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | UNDECIDED | Summary: Post-transcriptional gene-expression regulation remains ambiguous despite the protein-abundance experiments. Reason: Full PMID:23878393 Fig. 1 measures p62 protein and transcript abundance and demonstrates a large protein increase with a smaller transcript increase after ATG14 loss. It also shows BECN1 protein destabilization. GO:0010608 broadly covers regulation after transcript production; these data cannot be dismissed solely because ATG14 acts through autophagy. Whether the curated assertion reflects a direct gene-expression regulatory step or downstream protein turnover remains unresolved. Supporting Evidence: PMID:23878393 p62 transcript levels increased less than 2-fold in hAtg14 KO cells |
| GO:0016236 macroautophagy | IMP PMID:23878393 Role of membrane association and Atg14-dependent phosphoryla... | ACCEPT | Summary: Macroautophagy is a core ATG14 process. Reason: Accept as core. ATG14 is the autophagy-specific PI3KC3-C1 subunit required for macroautophagy initiation and autophagosome formation. Supporting Evidence: PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0005515 protein binding | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5672012 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5679205 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5679266 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5682385 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9755359 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-9921171 | ACCEPT | Summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context. Reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is generated for autophagosome formation. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0001933 negative regulation of protein phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: ATG14 controls substrate phosphorylation within the autophagy-initiation complex. Reason: PMID:23332761 explicitly establishes that ATG14L inhibits AMPK phosphorylation of VPS34 while increasing phosphorylation of BECN1. This is a direct complex-dependent regulatory mechanism central to autophagy initiation, without claiming ATG14 is itself a kinase. Supporting Evidence: PMID:23332761 Atg14L, an autophagy-essential gene present only in the proautophagy PMID:23332761 inhibits Vps34 phosphorylation but increases Beclin1 |
| GO:0001934 positive regulation of protein phosphorylation | ISS GO_REF:0000024 | ACCEPT | Summary: ATG14 controls substrate phosphorylation within the autophagy-initiation complex. Reason: PMID:23332761 explicitly establishes that ATG14L inhibits AMPK phosphorylation of VPS34 while increasing phosphorylation of BECN1. This is a direct complex-dependent regulatory mechanism central to autophagy initiation, without claiming ATG14 is itself a kinase. Supporting Evidence: PMID:23332761 Atg14L, an autophagy-essential gene present only in the proautophagy PMID:23332761 inhibits Vps34 phosphorylation but increases Beclin1 |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | ISS GO_REF:0000024 | MODIFY | Summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing PI3KC3-C1/type I autophagy complex. Reason: ATG14 defines the autophagy-associated class III PI3K complex I. The parent complex annotation is biologically correct; refinement to the established C1 term records the demonstrated complex composition. Proposed replacements: phosphatidylinositol 3-kinase complex, class III, type I Supporting Evidence: PMID:39913640 PI3KC3-C1 is a heterotetrameric complex that comprises one subunit each of the VPS34 lipid kinase, the regulatory scaffold VPS15 (vacuolar protein sorting 15, also known as PIK3R4, phosphoinositide-3-kinase regulatory subunit 4), BECN1 (beclin 1, autophagy related), and the autophagy specific subunit ATG14 PMID:18843052 human Atg14 and UVRAG interact with Beclin 1 and Vps34 PMID:19050071 direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III complex PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:25490155 early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14 PMID:40442316 PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and the regulatory subunits BECN1 and ATG14 file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0042149 cellular response to glucose starvation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Glucose starvation response is a valid induction context, not the primary ATG14 function. Reason: Keep as non-core. Nutrient/glucose starvation is an autophagy stimulus in ATG14 studies; the core annotatable role is autophagosome assembly and PI3KC3-C1 regulation. Supporting Evidence: PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER file:human/ATG14/ATG14-uniprot.txt Required for both basal and inducible autophagy; determines the localization of PI3KC3-C1 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1632857 | ACCEPT | Summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to autophagic membrane foci after induction. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5678313 | ACCEPT | Summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to autophagic membrane foci after induction. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5678315 | ACCEPT | Summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to autophagic membrane foci after induction. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5679266 | ACCEPT | Summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events. Reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to autophagic membrane foci after induction. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation |
| GO:0097629 extrinsic component of omegasome membrane | IDA PMID:21518905 Autophagosome targeting and membrane curvature sensing by Ba... | ACCEPT | Summary: ATG14 is a peripheral component of the indicated autophagic membrane. Reason: The BATS amphipathic region binds curved lipid membranes and targets the complex to early autophagic structures (PMID:21518905). Live QuickGO on 2026-09-20 confirms GO:0097629 and GO:0097632 remain valid; their extrinsic-component topology accurately describes ATG14. Obsolescence of related terms does not invalidate these terms. Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0097632 extrinsic component of phagophore assembly site membrane | IDA PMID:21518905 Autophagosome targeting and membrane curvature sensing by Ba... | ACCEPT | Summary: ATG14 is a peripheral component of the indicated autophagic membrane. Reason: The BATS amphipathic region binds curved lipid membranes and targets the complex to early autophagic structures (PMID:21518905). Live QuickGO on 2026-09-20 confirms GO:0097629 and GO:0097632 remain valid; their extrinsic-component topology accurately describes ATG14. Obsolescence of related terms does not invalidate these terms. Live QuickGO rechecked on 2026-09-22 retains GO:0097632 under the current name extrinsic component of phagophore membrane; GO:7770114 lists it as a part_of child. Its old phagophore-assembly-site wording is a related synonym. The ontology rewired this surviving term when GO:0034045 was obsoleted, so these two status statements are consistent. The machine-sourced GOA label is preserved. Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
| GO:0008333 endosome to lysosome transport | IGI PMID:22797916 Beclin-1-interacting autophagy protein Atg14L targets the SN... | ACCEPT | Summary: ATG14 promotes Snapin-dependent endosomal delivery to lysosomal degradation. Reason: PMID:22797916 demonstrates ATG14–Snapin interaction, delayed late endocytic traffic and receptor degradation after depletion, and rescue by wild-type but not Snapin-binding-defective ATG14. This distinct membrane-trafficking function is supported directly and belongs in the gene-level core synthesis alongside autophagy initiation and fusion. Supporting Evidence: PMID:22797916 Atg14L functions as a multivalent trafficking effector that regulates endosome maturation as well as autophagosome formation |
| GO:0005930 axoneme | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Axoneme localization is by similarity and is not the proteostasis-network core function. Reason: Keep as non-core. UniProt records ciliary axoneme localization by similarity, but the human ATG14 evidence reviewed here is dominated by autophagy-specific PI3KC3-C1 and autophagosome-fusion roles. Supporting Evidence: file:human/ATG14/ATG14-uniprot.txt Also localizes to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme by similarity |
| GO:0000045 autophagosome assembly | IMP PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Autophagosome assembly is a core ATG14 process. Reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome formation, ER-localized PI3P production, and autophagosome formation. Supporting Evidence: PMID:18843052 Silencing of human Atg14 in HeLa cells suppresses autophagosome formation PMID:19050071 compromises starvation- and rapamycin-induced LC3 lipidation PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation PMID:20713597 Atg14L recruits a subset of class III PI3-kinase to the ER PMID:21518905 PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain PMID:40442316 All forms of canonical autophagy, bulk and selective, are initiated upon the recruitment and activation PMID:39913640 PI3KC3-C1 produces phosphatidylinositol (PI) 3-phosphate (PI3P) on the phagophore, which is the precursor to the autophagosome |
| GO:0005515 protein binding | IPI PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. Supporting Evidence: PMID:19270696 Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner PMID:19270696 Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation file:human/ATG14/ATG14-uniprot.txt Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14 |
| GO:0005776 autophagosome | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | ACCEPT | Summary: Autophagosome localization/activity context is supported. Reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during autophagy and to mature autophagosomes during STX17-dependent fusion. Supporting Evidence: PMID:19270696 GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER PMID:25686604 ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes file:human/ATG14/ATG14-uniprot.txt Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane; autophagosome membrane |
| GO:0034045 phagophore assembly site membrane | IDA PMID:19270696 Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca... | MODIFY | Summary: Localization to the phagophore membrane is supported. Reason: Live QuickGO checked on 2026-09-20 marks GO:0034045 obsolete and provides the current GO:7770114 phagophore membrane. The demonstrated peripheral membrane localization should be retained with the current membrane term; a new term proposal is no longer necessary. Proposed replacements: phagophore membrane Supporting Evidence: PMID:21518905 the BATS domain directly binds to the membrane |
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Download this section (compressed HTML)Q: Which membrane or receptor context accounts for the mouse ATG14 phagocytic-vesicle annotation, and is the same localization conserved in human cells?
Q: Does ATG14 regulate an RNA or translation step underlying the post-transcriptional gene-expression annotation, or is the measured abundance change entirely due to autophagic turnover and complex stabilization?
Q: How do phosphorylation of ATG14 and its BATS-domain membrane interactions coordinate initiation, selective cargo sequestration and later fusion?
Experiment: Use ATG14 knockout cells rescued with coiled-coil, BATS-domain, ER-targeting, and cysteine-oligomerization mutants to measure DFCP1/WIPI recruitment, PI3P production, LC3 lipidation, and autophagic flux.
Hypothesis: ATG14 promotes autophagosome assembly by coupling PI3KC3-C1 to ER/phagophore membranes and enabling local PI3P production.
Type: PI3KC3-C1 autophagy-initiation rescue assay
Experiment: Separate ATG14 initiation and fusion activities using STX17-binding-defective and oligomerization-defective ATG14 mutants, then quantify autophagosome number, autolysosome formation, and cargo degradation.
Hypothesis: ATG14 has separable early PI3KC3-C1 recruitment and late STX17-SNAP29/VAMP8 fusion functions.
Type: autophagosome maturation separation-of-function assay
Experiment: Compare wild-type ATG14 and Snapin-binding-deficient mutants in synchronized endocytic receptor-degradation assays while monitoring autophagic flux in parallel.
Hypothesis: ATG14-dependent endosome maturation is a supported secondary trafficking function that can be separated from its core PI3KC3-C1 autophagy role.
Type: endocytic trafficking/autophagy separation assay
Experiment: Express a non-phosphorylatable ATG14 Ser29Ala mutant (versus wild-type and phosphomimetic) in ATG14-knockout cells and quantify starvation-induced VPS34 lipid-kinase activity, PI3P production, DFCP1/WIPI2 puncta, and LC3 lipidation.
Hypothesis: ULK1-mediated ATG14 Ser29 phosphorylation is required for PI3KC3-C1 activation and local PI3P production at autophagosome formation sites during autophagy initiation.
Type: ULK1-ATG14 phosphosite separation-of-function assay
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Download this section (compressed HTML)Source: Sun et al., JBC, DOI 10.1074/jbc.M110.126425, author-hosted full manuscript PDF, inspected 2026-09-20 after automated PMC retrieval failed. This is a manual evidence note, not a provider report or replacement publication cache.
Figure 4C/D measures VPS34 lipid kinase activity after coexpression with the indicated subunits. The Results, manuscript pages 4–5, state: “Both Barkor/Atg14(L) and UVRAG stimulated hVps34 lipid kinase activity”. ATG14 is therefore actually assayed and acts positively in this experiment; the inhibitor is Rubicon. The full manuscript does not present an AKT/protein-kinase-B readout. It establishes PI3P generation and autophagy regulation; these are not by themselves proof of the more specific pathway ending in PDK1/AKT activation. p150/VPS15 is recovered in the Rubicon-containing PI3KC3 complex (Figure 1), without a p150-specific AKT assay.
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