ATG14/Barkor/ATG14L is the autophagy-specific regulatory and membrane-adaptor subunit of the human class III PI3K complex I (PI3KC3-C1). It targets the PIK3C3/VPS34-PIK3R4/VPS15-BECN1 complex to ER-associated omegasome/phagophore membranes for local PI3P production and autophagosome assembly, and it also promotes later STX17-SNAP29/VAMP8-dependent autophagosome-endolysosome fusion. Its main cellular roles are autophagy initiation and autophagosome maturation rather than class I PI3K/AKT signaling.
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.
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.
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.
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: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction that matters for the PN autophagy branch.
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
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
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
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.
Summary: Mitophagy is too cargo-specific for the accessible ATG14 evidence.
Reason: Modify to autophagosome assembly. ATG14 is required for canonical autophagosome biogenesis and PI3KC3-C1 activation, but the cached ATG14 papers do not establish a direct ATG14-specific mitophagy function beyond the general requirement of core autophagy machinery.
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.
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.
GO:0097632
extrinsic component of phagophore assembly site membrane
IBA
GO_REF:0000033
ACCEPT
Summary: ATG14 is an extrinsic component of the phagophore assembly site membrane.
Reason: Accept as core location/context. ATG14 localizes to early autophagic membranes and recruits PI3KC3 activity needed for phagophore/omegasome PI3P production.
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.
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.
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
IPI
PMID:19050071
Identification of Barkor as a mammalian autophagy-specific f...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
IPI
PMID:20562859
Network organization of the human autophagy system.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:21062745
The RUN domain of rubicon is important for hVps34 binding, l...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:22493499
Receptor signaling lymphocyte-activation molecule family 1 (...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:23112296
Akt-mediated regulation of autophagy and tumorigenesis throu...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:23332761
Differential regulation of distinct Vps34 complexes by AMPK ...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:23954414
Beclin 2 functions in autophagy, degradation of G protein-co...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
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
IPI
PMID:24034250
EGFR-mediated Beclin 1 phosphorylation in autophagy suppress...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:24785657
NRBF2 regulates macroautophagy as a component of Vps34 Compl...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:25490155
Architecture and dynamics of the autophagic phosphatidylinos...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
IPI
PMID:25594178
A kinase-independent role for EGF receptor in autophagy init...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:28514442
Architecture of the human interactome defines protein commun...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:32296183
A reference map of the human binary protein interactome.
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:33422265
ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-m...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:34524948
Global Proximity Interactome of the Human Macroautophagy Pat...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
IPI
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human ce...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
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
Reason: Accept as core. ATG14/Barkor is repeatedly shown to be required for basal and inducible autophagy through PI3KC3-C1 recruitment and autophagosome formation.
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: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction that matters for the PN autophagy branch.
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
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
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.
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: Keep as non-core. ATG14 is reported in ER/autophagosome contexts and STX17-linked literature places ATG14 near ER-mitochondria contact sites, but this is not the main PN functional annotation.
Summary: Phagocytic vesicle localization is not directly established for ATG14 in the cached evidence.
Reason: Mark as over-annotated. ATG14 participates in antimicrobial/xenophagy contexts, but the reviewed evidence supports autophagic membranes and cytosol/ER/autophagosome locations rather than a direct phagocytic vesicle localization.
NAS
PMID:16467569
Regulation of membrane traffic by phosphoinositide 3-kinases...
MODIFY
Summary: Protein targeting to lysosome is too broad for ATG14; the supported trafficking role is endosome/autophagosome-to-lysosome maturation/fusion.
Reason: Modify to endosome to lysosome transport. ATG14 supports endosome maturation through Snapin and promotes autophagosome-endolysosome fusion, rather than acting as a general lysosomal protein-targeting factor.
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.
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
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.
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: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction that matters for the PN autophagy branch.
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
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
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: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction that matters for the PN autophagy branch.
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
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
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.
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.
MODIFY
Summary: Early-to-late endosome transport is better captured as ATG14-supported endosome-to-lysosome transport/endosome maturation.
Reason: Modify to endosome to lysosome transport. The original hVPS34/p150 Rab7 paper does not establish an ATG14-specific early-to-late endosome role, while ATG14-specific Snapin evidence supports endosome maturation and late endocytic trafficking.
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.
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.
EXP
PMID:18843052
Beclin 1 forms two distinct phosphatidylinositol 3-kinase co...
ACCEPT
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
EXP
PMID:19050071
Identification of Barkor as a mammalian autophagy-specific f...
ACCEPT
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
EXP
PMID:22314358
Imperfect interface of Beclin1 coiled-coil domain regulates ...
ACCEPT
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
GO:0061635
regulation of protein complex stability
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
MODIFY
Summary: Protein-complex stability is not the best description of the ATG14 evidence from this paper.
Reason: Modify to positive regulation of protein phosphorylation. The accessible evidence for this reference supports Atg14-dependent Beclin 1 phosphorylation required for maximal autophagy, not a direct protein-complex-stability function.
phosphorylation at these sites is necessary for maximal autophagy
file:human/ATG14/ATG14-uniprot.txt
Stimulates phosphorylation of BECN1, but suppresses phosphorylation of PIK3C3 by AMPK
GO:0043491
phosphatidylinositol 3-kinase/protein kinase B signal transduction
IDA
PMID:21062745
The RUN domain of rubicon is important for hVps34 binding, l...
REMOVE
Summary: PI3K/AKT signaling is not an appropriate ATG14 process annotation from the Rubicon paper.
Reason: Remove. PMID:21062745 supports Rubicon as a negative regulator of hVps34/PI3KC3 and autophagosome maturation; it does not make ATG14 a class I PI3K/AKT signaling component.
IDA
PMID:21062745
The RUN domain of rubicon is important for hVps34 binding, l...
REMOVE
Summary: PI3K inhibitor activity is Rubicon biology, not ATG14 biology.
Reason: Remove. The cited Rubicon paper identifies Rubicon as the PI3KC3 lipid-kinase inhibitor, whereas ATG14 is a positive autophagy-specific PI3KC3-C1 targeting/regulatory subunit.
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.
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.
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.
IPI
PMID:31806350
The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulat...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with ATG14
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
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.
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
MODIFY
Summary: Mitophagy is too cargo-specific for the accessible ATG14 evidence.
Reason: Modify to autophagosome assembly. ATG14 is required for canonical autophagosome biogenesis and PI3KC3-C1 activation, but the cached ATG14 papers do not establish a direct ATG14-specific mitophagy function beyond the general requirement of core autophagy machinery.
Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation
GO:0098780
response to mitochondrial depolarisation
IMP
PMID:23878393
Role of membrane association and Atg14-dependent phosphoryla...
MODIFY
Summary: Response to mitochondrial depolarization is too stimulus-specific for the accessible ATG14 evidence.
Reason: Modify to autophagosome assembly. The cited ATG14 evidence supports Beclin 1 phosphorylation and maximal autophagy, but does not directly establish ATG14 as a depolarization-response factor apart from core autophagy machinery requirements.
IPI
PMID:25686604
ATG14 promotes membrane tethering and fusion of autophagosom...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
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.
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.
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.
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...
REMOVE
Summary: Post-transcriptional regulation of gene expression is unsupported for ATG14 in the reviewed evidence.
Reason: Remove. PMID:23878393 concerns ATG14-dependent Beclin 1 phosphorylation and autophagy; it does not support ATG14 as a post-transcriptional gene-expression regulator.
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
IPI
PMID:25127057
TRIM proteins regulate autophagy and can target autophagic s...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
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:0001933
negative regulation of protein phosphorylation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Negative regulation of protein phosphorylation is supported as a secondary regulatory effect.
Reason: Keep as non-core. UniProt records ATG14 suppression of AMPK-dependent PIK3C3 phosphorylation, but the main PN role is PI3KC3-C1 autophagy initiation rather than protein-phosphorylation regulation per se.
Supporting Evidence:
file:human/ATG14/ATG14-uniprot.txt
Stimulates phosphorylation of BECN1, but suppresses phosphorylation of PIK3C3 by AMPK
human Atg14 is critical in controlling an autophagy-dependent phosphorylation of beclin-1
GO:0001934
positive regulation of protein phosphorylation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Positive regulation of protein phosphorylation is supported as a secondary ATG14 regulatory effect.
Reason: Keep as non-core. ATG14 stimulates autophagy-dependent BECN1 phosphorylation required for maximal autophagy, but this is a regulatory mechanism rather than the primary PN function.
phosphorylation at these sites is necessary for maximal autophagy
file:human/ATG14/ATG14-uniprot.txt
Stimulates phosphorylation of BECN1, but suppresses phosphorylation of PIK3C3 by AMPK
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: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction that matters for the PN autophagy branch.
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
early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the tumor suppressor BECN1, and the autophagy-specific subunit ATG14
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.
GO:0097632
extrinsic component of phagophore assembly site membrane
IDA
PMID:21518905
Autophagosome targeting and membrane curvature sensing by Ba...
ACCEPT
Summary: ATG14 is an extrinsic component of the phagophore assembly site membrane.
Reason: Accept as core location/context. ATG14 localizes to early autophagic membranes and recruits PI3KC3 activity needed for phagophore/omegasome PI3P production.
IGI
PMID:22797916
Beclin-1-interacting autophagy protein Atg14L targets the SN...
KEEP AS NON CORE
Summary: Endosome-to-lysosome transport is a supported but secondary ATG14 trafficking role.
Reason: Keep as non-core. ATG14 has a Snapin-dependent endosome maturation role and a STX17-dependent autophagosome-endolysosome fusion role, but the dominant PN core is autophagy initiation through PI3KC3-C1.
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
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.
IPI
PMID:19270696
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca...
MARK AS OVER ANNOTATED
Summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
Reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership, protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8 autophagosome-fusion biology rather than generic binding.
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.
IDA
PMID:19270696
Two Beclin 1-binding proteins, Atg14L and Rubicon, reciproca...
ACCEPT
Summary: Phagophore assembly site membrane localization is supported.
Reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps recruit PI3KC3-C1 to those early autophagic structures.
ATG14 is the autophagy-specific PI3KC3-C1 regulatory subunit that recruits and organizes the PIK3C3/VPS34 lipid-kinase complex at ER-associated omegasome/phagophore membranes, enabling local PI3P production for autophagosome assembly and macroautophagy initiation.
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
ATG14 uses membrane-targeting/curvature-sensing and oligomerization regions to bridge autophagy machinery to membranes. This includes BATS-domain targeting of PI3P-rich autophagic membranes and STX17-SNAP29 binding on mature autophagosomes to promote VAMP8-dependent autophagosome-endolysosome fusion.
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex.
Reactome:R-HSA-1632857
ULK1 phosphorylates AMBRA1:BECN1 complex
Reactome:R-HSA-5672012
Beclin-1 complex phosphorylates PtdIns
Reactome:R-HSA-5678313
AMBRA1:DYNLL1,DYNLL2 binds BECN1 complex
Reactome:R-HSA-5678315
BECN1 complex, p-AMBRA1 dissociate from DYNLL1,DYNLL2
Reactome:R-HSA-5679205
ULK1 phosphorylates Beclin-1
Reactome:R-HSA-5679266
Beclin-1 complex translocates to the ER
Reactome:R-HSA-5682385
The phagophore extends from the PIP3-enriched structure
Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy.
ULK1 phosphorylates ATG14L (at Ser29), and this phosphorylation is required for activation of the class III PI3-kinase (VPS34) and production of phosphatidylinositol 3-phosphate at autophagosome formation sites during autophagy initiation.
The human autophagy-initiating complexes ULK1C and PI3KC3-C1.
ATG14 is the autophagy-specific regulatory subunit of the class III PI3-kinase complex I (PI3KC3-C1; VPS34-VPS15-BECN1-ATG14), a key initiator of macroautophagy whose assembly and activation it helps coordinate at the molecular level.
file:human/ATG14/ATG14-uniprot.txt
UniProtKB record for ATG14
file:human/ATG14/ATG14-notes.md
ATG14 review notes
Suggested Questions for Experts
Q: Should all human ATG14 class III PI3K complex annotations be narrowed from the generic parent to PI3KC3-C1/type I complex membership?
Suggested experts: GO autophagy editors, ComplexPortal curators, Reactome autophagy curators
Q: Should ATG14 mitophagy and mitochondrial-depolarization annotations be retained only with direct cargo-specific evidence, or generalized to autophagosome assembly/macroautophagy?
Suggested experts: GO autophagy editors, mitophagy domain experts, ParkinsonsUK-UCL curators
Q: Is protein-membrane adaptor activity sufficient for the ATG14 BATS/SNARE roles, or would a more specific autophagosome-fusion adaptor/tether term improve annotation?
Suggested experts: GO molecular function editors, autophagosome fusion experts
Q: Should ATG14 be annotated as a direct ULK1 phosphorylation substrate (ULK1-mediated Ser29 phosphorylation required for VPS34 activation and PI3P production), e.g. via protein kinase substrate or a regulation-of-PI3K-activity term?
Suggested experts: GO autophagy editors, ULK1/PI3KC3 signaling experts
Suggested Experiments
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.
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.
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.
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.FalconEdison Scientific Literature22 citations2 artifacts2026-06-07T04:48:08.167609
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
Research report: Human ATG14 (ATG14L/Barkor; UniProt Q6ZNE5)—functional annotation and current understanding
1) Key concepts and definitions (current understanding)
Identity verification / nomenclature. The literature captured here consistently uses ATG14 synonym ATG14L (also “Barkor”) to denote the human Beclin 1–binding autophagy regulator that is the autophagy-specific subunit of class III PI3-kinase complex I (PI3KC3-C1), matching UniProt Q6ZNE5 (human ATG14 family) and avoiding symbol ambiguity. (chen2025thehumanautophagyinitiating pages 12-13, chen2025thehumanautophagyinitiating pages 4-5, liu2023membranecurvaturethe pages 6-7)
Primary biochemical function (what it “does”). ATG14 is a non-enzymatic regulatory/targeting subunit of PI3KC3-C1 (VPS34/PIK3C3 lipid kinase + VPS15/PIK3R4 + BECN1 + ATG14) that enables autophagy initiation by promoting PI(3)P (PI3P) production at early autophagosome formation sites. The enzyme catalysis (phosphorylation of phosphatidylinositol to PI3P) is performed by VPS34, but ATG14 is essential for complex identity, targeting, and activation in autophagy initiation. (chen2025thehumanautophagyinitiating pages 4-5, chen2025thehumanautophagyinitiating pages 12-13)
Complex definitions. Human PI3KC3 exists in two mutually exclusive assemblies: PI3KC3-C1 (ATG14-containing) functions primarily in autophagy initiation, whereas PI3KC3-C2 (UVRAG-containing) is linked to endolysosomal sorting and later autophagy-related trafficking. ATG14 is specifically associated with the complex I (C1) autophagy-initiating function. (chen2025thehumanautophagyinitiating pages 4-5, liu2023membranecurvaturethe pages 6-7)
Omegasome / ER initiation site. “Omegasomes” are PI3P-rich subdomains associated with the endoplasmic reticulum (ER) that act as sites for early autophagosome biogenesis; ATG14-containing PI3KC3-C1 is implicated in targeting/activating PI3P generation at these ER-associated initiation sites. (chen2025thehumanautophagyinitiating pages 12-13, liu2023membranecurvaturethe pages 6-7)
2) Molecular function, domains/motifs, and subcellular localization
Domain-level functional model (ATG14 as a membrane-targeting and curvature-sensing subunit). A 2023 review synthesizes evidence that mammalian ATG14L contains:
- an N-terminal zinc finger,
- a central coiled-coil domain (CCD),
- and a C-terminal BATS domain (≈ last ~80 aa) that includes a ~19-aa amphipathic α-helix.
Functionally, the BATS domain acts as a membrane curvature sensor and preferentially binds highly curved early isolation membranes, with affinity for membranes enriched in PI3P and PI(4,5)P. (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
ER targeting and omegasome localization. The same 2023 synthesis describes ATG14L as targeted to the ER via an N-terminal cysteine repeat sequence, and reports co-localization with DFCP1 (omegasome marker) and ATG16L1 at early autophagic membranes, supporting a role at ER/omegasome initiation sites. (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
Complex architecture context. A structural/biochemical synthesis describes PI3KC3-C1 as a ~360 kDa complex with 1:1:1:1 stoichiometry (VPS34:VPS15:BECN1:ATG14). Only ~11% of the complex mass corresponds to the VPS34 catalytic module, emphasizing that non-catalytic subunits (including ATG14) provide regulatory and targeting functions. (chen2025thehumanautophagyinitiating pages 4-5)
3) Pathways and mechanisms: ATG14 in autophagy initiation signaling
Canonical pathway position. ATG14 functions at the nucleation step of autophagy initiation by enabling PI3KC3-C1 recruitment/activation at ER-associated initiation sites to generate PI3P, which recruits PI3P-binding effectors that drive phagophore assembly. (chen2025thehumanautophagyinitiating pages 12-13, chen2025thehumanautophagyinitiating pages 4-5)
Regulation by ULK1 via ATG14 Ser29 phosphorylation (site-specific mechanism). A 2024 primary study in Nature Communications reports that ULK1 phosphorylates ATG14L at Ser29, and this modification is required for activation of VPS34 lipid kinase, PI3P production at autophagosome formation sites, and downstream autophagy initiation. Phospho-Ser29 is absent in ULK1/2 double knockout cells and in cells expressing kinase-dead ULK1, and is restored by wild-type ULK1 under starvation. (tabata2024palmitoylationofulk1 pages 7-8)
New 2024 mechanism upstream of ULK1→ATG14: ULK1 palmitoylation control. The same 2024 study shows that ULK1 palmitoylation (by ZDHHC13) is important for ULK1 signaling to ATG14: palmitoylation-deficient ULK1 mutants show markedly reduced ATG14L Ser29 phosphorylation; chemical inhibition of palmitoylation (2-bromopalmitate) suppresses starvation-induced ATG14 Ser29 phosphorylation. (tabata2024palmitoylationofulk1 pages 7-8, tabata2024palmitoylationofulk1 media d29506c2)
mTORC1/AMPK axis (expert-level interpretation in recent primary work). A 2023 Nature Communications study re-evaluates AMPK’s relationship to autophagy initiation signaling and supports that ATG14 is an upstream-kinase target in ULK1–ATG14–VPS34 signaling, placing ATG14 phosphorylation within nutrient/energy-stress kinase networks (ULK1, AMPK, mTORC1) that tune PI3KC3-C1 output. (park2023redefiningtherole pages 16-16)
4) Recent developments and latest research (prioritize 2023–2024)
2023: Consolidation of ATG14 curvature sensing and ER targeting concepts. The 2023 review in Cells provides a current conceptual model positioning ATG14’s BATS domain as a curvature sensor at early isolation membranes and tying ER targeting to an N-terminal cysteine-repeat element; it also frames feedback between PI3P enrichment, curvature, and ATG14 recruitment. (https://doi.org/10.3390/cells12081132; Apr 2023) (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
2024: Regulatory mechanisms governing the autophagy-initiating VPS34 complex (including ATG14 BATS as a membrane-binding determinant). A 2024 review in Biomolecules & Therapeutics emphasizes ATG14 as the Complex I-specific subunit and highlights the BATS domain as a primary determinant for membrane binding and higher PI3KC3-C1 activity; swapping ATG14 BATS into UVRAG reportedly increases membrane binding/activity of the Complex II-like assembly, underscoring BATS as a modular activity determinant. (https://doi.org/10.4062/biomolther.2024.094; Oct 2024) (lee2024regulatorymechanismsgoverning pages 1-2)
2024: ULK1 palmitoylation as a new control point for ATG14 Ser29 phosphorylation and PI3P generation. Tabata et al. (2024) identifies a mechanistic bridge between membrane-proximal ULK1 regulation and ATG14 phosphorylation in the earliest stages of autophagy initiation. (https://doi.org/10.1038/s41467-024-51402-w; Aug 2024) (tabata2024palmitoylationofulk1 pages 7-8, tabata2024palmitoylationofulk1 media d29506c2)
5) Current applications and real-world implementations
Experimental pharmacology and targetability of the ATG14/VPS34 initiation axis. The 2024 VPS34-complex review highlights that autophagy initiation via VPS34 complex I has become a drug discovery target, discussing inhibitors of VPS34 and mentioning a Beclin 1–ATG14L interaction inhibitor as a chemical tool/lead concept for blocking autophagy initiation machinery. (lee2024regulatorymechanismsgoverning pages 1-2)
Clinical implementation status (ATG14-specific). Searches of ClinicalTrials.gov within the retrieved trial set did not identify interventional trials that directly target ATG14 as a drug target; the retrieved trials largely concern broader autophagy modulation contexts (e.g., hydroxychloroquine) rather than ATG14-specific perturbation. (clinical trials retrieved; see tool state summary) (lee2024regulatorymechanismsgoverning pages 1-2)
6) Disease associations, expert opinion, and authoritative-source analysis
Database-backed disease links (hypothesis-generating). Open Targets lists ATG14 disease associations (e.g., neurodegenerative disease, COVID-19, dengue disease, lysosomal storage disease) with underlying evidence entries tied to PubMed literature and CRISPRi/phenotyping screens; these should be interpreted as association/evidence-of-involvement rather than direct causal proof of mechanism in each disease. (OpenTargets Search: -ATG14)
Mechanism-to-disease logic (expert interpretation grounded in evidence). Since ATG14 is required for PI3KC3-C1–mediated PI3P generation at ER-associated initiation sites and is regulated by nutrient/energy-stress kinases, dysregulation of ATG14 abundance, localization, or PTMs would be expected to alter autophagosome nucleation capacity, impacting conditions where proteostasis, stress resilience, or pathogen handling relies on autophagy initiation efficiency. This inference is consistent with ATG14’s placement as an early “gatekeeper” subunit of PI3KC3-C1 and with its coupling to ULK1 signaling. (chen2025thehumanautophagyinitiating pages 12-13, chen2025thehumanautophagyinitiating pages 4-5, park2023redefiningtherole pages 16-16)
7) Relevant statistics and quantitative data from recent studies
Complex size/stoichiometry: PI3KC3-C1 is described as ~360 kDa, 1:1:1:1 (VPS34:VPS15:BECN1:ATG14), with ~11% of mass catalytic and ~89% non-catalytic/regulatory, supporting the interpretation that ATG14’s main function is regulatory/targeting rather than enzymatic. (chen2025thehumanautophagyinitiating pages 4-5)
Regulatory PTM evidence (ULK1→ATG14 Ser29): phospho-Ser29 ATG14 depends on ULK1 activity and is abolished in ULK1/2 DKO or kinase-dead ULK1 contexts; ULK1 palmitoylation deficiency diminishes ATG14 Ser29 phosphorylation and prevents its starvation-induced increase. (tabata2024palmitoylationofulk1 pages 7-8)
Membrane trafficking colocalization (related upstream mechanism): ZDHHC13 co-precipitates with ATG9A membranes and colocalization values of 12.7% and 62.0% are reported in the Tabata et al. 2024 study, linking a palmitoylation enzyme and ATG9A-associated membranes to early autophagosome formation mechanisms upstream of ATG14 phosphorylation. (tabata2024palmitoylationofulk1 pages 7-8)
8) Visual evidence from primary literature
The following figure panels provide direct experimental evidence that ULK1 palmitoylation is required for ULK1 kinase output toward ATG14 Ser29 phosphorylation, which links membrane-proximal ULK1 regulation to PI3KC3-C1 activation in autophagy initiation. (tabata2024palmitoylationofulk1 media d29506c2, tabata2024palmitoylationofulk1 media c95ede9b)
ATG14 is the autophagy-specific subunit of PI3KC3-C1 and helps activate VPS34 lipid kinase to generate PI3P needed for early autophagosome formation (chen2025thehumanautophagyinitiating pages 12-13, chen2025thehumanautophagyinitiating pages 4-5, park2023redefiningtherole pages 16-16)
Positive regulation by ULK1 phosphorylation; negative regulation by mTORC1 on ATG14-containing VPS34 complexes; AMPK-linked pathway effects are context-dependent (park2023redefiningtherole pages 16-16, losier2025identificationofkinasemediated pages 24-28)
Tabata et al., Nature Communications (https://doi.org/10.1038/s41467-024-51402-w; Aug 2024); Lee et al., Biomolecules & Therapeutics (https://doi.org/10.4062/biomolther.2024.094; Oct 2024); Park et al., Nature Communications (https://doi.org/10.1038/s41467-023-38401-z; May 2023)
Human PI3KC3-C1 described as a ~360 kDa 1:1:1:1 heterotetramer; catalytic domain is ~11% of complex mass, emphasizing regulatory/non-catalytic roles of subunits including ATG14 (chen2025thehumanautophagyinitiating pages 4-5)
PI3P production downstream of ULK1
ULK1 phosphorylates ATG14 at Ser29, which is required for VPS34 activation and PI3P production at autophagosome formation sites (tabata2024palmitoylationofulk1 pages 7-8, chen2025thehumanautophagyinitiating pages 4-5)
ULK1 complex functionally coupled to PI3KC3-C1 through ATG14 and BECN1 (tabata2024palmitoylationofulk1 pages 7-8, park2023redefiningtherole pages 16-16)
ULK1 kinase activity; loss in ULK1/2 DKO or kinase-dead ULK1 blocks ATG14 Ser29 phosphorylation (tabata2024palmitoylationofulk1 pages 7-8)
Tabata et al., Nature Communications (https://doi.org/10.1038/s41467-024-51402-w; Aug 2024); Park et al., Nature Communications (https://doi.org/10.1038/s41467-023-38401-z; May 2023)
Phospho-Ser29 was absent in ULK1/2 double-KO and kinase-dead ULK1 settings; WT ULK1 restored starvation-induced phosphorylation (tabata2024palmitoylationofulk1 pages 7-8)
Membrane targeting and curvature sensing during early autophagosome biogenesis
ATG14 C-terminal BATS domain contains an amphiphilic helix and functions as a membrane curvature sensor; preferentially binds highly curved nascent isolation membranes and PI3P/PI(4,5)P-enriched membranes (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
ATG14-containing PI3KC3-C1; Beclin1 recruitment to isolation membrane/ER (liu2023membranecurvaturethe pages 6-7)
N-terminal cysteine-repeat sequence mediates ER targeting; membrane curvature and PI3P provide positive feedback for recruitment/activity (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
Liu et al., Cells (https://doi.org/10.3390/cells12081132; Apr 2023); Lee et al., Biomolecules & Therapeutics (https://doi.org/10.4062/biomolther.2024.094; Oct 2024)
Review summarizes BATS as ~last 80 aa with a 19-aa amphipathic helix; ATG14 co-localizes with ATG16L1 and DFCP1 at omegasomes (liu2023membranecurvaturethe pages 6-7)
LC3 lipidation support downstream of PI3P
ATG14-dependent PI3KC3-C1 activity supports recruitment of WIPI2 and ATG2A, enabling efficient LC3 lipidation; complex II cannot substitute functionally in this assay (brier2019regulationoflc3 pages 14-22, brier2019regulationoflc3 pages 1-14)
PI3KC3-C1, WIPI2, ATG2A; distinguishes ATG14 complex I from UVRAG complex II (chen2025thehumanautophagyinitiating pages 4-5, brier2019regulationoflc3 pages 14-22)
Depends on VPS34 catalytic activity and ATG14 ALPS/BATS-like curvature-sensing element (brier2019regulationoflc3 pages 14-22, brier2019regulationoflc3 pages 1-14)
No 2023–2024 primary assay source in gathered context; supported by Brier et al., Molecular Biology of the Cell (https://doi.org/10.1091/mbc.e18-11-0743; Apr 2019) and discussed in later reviews (brier2019regulationoflc3 pages 14-22, brier2019regulationoflc3 pages 1-14)
In ATG14-knockout cytosol reconstitution, PI3KC3-C1 supported LC3 lipidation, whereas curvature-sensing/ALPS-defective derivatives failed to complement (brier2019regulationoflc3 pages 14-22, brier2019regulationoflc3 pages 1-14)
ER/omegasome targeting of the autophagy-initiation machinery
ATG14 is required for ER targeting of the class III PI3K complex and thereby for nucleation of PI3P-rich omegasomes (chen2025thehumanautophagyinitiating pages 12-13, liu2023membranecurvaturethe pages 6-7, brier2019regulationoflc3 pages 1-14)
BECN1-binding ATG14 subunit of PI3KC3-C1; mutually exclusive with UVRAG in complex II (chen2025thehumanautophagyinitiating pages 4-5, liu2023membranecurvaturethe pages 6-7)
ER, omegasomes, early isolation membrane (chen2025thehumanautophagyinitiating pages 12-13, liu2023membranecurvaturethe pages 6-7)
Competitive assembly with UVRAG affects pathway specificity between autophagy initiation and endolysosomal sorting (chen2025thehumanautophagyinitiating pages 4-5, liu2023membranecurvaturethe pages 6-7)
Lee et al., Biomolecules & Therapeutics (https://doi.org/10.4062/biomolther.2024.094; Oct 2024); Liu et al., Cells (https://doi.org/10.3390/cells12081132; Apr 2023)
Complex I (ATG14-containing) is linked to initiation, whereas complex II (UVRAG-containing) functions in endolysosomal sorting/later autophagy stages (chen2025thehumanautophagyinitiating pages 4-5)
Coupling upstream membrane delivery to PI3KC3-C1 activation
ULK1 palmitoylation by ZDHHC13 promotes ULK1 translocation and enhances phosphorylation of ATG14, increasing PI3P production and autophagy initiation (tabata2024palmitoylationofulk1 pages 7-8, tabata2024palmitoylationofulk1 media d29506c2)
Tabata et al., Nature Communications (https://doi.org/10.1038/s41467-024-51402-w; Aug 2024)
Reported colocalization values: endogenous ZDHHC13 with ATG9A membranes 12.7% and 62.0% in distinct measurements; palmitoylation-deficient ULK1 mutants showed markedly reduced ATG14 Ser29 phosphorylation (tabata2024palmitoylationofulk1 pages 7-8)
Pharmacologic targeting relevance
ATG14’s BATS domain is a major membrane-binding determinant of PI3KC3-C1; reviews discuss VPS34 inhibitors and a Beclin1–ATG14L interaction inhibitor as tools/therapeutic leads for autophagy-initiation blockade (lee2024regulatorymechanismsgoverning pages 1-2, brier2019regulationoflc3 pages 14-22)
Lee et al., Biomolecules & Therapeutics (https://doi.org/10.4062/biomolther.2024.094; Oct 2024)
Gathered evidence supports pathway-level rather than ATG14-specific clinical implementation; no direct ATG14-targeted clinical trials were identified in the searched trials context (lee2024regulatorymechanismsgoverning pages 1-2)
Table: This table summarizes experimentally supported functions, mechanisms, localization, and regulation of human ATG14/ATG14L in autophagy initiation. It emphasizes recent 2023–2024 sources where available and includes quantitative findings from the gathered evidence.
10) Key takeaways (functional annotation summary)
Primary role: ATG14 is a non-enzymatic targeting/regulatory subunit that specifies PI3KC3-C1 for autophagy initiation and is required for efficient PI3P production at ER-associated initiation sites. (chen2025thehumanautophagyinitiating pages 12-13, chen2025thehumanautophagyinitiating pages 4-5)
Localization: Functions at ER/omegasome-associated early autophagic membranes; ER targeting is linked to N-terminal features and early-membrane recruitment correlates with DFCP1/ATG16L1-marked initiation sites. (liu2023membranecurvaturethe pages 6-7, liu2023membranecurvaturethe pages 7-8)
Domain/motif logic: The C-terminal BATS domain contains an amphipathic helix and is a key determinant for membrane binding and curvature sensing, aligning with ATG14’s role in positioning/activating PI3KC3-C1 on nascent curved membranes. (liu2023membranecurvaturethe pages 6-7, lee2024regulatorymechanismsgoverning pages 1-2)
Regulation: A key, experimentally supported PTM is ULK1-dependent ATG14 Ser29 phosphorylation, with a 2024 mechanistic advance showing ULK1 palmitoylation as a control point for this signaling. (tabata2024palmitoylationofulk1 pages 7-8, tabata2024palmitoylationofulk1 media d29506c2)
URLs and publication dates of key recent sources used
Liu L. et al. Cells — “Membrane Curvature: The Inseparable Companion of Autophagy” (Apr 2023). https://doi.org/10.3390/cells12081132 (liu2023membranecurvaturethe pages 6-7)
Park J.-M. et al. Nature Communications — “Redefining the role of AMPK in autophagy and the energy stress response” (May 2023). https://doi.org/10.1038/s41467-023-38401-z (park2023redefiningtherole pages 16-16)
Tabata K. et al. Nature Communications — “Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy” (Aug 2024). https://doi.org/10.1038/s41467-024-51402-w (tabata2024palmitoylationofulk1 pages 7-8)
Lee Y. et al. Biomolecules & Therapeutics — “Regulatory Mechanisms Governing the Autophagy-Initiating VPS34 Complex and Its inhibitors” (Oct 2024). https://doi.org/10.4062/biomolther.2024.094 (lee2024regulatorymechanismsgoverning pages 1-2)
Limitations of this evidence set
While ATG14 is frequently discussed in disease contexts, the retrieved evidence set contains limited ATG14-specific human disease-causality experiments and no ATG14-targeted clinical trials; disease links here are primarily association-level (Open Targets) and mechanism-to-disease inference based on ATG14’s established role in autophagy initiation. (OpenTargets Search: -ATG14, lee2024regulatorymechanismsgoverning pages 1-2)
References
(chen2025thehumanautophagyinitiating pages 12-13): Minghao Chen and James H. Hurley. The human autophagy-initiating complexes ulk1c and pi3kc3-c1. Journal of Biological Chemistry, 301:110391, Jul 2025. URL: https://doi.org/10.1016/j.jbc.2025.110391, doi:10.1016/j.jbc.2025.110391. This article has 17 citations and is from a domain leading peer-reviewed journal.
(chen2025thehumanautophagyinitiating pages 4-5): Minghao Chen and James H. Hurley. The human autophagy-initiating complexes ulk1c and pi3kc3-c1. Journal of Biological Chemistry, 301:110391, Jul 2025. URL: https://doi.org/10.1016/j.jbc.2025.110391, doi:10.1016/j.jbc.2025.110391. This article has 17 citations and is from a domain leading peer-reviewed journal.
(liu2023membranecurvaturethe pages 6-7): Lei Liu, Yu Tang, Zijuan Zhou, Yuan Huang, Rui Zhang, Hao Lyu, Shuai Xiao, Dong Guo, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Cefan Zhou, and Jingfeng Tang. Membrane curvature: the inseparable companion of autophagy. Cells, 12:1132, Apr 2023. URL: https://doi.org/10.3390/cells12081132, doi:10.3390/cells12081132. This article has 6 citations.
(liu2023membranecurvaturethe pages 7-8): Lei Liu, Yu Tang, Zijuan Zhou, Yuan Huang, Rui Zhang, Hao Lyu, Shuai Xiao, Dong Guo, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Cefan Zhou, and Jingfeng Tang. Membrane curvature: the inseparable companion of autophagy. Cells, 12:1132, Apr 2023. URL: https://doi.org/10.3390/cells12081132, doi:10.3390/cells12081132. This article has 6 citations.
(tabata2024palmitoylationofulk1 pages 7-8): Keisuke Tabata, Kenta Imai, Koki Fukuda, Kentaro Yamamoto, Hayato Kunugi, Toshiharu Fujita, Tatsuya Kaminishi, Christian Tischer, Beate Neumann, Sabine Reither, Fatima Verissimo, Rainer Pepperkok, Tamotsu Yoshimori, and Maho Hamasaki. Palmitoylation of ulk1 by zdhhc13 plays a crucial role in autophagy. Nature Communications, Aug 2024. URL: https://doi.org/10.1038/s41467-024-51402-w, doi:10.1038/s41467-024-51402-w. This article has 42 citations and is from a highest quality peer-reviewed journal.
(tabata2024palmitoylationofulk1 media d29506c2): Keisuke Tabata, Kenta Imai, Koki Fukuda, Kentaro Yamamoto, Hayato Kunugi, Toshiharu Fujita, Tatsuya Kaminishi, Christian Tischer, Beate Neumann, Sabine Reither, Fatima Verissimo, Rainer Pepperkok, Tamotsu Yoshimori, and Maho Hamasaki. Palmitoylation of ulk1 by zdhhc13 plays a crucial role in autophagy. Nature Communications, Aug 2024. URL: https://doi.org/10.1038/s41467-024-51402-w, doi:10.1038/s41467-024-51402-w. This article has 42 citations and is from a highest quality peer-reviewed journal.
(park2023redefiningtherole pages 16-16): Ji-Man Park, Da-Hye Lee, and Do-Hyung Kim. Redefining the role of ampk in autophagy and the energy stress response. Nature Communications, May 2023. URL: https://doi.org/10.1038/s41467-023-38401-z, doi:10.1038/s41467-023-38401-z. This article has 280 citations and is from a highest quality peer-reviewed journal.
(lee2024regulatorymechanismsgoverning pages 1-2): Yongook Lee, Nguyen Minh Tuan, Gi Jeong Lee, Boram Kim, Jung Ho Park, and Chang Hoon Lee. Regulatory mechanisms governing the autophagy-initiating vps34 complex and its inhibitors. Biomolecules & Therapeutics, 32:723-735, Oct 2024. URL: https://doi.org/10.4062/biomolther.2024.094, doi:10.4062/biomolther.2024.094. This article has 17 citations and is from a peer-reviewed journal.
(OpenTargets Search: -ATG14): Open Targets Query (-ATG14, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(tabata2024palmitoylationofulk1 media c95ede9b): Keisuke Tabata, Kenta Imai, Koki Fukuda, Kentaro Yamamoto, Hayato Kunugi, Toshiharu Fujita, Tatsuya Kaminishi, Christian Tischer, Beate Neumann, Sabine Reither, Fatima Verissimo, Rainer Pepperkok, Tamotsu Yoshimori, and Maho Hamasaki. Palmitoylation of ulk1 by zdhhc13 plays a crucial role in autophagy. Nature Communications, Aug 2024. URL: https://doi.org/10.1038/s41467-024-51402-w, doi:10.1038/s41467-024-51402-w. This article has 42 citations and is from a highest quality peer-reviewed journal.
(losier2025identificationofkinasemediated pages 24-28): T Losier. Identification of kinase-mediated signaling pathways regulating autophagy in response to cellular stresses. Unknown journal, 2025.
(brier2019regulationoflc3 pages 14-22): Livia W. Brier, Liang Ge, Goran Stjepanovic, Ashley M. Thelen, James H. Hurley, and Randy Schekman. Regulation of lc3 lipidation by the autophagy-specific class iii phosphatidylinositol-3 kinase complex. Molecular Biology of the Cell, 30:1098-1107, Apr 2019. URL: https://doi.org/10.1091/mbc.e18-11-0743, doi:10.1091/mbc.e18-11-0743. This article has 98 citations and is from a domain leading peer-reviewed journal.
(brier2019regulationoflc3 pages 1-14): Livia W. Brier, Liang Ge, Goran Stjepanovic, Ashley M. Thelen, James H. Hurley, and Randy Schekman. Regulation of lc3 lipidation by the autophagy-specific class iii phosphatidylinositol-3 kinase complex. Molecular Biology of the Cell, 30:1098-1107, Apr 2019. URL: https://doi.org/10.1091/mbc.e18-11-0743, doi:10.1091/mbc.e18-11-0743. This article has 98 citations and is from a domain leading peer-reviewed journal.
Started review from fetched UniProt/GOA-derived stub. ATG14 is a Beclin 1-associated autophagy factor and PI3KC3-C1 subunit; the UniProt record states that it is "required for both basal and inducible autophagy", determines localization of the autophagy-specific PI3-kinase complex PI3KC3-C1, enhances PIK3C3 activity in a BECN1-dependent manner, and promotes STX17/SNAP29/VAMP8-dependent autophagosome-endolysosome fusion [UniProt:Q6ZNE5].
Key early complex evidence: human Atg14 and UVRAG form mutually exclusive Beclin 1/Vps34 complexes; Atg14 localizes to autophagic isolation membranes and Atg14 silencing suppresses autophagosome formation [PMID:18843052 "Atg14 is present on autophagic isolation membranes"; PMID:18843052 "Silencing of human Atg14 in HeLa cells suppresses autophagosome formation"].
Barkor/Atg14L was identified as an autophagy-specific Beclin 1/class III PI3K factor; depletion reduces autophagy and autophagosome formation, whereas overexpression activates autophagy and increases autophagosomes [PMID:19050071 "Elimination of Barkor expression by RNA interference compromises starvation- and rapamycin-induced lipidation of LC3 and autophagosome formation"; PMID:19050071 "Overexpression of Barkor leads to autophagy activation"].
Atg14L and UVRAG bind Beclin 1 mutually exclusively; Atg14L localizes at ER, isolation membranes, autophagosomes, and unidentified puncta, and Atg14L knockout caused defective autophagosome formation [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"].
ER targeting evidence supports phagophore/ER-membrane localization: ATG14L cysteine repeats are required for ER localization and autophagosome formation, and the BATS domain is important for targeting the PI3K complex to the ER and autophagosome biogenesis PMID:20713597.
The C-terminal BATS domain targets Barkor/Atg14L to PtdIns(3)P-rich autophagic membranes and is required for PI3KC3 recruitment and autophagy stimulation PMID:21518905.
Structural and interaction studies place ATG14 as the autophagy-specific organizer of the Beclin 1-VPS34/PIK3C3 complex, supporting class III PI3K complex and protein-membrane adaptor/regulator annotations rather than generic protein binding [PMID:22314358 "Atg14L-containing complex is primarily involved in early stage autophagosome formation"; PMID:25490155 "Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex"].
ATG14 has a later autophagosome fusion role: it binds the STX17-SNAP29 t-SNARE complex on autophagosomes, primes it for VAMP8 interaction, and promotes autophagosome-endolysosome fusion [PMID:25686604 "ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes"; UniProt:Q6ZNE5].
BECN2 also interacts with ATG14 through a metastable coiled-coil to mediate autophagy, consistent with ATG14 acting as a PI3KC3-C1/BECN-family adaptor rather than only as a generic binding protein PMID:28218432.
Falcon deep research requested for ATG14 as part of the full review process.
Falcon deep research timed out after the configured 600 second limit and did not produce ATG14-deep-research-falcon.md; final review therefore relies on the cached UniProt, GOA, Reactome, and publication evidence above.
Description cleanup note
The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.
Moved out of the YAML description: the Proteostasis Network framing emphasized ATG14 as an autophagy-initiation/autophagosome-maturation component rather than a generic protein-binding or class I PI3K/AKT signaling factor.
Falcon deep research findings (2026-06-07)
The Falcon (Edison Scientific) report (ATG14-deep-research-falcon.md) was successfully generated (the prior 2026-06-02 timeout note is now superseded). It is consistent with the completed review and adds mostly mechanistic/regulatory detail rather than new core functions. Key points:
NEW (regulation): ULK1 phosphorylates ATG14L at Ser29, and this phosphorylation is required for VPS34/PI3KC3-C1 activation and PI3P production at autophagosome formation sites; phospho-Ser29 is abolished in ULK1/2 double-knockout or kinase-dead ULK1 cells and restored by WT ULK1 under starvation [PMID:39169022 "the ULK1 palmitoylated enhances the phosphorylation of ATG14L, which is required for activating PI3-Kinase and producing phosphatidylinositol 3-phosphate"; Tabata et al. 2024 Nat Commun, doi:10.1038/s41467-024-51402-w]. This adds an upstream ULK1-kinase->ATG14 site-specific link not previously cited in the review, complementing existing ATG14-dependent BECN1-phosphorylation annotations. The existing review already supports positive/negative regulation of protein phosphorylation involving ATG14; this adds that ATG14 is itself a ULK1 substrate.
NEW (upstream control, provisional/mechanistic): ULK1 palmitoylation by ZDHHC13 promotes ULK1 translocation to autophagosome formation sites and is required for ULK1->ATG14L Ser29 phosphorylation; 2-bromopalmitate suppresses starvation-induced ATG14 Ser29 phosphorylation [PMID:39169022, Tabata et al. 2024]. This is ULK1/ZDHHC13 biology upstream of ATG14, not a direct ATG14 molecular function - do NOT add as an ATG14 annotation.
CONFIRMS (complex/architecture): PI3KC3-C1 is a ~360 kDa 1:1:1:1 heterotetramer (VPS34/PIK3C3 : VPS15/PIK3R4 : BECN1 : ATG14) with only ~11% catalytic mass, reinforcing ATG14's non-enzymatic regulatory/targeting role; mutually exclusive with UVRAG-containing PI3KC3-C2 [Chen & Hurley 2025 J Biol Chem, doi:10.1016/j.jbc.2025.110391, PMID:40543587]. Matches existing GO:0035014 / GO:0034271 annotations.
CONFIRMS (domain/localization): C-terminal BATS domain (~last 80 aa, ~19-aa amphipathic helix) is a membrane-curvature sensor preferring highly curved PI3P/PI(4,5)P2-enriched isolation membranes; N-terminal cysteine-repeat mediates ER targeting; co-localizes with DFCP1/ATG16L1 at omegasomes [Liu et al. 2023 Cells, doi:10.3390/cells12081132 - review]. Already captured by existing BATS/omegasome/phagophore annotations.
CONFIRMS (downstream function): ATG14-dependent PI3KC3-C1 activity supports WIPI2/ATG2A recruitment and LC3 lipidation, and complex II cannot functionally substitute [Brier et al. 2019, doi:10.1091/mbc.e18-11-0743, PMID:30540564 (not cached)]. Consistent with existing autophagosome-assembly core function.
PROVISIONAL (disease, low-confidence): Open Targets lists association-level links (neurodegeneration, COVID-19, dengue, lysosomal storage disease); the report explicitly flags these as association/inference, not causal. No ATG14-targeted clinical trials identified. NOT used to change any annotation.
Pharmacology context (provisional): VPS34 inhibitors and a reported Beclin1-ATG14L interaction inhibitor are discussed as autophagy-initiation tool compounds [Lee et al. 2024 Biomol Ther, doi:10.4062/biomolther.2024.094 - review]. Tool-compound context only.
Action taken: added the two most citable, ATG14-relevant primary/key sources (Tabata 2024 PMID:39169022; Chen & Hurley 2025 PMID:40543587) to the review references: as statement-only findings (full_text_unavailable), plus one suggested question and one suggested experiment about the ULK1->ATG14 Ser29 axis. Review-only sources (Liu 2023, Lee 2024) and the non-resolved/uncached Brier paper are kept in notes only. No existing annotation action was changed - all Falcon findings either confirm existing calls or are upstream/association-level context.
Pn Notes
(ATG14-pn-notes.md)
ATG14 PN Consistency Notes
Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
Description: ATG14/Barkor/ATG14L is the autophagy-specific regulatory and membrane-adaptor subunit of the human class III PI3K complex I (PI3KC3-C1). It targets the PIK3C3/VPS34-PIK3R4/VPS15-BECN1 complex to ER-associated omegasome/phagophore membranes for local PI3P production and autophagosome assembly, and it also promotes later STX17-SNAP29/VAMP8-dependent autophagosome-endolysosome fusion. Its main cellular roles are autophagy initiation and autophagosome maturation rather than class I PI3K/AKT signaling.
Consistency: Strongly consistent. The PN dual placement (early PI3KC3-C1 component + late STX17-SNAP29/VAMP8 fusion regulator) is exactly the two-function picture the review builds: PI3KC3-C1 recruitment/PI3P production AND ATG14-promoted autophagosome-endolysosome tethering/fusion (GO:0016240, GO:0097352 accepted; PMID:25686604). The projected GO:0034271 is precisely the review's MODIFY target — every GO:0035032 row is MODIFY→GO:0034271. No contradiction.
PN story / NEW pressure: Already captured. The projected GO:0034271 is the review's own replacement term (not broader — it is narrower than existing GOA, the good direction). The late-fusion SNARE-regulator placement is already covered by accepted GO:0016240/GO:0097352. No new term warranted; PN adds no role the review lacks.
Evidence alignment: Partial overlap. PN cites the Nature paper "ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes" = review's PMID:25686604 (heavily used). PN's two review-article citations (Annual Review; tandfonline) are not in the review, which instead uses primary literature (PMID:20713597, 21518905, 40442316, etc.). Convergent on the load-bearing paper.
Verdict: Fully consistent; PN projection matches the review's own MODIFY. No edits needed.
PN placement: 2 rows, ALP — (1) Autophagophore initiation and elongation → Class 3 PI3K complex 1, direct → Class 3 PI3K complex 1 component; (2) Autophagosome closure maturation and lysosome fusion → Autophagosome-lysosome docking → Lysosome-autophagosome SNARE complex regulator. PN-node mapping: component leaf=mapped→GO:0034271 (PI3KC3 type I); SNARE-regulator leaf=no_mapping; ancestors context_only (GO:0035032, GO:0061909, GO:0016236). Projected: GO:0034271 (more_specific_than_existing_goa).
Consistency: Strongly consistent. The PN dual placement (early PI3KC3-C1 component + late STX17-SNAP29/VAMP8 fusion regulator) is exactly the two-function picture the review builds: PI3KC3-C1 recruitment/PI3P production AND ATG14-promoted autophagosome-endolysosome tethering/fusion (GO:0016240, GO:0097352 accepted; PMID:25686604). The projected GO:0034271 is precisely the review's MODIFY target — every GO:0035032 row is MODIFY→GO:0034271. No contradiction.
PN story / NEW pressure: Already captured. The projected GO:0034271 is the review's own replacement term (not broader — it is narrower than existing GOA, the good direction). The late-fusion SNARE-regulator placement is already covered by accepted GO:0016240/GO:0097352. No new term warranted; PN adds no role the review lacks.
Mapping strategy: No change needed. ATG14 strengthens the GO:0034271 mapping (it is the defining C1 subunit). The SNARE-regulator leaf's no_mapping is correct — ATG14's fusion role is already individually annotated, so leaf-level propagation would be redundant. This is the inverse of the TOMM20/HSPA8 over-reach pattern: here the projection is narrower than GOA, and the review agrees.
Evidence alignment: Partial overlap. PN cites the Nature paper "ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes" = review's PMID:25686604 (heavily used). PN's two review-article citations (Annual Review; tandfonline) are not in the review, which instead uses primary literature (PMID:20713597, 21518905, 40442316, etc.). Convergent on the load-bearing paper.
Verdict: Fully consistent; PN projection matches the review's own MODIFY. No edits needed.
PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Class 3 PI3K complex 1, direct | Class 3 PI3K complex 1 component
UniProt: Q6ZNE5
In branches: ALP
Notes: Member of class III PI3K complex 1 that produces PI(3)P at the site of phagophore nucleation. Targets the complex to the ER membrane. Also homooligomerizes and binds to STX17 in the STX17-SNAP29-VAMP8 SNARE complex to regulate autophagosome-lysosome fusion.
PN references (titles):
Mammalian Autophagy: How Does It Work? | Annual Review of Biochemistry (annualreviews.org)
Full article: Autophagy pathway: Cellular and molecular mechanisms (tandfonline.com)
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes | Nature
PN-node mapping records (path + ancestors):
[type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct|Class 3 PI3K complex 1 component
status=mapped scope=ok_for_propagation_to_go GO=[GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I]
rationale: This PN type is a curated component class for the direct autophagy- promoting class III PI3K complex 1. Propagation to the matching GO cellular-component term is appropriate, although the source is a component-role category rather than the complex term itself.
[group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct
status=context_only scope=too_broad_to_propagate GO=[GO:0035032 phosphatidylinositol 3-kinase complex, class III]
rationale: Reviewed as a class-III PI3K complex context or regulator bucket. This node is useful for curator interpretation, but it should not project cellular-component membership; only explicit complex-component leaves propagate to GO complex terms.
[class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
[branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
Notes: Member of class III PI3K complex 1 that produces PI(3)P at the site of phagophore nucleation. Targets the complex to the ER membrane. Also homooligomerizes and binds to STX17 in the STX17-SNAP29-VAMP8 SNARE complex to regulate autophagosome-lysosome fusion.
PN references (titles):
Mammalian Autophagy: How Does It Work? | Annual Review of Biochemistry (annualreviews.org)
Full article: Autophagy pathway: Cellular and molecular mechanisms (tandfonline.com)
ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes | Nature
PN-node mapping records (path + ancestors):
[type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Autophagosome-lysosome docking|Lysosome-autophagosome SNARE complex regulator
status=no_mapping scope= GO=[]
rationale: This PN leaf groups regulators placed around the lysosome-autophagosome SNARE complex, but the current member set mixes broad trafficking, ubiquitin, and autophagy-fusion factors rather than one clean shared GO term for SNARE-complex regulation.
[group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Autophagosome-lysosome docking
status=context_only scope=too_broad_to_propagate GO=[GO:0061909 autophagosome-lysosome fusion]
rationale: Reviewed as an autophagosome-lysosome docking context. The subtree mixes component buckets and modulators, so generic fusion propagation should come only from narrower reviewed mechanism leaves.
[class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
[branch] Autophagy-Lysosome Pathway
status=no_mapping scope= GO=[]
rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.
Projected GO annotations (1)
GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Class 3 PI3K complex 1, direct|Class 3 PI3K complex 1 component
Note
This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.
📄 View Raw YAML
id: Q6ZNE5
gene_symbol: ATG14
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: >-
ATG14/Barkor/ATG14L is the autophagy-specific regulatory and membrane-adaptor subunit of the human
class III PI3K complex I (PI3KC3-C1). It targets the PIK3C3/VPS34-PIK3R4/VPS15-BECN1 complex to
ER-associated omegasome/phagophore membranes for local PI3P production and autophagosome assembly,
and it also promotes later STX17-SNAP29/VAMP8-dependent autophagosome-endolysosome fusion. Its main
cellular roles are autophagy initiation and autophagosome maturation rather than class I PI3K/AKT
signaling.
alternative_products:
- name: '1'
id: Q6ZNE5-1
- name: '2'
id: Q6ZNE5-2
sequence_note: VSP_013931
existing_annotations:
- term:
id: GO:0035014
label: phosphatidylinositol 3-kinase regulator activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: ATG14 has a core PI3KC3-C1 regulatory role.
action: ACCEPT
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.
additional_reference_ids:
- GO_REF:0000033
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id001
reference_id: PMID:20713597
supporting_text: Atg14L recruits a subset of class III PI3-kinase to the ER
- &id005
reference_id: PMID:21518905
supporting_text: PI3KC3 recruitment and autophagy stimulation by Barkor/Atg14(L) require the BATS domain
- &id004
reference_id: PMID:40442316
supporting_text: PI3KC3-C1 contains one copy each of the lipid kinase VPS34, the pseudokinase VPS15 and
the regulatory subunits BECN1 and ATG14
- &id011
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Required for both basal and inducible autophagy; determines the localization of
PI3KC3-C1
- term:
id: GO:0043495
label: protein-membrane adaptor activity
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: enables
review:
summary: ATG14 acts as a protein-membrane adaptor for PI3KC3-C1 and for autophagosome fusion machinery.
action: ACCEPT
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.
additional_reference_ids:
- GO_REF:0000033
- PMID:20713597
- PMID:21518905
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- &id012
reference_id: PMID:21518905
supporting_text: the BATS domain directly binds to the membrane
- &id002
reference_id: PMID:25686604
supporting_text: ATG14 binds to the SNARE core domain of STX17 through its coiled-coil domain
- &id003
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Binds to STX17-SNAP29 binary t-SNARE complex on autophagosomes and primes it for VAMP8
interaction
- term:
id: GO:0016240
label: autophagosome membrane docking
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Autophagosome membrane docking is a core ATG14 late-autophagy function.
action: ACCEPT
reason: Accept as core. ATG14 oligomerization, membrane tethering, and STX17-SNAP29 binding prime
autophagosomes for VAMP8-dependent endolysosome fusion.
additional_reference_ids:
- GO_REF:0000033
- PMID:25686604
- PMID:37632749
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id009
reference_id: PMID:25686604
supporting_text: ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes
- *id002
- &id026
reference_id: PMID:25686604
supporting_text: autophagosomes still efficiently form but their fusion with endolysosomes is blocked
- *id003
- term:
id: GO:0035032
label: phosphatidylinositol 3-kinase complex, class III
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: part_of
review:
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.
action: MODIFY
reason: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific
PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction
that matters for the PN autophagy branch.
proposed_replacement_terms:
- &id015
id: GO:0034271
label: phosphatidylinositol 3-kinase complex, class III, type I
additional_reference_ids:
- GO_REF:0000033
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id040
reference_id: PMID:39913640
supporting_text: 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
- &id041
reference_id: PMID:39913640
supporting_text: 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
- &id017
reference_id: PMID:18843052
supporting_text: human Atg14 and UVRAG interact with Beclin 1 and Vps34
- &id019
reference_id: PMID:19050071
supporting_text: direct interaction with Beclin 1 in the human phosphatidylinositol 3-kinase class III
complex
- &id021
reference_id: PMID:19270696
supporting_text: Atg14L and UVRAG bind to Beclin 1 in a mutually exclusive manner
- &id020
reference_id: PMID:25490155
supporting_text: early autophagy consists of the lipid kinase VPS34, the scaffolding protein VPS15, the
tumor suppressor BECN1, and the autophagy-specific subunit ATG14
- *id004
- &id016
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Component of the PI3K complex I in which PIK3C3, PIK3R4 and BECN1 are associated with
ATG14
- term:
id: GO:0000045
label: autophagosome assembly
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Autophagosome assembly is a core ATG14 process.
action: ACCEPT
reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome
formation, ER-localized PI3P production, and autophagosome formation.
additional_reference_ids:
- GO_REF:0000033
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id007
reference_id: PMID:18843052
supporting_text: Silencing of human Atg14 in HeLa cells suppresses autophagosome formation
- &id010
reference_id: PMID:19050071
supporting_text: compromises starvation- and rapamycin-induced LC3 lipidation
- &id008
reference_id: PMID:19270696
supporting_text: Knockout of Atg14L in mouse ES cells caused a defect in autophagosome formation
- *id001
- *id005
- &id006
reference_id: PMID:40442316
supporting_text: All forms of canonical autophagy, bulk and selective, are initiated upon the
recruitment and activation
- &id042
reference_id: PMID:39913640
supporting_text: PI3KC3-C1 produces phosphatidylinositol (PI) 3-phosphate (PI3P) on the phagophore,
which is the precursor to the autophagosome
- term:
id: GO:0000423
label: mitophagy
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Mitophagy is too cargo-specific for the accessible ATG14 evidence.
action: MODIFY
reason: Modify to autophagosome assembly. ATG14 is required for canonical autophagosome biogenesis and
PI3KC3-C1 activation, but the cached ATG14 papers do not establish a direct ATG14-specific mitophagy
function beyond the general requirement of core autophagy machinery.
proposed_replacement_terms:
- &id031
id: GO:0000045
label: autophagosome assembly
additional_reference_ids:
- GO_REF:0000033
- PMID:18843052
- PMID:19270696
- PMID:20713597
- PMID:40442316
supported_by:
- *id006
- *id007
- *id001
- *id008
- term:
id: GO:0005776
label: autophagosome
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: Autophagosome localization/activity context is supported.
action: ACCEPT
reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during
autophagy and to mature autophagosomes during STX17-dependent fusion.
additional_reference_ids:
- GO_REF:0000033
- PMID:19270696
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id014
reference_id: PMID:19270696
supporting_text: GFP-Atg14L localized to the isolation membrane and autophagosome, as well as to the ER
- *id009
- &id013
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Cytoplasm; endoplasmic reticulum membrane; preautophagosomal structure membrane;
autophagosome membrane
- term:
id: GO:0009267
label: cellular response to starvation
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: Starvation response is a supported induction context, but the core process is
autophagy/autophagosome assembly.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- GO_REF:0000033
- PMID:19050071
- PMID:20713597
- PMID:23878393
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id001
- &id028
reference_id: PMID:23878393
supporting_text: phosphorylation at these sites is necessary for maximal autophagy
- *id011
- term:
id: GO:0097629
label: extrinsic component of omegasome membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: ATG14 is an extrinsic component of omegasome membranes during autophagy initiation.
action: ACCEPT
reason: Accept as core location/context. ATG14-dependent PI3KC3 recruitment creates PI3P at ER-associated
omegasomes, and the BATS domain targets curved PtdIns(3)P-rich autophagic membranes.
additional_reference_ids:
- GO_REF:0000033
- PMID:20713597
- PMID:21518905
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id030
reference_id: PMID:20713597
supporting_text: Knockdown of Atg14L leads to the disappearance of the DFCP1-positive omegasome
- *id012
- *id013
- term:
id: GO:0097632
label: extrinsic component of phagophore assembly site membrane
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: ATG14 is an extrinsic component of the phagophore assembly site membrane.
action: ACCEPT
reason: Accept as core location/context. ATG14 localizes to early autophagic membranes and recruits PI3KC3
activity needed for phagophore/omegasome PI3P production.
additional_reference_ids:
- GO_REF:0000033
- PMID:18843052
- PMID:20713597
- PMID:21518905
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- *id005
- &id018
reference_id: PMID:18843052
supporting_text: Atg14 is present on autophagic isolation membranes
- *id013
- term:
id: GO:0000421
label: autophagosome membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Autophagosome membrane localization is supported.
action: ACCEPT
reason: Accept as core location. ATG14 localizes to autophagosome membranes and binds autophagic SNARE
machinery on mature autophagosomes.
additional_reference_ids:
- GO_REF:0000044
- PMID:19270696
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id009
- *id013
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: located_in
review:
summary: Cytoplasmic localization is supported as the broad ATG14 location.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to
autophagic cytoplasmic foci after induction.
additional_reference_ids:
- GO_REF:0000120
- PMID:19050071
- PMID:37632749
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- GO_REF:0000044
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0032991
label: protein-containing complex
evidence_type: IEA
original_reference_id: GO_REF:0000117
qualifier: part_of
review:
summary: Protein-containing complex is true but too generic for ATG14.
action: MODIFY
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_replacement_terms:
- *id015
additional_reference_ids:
- GO_REF:0000117
- PMID:18843052
- PMID:40442316
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id004
- *id016
- *id017
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- GO_REF:0000044
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:22314358
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- &id027
reference_id: PMID:22314358
supporting_text: Atg14L-containing complex is primarily involved in early stage autophagosome formation
by promoting autophagosome nucleation and expansion
- *id013
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19050071
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id019
- *id010
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:20562859
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:20562859
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:21062745
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:21062745
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22081109
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:22081109
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22493499
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:22493499
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23112296
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:23112296
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23332761
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:23332761
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:23954414
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:23954414
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Interacts with BECN2 via the coiled-coil domain
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24034250
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:24034250
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:24785657
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:24785657
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25490155
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:25490155
- file:human/ATG14/ATG14-uniprot.txt
- PMID:40442316
supported_by:
- *id020
- *id004
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25594178
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:25594178
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:26496610
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:26496610
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:28514442
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:28514442
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:32296183
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33422265
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:33422265
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:33961781
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:33961781
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:34524948
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:34524948
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:35271311
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005930
label: axoneme
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: located_in
review:
summary: Axoneme localization is by similarity and is not the proteostasis-network core function.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- GO_REF:0000107
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id034
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Also localizes to discrete punctae along the ciliary axoneme and to the base of the
ciliary axoneme by similarity
- term:
id: GO:0006914
label: autophagy
evidence_type: IEA
original_reference_id: GO_REF:0000120
qualifier: involved_in
review:
summary: Autophagy is a core ATG14 process.
action: ACCEPT
reason: Accept as core. ATG14/Barkor is repeatedly shown to be required for basal and inducible autophagy
through PI3KC3-C1 recruitment and autophagosome formation.
additional_reference_ids:
- GO_REF:0000120
- PMID:19050071
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- &id022
reference_id: PMID:19050071
supporting_text: Overexpression of Barkor leads to autophagy activation and increased number and
enlarged volume of autophagosomes
- *id008
- *id001
- *id011
- term:
id: GO:0035032
label: phosphatidylinositol 3-kinase complex, class III
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: part_of
review:
summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing
PI3KC3-C1/type I autophagy complex.
action: MODIFY
reason: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific
PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction
that matters for the PN autophagy branch.
proposed_replacement_terms:
- *id015
additional_reference_ids:
- GO_REF:0000107
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id040
- *id017
- *id019
- *id021
- *id020
- *id004
- *id016
- term:
id: GO:0042149
label: cellular response to glucose starvation
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: involved_in
review:
summary: Glucose starvation response is a valid induction context, not the primary ATG14 function.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- GO_REF:0000107
- PMID:19050071
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id001
- *id011
- term:
id: GO:0044233
label: mitochondria-associated endoplasmic reticulum membrane contact site
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: located_in
review:
summary: Mitochondria-associated ER membrane contact-site localization is plausible but secondary.
action: KEEP_AS_NON_CORE
reason: Keep as non-core. ATG14 is reported in ER/autophagosome contexts and STX17-linked literature
places ATG14 near ER-mitochondria contact sites, but this is not the main PN functional annotation.
additional_reference_ids:
- GO_REF:0000107
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id009
- *id013
- term:
id: GO:0045335
label: phagocytic vesicle
evidence_type: IEA
original_reference_id: GO_REF:0000107
qualifier: located_in
review:
summary: Phagocytic vesicle localization is not directly established for ATG14 in the cached evidence.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. ATG14 participates in antimicrobial/xenophagy contexts, but the reviewed
evidence supports autophagic membranes and cytosol/ER/autophagosome locations rather than a direct
phagocytic vesicle localization.
additional_reference_ids:
- GO_REF:0000107
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id013
- term:
id: GO:0006622
label: protein targeting to lysosome
evidence_type: NAS
original_reference_id: PMID:16467569
qualifier: involved_in
review:
summary: Protein targeting to lysosome is too broad for ATG14; the supported trafficking role is
endosome/autophagosome-to-lysosome maturation/fusion.
action: MODIFY
reason: Modify to endosome to lysosome transport. ATG14 supports endosome maturation through Snapin and
promotes autophagosome-endolysosome fusion, rather than acting as a general lysosomal protein-targeting
factor.
proposed_replacement_terms:
- &id023
id: GO:0008333
label: endosome to lysosome transport
additional_reference_ids:
- PMID:16467569
- PMID:22797916
- PMID:25686604
supported_by:
- &id024
reference_id: PMID:22797916
supporting_text: Atg14L binds to and colocalizes with the fusogenic SNARE effector protein Snapin to
facilitate endosome maturation
- &id025
reference_id: PMID:22797916
supporting_text: atg14l knockdown significantly delayed the late stage of endocytic trafficking
- *id009
- term:
id: GO:0016236
label: macroautophagy
evidence_type: NAS
original_reference_id: PMID:40442316
qualifier: involved_in
review:
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.
action: ACCEPT
reason: Accept as core. ATG14 is the autophagy-specific PI3KC3-C1 subunit required for macroautophagy
initiation and autophagosome formation.
additional_reference_ids:
- PMID:40442316
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id006
- *id010
- *id008
- *id001
- *id040
- *id011
- term:
id: GO:0016241
label: regulation of macroautophagy
evidence_type: IDA
original_reference_id: PMID:10625637
qualifier: involved_in
review:
summary: ATG14 positively regulates macroautophagy through PI3KC3-C1.
action: ACCEPT
reason: Accept as core process regulation. Depletion impairs, and overexpression stimulates,
autophagy/autophagosome formation; structurally ATG14 is part of the PI3KC3-C1 initiation complex.
additional_reference_ids:
- PMID:10625637
- PMID:19050071
- PMID:40442316
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id022
- *id006
- *id011
- term:
id: GO:0035032
label: phosphatidylinositol 3-kinase complex, class III
evidence_type: IPI
original_reference_id: PMID:25490155
qualifier: part_of
review:
summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing
PI3KC3-C1/type I autophagy complex.
action: MODIFY
reason: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific
PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction
that matters for the PN autophagy branch.
proposed_replacement_terms:
- *id015
additional_reference_ids:
- PMID:25490155
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id040
- *id017
- *id019
- *id021
- *id020
- *id004
- *id016
- term:
id: GO:0035032
label: phosphatidylinositol 3-kinase complex, class III
evidence_type: IPI
original_reference_id: PMID:40442316
qualifier: part_of
review:
summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing
PI3KC3-C1/type I autophagy complex.
action: MODIFY
reason: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific
PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction
that matters for the PN autophagy branch.
proposed_replacement_terms:
- *id015
additional_reference_ids:
- PMID:40442316
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id040
- *id017
- *id019
- *id021
- *id020
- *id004
- *id016
- term:
id: GO:0036092
label: phosphatidylinositol-3-phosphate biosynthetic process
evidence_type: IDA
original_reference_id: PMID:8999962
qualifier: involved_in
review:
summary: ATG14 supports PI3P biosynthesis as the targeting/regulatory PI3KC3-C1 subunit, not as the
catalytic kinase.
action: ACCEPT
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.
additional_reference_ids:
- PMID:8999962
- PMID:20713597
- PMID:21518905
- PMID:40442316
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- *id005
- *id004
- *id016
- term:
id: GO:0045022
label: early endosome to late endosome transport
evidence_type: IDA
original_reference_id: PMID:14617358
qualifier: involved_in
review:
summary: Early-to-late endosome transport is better captured as ATG14-supported endosome-to-lysosome
transport/endosome maturation.
action: MODIFY
reason: Modify to endosome to lysosome transport. The original hVPS34/p150 Rab7 paper does not establish
an ATG14-specific early-to-late endosome role, while ATG14-specific Snapin evidence supports endosome
maturation and late endocytic trafficking.
proposed_replacement_terms:
- *id023
additional_reference_ids:
- PMID:14617358
- PMID:22797916
supported_by:
- *id024
- *id025
- term:
id: GO:0097352
label: autophagosome maturation
evidence_type: IDA
original_reference_id: PMID:10625637
qualifier: involved_in
review:
summary: Autophagosome maturation is supported by ATG14 fusion/tethering biology.
action: ACCEPT
reason: Accept as core late-autophagy process. ATG14 binds STX17-SNAP29 on mature autophagosomes and
promotes VAMP8-dependent autophagosome-endolysosome fusion.
additional_reference_ids:
- PMID:10625637
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id009
- *id002
- *id026
- *id003
- term:
id: GO:0005737
label: cytoplasm
evidence_type: EXP
original_reference_id: PMID:19050071
qualifier: located_in
review:
summary: Cytoplasmic localization is supported as the broad ATG14 location.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to
autophagic cytoplasmic foci after induction.
additional_reference_ids:
- PMID:19050071
- PMID:37632749
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id013
- term:
id: GO:0005737
label: cytoplasm
evidence_type: EXP
original_reference_id: PMID:37632749
qualifier: located_in
review:
summary: Cytoplasmic localization is supported as the broad ATG14 location.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and redistributes to
autophagic cytoplasmic foci after induction.
additional_reference_ids:
- PMID:37632749
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: EXP
original_reference_id: PMID:19270696
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: EXP
original_reference_id: PMID:20713597
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- PMID:20713597
- PMID:19270696
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: EXP
original_reference_id: PMID:18843052
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:22314358
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- *id027
- *id013
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: EXP
original_reference_id: PMID:19050071
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- PMID:19050071
- PMID:18843052
- PMID:19270696
- PMID:20713597
- PMID:22314358
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- *id027
- *id013
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: EXP
original_reference_id: PMID:22314358
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- PMID:22314358
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- *id027
- *id013
- term:
id: GO:0061635
label: regulation of protein complex stability
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Protein-complex stability is not the best description of the ATG14 evidence from this paper.
action: MODIFY
reason: Modify to positive regulation of protein phosphorylation. The accessible evidence for this
reference supports Atg14-dependent Beclin 1 phosphorylation required for maximal autophagy, not a direct
protein-complex-stability function.
proposed_replacement_terms:
- id: GO:0001934
label: positive regulation of protein phosphorylation
additional_reference_ids:
- PMID:23878393
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id032
reference_id: PMID:23878393
supporting_text: human Atg14 is critical in controlling an autophagy-dependent phosphorylation of
beclin-1
- *id028
- &id033
reference_id: file:human/ATG14/ATG14-uniprot.txt
supporting_text: Stimulates phosphorylation of BECN1, but suppresses phosphorylation of PIK3C3 by AMPK
- term:
id: GO:0043491
label: phosphatidylinositol 3-kinase/protein kinase B signal transduction
evidence_type: IDA
original_reference_id: PMID:21062745
qualifier: involved_in
review:
summary: PI3K/AKT signaling is not an appropriate ATG14 process annotation from the Rubicon paper.
action: REMOVE
reason: Remove. PMID:21062745 supports Rubicon as a negative regulator of hVps34/PI3KC3 and autophagosome
maturation; it does not make ATG14 a class I PI3K/AKT signaling component.
additional_reference_ids:
- PMID:21062745
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- &id029
reference_id: PMID:21062745
supporting_text: Rubicon serves as a negative regulator of PI3KC3 and autophagosome maturation
- *id011
- term:
id: GO:0141039
label: phosphatidylinositol 3-kinase inhibitor activity
evidence_type: IDA
original_reference_id: PMID:21062745
qualifier: enables
review:
summary: PI3K inhibitor activity is Rubicon biology, not ATG14 biology.
action: REMOVE
reason: Remove. The cited Rubicon paper identifies Rubicon as the PI3KC3 lipid-kinase inhibitor, whereas
ATG14 is a positive autophagy-specific PI3KC3-C1 targeting/regulatory subunit.
additional_reference_ids:
- PMID:21062745
- PMID:20713597
- PMID:21518905
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id029
- *id001
- *id005
- *id011
- term:
id: GO:0000045
label: autophagosome assembly
evidence_type: IDA
original_reference_id: PMID:20713597
qualifier: involved_in
review:
summary: Autophagosome assembly is a core ATG14 process.
action: ACCEPT
reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome
formation, ER-localized PI3P production, and autophagosome formation.
additional_reference_ids:
- PMID:20713597
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id007
- *id010
- *id008
- *id001
- *id005
- *id006
- *id042
- term:
id: GO:0000407
label: phagophore assembly site
evidence_type: IDA
original_reference_id: PMID:20713597
qualifier: is_active_in
review:
summary: Phagophore assembly site localization/activity context is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 localizes to and organizes the ER/phagophore assembly site
where PI3KC3-C1 produces PI3P for autophagosome formation.
additional_reference_ids:
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- *id030
- *id013
- term:
id: GO:0043495
label: protein-membrane adaptor activity
evidence_type: IDA
original_reference_id: PMID:20713597
qualifier: enables
review:
summary: ATG14 acts as a protein-membrane adaptor for PI3KC3-C1 and for autophagosome fusion machinery.
action: ACCEPT
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.
additional_reference_ids:
- PMID:20713597
- PMID:21518905
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- *id012
- *id002
- *id003
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:31806350
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:31806350
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5682385
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- Reactome:R-HSA-5682385
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:22314358
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- *id027
- *id013
- term:
id: GO:0051020
label: GTPase binding
evidence_type: IPI
original_reference_id: PMID:25891078
qualifier: enables
review:
summary: GTPase binding is supported for IRGM interaction but is not the ATG14 core function.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- PMID:25891078
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- reference_id: PMID:25891078
supporting_text: IRGM physically interacts with key autophagy regulators, ULK1, Beclin 1, ATG14L and
ATG16L1
- *id016
- term:
id: GO:0000423
label: mitophagy
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Mitophagy is too cargo-specific for the accessible ATG14 evidence.
action: MODIFY
reason: Modify to autophagosome assembly. ATG14 is required for canonical autophagosome biogenesis and
PI3KC3-C1 activation, but the cached ATG14 papers do not establish a direct ATG14-specific mitophagy
function beyond the general requirement of core autophagy machinery.
proposed_replacement_terms:
- *id031
additional_reference_ids:
- PMID:23878393
- PMID:18843052
- PMID:19270696
- PMID:20713597
- PMID:40442316
supported_by:
- *id006
- *id007
- *id001
- *id008
- term:
id: GO:0098780
label: response to mitochondrial depolarisation
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Response to mitochondrial depolarization is too stimulus-specific for the accessible ATG14
evidence.
action: MODIFY
reason: Modify to autophagosome assembly. The cited ATG14 evidence supports Beclin 1 phosphorylation and
maximal autophagy, but does not directly establish ATG14 as a depolarization-response factor apart from
core autophagy machinery requirements.
proposed_replacement_terms:
- *id031
additional_reference_ids:
- PMID:23878393
- PMID:40442316
supported_by:
- *id032
- *id028
- *id006
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25686604
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id002
- *id009
- *id003
- term:
id: GO:0005776
label: autophagosome
evidence_type: IDA
original_reference_id: PMID:25686604
qualifier: located_in
review:
summary: Autophagosome localization/activity context is supported.
action: ACCEPT
reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during
autophagy and to mature autophagosomes during STX17-dependent fusion.
additional_reference_ids:
- PMID:25686604
- PMID:19270696
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id009
- *id013
- term:
id: GO:0016240
label: autophagosome membrane docking
evidence_type: IDA
original_reference_id: PMID:25686604
qualifier: involved_in
review:
summary: Autophagosome membrane docking is a core ATG14 late-autophagy function.
action: ACCEPT
reason: Accept as core. ATG14 oligomerization, membrane tethering, and STX17-SNAP29 binding prime
autophagosomes for VAMP8-dependent endolysosome fusion.
additional_reference_ids:
- PMID:25686604
- PMID:37632749
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id009
- *id002
- *id026
- *id003
- term:
id: GO:0009267
label: cellular response to starvation
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Starvation response is a supported induction context, but the core process is
autophagy/autophagosome assembly.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- PMID:23878393
- PMID:19050071
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id001
- *id028
- *id011
- term:
id: GO:0010608
label: post-transcriptional regulation of gene expression
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Post-transcriptional regulation of gene expression is unsupported for ATG14 in the reviewed
evidence.
action: REMOVE
reason: Remove. PMID:23878393 concerns ATG14-dependent Beclin 1 phosphorylation and autophagy; it does not
support ATG14 as a post-transcriptional gene-expression regulator.
additional_reference_ids:
- PMID:23878393
supported_by:
- *id032
- *id028
- term:
id: GO:0016236
label: macroautophagy
evidence_type: IMP
original_reference_id: PMID:23878393
qualifier: involved_in
review:
summary: Macroautophagy is a core ATG14 process.
action: ACCEPT
reason: Accept as core. ATG14 is the autophagy-specific PI3KC3-C1 subunit required for macroautophagy
initiation and autophagosome formation.
additional_reference_ids:
- PMID:23878393
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id006
- *id010
- *id008
- *id001
- *id040
- *id011
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25127057
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:25127057
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id016
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5672012
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-5672012
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5679205
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-5679205
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5679266
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-5679266
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5682385
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-5682385
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9755359
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-9755359
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9921171
qualifier: located_in
review:
summary: Endoplasmic reticulum membrane localization is a core ATG14 autophagy-initiation context.
action: ACCEPT
reason: Accept as core location. ATG14 targets PI3KC3-C1 to the ER/omegasome platform where PI3P is
generated for autophagosome formation.
additional_reference_ids:
- Reactome:R-HSA-9921171
- PMID:19270696
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id001
- *id013
- term:
id: GO:0001933
label: negative regulation of protein phosphorylation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: Negative regulation of protein phosphorylation is supported as a secondary regulatory effect.
action: KEEP_AS_NON_CORE
reason: Keep as non-core. UniProt records ATG14 suppression of AMPK-dependent PIK3C3 phosphorylation, but
the main PN role is PI3KC3-C1 autophagy initiation rather than protein-phosphorylation regulation per
se.
additional_reference_ids:
- GO_REF:0000024
- PMID:23878393
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id033
- *id032
- term:
id: GO:0001934
label: positive regulation of protein phosphorylation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: Positive regulation of protein phosphorylation is supported as a secondary ATG14 regulatory
effect.
action: KEEP_AS_NON_CORE
reason: Keep as non-core. ATG14 stimulates autophagy-dependent BECN1 phosphorylation required for maximal
autophagy, but this is a regulatory mechanism rather than the primary PN function.
additional_reference_ids:
- GO_REF:0000024
- PMID:23878393
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id032
- *id028
- *id033
- term:
id: GO:0035032
label: phosphatidylinositol 3-kinase complex, class III
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: part_of
review:
summary: The class III PI3K complex assignment is correct but should be narrowed to the ATG14-containing
PI3KC3-C1/type I autophagy complex.
action: MODIFY
reason: Modify to the more specific class III PI3K complex type I term. ATG14 is the autophagy-specific
PI3KC3-C1 subunit, whereas the parent class III PI3K complex term obscures the C1 versus C2 distinction
that matters for the PN autophagy branch.
proposed_replacement_terms:
- *id015
additional_reference_ids:
- GO_REF:0000024
- PMID:18843052
- PMID:19050071
- PMID:19270696
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id040
- *id017
- *id019
- *id021
- *id020
- *id004
- *id016
- term:
id: GO:0042149
label: cellular response to glucose starvation
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: involved_in
review:
summary: Glucose starvation response is a valid induction context, not the primary ATG14 function.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- GO_REF:0000024
- PMID:19050071
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id010
- *id001
- *id011
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1632857
qualifier: located_in
review:
summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to
autophagic membrane foci after induction.
additional_reference_ids:
- Reactome:R-HSA-1632857
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id013
- *id010
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5678313
qualifier: located_in
review:
summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to
autophagic membrane foci after induction.
additional_reference_ids:
- Reactome:R-HSA-5678313
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id013
- *id010
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5678315
qualifier: located_in
review:
summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to
autophagic membrane foci after induction.
additional_reference_ids:
- Reactome:R-HSA-5678315
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id013
- *id010
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-5679266
qualifier: located_in
review:
summary: Cytosol is supported as a broad ATG14 location in nutrient-rich cells and Reactome events.
action: ACCEPT
reason: Accept as a broad location. ATG14 is cytosolic under nutrient-rich conditions and relocates to
autophagic membrane foci after induction.
additional_reference_ids:
- Reactome:R-HSA-5679266
- PMID:19050071
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id013
- *id010
- term:
id: GO:0097629
label: extrinsic component of omegasome membrane
evidence_type: IDA
original_reference_id: PMID:21518905
qualifier: located_in
review:
summary: ATG14 is an extrinsic component of omegasome membranes during autophagy initiation.
action: ACCEPT
reason: Accept as core location/context. ATG14-dependent PI3KC3 recruitment creates PI3P at ER-associated
omegasomes, and the BATS domain targets curved PtdIns(3)P-rich autophagic membranes.
additional_reference_ids:
- PMID:21518905
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id030
- *id012
- *id013
- term:
id: GO:0097632
label: extrinsic component of phagophore assembly site membrane
evidence_type: IDA
original_reference_id: PMID:21518905
qualifier: located_in
review:
summary: ATG14 is an extrinsic component of the phagophore assembly site membrane.
action: ACCEPT
reason: Accept as core location/context. ATG14 localizes to early autophagic membranes and recruits PI3KC3
activity needed for phagophore/omegasome PI3P production.
additional_reference_ids:
- PMID:21518905
- PMID:18843052
- PMID:20713597
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id001
- *id005
- *id018
- *id013
- term:
id: GO:0008333
label: endosome to lysosome transport
evidence_type: IGI
original_reference_id: PMID:22797916
qualifier: acts_upstream_of_or_within
review:
summary: Endosome-to-lysosome transport is a supported but secondary ATG14 trafficking role.
action: KEEP_AS_NON_CORE
reason: Keep as non-core. ATG14 has a Snapin-dependent endosome maturation role and a STX17-dependent
autophagosome-endolysosome fusion role, but the dominant PN core is autophagy initiation through
PI3KC3-C1.
additional_reference_ids:
- PMID:22797916
- PMID:25686604
supported_by:
- *id024
- *id025
- *id009
- term:
id: GO:0005930
label: axoneme
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: Axoneme localization is by similarity and is not the proteostasis-network core function.
action: KEEP_AS_NON_CORE
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.
additional_reference_ids:
- GO_REF:0000024
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id034
- term:
id: GO:0000045
label: autophagosome assembly
evidence_type: IMP
original_reference_id: PMID:19270696
qualifier: involved_in
review:
summary: Autophagosome assembly is a core ATG14 process.
action: ACCEPT
reason: Accept as core. Multiple studies show that ATG14/Barkor is required for LC3 lipidation, omegasome
formation, ER-localized PI3P production, and autophagosome formation.
additional_reference_ids:
- PMID:19270696
- PMID:18843052
- PMID:19050071
- PMID:20713597
- PMID:21518905
- PMID:22314358
- PMID:25490155
- PMID:40442316
- PMID:39913640
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id007
- *id010
- *id008
- *id001
- *id005
- *id006
- *id042
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:19270696
qualifier: enables
review:
summary: Generic protein binding is not an informative ATG14 molecular-function annotation.
action: MARK_AS_OVER_ANNOTATED
reason: Mark as over-annotated. The interaction evidence should be represented as PI3KC3-C1 membership,
protein-membrane adaptor/regulator activity, GTPase binding where appropriate, or STX17-SNAP29/VAMP8
autophagosome-fusion biology rather than generic binding.
additional_reference_ids:
- PMID:19270696
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id021
- *id008
- *id016
- term:
id: GO:0005776
label: autophagosome
evidence_type: IDA
original_reference_id: PMID:19270696
qualifier: located_in
review:
summary: Autophagosome localization/activity context is supported.
action: ACCEPT
reason: Accept as core localization. ATG14 localizes to isolation membranes/autophagosomes during
autophagy and to mature autophagosomes during STX17-dependent fusion.
additional_reference_ids:
- PMID:19270696
- PMID:25686604
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id014
- *id009
- *id013
- term:
id: GO:0034045
label: phagophore assembly site membrane
evidence_type: IDA
original_reference_id: PMID:19270696
qualifier: located_in
review:
summary: Phagophore assembly site membrane localization is supported.
action: ACCEPT
reason: Accept as core location/context. ATG14 is detected on isolation/phagophore membranes and helps
recruit PI3KC3-C1 to those early autophagic structures.
additional_reference_ids:
- PMID:19270696
- PMID:18843052
- PMID:19050071
- PMID:20713597
- PMID:22314358
- file:human/ATG14/ATG14-uniprot.txt
supported_by:
- *id018
- *id014
- *id001
- *id027
- *id013
references:
- id: GO_REF:0000024
title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment
of sequence similarity
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping,
accompanied by conservative changes to GO terms applied by UniProt
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl
Compara
findings: []
- id: GO_REF:0000117
title: Electronic Gene Ontology annotations created by ARBA machine learning models
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:10625637
title: Distinct classes of phosphatidylinositol 3'-kinases are involved in signaling pathways that control
macroautophagy in HT-29 cells.
findings: []
- id: PMID:14617358
title: Human VPS34 and p150 are Rab7 interacting partners.
findings: []
- id: PMID:16467569
title: Regulation of membrane traffic by phosphoinositide 3-kinases.
findings: []
- id: PMID:18843052
title: Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG.
findings: []
- id: PMID:19050071
title: Identification of Barkor as a mammalian autophagy-specific factor for Beclin 1 and class III
phosphatidylinositol 3-kinase.
findings: []
- id: PMID:19270696
title: Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different
stages.
findings: []
- id: PMID:20562859
title: Network organization of the human autophagy system.
findings: []
- id: PMID:20713597
title: Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14L.
findings: []
- id: PMID:21062745
title: The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy
suppression.
findings: []
- id: PMID:21518905
title: Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L).
findings: []
- id: PMID:22081109
title: Inhibition of autophagy by TAB2 and TAB3.
findings: []
- id: PMID:22314358
title: Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with
Atg14L and UVRAG.
findings: []
- id: PMID:22493499
title: Receptor signaling lymphocyte-activation molecule family 1 (Slamf1) regulates membrane fusion and
NADPH oxidase 2 (NOX2) activity by recruiting a Beclin-1/Vps34/ultraviolet radiation resistance-associated
gene (UVRAG) complex.
findings: []
- id: PMID:22797916
title: Beclin-1-interacting autophagy protein Atg14L targets the SNARE-associated protein Snapin to
coordinate endocytic trafficking.
findings: []
- id: PMID:23112296
title: Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation.
findings: []
- id: PMID:23332761
title: Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.
findings: []
- id: PMID:23878393
title: Role of membrane association and Atg14-dependent phosphorylation in beclin-1-mediated autophagy.
findings: []
- id: PMID:23954414
title: Beclin 2 functions in autophagy, degradation of G protein-coupled receptors, and metabolism.
findings: []
- id: PMID:24034250
title: EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor
chemoresistance.
findings: []
- id: PMID:24785657
title: NRBF2 regulates macroautophagy as a component of Vps34 Complex I.
findings: []
- id: PMID:25127057
title: TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
findings: []
- id: PMID:25490155
title: Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase complex.
findings: []
- id: PMID:25594178
title: A kinase-independent role for EGF receptor in autophagy initiation.
findings: []
- id: PMID:25686604
title: ATG14 promotes membrane tethering and fusion of autophagosomes to endolysosomes.
findings: []
- id: PMID:25891078
title: IRGM governs the core autophagy machinery to conduct antimicrobial defense.
findings: []
- id: PMID:26496610
title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
findings: []
- id: PMID:28514442
title: Architecture of the human interactome defines protein communities and disease networks.
findings: []
- id: PMID:31806350
title: The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy by Controlling the
Trafficking of the PtdIns(4)P Phosphatase SAC1.
findings: []
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings: []
- id: PMID:33422265
title: ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-mediated assembly of the SNARE complex
required for autolysosome formation.
findings: []
- id: PMID:33961781
title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
findings: []
- id: PMID:34524948
title: Global Proximity Interactome of the Human Macroautophagy Pathway.
findings: []
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings: []
- id: PMID:37632749
title: MARCH7-mediated ubiquitination decreases the solubility of ATG14 to inhibit autophagy.
findings: []
- id: PMID:40442316
title: Structure and activation of the human autophagy-initiating ULK1C:PI3KC3-C1 supercomplex.
findings: []
- id: PMID:39913640
title: Structural pathway for PI3-kinase regulation by VPS15 in autophagy.
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Cryo-EM (PDB 9MHF/9MHG/9MHH) of human PI3KC3-C1 resolving ATG14 as the autophagy-specific
subunit of the VPS34-VPS15-BECN1-ATG14 heterotetramer; VPS34 is the catalytic lipid kinase while ATG14
is a non-catalytic scaffolding/regulatory subunit.
findings: []
- id: PMID:8999962
title: Characterization of p150, an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase.
Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex.
findings: []
- id: Reactome:R-HSA-1632857
title: ULK1 phosphorylates AMBRA1:BECN1 complex
findings: []
- id: Reactome:R-HSA-5672012
title: Beclin-1 complex phosphorylates PtdIns
findings: []
- id: Reactome:R-HSA-5678313
title: AMBRA1:DYNLL1,DYNLL2 binds BECN1 complex
findings: []
- id: Reactome:R-HSA-5678315
title: BECN1 complex, p-AMBRA1 dissociate from DYNLL1,DYNLL2
findings: []
- id: Reactome:R-HSA-5679205
title: ULK1 phosphorylates Beclin-1
findings: []
- id: Reactome:R-HSA-5679266
title: Beclin-1 complex translocates to the ER
findings: []
- id: Reactome:R-HSA-5682385
title: The phagophore extends from the PIP3-enriched structure
findings: []
- id: Reactome:R-HSA-9755359
title: SARS-CoV-2 8:class I MHC binds BECN1
findings: []
- id: Reactome:R-HSA-9921171
title: NS1 binds Beclin-1
findings: []
- id: PMID:28218432
title: BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy.
findings: []
- id: PMID:39169022
title: Palmitoylation of ULK1 by ZDHHC13 plays a crucial role in autophagy.
full_text_unavailable: true
findings:
- statement: ULK1 phosphorylates ATG14L (at Ser29), and this phosphorylation is required for
activation of the class III PI3-kinase (VPS34) and production of phosphatidylinositol
3-phosphate at autophagosome formation sites during autophagy initiation.
- id: PMID:40543587
title: The human autophagy-initiating complexes ULK1C and PI3KC3-C1.
full_text_unavailable: true
findings:
- statement: ATG14 is the autophagy-specific regulatory subunit of the class III PI3-kinase
complex I (PI3KC3-C1; VPS34-VPS15-BECN1-ATG14), a key initiator of macroautophagy whose
assembly and activation it helps coordinate at the molecular level.
- id: file:human/ATG14/ATG14-uniprot.txt
title: UniProtKB record for ATG14
findings: []
- id: file:human/ATG14/ATG14-notes.md
title: ATG14 review notes
findings: []
core_functions:
- molecular_function:
id: GO:0035014
label: phosphatidylinositol 3-kinase regulator activity
in_complex: *id015
description: ATG14 is the autophagy-specific PI3KC3-C1 regulatory subunit that recruits and organizes the
PIK3C3/VPS34 lipid-kinase complex at ER-associated omegasome/phagophore membranes, enabling local PI3P
production for autophagosome assembly and macroautophagy initiation.
directly_involved_in:
- id: GO:0036092
label: phosphatidylinositol-3-phosphate biosynthetic process
- *id031
- id: GO:0016236
label: macroautophagy
locations:
- id: GO:0005789
label: endoplasmic reticulum membrane
- id: GO:0097629
label: extrinsic component of omegasome membrane
- &id036
id: GO:0034045
label: phagophore assembly site membrane
- &id035
id: GO:0000421
label: autophagosome membrane
supported_by:
- *id017
- *id010
- *id008
- *id001
- *id005
- *id004
- *id011
- molecular_function:
id: GO:0043495
label: protein-membrane adaptor activity
description: ATG14 uses membrane-targeting/curvature-sensing and oligomerization regions to bridge autophagy
machinery to membranes. This includes BATS-domain targeting of PI3P-rich autophagic membranes and
STX17-SNAP29 binding on mature autophagosomes to promote VAMP8-dependent autophagosome-endolysosome
fusion.
directly_involved_in:
- id: GO:0016240
label: autophagosome membrane docking
- id: GO:0097352
label: autophagosome maturation
- *id023
locations:
- id: GO:0005776
label: autophagosome
- *id035
- *id036
- id: GO:0005737
label: cytoplasm
supported_by:
- *id012
- *id009
- *id002
- *id026
- *id024
- *id003
proposed_new_terms: []
suggested_questions:
- question: Should all human ATG14 class III PI3K complex annotations be narrowed from the generic parent to
PI3KC3-C1/type I complex membership?
experts:
- GO autophagy editors
- ComplexPortal curators
- Reactome autophagy curators
- question: Should ATG14 mitophagy and mitochondrial-depolarization annotations be retained only with direct
cargo-specific evidence, or generalized to autophagosome assembly/macroautophagy?
experts:
- GO autophagy editors
- mitophagy domain experts
- ParkinsonsUK-UCL curators
- question: Is protein-membrane adaptor activity sufficient for the ATG14 BATS/SNARE roles, or would a more
specific autophagosome-fusion adaptor/tether term improve annotation?
experts:
- GO molecular function editors
- autophagosome fusion experts
- question: Should ATG14 be annotated as a direct ULK1 phosphorylation substrate (ULK1-mediated Ser29
phosphorylation required for VPS34 activation and PI3P production), e.g. via protein kinase substrate or
a regulation-of-PI3K-activity term?
experts:
- GO autophagy editors
- ULK1/PI3KC3 signaling experts
suggested_experiments:
- description: 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.
experiment_type: PI3KC3-C1 autophagy-initiation rescue assay
hypothesis: ATG14 promotes autophagosome assembly by coupling PI3KC3-C1 to ER/phagophore membranes and
enabling local PI3P production.
- description: Separate ATG14 initiation and fusion activities using STX17-binding-defective and
oligomerization-defective ATG14 mutants, then quantify autophagosome number, autolysosome formation, and
cargo degradation.
experiment_type: autophagosome maturation separation-of-function assay
hypothesis: ATG14 has separable early PI3KC3-C1 recruitment and late STX17-SNAP29/VAMP8 fusion functions.
- description: Compare wild-type ATG14 and Snapin-binding-deficient mutants in synchronized endocytic
receptor-degradation assays while monitoring autophagic flux in parallel.
experiment_type: endocytic trafficking/autophagy separation assay
hypothesis: ATG14-dependent endosome maturation is a supported secondary trafficking function that can be
separated from its core PI3KC3-C1 autophagy role.
- description: 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.
experiment_type: ULK1-ATG14 phosphosite separation-of-function assay
hypothesis: ULK1-mediated ATG14 Ser29 phosphorylation is required for PI3KC3-C1 activation and local PI3P
production at autophagosome formation sites during autophagy initiation.
