ATG7

id: O95352
gene_symbol: ATG7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  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.
existing_annotations:
  - term:
      id: GO:0000407
      label: phagophore assembly site
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: file:human/ATG7/ATG7-deep-research-falcon.md
          supporting_text: "ATG7 localizes at the phagophore assembly site where it
            activates ATG12 and ATG8/LC3"
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        ATG7 is a cytoplasmic protein where it functions in the LC3 lipidation module.
        Consistent with
        IDA evidence from PMID:20543840.
      action: ACCEPT
      reason: >-
        Core localization. ATG7 functions in the cytoplasm/cytosol. Supported by IDA
        evidence.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Here we report that cytosolic FoxO1, a forkhead O family
            protein, is a mediator of autophagy."
  - term:
      id: GO:0032446
      label: protein modification by small protein conjugation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:11096062
          supporting_text: "hApg7p is an authentic protein-activating enzyme for hApg12p
            and the three Apg8p homologs"
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Mitophagy requires canonical autophagy machinery including ATG7. Supported
        by IGI evidence
        from PMID:19279012 studying PINK1-dependent mitophagy.
      supported_by:
        - reference_id: PMID:19279012
          supporting_text: "RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8
            also decreased mitochondrial fragmentation"
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for autophagosome assembly. Supported by
        IMP evidence
        from PMID:22170151.
      supported_by:
        - reference_id: PMID:22170151
          supporting_text: "ATG7 is an autophagy-related E1-like enzyme that is essential
            for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation"
  - term:
      id: GO:0019778
      label: Atg12 activating enzyme activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      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).
      supported_by:
        - reference_id: PMID:11096062
          supporting_text: "Cys(572) of hApg7p is an authentic active site cysteine
            residue essential for the formation of the hApg7p.hApg12p intermediate"
  - term:
      id: GO:0006995
      label: cellular response to nitrogen starvation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        ATG7-dependent autophagy is induced by nitrogen starvation as a conserved
        response from yeast
        to mammals. This is a core autophagy-inducing stimulus.
      action: ACCEPT
      reason: >-
        ATG7-dependent autophagy is triggered by nitrogen/nutrient starvation. This
        represents a
        core autophagy induction context that is evolutionarily conserved.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Endogenous FoxO1 was required for autophagy in human cancer
            cell lines in response to oxidative stress or serum starvation"
  - term:
      id: GO:0019779
      label: Atg8 activating enzyme activity
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: ACCEPT
      reason: >-
        Core molecular function. ATG7 activates ATG8/LC3 family proteins for lipidation.
        Demonstrated experimentally in PMID:11096062 and PMID:16303767.
      supported_by:
        - reference_id: PMID:11096062
          supporting_text: "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"
  - term:
      id: GO:0034727
      label: piecemeal microautophagy of the nucleus
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      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.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0000407
      label: phagophore assembly site
    evidence_type: IEA
    original_reference_id: GO_REF:0000044
    review:
      summary: >-
        IEA annotation based on UniProtKB subcellular location mapping. Consistent
        with IBA and IDA
        evidence for this localization.
      action: ACCEPT
      reason: >-
        Electronic annotation consistent with experimental evidence. Duplicates IBA
        annotation
        but acceptable as supporting evidence.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation based on combined automated methods. Consistent with IBA and
        IDA evidence.
      action: ACCEPT
      reason: >-
        Electronic annotation consistent with experimental evidence for cytoplasmic
        localization.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IEA
    original_reference_id: GO_REF:0000120
    review:
      summary: >-
        IEA annotation for autophagy involvement. ATG7 is essential for canonical
        autophagy.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for autophagy. Electronic annotation consistent
        with
        extensive experimental evidence.
  - term:
      id: GO:0008641
      label: ubiquitin-like modifier activating enzyme activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        IEA based on InterPro domain mapping. ATG7 has the ThiF/MoeB/HesA domain characteristic
        of E1-like activating enzymes.
      action: ACCEPT
      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.
  - term:
      id: GO:0009896
      label: positive regulation of catabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA machine learning annotation. ATG7-dependent autophagy promotes protein
        catabolism.
      action: ACCEPT
      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.
  - term:
      id: GO:0015031
      label: protein transport
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        IEA based on UniProtKB keyword mapping. ATG7's role relates to autophagosome
        formation
        which involves membrane trafficking.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0031667
      label: response to nutrient levels
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA annotation. ATG7-dependent autophagy is induced by nutrient deprivation.
      action: ACCEPT
      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.
  - term:
      id: GO:0042981
      label: regulation of apoptotic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA annotation. ATG7 can influence apoptosis through autophagy-apoptosis
        crosstalk.
      action: KEEP_AS_NON_CORE
      reason: >-
        Secondary effect. ATG7's influence on apoptosis is indirect through autophagy.
        Supported by IMP evidence (PMID:20543840) for positive regulation of apoptotic
        process.
  - term:
      id: GO:0048511
      label: rhythmic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      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.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0060255
      label: regulation of macromolecule metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA annotation. High-level term - autophagy regulates protein degradation.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0080090
      label: regulation of primary metabolic process
    evidence_type: IEA
    original_reference_id: GO_REF:0000117
    review:
      summary: >-
        ARBA annotation. High-level term.
      action: KEEP_AS_NON_CORE
      reason: >-
        Very general term. Not informative about ATG7's specific function.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:16303767
    review:
      summary: >-
        IPI for protein binding based on interactions with GABARAP, GATE-16, LC3.
        These are
        functional substrates of ATG7.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:16303767
          supporting_text: "Each purified mutant Atg8 homolog with an exposed C-terminal
            Gly formed an E1-substrate intermediate with hAtg7 via a thioester bond"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18083104
    review:
      summary: >-
        IPI for interaction with LC3 (MAP1LC3B). This is a functional E1-substrate
        interaction.
      action: REMOVE
      reason: >-
        Uninformative. The specific molecular function (Atg8 activating enzyme activity)
        captures
        this relationship better than generic protein binding.
      supported_by:
        - reference_id: PMID:18083104
          supporting_text: Homeostatic levels of p62 control cytoplasmic 
            inclusion body formation in autophagy-deficient mice.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:18296641
    review:
      summary: >-
        IPI for interaction with SIRT1. SIRT1 regulates autophagy through deacetylation
        of autophagy
        proteins including ATG7.
      action: REMOVE
      reason: >-
        Uninformative generic term. ATG7 interaction with SIRT1 relates to its regulation
        but
        "protein binding" does not capture this regulatory relationship.
      supported_by:
        - reference_id: PMID:18296641
          supporting_text: A role for the NAD-dependent deacetylase Sirt1 in the
            regulation of autophagy.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20195357
    review:
      summary: >-
        IPI from transcription factor network study.
      action: REMOVE
      reason: >-
        Uninformative generic term from high-throughput study.
      supported_by:
        - reference_id: PMID:20195357
          supporting_text: A comprehensive resource of interacting protein 
            regions for refining human transcription factor networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20562859
    review:
      summary: >-
        IPI from systematic autophagy network study.
      action: REMOVE
      reason: >-
        Uninformative generic term. Network study identified interactions but specific
        MF terms
        are more appropriate.
      supported_by:
        - reference_id: PMID:20562859
          supporting_text: Network organization of the human autophagy system.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:21903422
    review:
      summary: >-
        IPI for interaction with IRF2 from innate immunity interactome study.
      action: REMOVE
      reason: >-
        Uninformative generic term from high-throughput study.
      supported_by:
        - reference_id: PMID:21903422
          supporting_text: 2011 Sep 8. Mapping a dynamic innate immunity protein
            interaction network regulating type I interferon production.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:28514442
    review:
      summary: >-
        IPI from human interactome study.
      action: REMOVE
      reason: >-
        Uninformative generic term from high-throughput study.
      supported_by:
        - reference_id: PMID:28514442
          supporting_text: Architecture of the human interactome defines protein
            communities and disease networks.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:33961781
    review:
      summary: >-
        IPI from cell-specific interactome study.
      action: REMOVE
      reason: >-
        Uninformative generic term from high-throughput study.
      supported_by:
        - reference_id: PMID:33961781
          supporting_text: 2021 May 6. Dual proteome-scale networks reveal 
            cell-specific remodeling of the human interactome.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:34524948
    review:
      summary: >-
        IPI from global macroautophagy proximity interactome study.
      action: REMOVE
      reason: >-
        Uninformative generic term from high-throughput study.
      supported_by:
        - reference_id: PMID:34524948
          supporting_text: 2021 Sep 15. Global Proximity Interactome of the 
            Human Macroautophagy Pathway.
  - term:
      id: GO:0019779
      label: Atg8 activating enzyme activity
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation based on sequence similarity to characterized orthologs.
      action: ACCEPT
      reason: >-
        Core molecular function. Consistent with IBA and experimental evidence.
  - term:
      id: GO:0000407
      label: phagophore assembly site
    evidence_type: IDA
    original_reference_id: PMID:37943659
    review:
      summary: >-
        Direct experimental evidence for ATG7 localization at the phagophore assembly
        site from
        the ATM-CHK2-TRIM32 study.
      action: ACCEPT
      reason: >-
        Core localization supported by direct experimental evidence.
      supported_by:
        - reference_id: PMID:37943659
          supporting_text: "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."
  - term:
      id: GO:0061739
      label: protein lipidation involved in autophagosome assembly
    evidence_type: IDA
    original_reference_id: PMID:37943659
    review:
      summary: >-
        IDA evidence for ATG7's role in protein lipidation (LC3 lipidation) during
        autophagosome
        assembly. This is a core function.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for LC3 lipidation which is required for
        autophagosome
        assembly. Directly demonstrated.
      supported_by:
        - reference_id: PMID:37943659
          supporting_text: "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."
  - term:
      id: GO:0033554
      label: cellular response to stress
    evidence_type: IDA
    original_reference_id: PMID:37943659
    review:
      summary: >-
        IDA for ATG7 involvement in cellular stress response. The study shows ATG7
        is activated
        under oxidative stress via the ATM-CHK2-TRIM32 pathway.
      action: ACCEPT
      reason: >-
        ATG7-dependent autophagy is activated in response to stress. While stress
        response is
        broad, this reflects ATG7's role in adaptive autophagy.
      supported_by:
        - reference_id: PMID:37943659
          supporting_text: "Oxidative stress-induced autophagy helps to prevent cellular
            damage and to maintain homeostasis"
  - term:
      id: GO:0019778
      label: Atg12 activating enzyme activity
    evidence_type: IDA
    original_reference_id: PMID:37943659
    review:
      summary: >-
        IDA evidence for ATG12 activating enzyme activity.
      action: ACCEPT
      reason: >-
        Core molecular function. Direct experimental demonstration of ATG7's E1-like
        activity
        for ATG12.
      supported_by:
        - reference_id: PMID:37943659
          supporting_text: 2023 Nov 9. ATM-CHK2-TRIM32 axis regulates ATG7 
            ubiquitination to initiate autophagy under oxidative stress.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:26043688
    review:
      summary: >-
        IPI for ATG7-ATG3 interaction. Study characterizes the linear region of ATG3
        that interacts
        with ATG7 in the E1-E2 transfer reaction.
      action: REMOVE
      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.
      supported_by:
        - reference_id: PMID:26043688
          supporting_text: "Identification and characterization of the linear region
            of ATG3 that interacts with ATG7"
  - term:
      id: GO:0000423
      label: mitophagy
    evidence_type: IGI
    original_reference_id: PMID:19279012
    review:
      summary: >-
        IGI evidence for ATG7 involvement in mitophagy from PINK1 loss-of-function
        study. ATG7
        knockdown decreased mitochondrial fragmentation/clearance.
      action: ACCEPT
      reason: >-
        ATG7 is required for mitophagy. The study demonstrates that RNAi knockdown
        of ATG7
        inhibits mitophagy in PINK1-deficient cells.
      supported_by:
        - reference_id: PMID:19279012
          supporting_text: "RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8
            also decreased mitochondrial fragmentation without affecting oxidative
            stress"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:24186333
    review:
      summary: >-
        IPI for ATG7-ATG3 interaction. Study shows binding to E1 and E3 is mutually
        exclusive for ATG3.
      action: REMOVE
      reason: >-
        Uninformative generic term. The E1-E2 interaction is functional and better
        captured by
        the Atg8 activating enzyme activity term.
      supported_by:
        - reference_id: PMID:24186333
          supporting_text: Binding to E1 and E3 is mutually exclusive for the 
            human autophagy E2 Atg3.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:37252361
    review:
      summary: >-
        IPI for ATG7-ATG3 interaction from LC3 probe study.
      action: REMOVE
      reason: >-
        Uninformative generic term. Functional E1-E2 interaction better captured by
        specific MF terms.
      supported_by:
        - reference_id: PMID:37252361
          supporting_text: eCollection 2023 May 24.
  - term:
      id: GO:0000045
      label: autophagosome assembly
    evidence_type: IMP
    original_reference_id: PMID:22170151
    review:
      summary: >-
        IMP evidence showing ATG7 is essential for autophagosome assembly. FAP motif
        mutants cannot
        rescue autophagosome formation in Atg7-deficient cells.
      action: ACCEPT
      reason: >-
        Core function. Direct mutant phenotype analysis demonstrates ATG7 is essential
        for
        autophagosome assembly.
      supported_by:
        - reference_id: PMID:22170151
          supporting_text: "ATG7 is an autophagy-related E1-like enzyme that is essential
            for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation"
  - term:
      id: GO:0019778
      label: Atg12 activating enzyme activity
    evidence_type: IMP
    original_reference_id: PMID:22170151
    review:
      summary: >-
        IMP evidence for ATG12 activating enzyme activity from FAP motif mutagenesis
        study.
      action: ACCEPT
      reason: >-
        Core molecular function. Mutant phenotype analysis demonstrates ATG7's E1-like
        activity
        for ATG12.
      supported_by:
        - reference_id: PMID:22170151
          supporting_text: "both mutant ATG7ΔFAP lacking the FAP motif and ATG7FAPtoDDD...
            could not complement defects in endogenous ATG12-conjugation"
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5681981
    review:
      summary: >-
        TAS from Reactome pathway for ATG3 transferring LC3 from ATG7.
      action: ACCEPT
      reason: >-
        Core localization. ATG7 functions in the cytosol.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5682011
    review:
      summary: >-
        TAS from Reactome pathway for LC3 binding ATG7 dimer.
      action: ACCEPT
      reason: >-
        Core localization. Consistent with other cytosol annotations.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5682896
    review:
      summary: >-
        TAS from Reactome pathway for LC3:ATG7 dimer binding ATG3.
      action: ACCEPT
      reason: >-
        Core localization. Consistent with other cytosol annotations.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-9020616
    review:
      summary: >-
        TAS from Reactome pathway for ATG12 forming thioester with ATG7 dimer.
      action: ACCEPT
      reason: >-
        Core localization. Consistent with other cytosol annotations.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IPI for ATG7-FOXO1 interaction. Acetylated FOXO1 binds ATG7 to influence autophagy.
      action: REMOVE
      reason: >-
        Uninformative generic term. FOXO1-ATG7 interaction is regulatory but "protein
        binding"
        does not capture this relationship meaningfully.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "the acetylated FoxO1 bound to Atg7, an E1-like protein,
            to influence the autophagic process"
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IGI
    original_reference_id: PMID:28389568
    review:
      summary: >-
        IGI for autophagy involvement from Hepatitis C virus study showing ATG7 role
        via IRGM.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for autophagy.
      supported_by:
        - reference_id: PMID:28389568
          supporting_text: Hepatitis C virus triggers Golgi fragmentation and 
            autophagy through the immunity-related GTPase M.
  - term:
      id: GO:0006497
      label: protein lipidation
    evidence_type: IDA
    original_reference_id: PMID:12890687
    review:
      summary: >-
        IDA for protein lipidation activity. The study shows ATG7 (with ATG10) facilitates
        LC3 lipidation (modification of soluble LC3 to membrane-bound form).
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for LC3 lipidation. The more specific term
        GO:0061739 (protein lipidation involved in autophagosome assembly) may be
        preferred.
      supported_by:
        - reference_id: PMID:12890687
          supporting_text: "the coexpression of Apg10p with Apg7p facilitates the
            modification of a soluble form of MAP-LC3 to a membrane-bound form"
  - term:
      id: GO:0031401
      label: positive regulation of protein modification process
    evidence_type: IDA
    original_reference_id: PMID:12890687
    review:
      summary: >-
        IDA annotation indicating ATG7 promotes protein modification (LC3 lipidation,
        ATG12
        conjugation).
      action: ACCEPT
      reason: >-
        ATG7 positively regulates protein modification through its E1-like activity.
        This
        is a high-level term but accurately reflects ATG7's role.
      supported_by:
        - reference_id: PMID:12890687
          supporting_text: 2003 Jul 30. The mouse APG10 homologue, an E2-like 
            enzyme for Apg12p conjugation, facilitates MAP-LC3 modification.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation for autophagy based on mouse ortholog.
      action: ACCEPT
      reason: >-
        Core function. Consistent with extensive experimental evidence.
  - term:
      id: GO:0042752
      label: regulation of circadian rhythm
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS annotation based on mouse studies showing ATG7 degrades CRY1 in a time-dependent
        manner to regulate the liver clock.
      action: MARK_AS_OVER_ANNOTATED
      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.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IMP for autophagy from FOXO1 study. Knockdown experiments demonstrate ATG7
        requirement
        for autophagy.
      action: ACCEPT
      reason: >-
        Core function with direct experimental evidence.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Endogenous FoxO1 was required for autophagy in human cancer
            cell lines in response to oxidative stress or serum starvation"
  - term:
      id: GO:0016236
      label: macroautophagy
    evidence_type: IMP
    original_reference_id: PMID:22354037
    review:
      summary: >-
        IMP for macroautophagy from genome-wide siRNA screen identifying ATG7 as required
        for
        amino acid starvation-induced autophagy.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for macroautophagy. This is more specific
        than
        general autophagy term.
      supported_by:
        - reference_id: PMID:22354037
          supporting_text: Genome-wide siRNA screen reveals amino acid 
            starvation-induced autophagy requires SCOC and WAC.
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:25327288
    review:
      summary: >-
        IMP for autophagy from VPS34 inhibitor study examining NCOA4 and ferritinophagy.
      action: ACCEPT
      reason: >-
        Core function. ATG7 is essential for autophagy.
      supported_by:
        - reference_id: PMID:25327288
          supporting_text: Selective VPS34 inhibitor blocks autophagy and 
            uncovers a role for NCOA4 in ferritin degradation and iron 
            homeostasis in vivo.
  - term:
      id: GO:0005576
      label: extracellular region
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6798748
    review:
      summary: >-
        TAS from Reactome for secretory granule exocytosis. ATG7 detected in secretory
        granule
        lumen which can be released extracellularly.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization. ATG7 can be found in secretory granules and released
        via
        exocytosis, but this is not its primary functional location.
  - term:
      id: GO:0005576
      label: extracellular region
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6800434
    review:
      summary: >-
        TAS from Reactome for ficolin-1-rich granule exocytosis.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization. ATG7 release via neutrophil degranulation is not its
        primary
        functional context.
  - term:
      id: GO:0034774
      label: secretory granule lumen
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6798748
    review:
      summary: >-
        TAS for secretory granule lumen localization.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization. ATG7's primary function is in the cytosol at autophagosome
        formation sites, not in secretory granules.
  - term:
      id: GO:1904813
      label: ficolin-1-rich granule lumen
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-6800434
    review:
      summary: >-
        TAS for ficolin-1-rich granule lumen localization in neutrophils.
      action: KEEP_AS_NON_CORE
      reason: >-
        Non-core localization specific to neutrophil biology, not ATG7's primary function.
  - term:
      id: GO:0005737
      label: cytoplasm
    evidence_type: IDA
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IDA for cytoplasmic localization from FOXO1 study.
      action: ACCEPT
      reason: >-
        Core localization with direct experimental evidence.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Here we report that cytosolic FoxO1, a forkhead O family
            protein, is a mediator of autophagy."
  - term:
      id: GO:0009267
      label: cellular response to starvation
    evidence_type: IDA
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IDA for cellular response to starvation. ATG7-dependent autophagy is induced
        by
        starvation conditions.
      action: ACCEPT
      reason: >-
        Core autophagy-inducing context. ATG7-dependent autophagy responds to starvation.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Endogenous FoxO1 was required for autophagy in human cancer
            cell lines in response to oxidative stress or serum starvation"
  - term:
      id: GO:0043065
      label: positive regulation of apoptotic process
    evidence_type: IMP
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IMP for positive regulation of apoptosis. The study shows FOXO1-ATG7-mediated
        autophagy
        leads to cell death in certain contexts.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "the acetylated FoxO1 bound to Atg7, an E1-like protein,
            to influence the autophagic process leading to cell death"
  - term:
      id: GO:0045732
      label: positive regulation of protein catabolic process
    evidence_type: IMP
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IMP for positive regulation of protein catabolism via autophagy.
      action: ACCEPT
      reason: >-
        Autophagy is a protein catabolic process and ATG7 is essential for it. This
        is a
        consequence of ATG7's core autophagy function.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: Cytosolic FoxO1 is essential for the induction of 
            autophagy and tumour suppressor activity.
  - term:
      id: GO:0071455
      label: cellular response to hyperoxia
    evidence_type: IDA
    original_reference_id: PMID:20543840
    review:
      summary: >-
        IDA for cellular response to hyperoxia (oxidative stress).
      action: ACCEPT
      reason: >-
        ATG7-dependent autophagy is induced by oxidative stress including hyperoxia.
        Consistent with PMID:37943659 showing oxidative stress activates ATG7.
      supported_by:
        - reference_id: PMID:20543840
          supporting_text: "Endogenous FoxO1 was required for autophagy in human cancer
            cell lines in response to oxidative stress"
  - term:
      id: GO:0006914
      label: autophagy
    evidence_type: IMP
    original_reference_id: PMID:24681637
    review:
      summary: >-
        IMP for autophagy from study of Atg7/Keap1-dependent autophagy in breast cancer
        cells
        under mitoquinone-induced oxidative stress.
      action: ACCEPT
      reason: >-
        Core function with direct experimental evidence.
      supported_by:
        - reference_id: PMID:24681637
          supporting_text: Atg7- and Keap1-dependent autophagy protects breast 
            cancer cell lines against mitoquinone-induced oxidative stress.
  - term:
      id: GO:0005930
      label: axoneme
    evidence_type: ISS
    original_reference_id: GO_REF:0000024
    review:
      summary: >-
        ISS based on mouse data. UniProt notes ATG7 localizes to discrete punctae
        along the
        ciliary axoneme.
      action: KEEP_AS_NON_CORE
      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.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5681980
    review:
      summary: >-
        TAS from Reactome for ATG12 binding ATG7 dimer in cytosol.
      action: ACCEPT
      reason: >-
        Core localization. Consistent with other cytosol annotations.
  - term:
      id: GO:0005829
      label: cytosol
    evidence_type: TAS
    original_reference_id: Reactome:R-HSA-5683593
    review:
      summary: >-
        TAS from Reactome for ATG7:ATG3:LC3 complex dissociation.
      action: ACCEPT
      reason: >-
        Core localization. Consistent with other cytosol annotations.
  - term:
      id: GO:0051607
      label: defense response to virus
    evidence_type: IMP
    original_reference_id: PMID:23290079
    review:
      summary: >-
        IMP for antiviral defense from study showing autophagy inhibits human papillomavirus
        infection in keratinocytes.
      action: KEEP_AS_NON_CORE
      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.
      supported_by:
        - reference_id: PMID:23290079
          supporting_text: Jan 4. Human papillomavirus infection is inhibited by
            host autophagy in primary human keratinocytes.
  - term:
      id: GO:0019778
      label: Atg12 activating enzyme activity
    evidence_type: ISS
    original_reference_id: PMID:20723759
    review:
      summary: >-
        ISS based on mouse data for ATG12 activating enzyme activity.
      action: ACCEPT
      reason: >-
        Core molecular function. Consistent with extensive experimental evidence.
      supported_by:
        - reference_id: PMID:20723759
          supporting_text: ATG12 conjugation to ATG3 regulates mitochondrial 
            homeostasis and cell death.
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11096062
    review:
      summary: >-
        IPI for ATG7 binding to ATG12, GABARAP, GATE-16, LC3. These are E1-substrate
        interactions in the conjugation systems.
      action: REMOVE
      reason: >-
        Uninformative. These are functional E1-substrate interactions better captured
        by
        the specific Atg8/Atg12 activating enzyme activity terms.
      supported_by:
        - reference_id: PMID:11096062
          supporting_text: "hApg7p is an authentic protein-activating enzyme for hApg12p
            and the three Apg8p homologs"
  - term:
      id: GO:0042803
      label: protein homodimerization activity
    evidence_type: IDA
    original_reference_id: PMID:11096062
    review:
      summary: >-
        IDA for protein homodimerization. ATG7 forms a functional homodimer required
        for
        trans-thioester transfer to E2 enzymes.
      action: ACCEPT
      reason: >-
        Core structural feature. ATG7 homodimerization is essential for its E1-like
        enzyme
        function, enabling trans-thioester transfer across protomers.
      supported_by:
        - reference_id: PMID:11096062
          supporting_text: "Cross-linking experiments and glycerol-gradient centrifugation
            analysis showed that the mammalian Apg7p homolog forms a homodimer as
            in yeast Apg7p"
  - term:
      id: GO:0005515
      label: protein binding
    evidence_type: IPI
    original_reference_id: PMID:11825910
    review:
      summary: >-
        IPI for ATG7-ATG3 interaction. This is a functional E1-E2 interaction in the
        LC3
        lipidation cascade.
      action: REMOVE
      reason: >-
        Uninformative. The ATG7-ATG3 E1-E2 interaction is functional and better captured
        by the Atg8 activating enzyme activity term.
      supported_by:
        - reference_id: PMID:11825910
          supporting_text: "Co-immunoprecipitation of hApg7p with hApg3p indicates
            that hApg3p forms an E1.E2 complex with hApg7p"
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with
      GO terms
    findings: []
  - 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:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 
      mapping
    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: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:11096062
    title: The human homolog of Saccharomyces cerevisiae Apg7p is a 
      Protein-activating enzyme for multiple substrates including human Apg12p, 
      GATE-16, GABARAP, and MAP-LC3.
    findings:
      - statement: ATG7 forms a homodimer
        supporting_text: "Cross-linking experiments and glycerol-gradient centrifugation
          analysis showed that the mammalian Apg7p homolog forms a homodimer as in
          yeast Apg7p"
      - statement: Cys572 is the active site cysteine essential for thioester 
          intermediate formation
        supporting_text: "Cys(572) of hApg7p is an authentic active site cysteine
          residue essential for the formation of the hApg7p.hApg12p intermediate"
      - statement: ATG7 is an E1-like enzyme for ATG12 and ATG8 family proteins
        supporting_text: "hApg7p is an authentic protein-activating enzyme for hApg12p
          and the three Apg8p homologs"
  - id: PMID:11825910
    title: Human Apg3p/Aut1p homologue is an authentic E2 enzyme for multiple 
      substrates, GATE-16, GABARAP, and MAP-LC3, and facilitates the conjugation
      of hApg12p to hApg5p.
    findings:
      - statement: ATG7 forms E1-E2 complex with ATG3
        supporting_text: "Co-immunoprecipitation of hApg7p with hApg3p indicates that
          hApg3p forms an E1.E2 complex with hApg7p"
  - id: PMID:12890687
    title: The mouse APG10 homologue, an E2-like enzyme for Apg12p conjugation, 
      facilitates MAP-LC3 modification.
    findings:
      - statement: ATG7 with ATG10 facilitates LC3 lipidation
        supporting_text: "the coexpression of Apg10p with Apg7p facilitates the modification
          of a soluble form of MAP-LC3 to a membrane-bound form"
  - id: PMID:16303767
    title: Phosphatidylserine in addition to phosphatidylethanolamine is an in 
      vitro target of the mammalian Atg8 modifiers, LC3, GABARAP, and GATE-16.
    findings:
      - statement: ATG7 forms thioester intermediate with ATG8 homologs
        supporting_text: "Each purified mutant Atg8 homolog with an exposed C-terminal
          Gly formed an E1-substrate intermediate with hAtg7 via a thioester bond"
  - id: PMID:18083104
    title: Homeostatic levels of p62 control cytoplasmic inclusion body 
      formation in autophagy-deficient mice.
    findings: []
  - id: PMID:18296641
    title: A role for the NAD-dependent deacetylase Sirt1 in the regulation of 
      autophagy.
    findings: []
  - id: PMID:19279012
    title: Loss of PINK1 function promotes mitophagy through effects on 
      oxidative stress and mitochondrial fission.
    findings:
      - statement: ATG7 knockdown decreases mitophagy
        supporting_text: "RNAi knockdown of autophagy proteins Atg7 and LC3/Atg8 also
          decreased mitochondrial fragmentation without affecting oxidative stress"
  - id: PMID:20195357
    title: A comprehensive resource of interacting protein regions for refining 
      human transcription factor networks.
    findings: []
  - id: PMID:20543840
    title: Cytosolic FoxO1 is essential for the induction of autophagy and 
      tumour suppressor activity.
    findings:
      - statement: Acetylated FOXO1 binds ATG7 to induce autophagy
        supporting_text: "the acetylated FoxO1 bound to Atg7, an E1-like protein,
          to influence the autophagic process"
      - statement: ATG7 required for autophagy under starvation and oxidative 
          stress
        supporting_text: "Endogenous FoxO1 was required for autophagy in human cancer
          cell lines in response to oxidative stress or serum starvation"
  - id: PMID:20562859
    title: Network organization of the human autophagy system.
    findings: []
  - id: PMID:20723759
    title: ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and 
      cell death.
    findings: []
  - id: PMID:21903422
    title: Mapping a dynamic innate immunity protein interaction network 
      regulating type I interferon production.
    findings: []
  - id: PMID:22170151
    title: The FAP motif within human ATG7, an autophagy-related E1-like enzyme,
      is essential for the E2-substrate reaction of LC3 lipidation.
    findings:
      - statement: FAP motif (F15-A16-P17) essential for ATG7-ATG3 interaction
        supporting_text: "the FAP motif of ATG7 is essential for the interaction of
          ATG7 with ATG3"
      - statement: FAP motif required for LC3 lipidation
        supporting_text: "ATG7 is an autophagy-related E1-like enzyme that is essential
          for two ubiquitination-like reactions, ATG12-conjugation and LC3-lipidation"
  - id: PMID:22354037
    title: Genome-wide siRNA screen reveals amino acid starvation-induced 
      autophagy requires SCOC and WAC.
    findings: []
  - id: PMID:23290079
    title: Human papillomavirus infection is inhibited by host autophagy in 
      primary human keratinocytes.
    findings: []
  - id: PMID:24186333
    title: Binding to E1 and E3 is mutually exclusive for the human autophagy E2
      Atg3.
    findings: []
  - id: PMID:24681637
    title: Atg7- and Keap1-dependent autophagy protects breast cancer cell lines
      against mitoquinone-induced oxidative stress.
    findings: []
  - id: PMID:25327288
    title: Selective VPS34 inhibitor blocks autophagy and uncovers a role for 
      NCOA4 in ferritin degradation and iron homeostasis in vivo.
    findings: []
  - id: PMID:26043688
    title: Identification and characterization of the linear region of ATG3 that
      interacts with ATG7 in higher eukaryotes.
    findings: []
  - id: PMID:28389568
    title: Hepatitis C virus triggers Golgi fragmentation and autophagy through 
      the immunity-related GTPase M.
    findings: []
  - id: PMID:28514442
    title: Architecture of the human interactome defines protein communities and
      disease networks.
    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:37252361
    title: Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical
      LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human 
      ATG3.
    findings: []
  - id: PMID:37943659
    title: ATM-CHK2-TRIM32 axis regulates ATG7 ubiquitination to initiate 
      autophagy under oxidative stress.
    findings:
      - statement: K63-linked ubiquitination of ATG7 at K45 by TRIM32
        supporting_text: "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."
      - statement: ATG7 ubiquitination promotes ATG8/ATG12 activating enzyme 
          activity
        supporting_text: "Oxidative stress-induced autophagy helps to prevent cellular
          damage and to maintain homeostasis"
      - statement: ATG7 localization at phagophore assembly site
        supporting_text: "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."
  - id: Reactome:R-HSA-5681980
    title: ATG12 binds ATG7 dimer
    findings: []
  - id: Reactome:R-HSA-5681981
    title: ATG3 transfers LC3 from ATG7 to ATG3
    findings: []
  - id: Reactome:R-HSA-5682011
    title: LC3 binds ATG7 dimer
    findings: []
  - id: Reactome:R-HSA-5682896
    title: LC3:ATG7 dimer binds ATG3
    findings: []
  - id: Reactome:R-HSA-5683593
    title: ATG7:ATG3:LC3 dissociates
    findings: []
  - id: Reactome:R-HSA-6798748
    title: Exocytosis of secretory granule lumen proteins
    findings: []
  - id: Reactome:R-HSA-6800434
    title: Exocytosis of ficolin-rich granule lumen proteins
    findings: []
  - id: Reactome:R-HSA-9020616
    title: ATG12 forms a thioester bond with ATG7 dimer
    findings: []
core_functions:
  - description: >-
      ATG7 is the E1-like activating enzyme for ATG12. It adenylates ATG12's C-terminal
      glycine,
      forms a thioester intermediate via Cys572, and transfers ATG12 to the E2 enzyme
      ATG10 for
      subsequent conjugation to ATG5.
    molecular_function:
      id: GO:0019778
      label: Atg12 activating enzyme activity
    directly_involved_in:
      - id: GO:0000045
        label: autophagosome assembly
    locations:
      - id: GO:0000407
        label: phagophore assembly site
      - id: GO:0005829
        label: cytosol
  - description: >-
      ATG7 is the E1-like activating enzyme for ATG8 family proteins (LC3, GABARAP,
      GATE-16).
      It adenylates the C-terminal glycine of processed ATG8 proteins, forms a thioester
      intermediate, and transfers ATG8 to the E2 enzyme ATG3 for lipidation with phosphatidylethanolamine.
    molecular_function:
      id: GO:0019779
      label: Atg8 activating enzyme activity
    directly_involved_in:
      - id: GO:0061739
        label: protein lipidation involved in autophagosome assembly
      - id: GO:0000045
        label: autophagosome assembly
    locations:
      - id: GO:0000407
        label: phagophore assembly site
      - id: GO:0005829
        label: cytosol
  - description: >-
      ATG7 forms a functional homodimer required for trans-thioester transfer of activated
      ubiquitin-like substrates (ATG12, ATG8) to their cognate E2 enzymes.
    molecular_function:
      id: GO:0042803
      label: protein homodimerization activity
    directly_involved_in:
      - id: GO:0000045
        label: autophagosome assembly
    locations:
      - id: GO:0005829
        label: cytosol