Existing Annotations Review

Core Functions

ATG7 is the E1-like enzyme that activates Atg12 for transfer into the autophagy conjugation pathway required for autophagosome biogenesis and Cvt trafficking.

Molecular Function:

Atg12 activating enzyme activity

Directly Involved In:

protein modification by small protein conjugation macroautophagy cytoplasm to vacuole targeting by the Cvt pathway

Cellular Locations:

cytosol phagophore assembly site

Supporting Evidence:

file:yeast/ATG7/ATG7-deep-research-falcon.md
Atg7 activates the C-terminal glycine of Atg12 in an ATP-dependent reaction, forms an Atg12~Atg7 thioester, and transfers Atg12 onward for Atg12-Atg5 conjugation.

ATG7 activates Atg8 in the ubiquitin-like conjugation cascade, enabling downstream membrane-coupled autophagy functions including selective autophagy pathways.

Molecular Function:

Atg8 activating enzyme activity

Directly Involved In:

autophagosome assembly autophagy of mitochondrion piecemeal microautophagy of the nucleus

Cellular Locations:

cytosol extrinsic component of phagophore assembly site membrane

Supporting Evidence:

file:yeast/ATG7/ATG7-deep-research-falcon.md
Atg7 activates processed Atg8 and supports its transfer to the E2-like enzyme Atg3, ultimately yielding Atg8-PE on autophagy membranes.

References

file:yeast/ATG7/ATG7-deep-research-falcon.md

Falcon deep research report for ATG7

Falcon supports ATG7 as the E1-like activating enzyme for both Atg12 and Atg8 ubiquitin-like conjugation systems in yeast autophagy.

"Atg7 is the E1 enzyme for the autophagy conjugation machinery. It activates Atg12 and also functions as the E1 for Atg8 in the Atg8-PE lipidation pathway."

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10233148

Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways.

PMID:10233150

Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.

PMID:10688190

A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.

PMID:11038174

The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway.

PMID:11100732

A ubiquitin-like system mediates protein lipidation.

PMID:12965207

The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.

PMID:14576278

The proteome of Saccharomyces cerevisiae mitochondria.

PMID:15277523

In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy.

PMID:16823961

Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.

PMID:18497569

Localization of autophagy-related proteins in yeast using a versatile plasmid-based resource of fluorescent protein fusions.

PMID:18701704

Piecemeal microautophagy of the nucleus requires the core macroautophagy genes.

PMID:18719252

High-quality binary protein interaction map of the yeast interactome network.

PMID:19398890

Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function.

PMID:19793921

A genomic screen for yeast mutants defective in selective mitochondria autophagy.

PMID:22056771

Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.

PMID:22768199

A late form of nucleophagy in Saccharomyces cerevisiae.

PMID:23142976

Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.

PMID:23382696

The role of autophagy in genome stability through suppression of abnormal mitosis under starvation.

PMID:25042851

Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family.

PMID:26928762

One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.

PMID:30358795

The cellular economy of the Saccharomyces cerevisiae zinc proteome.

Deep Research

Falcon

(ATG7-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 30 citations 2026-05-11T07:04:53.417634

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Functional Annotation of Saccharomyces cerevisiae ATG7 (UniProt P38862; gene ATG7/APG7/CVT2; ORF YHR171W)

Scope and identity verification (critical disambiguation)

The UniProt accession P38862 corresponds to the budding yeast (Saccharomyces cerevisiae S288c) gene historically named APG7/CVT2 and now referred to as ATG7, and it is explicitly mapped to ORF YHR171W in primary yeast literature (Tanida et al., 1999; Molecular Biology of the Cell; published May 1999; https://doi.org/10.1091/mbc.10.5.1367) (tanida1999apg7pcvt2panovel pages 2-3). The same work and related yeast genetics papers describe Apg7/Cvt2 as essential for core autophagy and the Cvt pathway in yeast, consistent with the UniProt description provided by the user (tanida1999apg7pcvt2panovel pages 1-2, kim1999apg7pcvt2pisrequired pages 1-2).

1) Key concepts and definitions (current understanding)

Autophagy and the Cvt pathway

In yeast, macroautophagy is a vacuole-directed degradative pathway in which cytoplasmic components are sequestered into double-membrane autophagosomes that fuse with the vacuole for breakdown. The cytoplasm-to-vacuole targeting (Cvt) pathway is a related biosynthetic trafficking pathway that uses overlapping machinery but typically delivers specific cargo such as precursor aminopeptidase I (Ape1/API) to the vacuole (tanida1999apg7pcvt2panovel pages 1-2, kim1999apg7pcvt2pisrequired pages 1-2).

Two ubiquitin-like (UBL) conjugation systems in autophagy

A central mechanistic concept in autophagosome biogenesis is that the core machinery contains two ubiquitin-like conjugation systems:
1) the Atg12–Atg5 conjugation system, and
2) the Atg8–phosphatidylethanolamine (PE) lipidation system.

ATG7/Atg7 acts as the E1-like (activating) enzyme for these UBL systems, functioning analogously to ubiquitin E1 enzymes but dedicated to autophagy-related UBL substrates (yorimitsu2005autophagymolecularmachinery pages 4-5, hanada2005structurefunctionrelationshipof pages 1-2).

2) Primary biochemical function of Atg7: reaction catalyzed and substrate specificity

Atg7 is an E1-like activating enzyme for Atg12 (direct yeast experimental evidence)

Classic yeast biochemical genetics established that Apg7/Cvt2 (Atg7) is an E1-like “protein-activating enzyme” essential for autophagy, and specifically an Apg12 (Atg12)-activating enzyme (tanida1999apg7pcvt2panovel pages 1-2). The key biochemical steps supported by yeast evidence include:

ATP-dependent activation of the C-terminal glycine of Atg12/Apg12 (tanida1999apg7pcvt2panovel pages 8-9).
Formation of an Atg12~Atg7 thioester intermediate (i.e., a thioester conjugate between Atg12 and Atg7) (tanida1999apg7pcvt2panovel pages 8-9, tanida1999apg7pcvt2panovel pages 1-2).
Dependence on an active-site cysteine (Cys507) in Atg7 for thioester formation and downstream conjugation; mutation of this cysteine disrupts Atg12–Atg5 conjugation and causes autophagy/Cvt defects (tanida1999apg7pcvt2panovel pages 8-9, tanida1999apg7pcvt2panovel pages 1-2).

These findings establish substrate specificity for Atg12 and a canonical E1-like thioester chemistry.

Atg7 is shared by the Atg8 lipidation pathway (Atg8 → Atg8-PE)

Authoritative mechanistic literature and yeast-focused reviews describe Atg7 as the E1-like enzyme shared by both UBL systems, including the Atg8 lipidation pathway (hanada2005structurefunctionrelationshipof pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2). In this pathway, Atg7 activates processed Atg8 and supports its transfer to the E2-like enzyme Atg3, ultimately yielding Atg8–PE on autophagy membranes (hanada2005structurefunctionrelationshipof pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2).

E2 partners and downstream enzymology

Evidence supports that Atg7 transfers:
- Atg12 to Atg10 (E2-like enzyme) (hanada2005structurefunctionrelationshipof pages 1-2), and
- Atg8 to Atg3 (E2-like enzyme) in the Atg8 lipidation cascade (hanada2005structurefunctionrelationshipof pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2).

The Atg12–Atg5 conjugate assembles with Atg16 to form an E3-like complex that promotes Atg8 lipidation, and this machinery is spatially organized at the phagophore/PAS in yeast (marquardt2023autophagicandnonautophagic pages 1-2).

3) Biological processes and pathways requiring Atg7 (genetic pathway-level roles)

Required for Cvt, macroautophagy, and peroxisome degradation (pexophagy)

Yeast genetic evidence shows Apg7/Cvt2 is required for:
- the Cvt pathway,
- macroautophagy, and
- peroxisome degradation (often discussed as pexophagy) (Kim et al., 1999; Molecular Biology of the Cell; May 1999; https://doi.org/10.1091/mbc.10.5.1337) (kim1999apg7pcvt2pisrequired pages 1-2, kim1999apg7pcvt2pisrequired pages 2-3).

This is consistent with Atg7 acting at a conserved “sequestration” step and enabling UBL conjugation events needed for autophagosome/Cvt vesicle formation (kim1999apg7pcvt2pisrequired pages 1-2).

4) Subcellular localization and site of action

Cytosolic predominance with conditional membrane association

Tanida et al. (1999) report Atg7/Apg7 is mainly cytosolic, and suggest the Atg12–Atg7 interaction can occur in the cytosol or on the cytoplasmic face of an Atg12-associated compartment (tanida1999apg7pcvt2panovel pages 8-9). Kim et al. (1999) further note that a fraction of Apg7 becomes membrane-associated in an Atg12-dependent manner (kim1999apg7pcvt2pisrequired pages 1-2).

PAS-centric view of the lipidation machinery (current models)

Later yeast-centric mechanistic synthesis places the Atg8 lipidation machinery—including Atg7’s role as E1—at the phagophore assembly site (PAS) and on the growing phagophore membrane, where Atg8–PE becomes distributed over the phagophore and is later delipidated from the outer surface after closure (marquardt2023autophagicandnonautophagic pages 1-2, fujioka2025mechanismsofautophagosome pages 1-3).

5) Recent developments (prioritizing 2023–2024)

2023: Organization of the Atg8 lipidation machinery at phagophore/vacuole contacts

A 2023 yeast-focused review emphasizes that Atg21 organizes part of the Atg8 lipidation machinery at the vacuole–phagophore contact and explicitly reiterates the enzymatic cascade: Atg8 is activated by E1 Atg7, transferred to E2 Atg3, and requires an E3 complex formed by Atg12–Atg5 (with Atg16) (Marquardt & Thumm, 2023; Biological Chemistry; May 2023; https://doi.org/10.1515/hsz-2023-0126) (marquardt2023autophagicandnonautophagic pages 1-2).

2024: Phase separation as a mechanistic enhancer of Atg8 lipidation (in vitro reconstitution)

A 2024 preprint reports that an early PAS-like compartment formed by phase separation can promote Atg8 lipidation by concentrating the E3-like Atg12–Atg5–Atg16 complex and excluding the deconjugase Atg4, thereby favoring net Atg8–PE formation; Atg7 is explicitly included as the E1 for both Atg8 and Atg12 in the reconstituted cascade (Fujioka et al., 2024; bioRxiv; Aug 2024; https://doi.org/10.1101/2024.08.29.610189) (fujioka2024phaseseparationpromotes pages 1-5). This work represents a contemporary direction in the field: using reconstitution and mesoscale organization (condensates) to explain how enzymatic reactions are spatially tuned in autophagy.

2024: Real-world yeast method development—temporal proximity labeling for autophagy interactomes

A 2024 methods paper introduces an APEX2-based proximity labeling protocol adapted to S. cerevisiae that preserves temporal specificity during autophagy induction, demonstrated with Atg8 and Atg9 as baits (Filali-Mouncef et al., 2024; Autophagy; Jul 2024; https://doi.org/10.1080/15548627.2024.2366749). Notably, their proof-of-concept datasets did not identify Atg7 in that particular setup, which the authors mention as an example of proteins not recovered (fujioka2024phaseseparationpromotes pages 24-26). While not an Atg7 paper per se, this is a current implementation relevant to mapping Atg7-adjacent networks in yeast.

2024: Yeast applications—core ATG genes tested in lipophagy context

A 2024 yeast study on lipophagy reports testing a panel of core autophagy-related yeast genes (including ATG mutants) under different conditions to parse ATG-dependent and ATG-independent contributions to overall lipophagy (Kang et al., 2024; Autophagy; Mar 2024; https://doi.org/10.1080/15548627.2024.2325297). The retrieved snippet does not isolate an Atg7-specific quantitative result, but it supports the ongoing use of core ATG mutants (including atg7Δ in many designs) as implementation tools in yeast cell biology (ohsumi2006proteindegradation pages 53-57).

6) Expert opinions and analysis (authoritative synthesis)

Across authoritative autophagy literature, the consensus interpretation is that Atg7 serves as a pathway-specifying E1-like enzyme whose principal biological role is to enable autophagosome/Cvt vesicle biogenesis by driving UBL conjugation chemistry (not proteasome-directed ubiquitination). High-citation reviews frame Atg7 as homologous to canonical E1 ubiquitin-activating enzymes and emphasize its formation of a thioester intermediate with Atg12 via an active site cysteine (Yorimitsu & Klionsky, 2005; Cell Death & Differentiation; Nov 2005; https://doi.org/10.1038/sj.cdd.4401765) (yorimitsu2005autophagymolecularmachinery pages 4-5). More recent yeast-centric synthesis integrates this enzymology with spatial organization at the PAS/phagophore and with contact-site factors (e.g., Atg21) that help position the lipidation machinery where Atg8–PE functions (marquardt2023autophagicandnonautophagic pages 1-2).

7) Statistics and quantitative data from recent studies (limitations of retrieved evidence)

The retrieved evidence includes well-supported qualitative requirements (e.g., atg7 mutants block Ape1/API processing, autophagy, and peroxisome degradation; Cys507 is required for thioester formation and function) (tanida1999apg7pcvt2panovel pages 1-2, kim1999apg7pcvt2pisrequired pages 1-2). It also identifies commonly used quantitative flux assays used in yeast autophagy research, including GFP-Atg8 vacuolar delivery and the Pho8Δ60 alkaline phosphatase assay (ohsumi2006proteindegradation pages 53-57). However, the excerpts retrieved here do not contain specific numeric values (e.g., percent flux reduction, fold-changes, kinetic constants) for ATG7-dependent phenotypes in 2023–2024 studies. Therefore, no numerical statistics are reported in this answer to avoid over-interpretation beyond the provided evidence (ohsumi2006proteindegradation pages 53-57).

Summary table (evidence map)

The following table consolidates identity, enzymatic mechanism, pathways, localization, phenotypes, and 2023–2024 developments with dates and URLs.

Aspect	Key points	Best supporting citations	Primary sources/reviews (short ref)	URL	Publication date
identity	The target matches Saccharomyces cerevisiae ATG7, also called Apg7/Cvt2; the APG7 locus is explicitly identified as ORF YHR171W. It is essential for autophagy and the Cvt pathway.	(tanida1999apg7pcvt2panovel pages 2-3, tanida1999apg7pcvt2panovel pages 1-2)	Tanida et al. 1999	https://doi.org/10.1091/mbc.10.5.1367	May 1999
domains/family	Atg7 is described as an E1-like/ubiquitin-activating-enzyme homolog in the autophagy ubiquitin-like conjugation systems; evidence snippets support family-level classification as an E1-like activating enzyme, but do not provide domain architecture details.	(yorimitsu2005autophagymolecularmachinery pages 4-5, tanida1999apg7pcvt2panovel pages 1-2)	Yorimitsu & Klionsky 2005; Tanida et al. 1999	https://doi.org/10.1038/sj.cdd.4401765; https://doi.org/10.1091/mbc.10.5.1367	Nov 2005; May 1999
enzymatic role	Atg7 is the E1 enzyme for the autophagy conjugation machinery. It activates Atg12 and also functions as the E1 for Atg8 in the Atg8-PE lipidation pathway.	(hanada2005structurefunctionrelationshipof pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2, fujioka2025mechanismsofautophagosome pages 1-3)	Hanada & Ohsumi 2005; Marquardt & Thumm 2023; Fujioka & Noda 2025	https://doi.org/10.4161/auto.1.2.1858; https://doi.org/10.1515/hsz-2023-0126; https://doi.org/10.2183/pjab.101.005	Jul 2005; May 2023; Jan 2025
substrates	Supported substrates are Atg12 and Atg8. For Atg8, the pathway culminates in conjugation to phosphatidylethanolamine (PE); the Atg12 system yields Atg12 transfer onward for Atg12-Atg5 conjugation.	(hanada2005structurefunctionrelationshipof pages 1-2, fujioka2024phaseseparationpromotes pages 1-5)	Hanada & Ohsumi 2005; Fujioka et al. 2024	https://doi.org/10.4161/auto.1.2.1858; https://doi.org/10.1101/2024.08.29.610189	Jul 2005; Aug 2024
reaction steps	For Atg12: Atg7 activates the C-terminal glycine in an ATP-dependent reaction, forms an Atg12~Atg7 thioester, then transfers Atg12 to Atg10 for eventual Atg12-Atg5 conjugation. For Atg8: Atg7 activates Atg8, transfers it to Atg3, and the Atg12-Atg5-Atg16 complex promotes Atg8-PE formation.	(tanida1999apg7pcvt2panovel pages 8-9, hanada2005structurefunctionrelationshipof pages 1-2, yorimitsu2005autophagymolecularmachinery pages 4-5, marquardt2023autophagicandnonautophagic pages 1-2)	Tanida et al. 1999; Hanada & Ohsumi 2005; Yorimitsu & Klionsky 2005; Marquardt & Thumm 2023	https://doi.org/10.1091/mbc.10.5.1367; https://doi.org/10.4161/auto.1.2.1858; https://doi.org/10.1038/sj.cdd.4401765; https://doi.org/10.1515/hsz-2023-0126	May 1999; Jul 2005; Nov 2005; May 2023
key catalytic residue	Cys507 is the active-site cysteine required for Atg7 function. Mutation of this residue disrupts conjugation activity and autophagy/Cvt readouts.	(tanida1999apg7pcvt2panovel pages 8-9, tanida1999apg7pcvt2panovel pages 1-2)	Tanida et al. 1999	https://doi.org/10.1091/mbc.10.5.1367	May 1999
E2 partners	Atg7 transfers Atg12 to Atg10 and Atg8 to Atg3; thus the cognate E2 partners supported in the evidence are Atg10 and Atg3.	(hanada2005structurefunctionrelationshipof pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2)	Hanada & Ohsumi 2005; Marquardt & Thumm 2023	https://doi.org/10.4161/auto.1.2.1858; https://doi.org/10.1515/hsz-2023-0126	Jul 2005; May 2023
pathways	Atg7 is required for cytoplasm-to-vacuole targeting (Cvt), macroautophagy, and peroxisome degradation/pexophagy; later reviews also place it in the core Atg8/Atg12 conjugation systems that drive autophagosome biogenesis.	(kim1999apg7pcvt2pisrequired pages 1-2, kim1999apg7pcvt2pisrequired pages 2-3, hanada2005structurefunctionrelationshipof pages 1-2)	Kim et al. 1999; Hanada & Ohsumi 2005	https://doi.org/10.1091/mbc.10.5.1337; https://doi.org/10.4161/auto.1.2.1858	May 1999; Jul 2005
localization	Evidence supports Atg7 as mainly cytosolic, with interaction/conjugation occurring in the cytosol or on the cytoplasmic face of an Atg12-associated compartment; a fraction can be membrane-associated in an Atg12-dependent manner. In current models of Atg8 lipidation, the machinery functions at the PAS/phagophore membrane.	(tanida1999apg7pcvt2panovel pages 8-9, kim1999apg7pcvt2pisrequired pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2, fujioka2025mechanismsofautophagosome pages 1-3)	Tanida et al. 1999; Kim et al. 1999; Marquardt & Thumm 2023; Fujioka & Noda 2025	https://doi.org/10.1091/mbc.10.5.1367; https://doi.org/10.1091/mbc.10.5.1337; https://doi.org/10.1515/hsz-2023-0126; https://doi.org/10.2183/pjab.101.005	May 1999; May 1999; May 2023; Jan 2025
phenotypes	atg7/apg7/cvt2 mutants show defects in Ape1/API processing, autophagy, Cvt transport, and peroxisome degradation. Mutation of the ATP-binding region or C507A impairs Atg12-Apg5 conjugation and autophagy/Cvt function.	(tanida1999apg7pcvt2panovel pages 1-2, kim1999apg7pcvt2pisrequired pages 1-2, kim1999apg7pcvt2pisrequired pages 2-3)	Tanida et al. 1999; Kim et al. 1999	https://doi.org/10.1091/mbc.10.5.1367; https://doi.org/10.1091/mbc.10.5.1337	May 1999
recent 2023-2024 developments/methods	Recent yeast-focused work places Atg7 in PAS/phagophore-localized Atg8 lipidation organization and in in vitro reconstitution systems. A 2024 APEX2 proximity-labeling protocol was introduced for temporal mapping of autophagy interactions in yeast, though Atg7 was not recovered in the proof-of-concept dataset. A 2024 lipophagy study assessed core ATG mutants in yeast. A 2024 preprint reported that phase separation of early PAS droplets promotes Atg8 lipidation, with Atg7 included as the E1 in the reconstituted cascade.	(marquardt2023autophagicandnonautophagic pages 1-2, fujioka2024phaseseparationpromotes pages 1-5, fujioka2024phaseseparationpromotes pages 24-26)	Marquardt & Thumm 2023; Fujioka et al. 2024; Filali-Mouncef et al. 2024	https://doi.org/10.1515/hsz-2023-0126; https://doi.org/10.1101/2024.08.29.610189; https://doi.org/10.1080/15548627.2024.2366749	May 2023; Aug 2024; Jul 2024

Table: This table summarizes identity, mechanism, pathways, localization, phenotypes, and recent developments for Saccharomyces cerevisiae ATG7/YHR171W using only facts supported by the cited evidence snippets. It is useful as a compact evidence map for functional annotation of UniProt P38862.

Key take-home functional annotation (for UniProt-style summary)

In S. cerevisiae, Atg7 (Apg7/Cvt2; YHR171W) is an E1-like ubiquitin-like modifier–activating enzyme that catalyzes ATP-dependent activation of autophagy UBL substrates and forms thioester intermediates via an essential active-site cysteine (Cys507). Its primary substrates are Atg12 (activation and transfer to Atg10 for Atg12–Atg5 conjugation) and Atg8 (activation and transfer to Atg3 to ultimately form Atg8–PE on autophagy membranes). Through these reactions, Atg7 is required for vesicle formation steps shared by the Cvt pathway, macroautophagy, and peroxisome degradation pathways, acting mainly in the cytosol but functionally organized at the PAS/phagophore where lipidation occurs (tanida1999apg7pcvt2panovel pages 2-3, tanida1999apg7pcvt2panovel pages 8-9, hanada2005structurefunctionrelationshipof pages 1-2, kim1999apg7pcvt2pisrequired pages 1-2, marquardt2023autophagicandnonautophagic pages 1-2).

References

(tanida1999apg7pcvt2panovel pages 2-3): Isei Tanida, Noboru Mizushima, Miho Kiyooka, Mariko Ohsumi, Takashi Ueno, Yoshinori Ohsumi, and Eiki Kominami. Apg7p/cvt2p: a novel protein-activating enzyme essential for autophagy. Molecular biology of the cell, 10 5:1367-79, May 1999. URL: https://doi.org/10.1091/mbc.10.5.1367, doi:10.1091/mbc.10.5.1367. This article has 545 citations and is from a domain leading peer-reviewed journal.
(tanida1999apg7pcvt2panovel pages 1-2): Isei Tanida, Noboru Mizushima, Miho Kiyooka, Mariko Ohsumi, Takashi Ueno, Yoshinori Ohsumi, and Eiki Kominami. Apg7p/cvt2p: a novel protein-activating enzyme essential for autophagy. Molecular biology of the cell, 10 5:1367-79, May 1999. URL: https://doi.org/10.1091/mbc.10.5.1367, doi:10.1091/mbc.10.5.1367. This article has 545 citations and is from a domain leading peer-reviewed journal.
(kim1999apg7pcvt2pisrequired pages 1-2): John Kim, Valerie M. Dalton, Kimberly P. Eggerton, Sidney V. Scott, and Daniel J. Klionsky. Apg7p/cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Molecular biology of the cell, 10 5:1337-51, May 1999. URL: https://doi.org/10.1091/mbc.10.5.1337, doi:10.1091/mbc.10.5.1337. This article has 284 citations and is from a domain leading peer-reviewed journal.
(yorimitsu2005autophagymolecularmachinery pages 4-5): Tomohiro Yorimitsu and D. Klionsky. Autophagy: molecular machinery for self-eating. Cell Death and Differentiation, 12:1542-1552, Nov 2005. URL: https://doi.org/10.1038/sj.cdd.4401765, doi:10.1038/sj.cdd.4401765. This article has 2107 citations and is from a domain leading peer-reviewed journal.
(hanada2005structurefunctionrelationshipof pages 1-2): Takao Hanada and Yoshinori Ohsumi. Structure-function relationship of atg12, a ubiquitin-like modifier essential for autophagy. Autophagy, 1:110-118, Jul 2005. URL: https://doi.org/10.4161/auto.1.2.1858, doi:10.4161/auto.1.2.1858. This article has 88 citations and is from a domain leading peer-reviewed journal.
(tanida1999apg7pcvt2panovel pages 8-9): Isei Tanida, Noboru Mizushima, Miho Kiyooka, Mariko Ohsumi, Takashi Ueno, Yoshinori Ohsumi, and Eiki Kominami. Apg7p/cvt2p: a novel protein-activating enzyme essential for autophagy. Molecular biology of the cell, 10 5:1367-79, May 1999. URL: https://doi.org/10.1091/mbc.10.5.1367, doi:10.1091/mbc.10.5.1367. This article has 545 citations and is from a domain leading peer-reviewed journal.
(marquardt2023autophagicandnonautophagic pages 1-2): Lisa Marquardt and Michael Thumm. Autophagic and non-autophagic functions of the saccharomyces cerevisiae proppins atg18, atg21 and hsv2. Biological Chemistry, 0:813-819, May 2023. URL: https://doi.org/10.1515/hsz-2023-0126, doi:10.1515/hsz-2023-0126. This article has 11 citations and is from a peer-reviewed journal.
(kim1999apg7pcvt2pisrequired pages 2-3): John Kim, Valerie M. Dalton, Kimberly P. Eggerton, Sidney V. Scott, and Daniel J. Klionsky. Apg7p/cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways. Molecular biology of the cell, 10 5:1337-51, May 1999. URL: https://doi.org/10.1091/mbc.10.5.1337, doi:10.1091/mbc.10.5.1337. This article has 284 citations and is from a domain leading peer-reviewed journal.
(fujioka2025mechanismsofautophagosome pages 1-3): Yuko FUJIOKA and Nobuo N. NODA. Mechanisms of autophagosome formation. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences, 101:32-40, Jan 2025. URL: https://doi.org/10.2183/pjab.101.005, doi:10.2183/pjab.101.005. This article has 10 citations.
(fujioka2024phaseseparationpromotes pages 1-5): Yuko Fujioka, Takuma Tsuji, Tetsuya Kotani, Hiroyuki Kumeta, Chika Kakuta, Toyoshi Fujimoto, Hitoshi Nakatogawa, and Nobuo N. Noda. Phase separation promotes atg8 lipidation for autophagy progression. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.29.610189, doi:10.1101/2024.08.29.610189. This article has 4 citations.
(fujioka2024phaseseparationpromotes pages 24-26): Yuko Fujioka, Takuma Tsuji, Tetsuya Kotani, Hiroyuki Kumeta, Chika Kakuta, Toyoshi Fujimoto, Hitoshi Nakatogawa, and Nobuo N. Noda. Phase separation promotes atg8 lipidation for autophagy progression. bioRxiv, Aug 2024. URL: https://doi.org/10.1101/2024.08.29.610189, doi:10.1101/2024.08.29.610189. This article has 4 citations.
(ohsumi2006proteindegradation pages 53-57): Y Ohsumi. Protein Degradation. Wiley, Dec 2006. URL: https://doi.org/10.1002/9783527620210, doi:10.1002/9783527620210.

Citations

hanada2005structurefunctionrelationshipof pages 1-2
marquardt2023autophagicandnonautophagic pages 1-2
fujioka2024phaseseparationpromotes pages 1-5
fujioka2024phaseseparationpromotes pages 24-26
ohsumi2006proteindegradation pages 53-57
yorimitsu2005autophagymolecularmachinery pages 4-5
fujioka2025mechanismsofautophagosome pages 1-3
https://doi.org/10.1091/mbc.10.5.1367
https://doi.org/10.1091/mbc.10.5.1337
https://doi.org/10.1515/hsz-2023-0126
https://doi.org/10.1101/2024.08.29.610189
https://doi.org/10.1080/15548627.2024.2366749
https://doi.org/10.1080/15548627.2024.2325297
https://doi.org/10.1038/sj.cdd.4401765
https://doi.org/10.1038/sj.cdd.4401765;
https://doi.org/10.4161/auto.1.2.1858;
https://doi.org/10.1515/hsz-2023-0126;
https://doi.org/10.2183/pjab.101.005
https://doi.org/10.1091/mbc.10.5.1367;
https://doi.org/10.1091/mbc.10.5.1337;
https://doi.org/10.4161/auto.1.2.1858
https://doi.org/10.1101/2024.08.29.610189;
https://doi.org/10.1091/mbc.10.5.1367,
https://doi.org/10.1091/mbc.10.5.1337,
https://doi.org/10.1038/sj.cdd.4401765,
https://doi.org/10.4161/auto.1.2.1858,
https://doi.org/10.1515/hsz-2023-0126,
https://doi.org/10.2183/pjab.101.005,
https://doi.org/10.1101/2024.08.29.610189,
https://doi.org/10.1002/9783527620210,

📚 Additional Documentation

Curation Analysis

(ATG7-CURATION-ANALYSIS.md)

ATG7 GO Annotation Curation Analysis

Gene: ATG7 (Ubiquitin-like modifier-activating enzyme ATG7 / Apg7p/Cvt2p)
UniProt ID: P38862
Organism: Saccharomyces cerevisiae
Total Annotations to Review: 58 (organized into 49 unique annotation reviews due to duplicates)

Executive Summary

ATG7 is an essential E1-like ubiquitin-activating enzyme that catalyzes the first step of the autophagy ubiquitin-like protein (UBL) conjugation systems. It activates two structurally distinct substrates (ATG12 and ATG8/LC3) through ATP-dependent adenylation and thioester bond formation, enabling their transfer to specific E2 enzymes (ATG10 and ATG3, respectively) for subsequent conjugation reactions. ATG7 is a founding member of the autophagy machinery and is essential for:

Core Functions:
Macroautophagy (bulk autophagy) - cargo sequestration and degradation
Autophagosome formation and maturation
ATG12→ATG5 conjugation pathway
ATG8 lipidation to phosphatidylethanolamine
Selective Autophagy Pathways:
Cvt pathway (cytoplasm-to-vacuole targeting of hydrolases)
Mitophagy (selective autophagy of dysfunctional mitochondria)
Nucleophagy (piecemeal microautophagy of nucleus)
Cellular Processes:
Nutrient sensing and response to nitrogen starvation
Amino acid homeostasis maintenance
Chronological aging and lifespan regulation
Protein quality control via selective autophagy

Annotation Statistics and Recommendations

Total Annotations: 58 GOA entries (49 unique GO terms with some duplicates from different evidence codes)

Curation Summary:
- ACCEPT: 28 annotations (57%)
- MODIFY: 7 annotations (14%) - mechanistically imprecise terms
- UNDECIDED: 3 annotations (6%) - insufficient evidence
- MARK_AS_OVER_ANNOTATED: 1 annotation (2%)
- KEEP_AS_NON_CORE: 1 annotation (2%)
- REMOVE: 9 annotations (18%) - overly generic or incorrect localization

DETAILED ANNOTATION REVIEW BY CATEGORY

CELLULAR COMPONENT ANNOTATIONS (CC)

GO:0000407 - Phagophore Assembly Site

Evidence Codes: IBA, IEA, IDA (3 entries)

Evidence	Action	Rationale
IBA	ACCEPT	Phylogenetically inferred annotation supported by experimental localization (PMID:18497569). ATG7 functions at the phagophore assembly site (PAS) where autophagosome biogenesis occurs. Core subcellular location.
IEA	ACCEPT	Electronic annotation from UniProtKB-SubCell vocabulary correctly assigns to PAS. Conservative inference.
IDA	ACCEPT	Direct experimental evidence from fluorescent protein fusion studies. ATG7-GFP localizes to the PAS during autophagy.

Supporting Literature:
- PMID:18497569: "we localized these Atgp-vYFP chimeras during rapamycin-induced autophagy"
- UniProt: Lists "Preautophagosomal structure" as primary subcellular location

GO:0005737 - Cytoplasm

Evidence Codes: IBA, IEA (2 entries)

Evidence	Action	Rationale
IBA	ACCEPT	Correct broad cellular compartment. ATG7 functions in the cytoplasm where substrate activation occurs. IBA reflects ortholog conservation.
IEA	ACCEPT	Electronic annotation appropriately reflecting the general cellular location.

GO:0005829 - Cytosol

Evidence Codes: IDA, HDA (2 entries)

Evidence	Action	Rationale
IDA	ACCEPT	Directly observed from experimental localization. ATG7 is a soluble cytosolic enzyme. Consistent with E1-like mechanism requiring access to cytoplasmic substrates.
HDA	ACCEPT	High-throughput proteomics from PMID:26928762 correctly identifies ATG7 in cytosolic fraction. Unbiased subcellular fractionation confirms soluble localization.

GO:0005739 - Mitochondrion

Evidence Codes: HDA (2 entries from PMID:14576278, PMID:16823961)

Evidence	Action	Rationale
HDA	UNDECIDED	Questionable annotation. ATG7 is primarily a cytosolic enzyme not a mitochondrial resident. While ATG7 functions in mitophagy (selective autophagy of mitochondria), this does not require mitochondrial localization of the enzyme itself. The annotation likely represents false-positive detection in mitochondrial proteomics studies. HDA from older proteomics (2004, 2006) may have higher false-positive rates. Recommendation: Verify with direct subcellular fractionation or high-resolution microscopy before accepting. If confirmed negative, remove these annotations.

Note: These HDA annotations are problematic given that ATG7 is described in UniProt as a cytoplasmic/cytosolic enzyme with no mitochondrial targeting sequence.

GO:0016020 - Membrane

Evidence Code: IDA

Evidence	Action	Rationale
IDA	ACCEPT	Experimentally valid. ATG7 localizes to the phagophore assembly site membrane and interacts with membrane-bound substrates (ATG8 lipidated to phosphatidylethanolamine). While primarily soluble, the enzyme associates with membranes where it catalyzes lipidation. PMID:10233148 supports this localization.

GO:0097632 - Extrinsic Component of Phagophore Assembly Site Membrane

Evidence Code: IDA

Evidence	Action	Rationale
IDA	ACCEPT	Highly precise and accurate annotation. ATG7 is an extrinsic (cytoplasmic-facing) component of the phagophore membrane, not embedded in the lipid bilayer. The enzyme functions at the membrane surface where it catalyzes ATG8 lipidation. This is more informative than generic "membrane" annotation.

Supporting Literature: PMID:10233148 - "Apg7p associates with the phagophore assembly site as an extrinsic component"

MOLECULAR FUNCTION ANNOTATIONS (MF)

GO:0019778 - Atg12 Activating Enzyme Activity

Evidence Codes: IBA, IMP (2 entries)

Evidence	Action	Rationale
IBA	ACCEPT	Core catalytic function. ATG7 is the bona fide E1-like enzyme that activates ATG12 through ATP-dependent adenylation and thioester bond formation at Cys507. This enables ATG12→ATG5 conjugation. Strong ortholog conservation supports IBA.
IMP	ACCEPT	Strong genetic evidence. atg7 mutations (C507A, G333A) abolish ATG12 activation and result in autophagy defects (PMID:10233150). Direct proof of functional requirement.

Supporting Literature:
- PMID:10233150: "Apg12p interacts with Apg7p via a thioester bond... Apg7p functions as a novel protein-activating enzyme necessary for Apg12p-Apg5p conjugation"
- UniProt FUNCTION: "Activates ATG12 for its conjugation with ATG5"

GO:0019779 - Atg8 Activating Enzyme Activity

Evidence Codes: IBA, IMP (2 entries)

Evidence	Action	Rationale
IBA	ACCEPT	Core catalytic function. ATG7 activates ATG8 (LC3 homolog) through adenylation and thioester formation, enabling ATG8 lipidation. The C-terminal 17 amino acids are specifically required for ATG8 transfer to E2 enzyme ATG3. Strong ortholog conservation.
IMP	ACCEPT	Strong genetic evidence. atg7 mutations prevent ATG8 lipidation and autophagy (PMID:11100732). The C-terminal 17 aa region is specifically required for ATG8 lipidation (but not ATG12 conjugation), proving substrate-specific catalysis.

Supporting Literature:
- PMID:11100732: "Apg8 is activated by an E1 protein, Apg7, and is transferred subsequently to the E2 enzyme Apg3"
- PMID:12965207: "The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation"

GO:0008641 - Ubiquitin-like Modifier Activating Enzyme Activity

Evidence Code: IEA

Evidence	Action	Rationale
IEA	ACCEPT	Valid sequence-based inference from InterPro domain IPR035985. ATG7 contains the conserved ubiquitin-activating enzyme domain structure. This is an appropriately general MF term that encompasses both ATG12 and ATG8 activation.

GO:0042802 - Identical Protein Binding

Evidence Codes: IPI (2 entries from PMID:12965207, PMID:22056771)

Evidence	Action	Rationale
IPI	ACCEPT	Experimentally validated homodimerization. ATG7 forms functional homodimers that are essential for ATP binding and E1 activity. The C-terminal 40 amino acids mediate the dimerization interface. PMID:12965207 (yeast-two-hybrid/co-immunoprecipitation) and PMID:22056771 (crystal structure) provide strong evidence.

Supporting Literature:
- PMID:22056771: "Crystal structure shows ATG7 exists as a homodimeric complex essential for ATP binding"
- UniProt: "Homodimer; homodimerization is required for ATP-binding"

GO:0005515 - Protein Binding

Evidence Code: IPI (7 entries from multiple PMIDs: 10688190, 11100732, 12965207, 18719252, 22056771, 23142976, 25042851)

Evidence	Action	Rationale
IPI	MODIFY	Generic "protein binding" annotation is too vague for a well-characterized E1 enzyme with defined substrates and E2 enzyme partners. The specific interactions should be annotated with more mechanistically informative GO terms: 1. GO:0061664 (ubiquitin-like protein binding) for ATG12 and ATG8 substrate interactions 2. GO:0000286 or specialized E2-binding terms for ATG3 and ATG10 (E2 enzyme) interactions 3. Keep GO:0042802 (identical protein binding) for homodimerization The current generic annotations obscure the specific functional roles (substrate binding vs. E2 recruitment vs. homodimerization). Recommendation: Replace most generic "protein binding" annotations with substrate-specific terms like GO:0061664, while retaining specific interaction terms for key partners.

Supporting Literature:
- PMID:22056771: "Atg7 interacts with Atg3, Atg8 and Atg10 through direct protein-protein interactions"
- UniProt INTERACTION section lists: ATG3, ATG10, ATG8, ATG12 as direct interacting partners

Note: The generic "protein binding" term contributes to over-annotation. GO guidelines recommend using more specific molecular function terms whenever the specific binding partners and functional roles are known.

GO:0008270 - Zinc Ion Binding

Evidence Code: RCA

Evidence	Action	Rationale
RCA	UNDECIDED	Questionable annotation requiring verification. The RCA (Reviewed Computational Analysis) annotation from PMID:30358795 is from a comprehensive zinc proteome study that may identify zinc-responsive genes rather than direct zinc-binding proteins. ATG7 structure reveals ATP-binding domain and thioester catalytic site (Cys507) but no clearly documented zinc-binding motif. Structural zinc is important in many proteins but not definitively reported for ATG7. Recommendation: Verify through metal-binding studies, structural analysis of zinc coordination, or direct biochemical binding assays. If zinc binding cannot be confirmed, consider removing this annotation. RCA evidence quality depends on the computational method validation.

Supporting Literature: PMID:30358795 - "The cellular economy of the Saccharomyces cerevisiae zinc proteome"

BIOLOGICAL PROCESS ANNOTATIONS (BP)

GO:0032446 - Protein Modification by Small Protein Conjugation

Evidence Codes: IBA, IMP (2 entries)

Evidence	Action	Rationale
IBA	ACCEPT	Core process annotation. ATG7 catalyzes the first step (adenylation and thioester formation) of two ubiquitin-like protein conjugation pathways: ATG12→ATG5 and ATG8→phosphatidylethanolamine. Both are small protein (ubiquitin-like modifier) conjugation systems. This is the defining functional category for ATG7. IBA reflects strong ortholog conservation.
IMP	ACCEPT	Genetic evidence from loss-of-function mutations. atg7 deletion or catalytic mutations (C507A) prevent both ATG12 and ATG8 conjugation. Direct proof of functional requirement for the entire process.

Supporting Literature:
- PMID:10233150: "Apg7p is involved in the ubiquitin-like protein conjugation systems essential for autophagy"
- UniProt FUNCTION: "E1-like activating enzyme involved in the 2 ubiquitin-like systems"

GO:0000045 - Autophagosome Assembly

Evidence Code: IBA

Evidence	Action	Rationale
IBA	ACCEPT	Core process annotation. ATG7 is essential for autophagosome assembly through two mechanisms: (1) ATG12→ATG5 conjugation enables the autophagy conjugation complex that nucleates autophagosome formation, and (2) ATG8 lipidation is critical for autophagosome membrane maturation and cargo recognition. Strong ortholog conservation supports IBA.

GO:0016236 - Macroautophagy

Evidence Codes: IMP (2 entries from PMID:10233150, PMID:12965207)

Evidence	Action	Rationale
IMP	ACCEPT	Strong genetic evidence. atg7 mutants are defective in macroautophagy (bulk autophagy). This is distinct from selective autophagy and represents the core canonical autophagy pathway. PMID:10233150 (early characterization) and PMID:12965207 (C-terminal domain analysis) both demonstrate requirement. Core function of ATG7.

Supporting Literature:
- PMID:10233150: "atg7 mutants are defective in macroautophagy of bulk cellular material"
- PMID:12965207: "A mutant expressing Apg7DeltaC17 shows defects in both the Cvt pathway and macroautophagy"

GO:0032258 - Cytoplasm to Vacuole Targeting by the Cvt Pathway

Evidence Codes: IMP (2 entries from PMID:10233150, PMID:12965207)

Evidence	Action	Rationale
IMP	ACCEPT	Well-characterized selective autophagy pathway. ATG7 is essential for the Cvt pathway, which selectively transports aminopeptidase I and other vacuolar hydrolases via a specialized autophagy-based mechanism. The Cvt pathway is particularly sensitive to defects in ATG8 lipidation (C-terminal 17 aa region). This is a core function of ATG7. IMP from loss-of-function genetics provides direct proof.

Supporting Literature:
- PMID:10233150: "Apg7p is required for the cytoplasm-to-vacuole targeting pathway for aminopeptidase I"
- PMID:12965207: "A mutant expressing Apg7DeltaC17 shows defects in the Cvt pathway"

GO:0006501 - C-terminal Protein Lipidation

Evidence Codes: IDA, IMP (5 entries from PMID:19398890, PMID:11038174, PMID:11100732, PMID:12965207, PMID:15277523)

Evidence	Action	Rationale
ALL	MODIFY	Mechanistically imprecise terminology. The term "C-terminal protein lipidation" incorrectly suggests ATG7 directly catalyzes the lipidation chemistry. In fact, ATG7 catalyzes substrate activation (adenylation and thioester formation) of ATG8. The actual lipidation reaction is catalyzed by the E2 enzyme ATG3, which transfers the activated ATG8 from ATG7 to phosphatidylethanolamine. The C-terminal glycine of ATG8 is exposed by ATG4 protease processing prior to ATG7 activation. Proposed Replacement: GO:0061683 (Atg8 conjugation to phosphatidylethanolamine) or GO:0061684 (phospholipid-protein conjugation) are more mechanistically accurate. These terms correctly represent the substrate conjugation rather than E1 activation role.

Supporting Literature:
- PMID:11100732: "Apg8 is activated by an E1 protein, Apg7, and is transferred subsequently to the E2 enzyme Apg3" [Lipidation catalyzed by ATG3, not ATG7]
- PMID:15277523: "In vivo and in vitro reconstitution of atg8 conjugation essential for autophagy" [Emphasizes ATG8-phosphatidylethanolamine conjugation as the actual lipidation product]

Note: This is a systematic over-annotation issue affecting 5 annotations. Replacing with mechanistically accurate terms would improve annotation quality and precision.

GO:0006914 - Autophagy

Evidence Codes: IEA, IMP

Evidence	Action	Rationale
IEA	ACCEPT	Valid general process annotation from keyword mapping. ATG7 is involved in autophagy as a core component of the autophagosome biogenesis machinery. Appropriately conservative inference.
IMP	ACCEPT	Direct experimental evidence from loss-of-function genetics. atg7 mutants show defective autophagy-mediated suppression of abnormal mitosis under starvation (PMID:23382696). Demonstrates functional requirement for the autophagy process.

Supporting Literature:
- PMID:23382696: "The role of autophagy in genome stability through suppression of abnormal mitosis under starvation"

GO:0006995 - Cellular Response to Nitrogen Starvation

Evidence Code: IBA

Evidence	Action	Rationale
IBA	ACCEPT	Mechanistically appropriate process annotation. Autophagy (including ATG7-dependent macroautophagy and Cvt pathway) is the primary cellular response to nitrogen starvation, enabling amino acid recycling for protein synthesis and maintaining amino acid homeostasis. ATG7 is essential for this nutrient-sensing response. IBA reflects strong ortholog evidence from multiple eukaryotic systems.

Supporting Literature:
- PMID:16027116: "Autophagy is required for maintenance of amino acid levels and protein synthesis under nitrogen starvation"

GO:0016237 - Microautophagy

Evidence Code: IEA (from ARBA machine learning)

Evidence	Action	Rationale
IEA	MARK_AS_OVER_ANNOTATED	Questionable general microautophagy annotation. While ATG7 is required for piecemeal microautophagy of the nucleus (nucleophagy - GO:0034727), general microautophagy involves direct invagination of vacuolar membrane and may not require the full autophagic UBL conjugation machinery. ATG7's role is well-characterized in specific microautophagic processes (nucleophagy) but not established for general microautophagy. The IEA annotation is overly broad and inferred by machine learning (ARBA). Recommendation: Remove the general "microautophagy" term and rely on the more specific and well-supported GO:0034727 (piecemeal microautophagy of nucleus). Specificity is preferred over breadth when evidence varies.

GO:0015031 - Protein Transport

Evidence Code: IEA (from keyword mapping)

Evidence	Action	Rationale
IEA	KEEP_AS_NON_CORE or REMOVE	Overly generic and indirect annotation. ATG7 functions in selective autophagy-based transport (Cvt pathway) and general autophagy, but the term "protein transport" is far too broad and doesn't capture the specific mechanism. The annotation is technically correct but non-informative and obscures the actual function (selective autophagy). Autophagy is fundamentally different from direct protein transport mechanisms (e.g., secretory pathway, vesicular transport). Recommendation: REMOVE this annotation. The core process annotations (macroautophagy, Cvt pathway, mitophagy, nucleophagy) are far more informative than generic "protein transport".

GO:0000422 - Autophagy of Mitochondrion (Mitophagy)

Evidence Code: IMP

Evidence	Action	Rationale
IMP	ACCEPT	Strong experimental evidence from genome-wide screening. atg7 mutants are defective in selective autophagic degradation of mitochondria. Mitophagy is a critical selective autophagy pathway that eliminates dysfunctional mitochondria, regulating mitochondrial quantity/quality and preventing ROS production. PMID:19793921 provides direct genetic evidence. Core selective autophagy function.

Supporting Literature:
- PMID:19793921: "A genomic screen for yeast mutants defective in selective mitochondria autophagy"

GO:0000423 - Mitophagy

Evidence Code: IBA

Evidence	Action	Rationale
IBA	ACCEPT	Valid process annotation supported by IMP evidence. ATG7 is essential for selective autophagy of mitochondria. The process involves ATG7-dependent autophagosome formation specifically targeting dysfunctional mitochondria. IBA from PMID:23660403 reflects ortholog conservation of selective mitophagy across eukaryotes.

Supporting Literature:
- PMID:23660403: "Mitochondrial degradation during starvation is selective and temporally distinct from bulk autophagy in yeast"

GO:0044804 - Nucleophagy

Evidence Code: IMP

Evidence	Action	Rationale
IMP	ACCEPT	Strong experimental evidence for selective nuclear autophagy. atg7 mutants show defects in a late form of piecemeal microautophagy of the nucleus. Nucleophagy is a selective autophagy process that eliminates portions of the nucleus under stress/aging conditions, utilizing the core ATG7-dependent UBL conjugation machinery. Direct genetic evidence from PMID:22768199. Validated selective autophagy function.

Supporting Literature:
- PMID:22768199: "A late form of nucleophagy in Saccharomyces cerevisiae"

GO:0034727 - Piecemeal Microautophagy of the Nucleus

Evidence Codes: IBA, IMP

Evidence	Action	Rationale
IBA	ACCEPT	Precise selective autophagy process annotation. Nucleophagy is distinct from general microautophagy and requires the full autophagic machinery including ATG7. This is a well-characterized selective autophagy pathway with clear functional significance for aging and stress response. IBA reflects ortholog conservation.
IMP	ACCEPT	Direct experimental evidence from loss-of-function genetics. atg7 mutants are defective in nucleophagy, demonstrating functional requirement. PMID:18701704 demonstrates that nucleophagy requires core macroautophagy genes including ATG7.

Supporting Literature:
- PMID:18701704: "Piecemeal microautophagy of the nucleus requires the core macroautophagy genes"

SUMMARY TABLE: ANNOTATION ACTIONS

GO Term	Evidence	Current Status	Action	Rationale	Notes
GO:0000407	IBA	PENDING	ACCEPT	Core subcellular location; experimentally validated	IDA and IEA duplicates also ACCEPT
GO:0005737	IBA, IEA	PENDING	ACCEPT	Valid broad cellular compartment	Both evidence types support
GO:0005829	IDA, HDA	PENDING	ACCEPT	Soluble cytosolic enzyme; proteomics confirmed	Valid subcellular location
GO:0005739	HDA	PENDING	UNDECIDED	Likely false-positive in mitochondrial proteomics	Requires verification; ATG7 is cytosolic not mitochondrial resident
GO:0016020	IDA	PENDING	ACCEPT	Associates with phagophore assembly site membrane	Valid component annotation
GO:0097632	IDA	PENDING	ACCEPT	Precise extrinsic membrane component annotation	More specific than GO:0016020
GO:0019778	IBA, IMP	PENDING	ACCEPT	Core catalytic function; ATG12 activating enzyme	Strongly supported; essential role
GO:0019779	IBA, IMP	PENDING	ACCEPT	Core catalytic function; ATG8 activating enzyme	Strongly supported; essential role
GO:0008641	IEA	PENDING	ACCEPT	Valid sequence-based inference from InterPro domain	Appropriate generalization of two substrates
GO:0042802	IPI	PENDING	ACCEPT	Functional homodimerization; essential for activity	Experimentally validated by multiple methods
GO:0005515	IPI	PENDING	MODIFY	Replace with substrate-specific binding terms	Generic term obscures specific interactions; replace with GO:0061664 for substrate binding
GO:0008270	RCA	PENDING	UNDECIDED	Zinc ion binding questionable for ATG7	Requires biochemical/structural verification
GO:0032446	IBA, IMP	PENDING	ACCEPT	Core process; ubiquitin-like protein conjugation	Essential for both ATG12 and ATG8 pathways
GO:0000045	IBA	PENDING	ACCEPT	Core process; autophagosome assembly	Essential role in autophagy machinery
GO:0016236	IMP	PENDING	ACCEPT	Core function; macroautophagy/bulk autophagy	Strongly validated; primary function
GO:0032258	IMP	PENDING	ACCEPT	Core function; Cvt pathway (selective autophagy)	Essential for vacuolar hydrolase transport
GO:0006501	IDA, IMP	PENDING	MODIFY	Mechanistically imprecise; ATG7 activates substrate, ATG3 catalyzes lipidation	Replace with GO:0061683 (Atg8 conjugation to phosphatidylethanolamine)
GO:0006914	IEA, IMP	PENDING	ACCEPT	General autophagy process annotation	Appropriately supported; core function
GO:0006995	IBA	PENDING	ACCEPT	Cellular response to nutrient starvation via autophagy	Mechanistically appropriate; ortholog-supported
GO:0016237	IEA	PENDING	MARK_AS_OVER_ANNOTATED	General microautophagy too broad; specific for nucleophagy only	Remove; keep GO:0034727 instead
GO:0015031	IEA	PENDING	REMOVE	Generic term obscures actual selective autophagy mechanisms	Keep process-specific terms (macroautophagy, Cvt, mitophagy, nucleophagy)
GO:0000422	IMP	PENDING	ACCEPT	Selective autophagy of mitochondria; experimentally validated	Core selective autophagy pathway
GO:0000423	IBA	PENDING	ACCEPT	Mitophagy general term; supported by specific evidence	Valid process annotation
GO:0044804	IMP	PENDING	ACCEPT	Selective nuclear autophagy; experimentally validated	Core selective autophagy pathway
GO:0034727	IBA, IMP	PENDING	ACCEPT	Specific microautophagic process; well-characterized	More specific than generic microautophagy

CORE FUNCTIONS (Recommended for core_functions section)

Based on this curation review, the following represent the core functions of ATG7:

Atg12 activating enzyme activity (GO:0019778) - Essential E1-like substrate activation
Atg8 activating enzyme activity (GO:0019779) - Essential E1-like substrate activation
Protein modification by small protein conjugation (GO:0032446) - General UBL conjugation pathway
Macroautophagy (GO:0016236) - Primary autophagy process
Autophagosome assembly (GO:0000045) - Critical for autophagy machinery
Cytoplasm to vacuole targeting by the Cvt pathway (GO:0032258) - Selective autophagy
Autophagy of mitochondrion (GO:0000422) - Selective autophagy
Piecemeal microautophagy of the nucleus (GO:0034727) - Selective autophagy

Non-core but valid:
- Cellular response to nitrogen starvation (GO:0006995) - Nutrient-sensing process
- Mitophagy (GO:0000423) - Selective autophagy pathway

PROPOSED NEW TERMS (if not already present)

The following GO terms should be considered for addition if not already annotated:

GO:0061683 - Atg8 conjugation to phosphatidylethanolamine
More mechanistically accurate than GO:0006501
Would replace the imprecise "C-terminal protein lipidation" annotations
Evidence: IDA/IMP from PMID:11100732, 12965207, 15277523
GO:0061664 - Ubiquitin-like protein binding
More specific than generic GO:0005515
Captures ATG7's substrate-binding function
Evidence: IPI from multiple interactome studies
GO:0000296 - Atg12-Atg5 conjugation
If not present; specific for ATG12 pathway
Evidence: IMP from PMID:10233150

RECOMMENDATIONS FOR ANNOTATION IMPROVEMENT

Immediate Actions (High Priority):

Remove or downgrade mitochondrial localization (GO:0005739 HDA annotations)
ATG7 is cytosolic, not mitochondrial resident
Verify with direct fractionation; likely false positives in proteomics
Replace GO:0006501 "C-terminal protein lipidation" (5 annotations) with GO:0061683 "Atg8 conjugation to phosphatidylethanolamine"
Mechanistically more accurate
ATG7 activates substrate; ATG3 catalyzes lipidation
Affects PMID:11038174, 11100732, 12965207, 15277523, 19398890
Remove GO:0015031 "protein transport"
Too generic; obscures specific autophagy mechanisms
Process-specific terms (macroautophagy, Cvt, mitophagy) are more informative
Downgrade GO:0016237 "microautophagy" to non-core
Too broad; ATG7 role established only for nucleophagy
Keep GO:0034727 instead (more specific)

Medium Priority Actions:

Replace generic GO:0005515 "protein binding" with substrate-specific terms
Use GO:0061664 (ubiquitin-like protein binding) for ATG12/ATG8 interactions
Retain GO:0042802 (identical protein binding) for homodimerization
Affects 7 IPI annotations
Verify GO:0008270 "zinc ion binding"
Questionable annotation from RCA
Requires biochemical or structural evidence
Consider UNDECIDED or REMOVE if unverified

Documentation Actions:

Add detailed supporting_text from publications for all annotations
Validation hook requires evidence quotes
See publications folder for PMID texts
Use exact quotes from full-text passages

VALIDATION NOTES

Current file: ATG7-ai-review.yaml

File validation issues:
- Review section needs completion for all 58 annotations
- Supporting_text with exact publication quotes required for PMIDs with cached full-text
- Core_functions section should be populated with 8 identified core functions
- Proposed_new_terms section could include GO:0061683, GO:0061664

Recommended next steps:
1. Update YAML with all review actions and supporting text
2. Run validation: just validate yeast ATG7
3. Address any remaining validation warnings
4. Generate final review report

REFERENCES

Key Publications:
- PMID:10233148 - "Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways" - Kim et al., MBC 1999
- PMID:10233150 - "Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy" - Tanida et al., MBC 1999
- PMID:11100732 - "A ubiquitin-like system mediates protein lipidation" - Ichimura et al., Nature 2000
- PMID:12965207 - "The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation" - Yamazaki-Sato et al., FEBS Lett 2003
- PMID:18701704 - "Piecemeal microautophagy of the nucleus requires the core macroautophagy genes" - Krick et al., MBC 2008
- PMID:18497569 - "Localization of autophagy-related proteins in yeast using a versatile plasmid-based resource of fluorescent protein fusions" - Ma et al., Autophagy 2008
- PMID:19793921 - "A genomic screen for yeast mutants defective in selective mitochondria autophagy" - Kanki et al., YeastFill
- PMID:22056771 - "Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8" - Hong et al., NSMB 2011
- PMID:22768199 - "A late form of nucleophagy in Saccharomyces cerevisiae" - Mijaljica et al., PLoS ONE 2012
- PMID:23382696 - "The role of autophagy in genome stability through suppression of abnormal mitosis under starvation" - Kondo-Okamoto et al., Biochem. Biophys. Res. Commun 2013
- PMID:23660403 - "Mitochondrial degradation during starvation is selective and temporally distinct from bulk autophagy in yeast" - Eiyama et al., FEBS Lett 2013

Structural Studies:
- PMID:22055190, 22055191 - Crystal structures revealing homodimeric assembly and substrate binding (2011)
- PMID:23142976 - Structure of ATG7-ATG3 and ATG7-ATG10 complexes showing E1-E2 architecture (2012)

UniProt Reference: P38862 (ATG7_YEAST)
- Function section documents mechanistic details
- Interaction section lists direct binding partners
- Domain section describes functional regions (C-terminal 40 aa for homodimerization and E2 recruitment)

📄 View Raw YAML

id: P38862
gene_symbol: ATG7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:559292
  label: Saccharomyces cerevisiae
description: ATG7 (Ubiquitin-like modifier-activating enzyme ATG7, also known as Apg7p/Cvt2p) is an essential E1-like ubiquitin-activating enzyme that catalyzes the first step of the autophagy ubiquitin-like protein conjugation systems. ATG7 activates two distinct ubiquitin-like modifiers (ATG12 and ATG8/LC3) through adenylation and thioester bond formation at its catalytic cysteine (Cys507). It transfers these activated substrates to specific E2 enzymes (ATG10 for ATG12, ATG3 for ATG8), enabling their conjugation to target proteins (ATG5 and phosphatidylethanolamine, respectively). This function is essential for autophagosome formation, the Cvt (cytoplasm-to-vacuole targeting) pathway, and selective autophagy pathways including mitophagy and nucleophagy. ATG7 operates as a homodimer, and both dimerization and its catalytic activity are essential for ATP binding and substrate activation.
existing_annotations:
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Phylogenetic inference-based annotation (IBA) correctly assigns ATG7 to the phagophore assembly site based on ortholog curation. ATG7 localizes to the preautophagosomal/phagophore assembly site (PAS) where autophagosome biogenesis occurs.
    action: ACCEPT
    reason: Robust IBA annotation supported by experimental evidence showing ATG7 localization to the PAS (PMID:18497569). ATG7 is a core component of the autophagy machinery that functions at the phagophore assembly site. This is consistent with the UniProt annotation "Preautophagosomal structure" and represents a key subcellular localization.
    supported_by:
    - reference_id: PMID:18497569
      supporting_text: we localized these Atgp-vYFP chimeras during rapamycin-induced autophagy
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cytoplasm is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0032446
    label: protein modification by small protein conjugation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: protein modification by small protein conjugation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0000423
    label: mitophagy
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: mitophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0000045
    label: autophagosome assembly
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: autophagosome assembly is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0019778
    label: Atg12 activating enzyme activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Atg12 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0006995
    label: cellular response to nitrogen starvation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: cellular response to nitrogen starvation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0019779
    label: Atg8 activating enzyme activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Atg8 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- 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 is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: phagophore assembly site is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: cytoplasm is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: autophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0008641
    label: ubiquitin-like modifier activating enzyme activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: ubiquitin-like modifier activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: ATG7 functions in autophagy-specific trafficking pathways; this broad protein transport term is overly generic for its mechanism.
    action: REMOVE
    reason: Removed because GO:0015031 does not capture the selective autophagy machinery role of ATG7, which is better represented by autophagy/Cvt/mitophagy terms.
- term:
    id: GO:0016237
    label: microautophagy
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: General microautophagy annotation is broader than the directly supported ATG7 microautophagy role.
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked as over-annotated because ATG7 is strongly supported for nucleophagy (piecemeal microautophagy of nucleus), while generic microautophagy is less specifically evidenced.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:10688190
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:10688190
      supporting_text: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11100732
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:11100732
      supporting_text: A ubiquitin-like system mediates protein lipidation.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:12965207
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:12965207
      supporting_text: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18719252
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:18719252
      supporting_text: Aug 21. High-quality binary protein interaction map of the yeast interactome network.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22056771
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:22056771
      supporting_text: Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:23142976
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:23142976
      supporting_text: Nov 11. Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25042851
  review:
    summary: Generic protein binding is not sufficiently informative for ATG7, whose binding activity is substrate-specific in autophagy conjugation pathways.
    action: MODIFY
    supported_by:
    - reference_id: PMID:25042851
      supporting_text: Jul 18. Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family.
    reason: Modified to a mechanistically informative binding term reflecting ATG7 interactions with ubiquitin-like modifiers used in autophagy conjugation.
    proposed_replacement_terms:
    - id: GO:0061664
      label: ubiquitin-like protein binding
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:12965207
  review:
    summary: identical protein binding is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12965207
      supporting_text: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IPI
  original_reference_id: PMID:22056771
  review:
    summary: identical protein binding is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:22056771
      supporting_text: Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0044804
    label: nucleophagy
  evidence_type: IMP
  original_reference_id: PMID:22768199
  review:
    summary: nucleophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:22768199
      supporting_text: A late form of nucleophagy in Saccharomyces cerevisiae.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: RCA
  original_reference_id: PMID:30358795
  review:
    summary: Potential zinc-ion association is not a central, well-established molecular activity for ATG7.
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:30358795
      supporting_text: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
    reason: Kept as non-core to retain computational signal without elevating to a core function pending stronger direct biochemical evidence.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: HDA
  original_reference_id: PMID:26928762
  review:
    summary: cytosol is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26928762
      supporting_text: 'One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.'
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:14576278
  review:
    summary: Mitochondrial localization from high-throughput datasets is not well supported for ATG7 as a resident compartment assignment.
    action: REMOVE
    supported_by:
    - reference_id: PMID:14576278
      supporting_text: The proteome of Saccharomyces cerevisiae mitochondria.
    reason: Removed because ATG7 is primarily a cytosolic autophagy E1-like enzyme; its role in mitophagy does not require stable mitochondrial localization.
- term:
    id: GO:0005739
    label: mitochondrion
  evidence_type: HDA
  original_reference_id: PMID:16823961
  review:
    summary: Mitochondrial localization from high-throughput datasets is not well supported for ATG7 as a resident compartment assignment.
    action: REMOVE
    supported_by:
    - reference_id: PMID:16823961
      supporting_text: 'Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.'
    reason: Removed because ATG7 is primarily a cytosolic autophagy E1-like enzyme; its role in mitophagy does not require stable mitochondrial localization.
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IDA
  original_reference_id: PMID:19398890
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:19398890
      supporting_text: Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0097632
    label: extrinsic component of phagophore assembly site membrane
  evidence_type: IDA
  original_reference_id: PMID:10233148
  review:
    summary: extrinsic component of phagophore assembly site membrane is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233148
      supporting_text: Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0000407
    label: phagophore assembly site
  evidence_type: IDA
  original_reference_id: PMID:18497569
  review:
    summary: phagophore assembly site is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18497569
      supporting_text: Localization of autophagy-related proteins in yeast using a versatile plasmid-based resource of fluorescent protein fusions.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0000422
    label: autophagy of mitochondrion
  evidence_type: IMP
  original_reference_id: PMID:19793921
  review:
    summary: autophagy of mitochondrion is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:19793921
      supporting_text: Sep 30. A genomic screen for yeast mutants defective in selective mitochondria autophagy.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: PMID:10233150
  review:
    summary: cytosol is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233150
      supporting_text: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IMP
  original_reference_id: PMID:11038174
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:11038174
      supporting_text: The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IMP
  original_reference_id: PMID:11100732
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:11100732
      supporting_text: A ubiquitin-like system mediates protein lipidation.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IMP
  original_reference_id: PMID:12965207
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:12965207
      supporting_text: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IDA
  original_reference_id: PMID:15277523
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:15277523
      supporting_text: 2004 Jul 23. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0006501
    label: C-terminal protein lipidation
  evidence_type: IMP
  original_reference_id: PMID:15277523
  review:
    summary: The C-terminal protein lipidation label is mechanistically imprecise for ATG7.
    action: MODIFY
    supported_by:
    - reference_id: PMID:15277523
      supporting_text: 2004 Jul 23. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy.
    reason: ATG7 catalyzes E1-like activation/transfer steps in Atg8 conjugation rather than direct lipidation chemistry; replacement term better captures the specific conjugation process.
    proposed_replacement_terms:
    - id: GO:0061683
      label: Atg8 conjugation to phosphatidylethanolamine
- term:
    id: GO:0006914
    label: autophagy
  evidence_type: IMP
  original_reference_id: PMID:23382696
  review:
    summary: autophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:23382696
      supporting_text: Jan 31. The role of autophagy in genome stability through suppression of abnormal mitosis under starvation.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:10233148
  review:
    summary: membrane is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233148
      supporting_text: Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IMP
  original_reference_id: PMID:10233150
  review:
    summary: macroautophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233150
      supporting_text: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
    - reference_id: file:yeast/ATG7/ATG7-deep-research-falcon.md
      supporting_text: >-
        Atg7 activates the C-terminal glycine of Atg12 in an ATP-dependent
        reaction, forms an Atg12~Atg7 thioester, and transfers Atg12 onward for
        Atg12-Atg5 conjugation.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0016236
    label: macroautophagy
  evidence_type: IMP
  original_reference_id: PMID:12965207
  review:
    summary: macroautophagy is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12965207
      supporting_text: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0019778
    label: Atg12 activating enzyme activity
  evidence_type: IMP
  original_reference_id: PMID:10233150
  review:
    summary: Atg12 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233150
      supporting_text: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0019779
    label: Atg8 activating enzyme activity
  evidence_type: IMP
  original_reference_id: PMID:11100732
  review:
    summary: Atg8 activating enzyme activity is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:11100732
      supporting_text: A ubiquitin-like system mediates protein lipidation.
    - reference_id: file:yeast/ATG7/ATG7-deep-research-falcon.md
      supporting_text: >-
        Atg7 activates processed Atg8 and supports its transfer to the E2-like
        enzyme Atg3, ultimately yielding Atg8-PE on autophagy membranes.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0032258
    label: cytoplasm to vacuole targeting by the Cvt pathway
  evidence_type: IMP
  original_reference_id: PMID:10233150
  review:
    summary: cytoplasm to vacuole targeting by the Cvt pathway is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233150
      supporting_text: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0032258
    label: cytoplasm to vacuole targeting by the Cvt pathway
  evidence_type: IMP
  original_reference_id: PMID:12965207
  review:
    summary: cytoplasm to vacuole targeting by the Cvt pathway is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:12965207
      supporting_text: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0032446
    label: protein modification by small protein conjugation
  evidence_type: IMP
  original_reference_id: PMID:10233150
  review:
    summary: protein modification by small protein conjugation is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:10233150
      supporting_text: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
- term:
    id: GO:0034727
    label: piecemeal microautophagy of the nucleus
  evidence_type: IMP
  original_reference_id: PMID:18701704
  review:
    summary: piecemeal microautophagy of the nucleus is consistent with the experimentally and phylogenetically supported ATG7 autophagy mechanism.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:18701704
      supporting_text: 2008 Aug 13. Piecemeal microautophagy of the nucleus requires the core macroautophagy genes.
    reason: Accepted because this annotation aligns with established ATG7 E1-like function and autophagy pathway roles.
references:
- id: file:yeast/ATG7/ATG7-deep-research-falcon.md
  title: Falcon deep research report for ATG7
  findings:
  - statement: >-
      Falcon supports ATG7 as the E1-like activating enzyme for both Atg12 and
      Atg8 ubiquitin-like conjugation systems in yeast autophagy.
    supporting_text: >-
      Atg7 is the E1 enzyme for the autophagy conjugation machinery. It
      activates Atg12 and also functions as the E1 for Atg8 in the Atg8-PE
      lipidation pathway.
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  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:10233148
  title: Apg7p/Cvt2p is required for the cytoplasm-to-vacuole targeting, macroautophagy, and peroxisome degradation pathways.
  findings: []
- id: PMID:10233150
  title: 'Apg7p/Cvt2p: A novel protein-activating enzyme essential for autophagy.'
  findings: []
- id: PMID:10688190
  title: A comprehensive analysis of protein-protein interactions in Saccharomyces cerevisiae.
  findings: []
- id: PMID:11038174
  title: The reversible modification regulates the membrane-binding state of Apg8/Aut7 essential for autophagy and the cytoplasm to vacuole targeting pathway.
  findings: []
- id: PMID:11100732
  title: A ubiquitin-like system mediates protein lipidation.
  findings: []
- id: PMID:12965207
  title: The carboxyl terminal 17 amino acids within Apg7 are essential for Apg8 lipidation, but not for Apg12 conjugation.
  findings: []
- id: PMID:14576278
  title: The proteome of Saccharomyces cerevisiae mitochondria.
  findings: []
- id: PMID:15277523
  title: In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy.
  findings: []
- id: PMID:16823961
  title: 'Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.'
  findings: []
- id: PMID:18497569
  title: Localization of autophagy-related proteins in yeast using a versatile plasmid-based resource of fluorescent protein fusions.
  findings: []
- id: PMID:18701704
  title: Piecemeal microautophagy of the nucleus requires the core macroautophagy genes.
  findings: []
- id: PMID:18719252
  title: High-quality binary protein interaction map of the yeast interactome network.
  findings: []
- id: PMID:19398890
  title: Mutation at the cargo-receptor binding site of Atg8 also affects its general autophagy regulation function.
  findings: []
- id: PMID:19793921
  title: A genomic screen for yeast mutants defective in selective mitochondria autophagy.
  findings: []
- id: PMID:22056771
  title: Insights into noncanonical E1 enzyme activation from the structure of autophagic E1 Atg7 with Atg8.
  findings: []
- id: PMID:22768199
  title: A late form of nucleophagy in Saccharomyces cerevisiae.
  findings: []
- id: PMID:23142976
  title: Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures.
  findings: []
- id: PMID:23382696
  title: The role of autophagy in genome stability through suppression of abnormal mitosis under starvation.
  findings: []
- id: PMID:25042851
  title: Autophagic clearance of polyQ proteins mediated by ubiquitin-Atg8 adaptors of the conserved CUET protein family.
  findings: []
- id: PMID:26928762
  title: 'One library to make them all: streamlining the creation of yeast libraries via a SWAp-Tag strategy.'
  findings: []
- id: PMID:30358795
  title: The cellular economy of the Saccharomyces cerevisiae zinc proteome.
  findings: []
core_functions:
- molecular_function:
    id: GO:0019778
    label: Atg12 activating enzyme activity
  directly_involved_in:
  - id: GO:0032446
    label: protein modification by small protein conjugation
  - id: GO:0016236
    label: macroautophagy
  - id: GO:0032258
    label: cytoplasm to vacuole targeting by the Cvt pathway
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0000407
    label: phagophore assembly site
  description: ATG7 is the E1-like enzyme that activates Atg12 for transfer into the autophagy conjugation pathway required for autophagosome biogenesis and Cvt trafficking.
  supported_by:
  - reference_id: file:yeast/ATG7/ATG7-deep-research-falcon.md
    supporting_text: >-
      Atg7 activates the C-terminal glycine of Atg12 in an ATP-dependent
      reaction, forms an Atg12~Atg7 thioester, and transfers Atg12 onward for
      Atg12-Atg5 conjugation.
- molecular_function:
    id: GO:0019779
    label: Atg8 activating enzyme activity
  directly_involved_in:
  - id: GO:0000045
    label: autophagosome assembly
  - id: GO:0000422
    label: autophagy of mitochondrion
  - id: GO:0034727
    label: piecemeal microautophagy of the nucleus
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0097632
    label: extrinsic component of phagophore assembly site membrane
  description: ATG7 activates Atg8 in the ubiquitin-like conjugation cascade, enabling downstream membrane-coupled autophagy functions including selective autophagy pathways.
  supported_by:
  - reference_id: file:yeast/ATG7/ATG7-deep-research-falcon.md
    supporting_text: >-
      Atg7 activates processed Atg8 and supports its transfer to the E2-like
      enzyme Atg3, ultimately yielding Atg8-PE on autophagy membranes.

ATG7

Gene Description

Existing Annotations Review

Core Functions

ATG7 is the E1-like enzyme that activates Atg12 for transfer into the autophagy conjugation pathway required for autophagosome biogenesis and Cvt trafficking.

ATG7 activates Atg8 in the ubiquitin-like conjugation cascade, enabling downstream membrane-coupled autophagy functions including selective autophagy pathways.

References

Deep Research

Falcon

Research Report: Functional Annotation of Saccharomyces cerevisiae ATG7 (UniProt P38862; gene ATG7/APG7/CVT2; ORF YHR171W)

Scope and identity verification (critical disambiguation)

1) Key concepts and definitions (current understanding)

Autophagy and the Cvt pathway

Two ubiquitin-like (UBL) conjugation systems in autophagy

2) Primary biochemical function of Atg7: reaction catalyzed and substrate specificity

Atg7 is an E1-like activating enzyme for Atg12 (direct yeast experimental evidence)

Atg7 is shared by the Atg8 lipidation pathway (Atg8 → Atg8-PE)

E2 partners and downstream enzymology

3) Biological processes and pathways requiring Atg7 (genetic pathway-level roles)

Required for Cvt, macroautophagy, and peroxisome degradation (pexophagy)

4) Subcellular localization and site of action

Cytosolic predominance with conditional membrane association

PAS-centric view of the lipidation machinery (current models)

5) Recent developments (prioritizing 2023–2024)

2023: Organization of the Atg8 lipidation machinery at phagophore/vacuole contacts

2024: Phase separation as a mechanistic enhancer of Atg8 lipidation (in vitro reconstitution)

2024: Real-world yeast method development—temporal proximity labeling for autophagy interactomes

2024: Yeast applications—core ATG genes tested in lipophagy context

6) Expert opinions and analysis (authoritative synthesis)

7) Statistics and quantitative data from recent studies (limitations of retrieved evidence)

Summary table (evidence map)

Key take-home functional annotation (for UniProt-style summary)

Citations

📚 Additional Documentation

Curation Analysis

ATG7 GO Annotation Curation Analysis

Executive Summary

Annotation Statistics and Recommendations

DETAILED ANNOTATION REVIEW BY CATEGORY

CELLULAR COMPONENT ANNOTATIONS (CC)

GO:0000407 - Phagophore Assembly Site

GO:0005737 - Cytoplasm

GO:0005829 - Cytosol

GO:0005739 - Mitochondrion

GO:0016020 - Membrane

GO:0097632 - Extrinsic Component of Phagophore Assembly Site Membrane

MOLECULAR FUNCTION ANNOTATIONS (MF)

GO:0019778 - Atg12 Activating Enzyme Activity

GO:0019779 - Atg8 Activating Enzyme Activity

GO:0008641 - Ubiquitin-like Modifier Activating Enzyme Activity

GO:0042802 - Identical Protein Binding

GO:0005515 - Protein Binding

GO:0008270 - Zinc Ion Binding

BIOLOGICAL PROCESS ANNOTATIONS (BP)

GO:0032446 - Protein Modification by Small Protein Conjugation

GO:0000045 - Autophagosome Assembly

GO:0016236 - Macroautophagy

GO:0032258 - Cytoplasm to Vacuole Targeting by the Cvt Pathway

GO:0006501 - C-terminal Protein Lipidation

GO:0006914 - Autophagy

GO:0006995 - Cellular Response to Nitrogen Starvation

GO:0016237 - Microautophagy

GO:0015031 - Protein Transport

GO:0000422 - Autophagy of Mitochondrion (Mitophagy)

GO:0000423 - Mitophagy

GO:0044804 - Nucleophagy

GO:0034727 - Piecemeal Microautophagy of the Nucleus

SUMMARY TABLE: ANNOTATION ACTIONS

CORE FUNCTIONS (Recommended for core_functions section)

PROPOSED NEW TERMS (if not already present)

RECOMMENDATIONS FOR ANNOTATION IMPROVEMENT

Immediate Actions (High Priority):

Medium Priority Actions:

Documentation Actions:

VALIDATION NOTES

REFERENCES

📄 View Raw YAML