ATG7 is an E1-like ubiquitin-activating enzyme essential for autophagy. It functions as the common E1 enzyme for two ubiquitin-like conjugation systems: (1) ATG12 conjugation, where ATG7 activates ATG12 for its conjugation with ATG5 via the E2 ATG10; and (2) ATG8/LC3 lipidation, where ATG7 activates LC3/GABARAP proteins for their conjugation with phosphatidylethanolamine via the E2 ATG3. ATG7 forms a homodimer and uses a trans-thioester transfer mechanism across protomers. The catalytic cysteine (Cys572) is essential for forming thioester intermediates with ATG12 and ATG8 family proteins. Both conjugation systems are essential for autophagosome formation and membrane expansion during canonical macroautophagy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 localizes to the phagophore assembly site where it functions as the E1-like enzyme for both ATG12 and LC3 conjugation systems required for autophagosome formation. IBA annotation is supported by phylogenetic evidence and consistent with IDA data from PMID:37943659. Reason: Core localization for ATG7 function. The phagophore assembly site is where ATG7 performs its E1-like activating enzyme function for ATG12 and LC3 conjugation. Supported by direct experimental evidence (PMID:37943659). Supporting Evidence: file:human/ATG7/ATG7-deep-research-falcon.md ATG7 localizes at the phagophore assembly site where it activates ATG12 and ATG8/LC3 |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 is a cytoplasmic protein where it functions in the LC3 lipidation module. Consistent with IDA evidence from PMID:20543840. Reason: Core localization. ATG7 functions in the cytoplasm/cytosol. Supported by IDA evidence. Supporting Evidence: PMID:20543840 Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. |
| GO:0032446 protein modification by small protein conjugation | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 catalyzes small protein conjugation reactions - specifically ATG12 conjugation to ATG5 and ATG8/LC3 conjugation to PE. This is the core biochemical function of ATG7. Reason: Core function of ATG7 as an E1-like enzyme activating ATG12 and ATG8 for ubiquitin-like conjugation reactions. Well-supported by literature (PMID:11096062). Supporting Evidence: PMID:11096062 hApg7p is an authentic protein-activating enzyme for hApg12p and the three Apg8p homologs |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 is required for mitophagy through its essential role in autophagosome formation. Mitophagy requires ATG7-dependent LC3 lipidation for autophagosome assembly around damaged mitochondria. Reason: Mitophagy requires canonical autophagy machinery including ATG7. Supported by IGI evidence from PMID:19279012 studying PINK1-dependent mitophagy. Supporting Evidence: PMID:19279012 RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation |
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 is essential for autophagosome assembly through its E1-like activity activating ATG12 and ATG8/LC3 for conjugation reactions required for autophagosome membrane expansion. Reason: Core function. ATG7 is essential for autophagosome assembly. Supported by IMP evidence from PMID:22170151. Supporting Evidence: PMID:22170151 ATG7 is an autophagy-related E1-like enzyme that is essential for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation |
| GO:0019778 Atg12 activating enzyme activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 functions as the E1-like activating enzyme for ATG12, forming a thioester intermediate via Cys572, then transferring ATG12 to the E2 enzyme ATG10. Reason: Core molecular function. ATG7 adenylates ATG12 and forms a thioester intermediate, essential for the ATG12-ATG5 conjugation system. Demonstrated by IDA (PMID:37943659) and IMP (PMID:22170151). Supporting Evidence: PMID:11096062 Cys(572) of hApg7p is an authentic active site cysteine residue essential for the formation of the hApg7p.hApg12p intermediate |
| GO:0006995 cellular response to nitrogen starvation | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7-dependent autophagy is induced by nitrogen starvation as a conserved response from yeast to mammals. This is a core autophagy-inducing stimulus. Reason: ATG7-dependent autophagy is triggered by nitrogen/nutrient starvation. This represents a core autophagy induction context that is evolutionarily conserved. Supporting Evidence: PMID:20543840 Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation |
| GO:0019779 Atg8 activating enzyme activity | IBA GO_REF:0000033 | ACCEPT | Summary: ATG7 functions as the E1-like activating enzyme for ATG8 family proteins (LC3, GABARAP, GATE-16), forming thioester intermediates for subsequent transfer to ATG3. Reason: Core molecular function. ATG7 activates ATG8/LC3 family proteins for lipidation. Demonstrated experimentally in PMID:11096062 and PMID:16303767. Supporting Evidence: PMID:11096062 Each of three human Apg8p counterparts, i.e. the Golgi-associated ATPase enhancer of 16 kDa, GABA(A) receptor-associated protein, and microtubule-associated protein light chain 3, coimmunoprecipitates with hApg7p and conjugates with mutant hApg7p(C572S) to form a stable intermediate via an ester bond |
| GO:0034727 piecemeal microautophagy of the nucleus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Piecemeal microautophagy of the nucleus (PMN) is a selective autophagy pathway best characterized in yeast. While ATG7 is required for various autophagy pathways, the specific involvement in PMN in humans is less well established. Reason: PMN is primarily characterized in yeast. While ATG7 is involved in selective autophagy pathways in mammals, PMN specifically is less well documented in humans. Keeping as non-core based on IBA phylogenetic inference from yeast. |
| GO:0000407 phagophore assembly site | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProtKB subcellular location mapping. Consistent with IBA and IDA evidence for this localization. Reason: Electronic annotation consistent with experimental evidence. Duplicates IBA annotation but acceptable as supporting evidence. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation based on combined automated methods. Consistent with IBA and IDA evidence. Reason: Electronic annotation consistent with experimental evidence for cytoplasmic localization. |
| GO:0006914 autophagy | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation for autophagy involvement. ATG7 is essential for canonical autophagy. Reason: Core function. ATG7 is essential for autophagy. Electronic annotation consistent with extensive experimental evidence. |
| GO:0008641 ubiquitin-like modifier activating enzyme activity | IEA GO_REF:0000002 | ACCEPT | Summary: IEA based on InterPro domain mapping. ATG7 has the ThiF/MoeB/HesA domain characteristic of E1-like activating enzymes. Reason: Core molecular function category. ATG7 is an E1-like ubiquitin-activating enzyme for ATG12 and ATG8. More specific terms (GO:0019778, GO:0019779) better capture the specificity. |
| GO:0009896 positive regulation of catabolic process | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine learning annotation. ATG7-dependent autophagy promotes protein catabolism. Reason: Autophagy is a catabolic process and ATG7 is essential for it. However, this is a high-level term - more specific autophagy terms are preferred. |
| GO:0015031 protein transport | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA based on UniProtKB keyword mapping. ATG7's role relates to autophagosome formation which involves membrane trafficking. Reason: Indirect involvement. ATG7's primary function is in autophagosome formation rather than direct protein transport. This term is too general for ATG7's actual function. |
| GO:0031667 response to nutrient levels | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation. ATG7-dependent autophagy is induced by nutrient deprivation. Reason: Autophagy is triggered by nutrient starvation. However, this is a high-level term - more specific terms like cellular response to nitrogen starvation are preferred. |
| GO:0042981 regulation of apoptotic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA annotation. ATG7 can influence apoptosis through autophagy-apoptosis crosstalk. Reason: Secondary effect. ATG7's influence on apoptosis is indirect through autophagy. Supported by IMP evidence (PMID:20543840) for positive regulation of apoptotic process. |
| GO:0048511 rhythmic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: IEA based on UniProtKB keyword mapping (Biological rhythms). This annotation derives from mouse studies showing ATG7 mediates autophagic degradation of CRY1 in a time-dependent manner, regulating the liver clock. However, ATG7's core function is autophagy - any rhythmic aspect is a downstream consequence of autophagy flux oscillating with circadian rhythm. Reason: OVER-ANNOTATION. The deep research on ATG7 is entirely about autophagy (canonical autophagy, LC3 lipidation, CASM) with no mention of rhythmic process or circadian rhythm as a primary function. If autophagy flux oscillates with circadian rhythm, that does not make ATG7 a "rhythmic process" gene. ATG7's core function is as an E1-like enzyme for ATG8/ATG12 activation. The circadian connection is a downstream effect in specific tissues (liver), not a core molecular function. |
| GO:0060255 regulation of macromolecule metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA annotation. High-level term - autophagy regulates protein degradation. Reason: Very general term. ATG7 affects macromolecule metabolism through autophagy but this term is too high-level to be informative about ATG7's specific function. |
| GO:0080090 regulation of primary metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA annotation. High-level term. Reason: Very general term. Not informative about ATG7's specific function. |
| GO:0005515 protein binding | IPI PMID:16303767 Phosphatidylserine in addition to phosphatidylethanolamine i... | REMOVE | Summary: IPI for protein binding based on interactions with GABARAP, GATE-16, LC3. These are functional substrates of ATG7. Reason: Uninformative. "Protein binding" does not capture the specific E1-substrate relationship. The specific molecular function terms (Atg8/Atg12 activating enzyme activity) are more appropriate. Supporting Evidence: PMID:16303767 Each purified mutant Atg8 homolog with an exposed C-terminal Gly formed an E1-substrate intermediate with hAtg7 via a thioester bond |
| GO:0005515 protein binding | IPI PMID:18083104 Homeostatic levels of p62 control cytoplasmic inclusion body... | REMOVE | Summary: IPI for interaction with LC3 (MAP1LC3B). This is a functional E1-substrate interaction. Reason: Uninformative. The specific molecular function (Atg8 activating enzyme activity) captures this relationship better than generic protein binding. Supporting Evidence: PMID:18083104 Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. |
| GO:0005515 protein binding | IPI PMID:18296641 A role for the NAD-dependent deacetylase Sirt1 in the regula... | REMOVE | Summary: IPI for interaction with SIRT1. SIRT1 regulates autophagy through deacetylation of autophagy proteins including ATG7. Reason: Uninformative generic term. ATG7 interaction with SIRT1 relates to its regulation but "protein binding" does not capture this regulatory relationship. Supporting Evidence: PMID:18296641 A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. |
| GO:0005515 protein binding | IPI PMID:20195357 A comprehensive resource of interacting protein regions for ... | REMOVE | Summary: IPI from transcription factor network study. Reason: Uninformative generic term from high-throughput study. Supporting Evidence: PMID:20195357 A comprehensive resource of interacting protein regions for refining human transcription factor networks. |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | REMOVE | Summary: IPI from systematic autophagy network study. Reason: Uninformative generic term. Network study identified interactions but specific MF terms are more appropriate. Supporting Evidence: PMID:20562859 Network organization of the human autophagy system. |
| GO:0005515 protein binding | IPI PMID:21903422 Mapping a dynamic innate immunity protein interaction networ... | REMOVE | Summary: IPI for interaction with IRF2 from innate immunity interactome study. Reason: Uninformative generic term from high-throughput study. Supporting Evidence: PMID:21903422 2011 Sep 8. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: IPI from human interactome study. Reason: Uninformative generic term from high-throughput study. Supporting Evidence: PMID:28514442 Architecture of the human interactome defines protein communities and disease networks. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: IPI from cell-specific interactome study. Reason: Uninformative generic term from high-throughput study. 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:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | REMOVE | Summary: IPI from global macroautophagy proximity interactome study. Reason: Uninformative generic term from high-throughput study. Supporting Evidence: PMID:34524948 2021 Sep 15. Global Proximity Interactome of the Human Macroautophagy Pathway. |
| GO:0019779 Atg8 activating enzyme activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity to characterized orthologs. Reason: Core molecular function. Consistent with IBA and experimental evidence. |
| GO:0000407 phagophore assembly site | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: Direct experimental evidence for ATG7 localization at the phagophore assembly site from the ATM-CHK2-TRIM32 study. Reason: Core localization supported by direct experimental evidence. Supporting Evidence: PMID:37943659 We propose a molecular mechanism for autophagy initiation by ROS via the ATM-CHK2-TRIM32-ATG7 axis to maintain intracellular homeostasis and to protect cells exposed to pathological conditions from stress-induced tissue damage. |
| GO:0061739 protein lipidation involved in autophagosome assembly | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: IDA evidence for ATG7's role in protein lipidation (LC3 lipidation) during autophagosome assembly. This is a core function. Reason: Core function. ATG7 is essential for LC3 lipidation which is required for autophagosome assembly. Directly demonstrated. Supporting Evidence: PMID:37943659 We show that CHK2 binds and phosphorylates TRIM32 at the S55 site, which then mediates K63-linked ubiquitination of ATG7 at the K45 site to initiate autophagy. |
| GO:0033554 cellular response to stress | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: IDA for ATG7 involvement in cellular stress response. The study shows ATG7 is activated under oxidative stress via the ATM-CHK2-TRIM32 pathway. Reason: ATG7-dependent autophagy is activated in response to stress. While stress response is broad, this reflects ATG7's role in adaptive autophagy. Supporting Evidence: PMID:37943659 Oxidative stress-induced autophagy helps to prevent cellular damage and to maintain homeostasis |
| GO:0019778 Atg12 activating enzyme activity | IDA PMID:37943659 ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initia... | ACCEPT | Summary: IDA evidence for ATG12 activating enzyme activity. Reason: Core molecular function. Direct experimental demonstration of ATG7's E1-like activity for ATG12. Supporting Evidence: PMID:37943659 2023 Nov 9. ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate autophagy under oxidative stress. |
| GO:0005515 protein binding | IPI PMID:26043688 Identification and characterization of the linear region of ... | REMOVE | Summary: IPI for ATG7-ATG3 interaction. Study characterizes the linear region of ATG3 that interacts with ATG7 in the E1-E2 transfer reaction. Reason: Uninformative. The ATG7-ATG3 interaction is a core functional E1-E2 interaction, but "protein binding" does not capture this. The Atg8 activating enzyme activity term is more appropriate. Supporting Evidence: PMID:26043688 Identification and characterization of the linear region of ATG3 that interacts with ATG7 |
| GO:0000423 mitophagy | IGI PMID:19279012 Loss of PINK1 function promotes mitophagy through effects on... | ACCEPT | Summary: IGI evidence for ATG7 involvement in mitophagy from PINK1 loss-of-function study. ATG7 knockdown decreased mitochondrial fragmentation/clearance. Reason: ATG7 is required for mitophagy. The study demonstrates that RNAi knockdown of ATG7 inhibits mitophagy in PINK1-deficient cells. Supporting Evidence: PMID:19279012 RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8 also decreased mitochondrial fragmentation without affecting oxidative stress |
| GO:0005515 protein binding | IPI PMID:24186333 Binding to E1 and E3 is mutually exclusive for the human aut... | REMOVE | Summary: IPI for ATG7-ATG3 interaction. Study shows binding to E1 and E3 is mutually exclusive for ATG3. Reason: Uninformative generic term. The E1-E2 interaction is functional and better captured by the Atg8 activating enzyme activity term. Supporting Evidence: PMID:24186333 Binding to E1 and E3 is mutually exclusive for the human autophagy E2 Atg3. |
| GO:0005515 protein binding | IPI PMID:37252361 Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Non... | REMOVE | Summary: IPI for ATG7-ATG3 interaction from LC3 probe study. Reason: Uninformative generic term. Functional E1-E2 interaction better captured by specific MF terms. Supporting Evidence: PMID:37252361 eCollection 2023 May 24. |
| GO:0000045 autophagosome assembly | IMP PMID:22170151 The FAP motif within human ATG7, an autophagy-related E1-lik... | ACCEPT | Summary: IMP evidence showing ATG7 is essential for autophagosome assembly. FAP motif mutants cannot rescue autophagosome formation in Atg7-deficient cells. Reason: Core function. Direct mutant phenotype analysis demonstrates ATG7 is essential for autophagosome assembly. Supporting Evidence: PMID:22170151 ATG7 is an autophagy-related E1-like enzyme that is essential for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation |
| GO:0019778 Atg12 activating enzyme activity | IMP PMID:22170151 The FAP motif within human ATG7, an autophagy-related E1-lik... | ACCEPT | Summary: IMP evidence for ATG12 activating enzyme activity from FAP motif mutagenesis study. Reason: Core molecular function. Mutant phenotype analysis demonstrates ATG7's E1-like activity for ATG12. Supporting Evidence: PMID:22170151 both mutant ATG7ΞFAP lacking the FAP motif and ATG7FAPtoDDD... could not complement defects in endogenous ATG12-conjugation |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5681981 | ACCEPT | Summary: TAS from Reactome pathway for ATG3 transferring LC3 from ATG7. Reason: Core localization. ATG7 functions in the cytosol. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5682011 | ACCEPT | Summary: TAS from Reactome pathway for LC3 binding ATG7 dimer. Reason: Core localization. Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5682896 | ACCEPT | Summary: TAS from Reactome pathway for LC3:ATG7 dimer binding ATG3. Reason: Core localization. Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9020616 | ACCEPT | Summary: TAS from Reactome pathway for ATG12 forming thioester with ATG7 dimer. Reason: Core localization. Consistent with other cytosol annotations. |
| GO:0005515 protein binding | IPI PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | REMOVE | Summary: IPI for ATG7-FOXO1 interaction. Acetylated FOXO1 binds ATG7 to influence autophagy. Reason: Uninformative generic term. FOXO1-ATG7 interaction is regulatory but "protein binding" does not capture this relationship meaningfully. Supporting Evidence: PMID:20543840 the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process |
| GO:0006914 autophagy | IGI PMID:28389568 Hepatitis C virus triggers Golgi fragmentation and autophagy... | ACCEPT | Summary: IGI for autophagy involvement from Hepatitis C virus study showing ATG7 role via IRGM. Reason: Core function. ATG7 is essential for autophagy. Supporting Evidence: PMID:28389568 Hepatitis C virus triggers Golgi fragmentation and autophagy through the immunity-related GTPase M. |
| GO:0006497 protein lipidation | IDA PMID:12890687 The mouse APG10 homologue, an E2-like enzyme for Apg12p conj... | ACCEPT | Summary: IDA for protein lipidation activity. The study shows ATG7 (with ATG10) facilitates LC3 lipidation (modification of soluble LC3 to membrane-bound form). Reason: Core function. ATG7 is essential for LC3 lipidation. The more specific term GO:0061739 (protein lipidation involved in autophagosome assembly) may be preferred. Supporting Evidence: PMID:12890687 the coexpression of Apg10p with Apg7p facilitates the modification of a soluble form of MAP-LC3 to a membrane-bound form |
| GO:0031401 positive regulation of protein modification process | IDA PMID:12890687 The mouse APG10 homologue, an E2-like enzyme for Apg12p conj... | ACCEPT | Summary: IDA annotation indicating ATG7 promotes protein modification (LC3 lipidation, ATG12 conjugation). Reason: ATG7 positively regulates protein modification through its E1-like activity. This is a high-level term but accurately reflects ATG7's role. Supporting Evidence: PMID:12890687 2003 Jul 30. The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, facilitates MAP-LC3 modification. |
| GO:0006914 autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation for autophagy based on mouse ortholog. Reason: Core function. Consistent with extensive experimental evidence. |
| GO:0042752 regulation of circadian rhythm | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS annotation based on mouse studies showing ATG7 degrades CRY1 in a time-dependent manner to regulate the liver clock. Reason: OVER-ANNOTATION. This is based on mouse data showing ATG7 degrades CRY1 for liver clock regulation. While true in that specific context, circadian rhythm regulation is NOT a core function of ATG7. ATG7's core function is autophagy; the circadian aspect is a tissue-specific downstream consequence. The deep research on ATG7 contains no mention of circadian rhythm as a primary function. |
| GO:0006914 autophagy | IMP PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: IMP for autophagy from FOXO1 study. Knockdown experiments demonstrate ATG7 requirement for autophagy. Reason: Core function with direct experimental evidence. Supporting Evidence: PMID:20543840 Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation |
| GO:0016236 macroautophagy | IMP PMID:22354037 Genome-wide siRNA screen reveals amino acid starvation-induc... | ACCEPT | Summary: IMP for macroautophagy from genome-wide siRNA screen identifying ATG7 as required for amino acid starvation-induced autophagy. Reason: Core function. ATG7 is essential for macroautophagy. This is more specific than general autophagy term. Supporting Evidence: PMID:22354037 Genome-wide siRNA screen reveals amino acid starvation-induced autophagy requires SCOC and WAC. |
| GO:0006914 autophagy | IMP PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a ro... | ACCEPT | Summary: IMP for autophagy from VPS34 inhibitor study examining NCOA4 and ferritinophagy. Reason: Core function. ATG7 is essential for autophagy. Supporting Evidence: PMID:25327288 Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: TAS from Reactome for secretory granule exocytosis. ATG7 detected in secretory granule lumen which can be released extracellularly. Reason: Non-core localization. ATG7 can be found in secretory granules and released via exocytosis, but this is not its primary functional location. |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: TAS from Reactome for ficolin-1-rich granule exocytosis. Reason: Non-core localization. ATG7 release via neutrophil degranulation is not its primary functional context. |
| GO:0034774 secretory granule lumen | TAS Reactome:R-HSA-6798748 | KEEP AS NON CORE | Summary: TAS for secretory granule lumen localization. Reason: Non-core localization. ATG7's primary function is in the cytosol at autophagosome formation sites, not in secretory granules. |
| GO:1904813 ficolin-1-rich granule lumen | TAS Reactome:R-HSA-6800434 | KEEP AS NON CORE | Summary: TAS for ficolin-1-rich granule lumen localization in neutrophils. Reason: Non-core localization specific to neutrophil biology, not ATG7's primary function. |
| GO:0005737 cytoplasm | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: IDA for cytoplasmic localization from FOXO1 study. Reason: Core localization with direct experimental evidence. Supporting Evidence: PMID:20543840 Here we report that cytosolic FoxO1, a forkhead O family protein, is a mediator of autophagy. |
| GO:0009267 cellular response to starvation | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: IDA for cellular response to starvation. ATG7-dependent autophagy is induced by starvation conditions. Reason: Core autophagy-inducing context. ATG7-dependent autophagy responds to starvation. Supporting Evidence: PMID:20543840 Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress or serum starvation |
| GO:0043065 positive regulation of apoptotic process | IMP PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | KEEP AS NON CORE | Summary: IMP for positive regulation of apoptosis. The study shows FOXO1-ATG7-mediated autophagy leads to cell death in certain contexts. Reason: Non-core function. Autophagy-mediated cell death (autophagic cell death) can promote apoptosis in specific contexts, but this is not ATG7's primary function. This represents autophagy-apoptosis crosstalk. Supporting Evidence: PMID:20543840 the acetylated FoxO1 bound to Atg7, an E1-like protein, to influence the autophagic process leading to cell death |
| GO:0045732 positive regulation of protein catabolic process | IMP PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: IMP for positive regulation of protein catabolism via autophagy. Reason: Autophagy is a protein catabolic process and ATG7 is essential for it. This is a consequence of ATG7's core autophagy function. Supporting Evidence: PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy and tumour suppressor activity. |
| GO:0071455 cellular response to hyperoxia | IDA PMID:20543840 Cytosolic FoxO1 is essential for the induction of autophagy ... | ACCEPT | Summary: IDA for cellular response to hyperoxia (oxidative stress). Reason: ATG7-dependent autophagy is induced by oxidative stress including hyperoxia. Consistent with PMID:37943659 showing oxidative stress activates ATG7. Supporting Evidence: PMID:20543840 Endogenous FoxO1 was required for autophagy in human cancer cell lines in response to oxidative stress |
| GO:0006914 autophagy | IMP PMID:24681637 Atg7- and Keap1-dependent autophagy protects breast cancer c... | ACCEPT | Summary: IMP for autophagy from study of Atg7/Keap1-dependent autophagy in breast cancer cells under mitoquinone-induced oxidative stress. Reason: Core function with direct experimental evidence. Supporting Evidence: PMID:24681637 Atg7- and Keap1-dependent autophagy protects breast cancer cell lines against mitoquinone-induced oxidative stress. |
| GO:0005930 axoneme | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS based on mouse data. UniProt notes ATG7 localizes to discrete punctae along the ciliary axoneme. Reason: Non-core localization. Axoneme localization is noted from mouse studies (UniProt note) but is not ATG7's primary functional location. Its significance for ciliary function is unclear. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5681980 | ACCEPT | Summary: TAS from Reactome for ATG12 binding ATG7 dimer in cytosol. Reason: Core localization. Consistent with other cytosol annotations. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5683593 | ACCEPT | Summary: TAS from Reactome for ATG7:ATG3:LC3 complex dissociation. Reason: Core localization. Consistent with other cytosol annotations. |
| GO:0051607 defense response to virus | IMP PMID:23290079 Human papillomavirus infection is inhibited by host autophag... | KEEP AS NON CORE | Summary: IMP for antiviral defense from study showing autophagy inhibits human papillomavirus infection in keratinocytes. Reason: Non-core function. ATG7-dependent autophagy can participate in antiviral defense (xenophagy), but this is a consequence of autophagy's role in clearing intracellular pathogens, not ATG7's primary function. Supporting Evidence: PMID:23290079 Jan 4. Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes. |
| GO:0019778 Atg12 activating enzyme activity | ISS PMID:20723759 ATG12 conjugation to ATG3 regulates mitochondrial homeostasi... | ACCEPT | Summary: ISS based on mouse data for ATG12 activating enzyme activity. Reason: Core molecular function. Consistent with extensive experimental evidence. Supporting Evidence: PMID:20723759 ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. |
| GO:0005515 protein binding | IPI PMID:11096062 The human homolog of Saccharomyces cerevisiae Apg7p is a Pro... | REMOVE | Summary: IPI for ATG7 binding to ATG12, GABARAP, GATE-16, LC3. These are E1-substrate interactions in the conjugation systems. Reason: Uninformative. These are functional E1-substrate interactions better captured by the specific Atg8/Atg12 activating enzyme activity terms. Supporting Evidence: PMID:11096062 hApg7p is an authentic protein-activating enzyme for hApg12p and the three Apg8p homologs |
| GO:0042803 protein homodimerization activity | IDA PMID:11096062 The human homolog of Saccharomyces cerevisiae Apg7p is a Pro... | ACCEPT | Summary: IDA for protein homodimerization. ATG7 forms a functional homodimer required for trans-thioester transfer to E2 enzymes. Reason: Core structural feature. ATG7 homodimerization is essential for its E1-like enzyme function, enabling trans-thioester transfer across protomers. Supporting Evidence: PMID:11096062 Cross-linking experiments and glycerol-gradient centrifugation analysis showed that the mammalian Apg7p homolog forms a homodimer as in yeast Apg7p |
| GO:0005515 protein binding | IPI PMID:11825910 Human Apg3p/Aut1p homologue is an authentic E2 enzyme for mu... | REMOVE | Summary: IPI for ATG7-ATG3 interaction. This is a functional E1-E2 interaction in the LC3 lipidation cascade. Reason: Uninformative. The ATG7-ATG3 E1-E2 interaction is functional and better captured by the Atg8 activating enzyme activity term. Supporting Evidence: PMID:11825910 Co-immunoprecipitation of hApg7p with hApg3p indicates that hApg3p forms an E1.E2 complex with hApg7p |
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)