ATG5

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000045 autophagosome assembly	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 is essential for autophagosome assembly as a core component of the ATG12-ATG5-ATG16L1 complex. The complex functions as an E3-like enzyme for LC3 lipidation, which is required for autophagosome formation. Structural and biochemical studies confirm ATG5's central role in this process (PMID:23202584). Reason: Core function of ATG5. Phylogenetically conserved from yeast to human. IBA annotation is well-supported by extensive experimental evidence across species. Supporting Evidence: PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. PMID:9852036 Mutagenic analyses suggested that this conjugation was formed via an isopeptide bond between the C-terminal glycine of hApg12 and Lys-130 of hApg5. file:human/ATG5/ATG5-deep-research-falcon.md ATG5 is a core human autophagy protein in the ATG5 family, bearing ubiquitin-like folds that enable conjugation with ATG12 and assembly of the ATG12-ATG5-ATG16L1 complex, which functions as an E3-like ligase for LC3/ATG8 lipidation during autophagosome biogenesis
GO:0034045 phagophore assembly site membrane	IBA GO_REF:0000033	MODIFY	Summary: ATG5, as part of the ATG12-ATG5-ATG16L1 complex, localizes to the phagophore assembly site membrane. Recent studies show the complex preferentially associates with the convex surface of growing phagophores and participates in membrane remodeling. Reason: Well-supported cellular component annotation. The deep research confirms the complex preferentially associates with the convex surface of the growing isolation membrane (phagophore) and detaches/recycles once autophagosome closure is achieved. [2026-08 re-review against GO issue #29437] The cited evidence names the phagophore, not a membrane bounding the assembly site: PMID:32960676 shows RAB33B recruiting the ATG16L1 complex to phagophores, and RAB33B and ATG16L1 mutually determining each other's localization on phagophores. GO:0034045 asserts via bounding_layer_of that a membrane bounds the PAS, which is a protein condensate with no bounding bilayer (PMID:32025038); it also carries 'phagophore' as a synonym, competing directly with GO:0061908. Move to the term the paper actually uses. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000315667 · ATG5 ancestral node SUPPORTS TRANSFER The node places ATG5 correctly on early autophagic membranes; the defect is that the propagated term names a membrane bounding the assembly site, which does not exist. UniProtKB:Q9H1Y0 · ATG5 (human) SOURCE WEAK OR INFERRED Seed carries the same UniProt SL-0221-derived location, so the propagation adds no independent evidence for a PAS membrane. Proposed replacements: phagophore Supporting Evidence: PMID:32960676 RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.
GO:0000423 mitophagy	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 participates in mitophagy as part of the general autophagy machinery. The ATG12-ATG5-ATG16L1 complex is required for LC3 lipidation, which is essential for selective autophagy pathways including mitophagy. Reason: Valid annotation. Mitophagy requires the core autophagy machinery including ATG5. UniProt notes ATG5 is involved in mitochondrial quality control after oxidative damage.
GO:0035973 aggrephagy	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 is involved in aggrephagy (selective autophagy of protein aggregates). The ATG12-ATG5 conjugate interacts with ALFY/WDFY3, which targets protein aggregates for autophagic degradation. Reason: Valid annotation supported by IBA and experimental evidence (IMP PMID:22982048). ATG5 interacts with WDFY3/ALFY which targets aggregates for degradation. Supporting Evidence: PMID:20417604 Alfy is recruited to intracellular inclusions and scaffolds a complex between p62(SQSTM1)-positive proteins and the autophagic effectors Atg5, Atg12, Atg16L, and LC3.
GO:0005776 autophagosome	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 localizes to autophagosomes as part of the ATG12-ATG5-ATG16L1 complex during autophagosome formation. Direct experimental evidence from imaging studies (IDA PMID:15292400). Reason: Well-supported localization. Also supported by IDA evidence (PMID:15292400). Supporting Evidence: PMID:15292400 When HeLa cells are starved or treated with a proteasome inhibitor, Alfy relocalizes to characteristic filamentous cytoplasmic structures located close to autophagic membranes and ubiquitin-containing protein aggregates.
GO:0034727 piecemeal microautophagy of the nucleus	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: This annotation is based on phylogenetic inference. Piecemeal microautophagy of the nucleus (PMN) is primarily characterized in yeast. While the autophagy machinery is conserved, evidence for this specific process in human cells is limited. Reason: IBA annotation based on yeast ortholog function. PMN is well-characterized in yeast but less established in human cells. Keep as non-core function since ATG5's primary role is macroautophagy.
GO:0061908 phagophore	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 localizes to the phagophore (isolation membrane) as part of the ATG12-ATG5-ATG16L1 complex. This is well-supported by structural and cell biology studies. Reason: Core localization site for ATG5 function. The complex acts at the phagophore to catalyze LC3 lipidation. Supporting Evidence: PMID:32960676 RAB33B plays a key role in recruiting the ATG16L1 complex to phagophores during starvation-induced autophagy.
GO:0034274 Atg12-Atg5-Atg16 complex	IBA GO_REF:0000033	ACCEPT	Summary: ATG5 is a core component of the Atg12-Atg5-Atg16 complex. This is the defining complex for ATG5 function, extensively supported by structural studies (PMID:23202584, PMID:24191030). Reason: Definitive complex membership. ATG5 is covalently conjugated to ATG12 and associates with ATG16L1 to form this E3-like complex. Supporting Evidence: PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy. PMID:24191030 Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12.
GO:0006995 cellular response to nitrogen starvation	IBA GO_REF:0000033	ACCEPT	Summary: Autophagy is induced by nitrogen starvation, and ATG5 as a core autophagy component is involved in this response. This is a conserved response across eukaryotes. Reason: Valid annotation. Starvation-induced autophagy is a major trigger for ATG5 function.
GO:0098794 postsynapse	IEA GO_REF:0000108	KEEP AS NON CORE	Summary: Inferred from logical inference based on GO:0099170 (postsynaptic modulation). ATG5 has roles in synaptic autophagy, but this is a specialized context-dependent localization. Reason: IEA annotation based on logical inference. While autophagy occurs at synapses and ATG5 is involved, this is not a core localization for ATG5.
GO:0002376 immune system process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Inferred from UniProt keyword Immunity. ATG5 has roles in innate immunity through its involvement in xenophagy and regulation of interferon responses. However, this is a very broad term. Reason: Too general. The ATG12-ATG5 conjugate negatively regulates type I IFN production (PMID:17709747), but this is secondary to its autophagy function. Supporting Evidence: PMID:17709747 The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
GO:0005737 cytoplasm	IEA GO_REF:0000120	ACCEPT	Summary: ATG5 localizes to the cytoplasm where it forms the ATG12-ATG5-ATG16L1 complex before recruitment to phagophores. Reason: Valid general localization. ATG5 is cytoplasmic before recruitment to membranes.
GO:0006914 autophagy	IEA GO_REF:0000120	ACCEPT	Summary: ATG5 is essential for autophagy. This is the core biological process annotation for ATG5. Reason: Core function. ATG5 is essential for autophagy as demonstrated across multiple species and supported by extensive experimental evidence. Supporting Evidence: PMID:26812546 Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay.
GO:0006915 apoptotic process	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: This annotation is based on the UniProt keyword Apoptosis and the alternative name Apoptosis-specific protein (ASP). However, this reflects early nomenclature before ATG5's core autophagy function was understood. The apoptotic role is primarily through calpain-cleavage of ATG5 generating a pro-apoptotic N-terminal fragment that translocates to mitochondria - this is NOT the full-length ATG5's evolved function. Reason: Over-annotation. ATG5's core evolved function is autophagosome biogenesis, not apoptosis. The UniProt alias Apoptosis-specific protein is historical nomenclature. While calpain- cleaved ATG5 can promote apoptosis, full-length ATG5 functions in autophagy. The deep research clearly states apoptosis crosstalk is secondary: calpain-mediated cleavage of ATG5 produces an N-terminal fragment that translocates to mitochondria and promotes apoptosis. This is a cleavage product, not the primary protein function.
GO:0034045 phagophore assembly site membrane	IEA GO_REF:0000120	MODIFY	Summary: Duplicate of IBA annotation above. ATG5 localizes to phagophore assembly site membrane. Reason: Valid localization, duplicate of IBA annotation. Keep as IEA provides additional computational support. [2026-08 re-review against GO issue #29437] The cited evidence names the phagophore, not a membrane bounding the assembly site: PMID:32960676 shows RAB33B recruiting the ATG16L1 complex to phagophores, and RAB33B and ATG16L1 mutually determining each other's localization on phagophores. GO:0034045 asserts via bounding_layer_of that a membrane bounds the PAS, which is a protein condensate with no bounding bilayer (PMID:32025038); it also carries 'phagophore' as a synonym, competing directly with GO:0061908. Move to the term the paper actually uses. Proposed replacements: phagophore
GO:0043069 negative regulation of programmed cell death	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine learning prediction. This reflects autophagy's role as a survival mechanism that can prevent cell death under stress. However, this is an indirect effect of ATG5's autophagy function rather than a direct molecular function. Reason: Indirect effect. Autophagy generally promotes cell survival, so ATG5 indirectly affects programmed cell death. Not a core annotation.
GO:0005515 protein binding	IPI PMID:17353931 Large-scale mapping of human protein-protein interactions by...	REMOVE	Summary: High-throughput mass spectrometry interaction data. Uninformative term - does not specify the binding partner or functional significance. Reason: Uninformative annotation. Protein binding alone provides no functional insight. The specific interactions (with ATG12, ATG16L1, ATG3, etc.) are more informative. Supporting Evidence: PMID:17353931 Large-scale mapping of human protein-protein interactions by mass spectrometry.
GO:0005515 protein binding	IPI PMID:17709747 The Atg5 Atg12 conjugate associates with innate antiviral im...	REMOVE	Summary: Interaction with RIG-I (O95786-1) and MAVS (Q7Z434-1). This demonstrates ATG5's role in modulating innate immune signaling through direct protein interactions. Reason: Uninformative generic term. The specific interactions with RIG-I and MAVS are better captured by more specific MF or BP annotations. Generic protein binding should be replaced with more specific terms. Supporting Evidence: PMID:17709747 The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
GO:0005515 protein binding	IPI PMID:20417604 The selective macroautophagic degradation of aggregated prot...	REMOVE	Summary: Interaction with WDFY3/ALFY (Q8IZQ1) for selective autophagy of aggregates. Reason: Generic protein binding is uninformative. The functional consequence (aggrephagy) is captured by the aggrephagy BP annotation. Supporting Evidence: PMID:20417604 The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.
GO:0005515 protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	REMOVE	Summary: Network mapping of autophagy system interactions. Reason: Generic protein binding from high-throughput study. Uninformative. Supporting Evidence: PMID:20562859 Network organization of the human autophagy system.
GO:0005515 protein binding	IPI PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3...	REMOVE	Summary: Structural study showing ATG5 interaction with ATG16L1 (Q676U5). Reason: Generic protein binding is uninformative. The ATG12-ATG5-ATG16 complex membership annotation is more informative. Supporting Evidence: PMID:23202584 Dec 2. Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy.
GO:0005515 protein binding	IPI PMID:23262492 Interaction between FIP200 and ATG16L1 distinguishes ULK1 co...	REMOVE	Summary: Interaction between FIP200/RB1CC1 and ATG16L1 complex. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:23262492 Dec 23. Interaction between FIP200 and ATG16L1 distinguishes ULK1 complex-dependent and -independent autophagy.
GO:0005515 protein binding	IPI PMID:23392225 FIP200 regulates targeting of Atg16L1 to the isolation membr...	REMOVE	Summary: FIP200 regulation of Atg16L1 targeting. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:23392225 FIP200 regulates targeting of Atg16L1 to the isolation membrane.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	REMOVE	Summary: High-throughput genetic variant effect on protein interactions. Reason: Generic protein binding from high-throughput study. Uninformative. Supporting Evidence: PMID:31515488 Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	REMOVE	Summary: Reference map of human binary protein interactome. Reason: Generic protein binding from high-throughput interactome study. Uninformative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	REMOVE	Summary: Interactome mapping in neurodegeneration context. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Dual proteome-scale network study. Reason: Generic protein binding from high-throughput study. Uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: OpenCell endogenous tagging study. Reason: Generic protein binding from high-throughput study. Uninformative. Supporting Evidence: PMID:35271311 2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	REMOVE	Summary: Multimodal cell mapping study. Reason: Generic protein binding from high-throughput study. Uninformative. Supporting Evidence: PMID:40205054 Apr 9. Multimodal cell maps as a foundation for structural and functional genomics.
GO:0000045 autophagosome assembly	IEA GO_REF:0000120	ACCEPT	Summary: Combined automated annotation supporting autophagosome assembly role. Reason: Core function, duplicate of IBA annotation. Computational support for core function.
GO:0005776 autophagosome	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara transfer from mouse ortholog. Reason: Valid localization, consistent with IBA and IDA annotations.
GO:0005930 axoneme	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. ATG5 localizes to ciliary axoneme and is involved in ciliogenesis regulation. Reason: Specialized localization related to ATG5's role in cilium assembly regulation. Non-core function.
GO:0010040 response to iron(II) ion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. Iron can induce autophagy-related processes including ferroptosis. Reason: Context-specific response. Not a core function of ATG5.
GO:0010508 positive regulation of autophagy	IEA GO_REF:0000107	ACCEPT	Summary: Transfer from rat ortholog. ATG5 is essential for autophagy execution rather than regulation per se. Reason: While ATG5 is more of an essential component than a regulator, its presence does positively enable autophagy to occur.
GO:0030424 axon	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. ATG5 is involved in axon maintenance through autophagy. Reason: Context-specific localization. UniProt notes ATG5 is involved in the maintenance of axon morphology and membrane structures. Non-core tissue-specific function.
GO:0032480 negative regulation of type I interferon production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: The ATG12-ATG5 conjugate negatively regulates type I IFN production by associating with RIG-I and MAVS (PMID:17709747). Reason: This is a secondary function of ATG5, not its core autophagy role. The ATG12-ATG5 conjugate moonlights as an immune modulator. Supporting Evidence: PMID:17709747 the Atg5-Atg12 conjugate negatively regulates the type I IFN production pathway by direct association with the retinoic acid-inducible gene I (RIG-I) and IFN-beta promoter stimulator 1 (IPS-1)
GO:0032991 protein-containing complex	IEA GO_REF:0000120	REMOVE	Summary: Generic annotation indicating ATG5 is part of a protein complex. Reason: Too generic. The specific ATG12-ATG5-ATG16 complex annotation is more informative.
GO:0035973 aggrephagy	IEA GO_REF:0000107	ACCEPT	Summary: Duplicate of IBA annotation. Transfer from mouse ortholog. Reason: Valid annotation, duplicate support for aggrephagy role.
GO:0043066 negative regulation of apoptotic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. This reflects autophagy's survival-promoting effects. Reason: Indirect effect of autophagy function. Autophagy promotes survival, thereby indirectly inhibiting apoptosis. Not a direct function.
GO:0043687 post-translational protein modification	IEA GO_REF:0000107	ACCEPT	Summary: ATG5 is involved in the LC3 lipidation (post-translational modification) process. Reason: Valid annotation. LC3 lipidation to PE is a post-translational modification catalyzed by the ATG12-ATG5-ATG16L1 complex.
GO:0044233 mitochondria-associated endoplasmic reticulum membrane contact site	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: MAM contact sites are reported as sites of autophagosome formation. ATG5 may localize here during autophagosome biogenesis. Reason: Specialized localization. MAM sites can serve as platforms for autophagosome formation but this is context-specific.
GO:0045202 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. ATG5 functions in synaptic autophagy. Reason: Tissue-specific localization. Autophagy occurs at synapses but this is not a core localization for ATG5.
GO:0045824 negative regulation of innate immune response	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Related to ATG5's role in suppressing type I IFN responses through RIG-I/MAVS interaction. Reason: Secondary function. Not core autophagy role. Supporting Evidence: PMID:17709747 The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
GO:0050687 negative regulation of defense response to virus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. ATG5 suppresses antiviral responses. Reason: Secondary function related to immune modulation. Supporting Evidence: PMID:17709747 The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
GO:0061684 chaperone-mediated autophagy	IEA GO_REF:0000107	UNDECIDED	Summary: Transfer from rat ortholog. CMA is a distinct autophagy pathway that does not classically require ATG5. Reason: CMA is mechanistically distinct from macroautophagy and typically does not require ATG5. This annotation may be questionable. Unable to verify specific role.
GO:0062029 positive regulation of stress granule assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. Autophagy can affect stress granule dynamics. Reason: Indirect effect. Not a core ATG5 function.
GO:0071500 cellular response to nitrosative stress	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. Autophagy is induced by nitrosative stress. Reason: Stress response involving autophagy. Not a core ATG5 function.
GO:0098685 Schaffer collateral - CA1 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. Specific synapse type localization. Reason: Highly specific tissue/cell-type localization. Not core function.
GO:0098930 axonal transport	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. ATG5 may affect axonal transport through autophagy. Reason: Indirect effect through autophagy in neurons. Not a core function.
GO:0098978 glutamatergic synapse	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Combined annotation indicating localization at glutamatergic synapses. Reason: Tissue-specific localization. Not a core function.
GO:0099072 regulation of postsynaptic membrane neurotransmitter receptor levels	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. Autophagy can regulate receptor turnover. Reason: Specialized neuronal function. Not a core ATG5 function.
GO:0099170 postsynaptic modulation of chemical synaptic transmission	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from mouse ortholog. Related to synaptic autophagy. Reason: Specialized neuronal function. Not a core ATG5 function.
GO:1902017 regulation of cilium assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: ATG5 promotes ciliogenesis through autophagic degradation of ciliogenesis regulators like OFD1 and IFT20. Reason: Documented function but secondary to core autophagy role.
GO:1902617 response to fluoride	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Transfer from rat ortholog. Fluoride can induce autophagy. Reason: Context-specific stress response. Not a core function.
GO:0016236 macroautophagy	IMP PMID:25484072 Insights into autophagosome maturation revealed by the struc...	ACCEPT	Summary: Experimental evidence from ComplexPortal showing ATG5 role in macroautophagy. Reason: Core function. Macroautophagy is the primary autophagy pathway that ATG5 participates in. Supporting Evidence: PMID:25484072 Insights into autophagosome maturation revealed by the structures of ATG5 with its interacting partners.
GO:0050687 negative regulation of defense response to virus	IDA PMID:19666601 The autophagy machinery is required to initiate hepatitis C ...	KEEP AS NON CORE	Summary: Direct experimental evidence showing ATG5 is required for HCV replication initiation, thereby suppressing antiviral defense. Reason: Well-supported but secondary function. ATG5 acts as a proviral factor in HCV infection. Supporting Evidence: PMID:19666601 autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA
GO:1901096 regulation of autophagosome maturation	IMP PMID:22342342 A mammalian autophagosome maturation mechanism mediated by T...	ACCEPT	Summary: ATG5 via the ATG12-ATG5 conjugate interacts with TECPR1 to regulate autophagosome- lysosome fusion. Reason: Important function related to autophagy completion. Supporting Evidence: PMID:22342342 TECPR1 binds to the Atg12-Atg5 conjugate and phosphatidylinositol 3-phosphate (PtdIns[3]P) to promote autophagosome-lysosome fusion.
GO:1904973 positive regulation of viral translation	IDA PMID:19666601 The autophagy machinery is required to initiate hepatitis C ...	KEEP AS NON CORE	Summary: ATG5 is required for translation of incoming HCV RNA, demonstrating a proviral role. Reason: Context-specific function during viral infection. Not core autophagy function. Supporting Evidence: PMID:19666601 autophagy proteins (i.e., Beclin-1, Atg4B, Atg5, and Atg12) are proviral factors required for translation of incoming hepatitis C virus (HCV) RNA
GO:0000045 autophagosome assembly	IDA PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3...	ACCEPT	Summary: Crystal structure of ATG12-ATG5 conjugate demonstrates its essential role in LC3 lipidation and autophagosome assembly. Reason: Core function with high-quality structural evidence. Supporting Evidence: PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy.
GO:0019776 Atg8-family ligase activity	IDA PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3...	ACCEPT	Summary: The ATG12-ATG5-ATG16L1 complex functions as an E3-like ligase for LC3/ATG8 lipidation. This is the core molecular function of ATG5. Reason: Core molecular function. The ATG12-ATG5 conjugate with ATG16L1 allosterically activates ATG3 to catalyze LC3 transfer to PE. Supporting Evidence: PMID:23202584 Structure of the human ATG12~ATG5 conjugate required for LC3 lipidation in autophagy.
GO:0005515 protein binding	IPI PMID:32960676 RAB33B recruits the ATG16L1 complex to the phagophore via a ...	REMOVE	Summary: Interaction with ATG16L1 and RAB33B. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:32960676 2020 Sep 22. RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.
GO:0034045 phagophore assembly site membrane	IDA PMID:32960676 RAB33B recruits the ATG16L1 complex to the phagophore via a ...	MODIFY	Summary: Direct evidence for ATG5 localization at phagophore assembly site membrane via RAB33B recruitment. Reason: Core localization with direct experimental evidence. [2026-08 re-review against GO issue #29437] The cited evidence names the phagophore, not a membrane bounding the assembly site: PMID:32960676 shows RAB33B recruiting the ATG16L1 complex to phagophores, and RAB33B and ATG16L1 mutually determining each other's localization on phagophores. GO:0034045 asserts via bounding_layer_of that a membrane bounds the PAS, which is a protein condensate with no bounding bilayer (PMID:32025038); it also carries 'phagophore' as a synonym, competing directly with GO:0061908. Move to the term the paper actually uses. Proposed replacements: phagophore Supporting Evidence: PMID:32960676 RAB33B recruits the ATG16L1 complex to the phagophore via a noncanonical RAB binding protein.
GO:0005515 protein binding	IPI PMID:24191030 Structural basis of ATG3 recognition by the autophagic ubiqu...	REMOVE	Summary: Structural study showing ATG3 recognition by ATG12. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:24191030 Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12.
GO:1904093 negative regulation of autophagic cell death	IMP PMID:19273585 Hypoxia-induced autophagy is mediated through hypoxia-induci...	UNDECIDED	Summary: Study on hypoxia-induced autophagy. Note: This study primarily examines BNIP3/BNIP3L, not ATG5 directly. ATG5's role here is as part of general autophagy machinery. Reason: The referenced paper (PMID:19273585) focuses on BNIP3/BNIP3L and Beclin1 rather than ATG5 specifically. The annotation may be transferred from the autophagy context but direct ATG5 evidence is unclear from this publication. Supporting Evidence: PMID:19273585 Mar 9. Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains.
GO:0006914 autophagy	IGI PMID:28389568 Hepatitis C virus triggers Golgi fragmentation and autophagy...	ACCEPT	Summary: Genetic interaction study showing ATG5 involvement in HCV-triggered autophagy through IRGM pathway. Reason: Valid autophagy annotation with genetic interaction evidence. Supporting Evidence: PMID:28389568 We show that IRGM is localized at the Golgi apparatus and regulates the fragmentation of Golgi membranes in response to HCV infection, leading to colocalization of Golgi vesicles with replicating HCV.
GO:0005515 protein binding	IPI PMID:26812546 Mutation in ATG5 reduces autophagy and leads to ataxia with ...	REMOVE	Summary: Disease mutation study showing ATG5 interaction with ATG12. Reason: Generic protein binding. Uninformative. The ATG12-ATG5 conjugation is better captured by complex membership annotation. Supporting Evidence: PMID:26812546 Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay.
GO:0006914 autophagy	IMP PMID:26812546 Mutation in ATG5 reduces autophagy and leads to ataxia with ...	ACCEPT	Summary: Disease mutation (E122D) in ATG5 reduces autophagy and causes ataxia with developmental delay, demonstrating ATG5's essential role in autophagy. Reason: Strong genetic evidence that ATG5 is essential for autophagy in humans. Supporting Evidence: PMID:26812546 Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay.
GO:0030670 phagocytic vesicle membrane	TAS Reactome:R-HSA-5205663	KEEP AS NON CORE	Summary: Reactome annotation for LC3-associated phagocytosis (LAP). ATG5 participates in LC3 lipidation on phagosome membranes during LAP. Reason: Non-canonical autophagy pathway (LAP/CASM). Valid but not core macroautophagy function.
GO:0030670 phagocytic vesicle membrane	TAS Reactome:R-HSA-8959571	KEEP AS NON CORE	Summary: Duplicate Reactome annotation for phagocytic vesicle membrane localization. Reason: Duplicate of above. Non-canonical autophagy pathway.
GO:0035973 aggrephagy	IMP PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys...	ACCEPT	Summary: Experimental evidence for ATG5 role in aggrephagy. Reason: Direct experimental evidence for selective autophagy of aggregates. Supporting Evidence: PMID:22982048 Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts.
GO:0005829 cytosol	TAS Reactome:R-HSA-5678490	ACCEPT	Summary: Reactome annotation for cytosolic localization during LC3 lipidation. Reason: Valid localization. ATG5 is initially cytosolic before membrane recruitment.
GO:0005829 cytosol	TAS Reactome:R-HSA-5679255	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-5682010	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-5682012	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-5682690	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-5683588	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0005829 cytosol	TAS Reactome:R-HSA-9936620	ACCEPT	Summary: Duplicate Reactome cytosol annotation. Reason: Valid localization, duplicate annotation.
GO:0016020 membrane	IDA PMID:23093945 Regulation of ATG4B stability by RNF5 limits basal levels of...	ACCEPT	Summary: Study on RNF5 regulation of ATG4B. ATG5 membrane localization is indirect from this study. Reason: ATG5 associates with membranes during autophagosome formation. Supporting Evidence: PMID:23093945 Oct 18. Regulation of ATG4B stability by RNF5 limits basal levels of autophagy and influences susceptibility to bacterial infection.
GO:0005930 axoneme	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse ortholog for axoneme localization. Reason: Specialized localization related to ciliogenesis function.
GO:1902017 regulation of cilium assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse ortholog for cilium assembly regulation. Reason: Secondary function through autophagic degradation of ciliogenesis regulators.
GO:0005515 protein binding	IPI PMID:21575909 A Tecpr1-dependent selective autophagy pathway targets bacte...	REMOVE	Summary: TECPR1 interaction study for bacterial pathogen targeting. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:21575909 A Tecpr1-dependent selective autophagy pathway targets bacterial pathogens.
GO:0005515 protein binding	IPI PMID:22342342 A mammalian autophagosome maturation mechanism mediated by T...	REMOVE	Summary: TECPR1 interaction for autophagosome maturation. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:22342342 2012 Feb 16. A mammalian autophagosome maturation mechanism mediated by TECPR1 and the Atg12-Atg5 conjugate.
GO:0034045 phagophore assembly site membrane	ISS GO_REF:0000024	MODIFY	Summary: ISS from mouse ortholog for phagophore localization. Reason: Core localization, consistent with other evidence. [2026-08 re-review against GO issue #29437] The cited evidence names the phagophore, not a membrane bounding the assembly site: PMID:32960676 shows RAB33B recruiting the ATG16L1 complex to phagophores, and RAB33B and ATG16L1 mutually determining each other's localization on phagophores. GO:0034045 asserts via bounding_layer_of that a membrane bounds the PAS, which is a protein condensate with no bounding bilayer (PMID:32025038); it also carries 'phagophore' as a synonym, competing directly with GO:0061908. Move to the term the paper actually uses. Proposed replacements: phagophore
GO:0000045 autophagosome assembly	ISS GO_REF:0000024	ACCEPT	Summary: ISS from mouse ortholog for autophagosome assembly. Reason: Core function, consistent with other evidence.
GO:0005737 cytoplasm	ISS GO_REF:0000024	ACCEPT	Summary: ISS from mouse ortholog for cytoplasm localization. Reason: Valid general localization.
GO:0006914 autophagy	ISS GO_REF:0000024	ACCEPT	Summary: ISS from mouse ortholog for autophagy. Reason: Core function.
GO:0043687 post-translational protein modification	ISS GO_REF:0000024	ACCEPT	Summary: ISS from mouse ortholog for post-translational modification (LC3 lipidation). Reason: Valid annotation related to LC3 lipidation function.
GO:0005515 protein binding	IPI PMID:9852036 A new protein conjugation system in human. The counterpart o...	REMOVE	Summary: Foundational paper demonstrating ATG12-ATG5 conjugation in human cells. Reason: Generic protein binding. Uninformative. The conjugation is better captured by complex and function annotations. Supporting Evidence: PMID:9852036 A new protein conjugation system in human.
GO:0005515 protein binding	IPI PMID:11096062 The human homolog of Saccharomyces cerevisiae Apg7p is a Pro...	REMOVE	Summary: Paper showing ATG7 as E1-like enzyme for ATG12 conjugation. Reason: Generic protein binding. Uninformative. Supporting Evidence: PMID:11096062 Nov 28. The human homolog of Saccharomyces cerevisiae Apg7p is a Protein-activating enzyme for multiple substrates including human Apg12p, GATE-16, GABARAP, and MAP-LC3.
GO:0005776 autophagosome	IDA PMID:15292400 Alfy, a novel FYVE-domain-containing protein associated with...	ACCEPT	Summary: ALFY study showing ATG5 localization at autophagic membranes. Reason: Core localization with direct experimental evidence. Supporting Evidence: PMID:15292400 Alfy relocalizes to characteristic filamentous cytoplasmic structures located close to autophagic membranes and ubiquitin-containing protein aggregates.

Gene Description

Existing Annotations Review

Core Functions

ATG5, as part of the ATG12-ATG5-ATG16L1 complex, functions as an E3-like enzyme that promotes the covalent conjugation of LC3/ATG8 family proteins to phosphatidylethanolamine (PE) on autophagosomal membranes. This lipidation is essential for autophagosome formation and maturation.

References

Tags

Deep Research

Falcon

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