Affinage

ATG3

Ubiquitin-like-conjugating enzyme ATG3 · UniProt Q9NT62

Length
314 aa
Mass
35.9 kDa
Annotated
2026-04-28
100 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATG3 is a noncanonical E2-like conjugating enzyme central to autophagosome biogenesis, catalyzing the covalent attachment of ATG8-family proteins (LC3/GABARAP) to phosphatidylethanolamine (PE) on autophagosomal membranes. ATG3 receives activated ATG8 from the homodimeric E1 enzyme ATG7 via a trans-protomer thioester transfer mechanism (PMID:22055190, PMID:23142976), and its catalytic activity is conformationally suppressed in the resting state by an intramolecular brace (E123IR) that is relieved upon engagement with ATG7 or the ATG12–ATG5–ATG16L1 E3 complex, which reorients the catalytic cysteine toward a conserved threonine to activate conjugation (PMID:23503366, PMID:31399562, PMID:24191030). Membrane targeting is governed by an N-terminal amphipathic helix that senses lipid-packing defects and membrane curvature, coupling membrane association to catalytic competence through a conserved N-terminal region and direct C-terminal catalytic-domain membrane contacts (PMID:24747438, PMID:33446636, PMID:37679347). Beyond canonical autophagy, the covalent ATG12–ATG3 conjugate regulates late endosome trafficking and exosome biogenesis through interaction with Alix/PDCD6IP (PMID:25686249), and ATG3 has autophagy-independent roles in mitochondrial homeostasis (PMID:20723759) and hepatic lipid metabolism via the JNK1–SIRT1–CPT1a axis (PMID:34555423).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2007 High

    Determining whether ATG3 structurally resembles canonical E2 ubiquitin-conjugating enzymes established the topological basis for its conjugase activity while revealing two unique inserted regions that mediate E1 and substrate binding.

    Evidence 2.5 Å X-ray crystal structure of yeast Atg3 with binding assays

    PMID:17227760

    Open questions at the time
    • No structure of ATG3 in complex with E1 or substrate
    • PE-binding site inferred from sulfate ion, not confirmed with lipid
  2. 2010 High

    Discovery that ATG3 recognizes ATG8 via a canonical AIM/LIR motif (WEDL) explained how the thioester intermediate is resolved to transfer ATG8 to PE, and revealed pathway-selective requirements for this motif.

    Evidence NMR, in vitro lipidation, and mutagenesis in yeast

    PMID:20615880

    Open questions at the time
    • Whether mammalian ATG3 uses the same or additional LIR motifs
    • Structural basis of AIM-dependent PE transfer not resolved
  3. 2010 High

    Identification of the covalent ATG12–ATG3 conjugate revealed an autophagy-independent function for ATG3 in mitochondrial homeostasis and cell death.

    Evidence Co-IP, mass spectrometry, ATG3 knockout, mitochondrial assays

    PMID:20723759

    Open questions at the time
    • Mechanism linking ATG12–ATG3 to mitochondrial phenotypes undefined
    • Whether ATG12–ATG3 acts as a scaffold or enzyme in this context unknown
  4. 2011 High

    Structural elucidation of the ATG7 homodimer–ATG3 complex revealed a trans-protomer mechanism for thioester relay from E1 to E2, explaining how the noncanonical E1 architecture supports ATG8 transfer.

    Evidence X-ray crystallography of Atg7NTD–Atg3FR complex, SAXS, crosslinking, and biochemical transfer assays

    PMID:22055190 PMID:23142976

    Open questions at the time
    • Full-length Atg7–Atg3 complex structure not available
    • Dynamics of E1-to-E2 handoff in the membrane context unknown
  5. 2012 High

    Demonstrating that caspase-8 directly cleaves ATG3 during apoptosis established a cross-talk mechanism that inactivates autophagy during programmed cell death.

    Evidence In vitro caspase cleavage, site-directed mutagenesis, TRAIL/TNF-α treatment

    PMID:22644571

    Open questions at the time
    • In vivo physiological relevance of caspase-8 cleavage not assessed in animal models
    • Identity of cleavage products and whether fragments have gain-of-function activity unknown
  6. 2013 High

    Biochemical and structural studies established that the ATG12–ATG5 conjugate functions as an E3 enzyme by allosterically rearranging ATG3's catalytic site, explaining how the E3 stimulates lipidation, and revealed that E1 and E3 binding to ATG3 is mutually exclusive.

    Evidence Crystal structure of ATG12–ATG5–ATG16L1 with ATG3 fragment, reconstitution, mutagenesis, peptide competition

    PMID:23503366 PMID:24186333 PMID:24191030

    Open questions at the time
    • Full ternary complex on a membrane not structurally resolved
    • How ATG3 cycles between E1-bound and E3-bound states in real time unknown
  7. 2014 High

    Discovery that ATG3's N-terminal amphipathic helix senses membrane curvature and lipid-packing defects established the mechanism by which ATG3 targets the phagophore for site-specific LC3 lipidation.

    Evidence In vitro lipidation reconstitution on defined liposomes, amphipathic helix mutagenesis, Atg3-KO rescue

    PMID:24747438

    Open questions at the time
    • Which specific lipid compositions are sensed in vivo unknown
    • How curvature sensing is coordinated with E3 complex recruitment not established
  8. 2015 High

    Identification of the ATG12–ATG3/Alix interaction expanded ATG3's functional repertoire beyond autophagy to late endosome trafficking and exosome biogenesis.

    Evidence Co-IP, loss-of-function, endolysosomal trafficking and exosome assays

    PMID:25686249

    Open questions at the time
    • Structural basis of ATG12–ATG3/Alix interaction not determined
    • Whether this function is regulated independently of canonical autophagy signals unclear
  9. 2015 Medium

    NMR mapping of the ATG7-interacting region on human ATG3 confirmed overlap with the E3-binding region, providing the molecular explanation for mutually exclusive E1/E3 engagement and defining critical residues for E1 interaction.

    Evidence NMR and mutagenesis with GABARAP transfer assay

    PMID:26043688

    Open questions at the time
    • Single-lab finding without independent replication
    • Kinetics of E1–E3 switching on ATG3 not measured
  10. 2017 High

    Demonstration that acetylation at K19/K48 promotes ATG3 membrane binding, and that PTK2 phosphorylation at Y203 targets ATG3 for degradation, established post-translational control layers governing ATG3 activity and stability.

    Evidence Semisynthetic diacetylated ATG3 with in vitro reconstitution; mass spectrometry, phospho-specific antibody, kinase inhibitor, and siRNA for PTK2–ATG3

    PMID:28103122 PMID:28327644

    Open questions at the time
    • Acetyltransferase responsible for K19/K48 acetylation in vivo not identified
    • Phosphatase reversing Y203 phosphorylation unknown
    • Whether acetylation and phosphorylation are coordinated not tested
  11. 2018 Medium

    Finding that eIF5A is required for efficient ATG3 translation revealed a translational control checkpoint for autophagy capacity.

    Evidence High-throughput screen, polysome profiling, validation in C. elegans

    PMID:29712776

    Open questions at the time
    • Specific ribosome-stalling motif in ATG3 mRNA not fully characterized
    • Single-lab finding; contribution relative to other autophagy gene translation not compared
  12. 2019 High

    Identification of the E123IR allosteric switch explained how ATG3's catalytic activity is suppressed in the apo state and activated by E1 or E3 engagement, unifying prior observations of mutually exclusive binding and E3 stimulation.

    Evidence NMR, X-ray crystallography, biochemical assays, yeast genetics

    PMID:31399562

    Open questions at the time
    • Whether E123IR dynamics are modulated by post-translational modifications not tested
    • Conformational pathway from E1-released to E3-bound state not tracked in real time
  13. 2021 High

    NMR-based demonstration that a conserved N-terminal region couples membrane curvature sensing to catalytic core activation resolved how membrane binding and enzymatic activity are mechanistically linked.

    Evidence NMR, in vitro conjugation, mutagenesis, Atg3-KO rescue in cells

    PMID:33446636

    Open questions at the time
    • Atomic-resolution structure of membrane-bound ATG3 not available
    • Whether coupling mechanism differs for LC3 vs GABARAP subfamilies unknown
  14. 2021 Medium

    Hepatic ATG3 knockdown improved fatty acid oxidation via JNK1–SIRT1–CPT1a independently of autophagy, establishing an autophagy-independent metabolic role for ATG3.

    Evidence Genetic knockdown in mice and human hepatocytes, epistasis with SIRT1/CPT1a

    PMID:34555423

    Open questions at the time
    • Direct molecular target of ATG3 in JNK1 regulation not identified
    • Whether this reflects catalytic or scaffolding function of ATG3 unknown
    • Single-lab finding
  15. 2023 High

    Structural and simulation studies revealed that ATG3's C-terminal catalytic domain directly contacts the phagophore membrane, that its amphipathic helix has uniquely low hydrophobicity to enable transient association, and that a noncanonical LIR in the flexible region is required for thioester formation — collectively defining the multi-contact mechanism of membrane-coupled catalysis.

    Evidence NMR, MD simulations, X-ray crystallography of ATG3-LIR/LC3 complex, CRISPR mutagenesis, live-cell imaging

    PMID:37252361 PMID:37352354 PMID:37679347

    Open questions at the time
    • Integrated structural model of full ATG3 on the membrane with LC3 thioester not yet determined
    • Relative contributions of AH, C-terminal contacts, and LIR to membrane dwell time not quantified
  16. 2024 Medium

    A three-step membrane docking model — WIPI2-mediated recruitment, ATG16L1 helix insertion, then ATG3 membrane engagement with PE concentration around the thioester — provided an integrated pathway-level view of the lipidation reaction on PI3P-containing membranes.

    Evidence Molecular dynamics simulations, in vitro reconstitution, cellular assays

    PMID:38324698

    Open questions at the time
    • Docking model relies substantially on simulation; experimental validation of PE concentration around thioester needed
    • Roles of the two conserved histidines in catalysis not confirmed by mutagenesis in this study
  17. 2025 High

    Crystal structure of the GABARAP~ATG3 isopeptide conjugate and discovery that HDAC6 ubiquitinates ATG3 at K272 for proteasomal degradation refined understanding of both the backside E2–substrate interface and a new degradation-based regulatory mechanism.

    Evidence X-ray crystallography and NMR of GABARAP~ATG3; Co-IP, mutagenesis, ubiquitination assays for HDAC6–ATG3

    PMID:40628661 PMID:40739328

    Open questions at the time
    • Whether HDAC6-mediated ubiquitination competes with acetylation at overlapping lysines not tested
    • Backside interaction validated for GABARAP but not tested for LC3 subfamily members

Open questions

Synthesis pass · forward-looking unresolved questions
  • A complete atomic-resolution structure of the full ATG12–ATG5–ATG16L1/ATG3~LC3 complex on a membrane, the identity of the acetyltransferase(s) modifying ATG3, and the direct molecular basis of ATG3's autophagy-independent metabolic functions remain unresolved.
  • No full membrane-bound ternary/quaternary complex structure
  • Acetyltransferase for K19/K48 unknown
  • Mechanism of ATG3 action on JNK1 pathway uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 12
Localization
GO:0005829 cytosol 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-9612973 Autophagy 8 R-HSA-392499 Metabolism of proteins 2 R-HSA-5357801 Programmed Cell Death 1 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ATG12ATG16L1ATG5ATG7BAG3HDAC6PDCD6IPPTK2
Complex memberships
ATG12-ATG3 conjugateATG12-ATG5-ATG16L1 E3 complex (transient E2-E3)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Crystal structure of yeast Atg3 at 2.5 Å resolution reveals an α/β-fold with a core topologically similar to canonical E2 enzymes, two unique inserted regions (one disordered ~80-residue region responsible for Atg7 binding, and one long α-helical region responsible for Atg8 binding), and a sulfate ion near the catalytic cysteine suggesting a PE phosphate-binding site. X-ray crystallography, in vivo and in vitro binding assays The Journal of biological chemistry High 17227760
2010 ATG3 is a substrate for ATG12 conjugation; complex formation requires ATG7 as E1 and ATG3 autocatalytic activity as E2, resulting in covalent linkage of ATG12 onto a single lysine on ATG3. ATG12-ATG3 complex is required for mitochondrial homeostasis and mitochondrial pathway cell death, but not starvation-induced autophagy. Co-immunoprecipitation, mass spectrometry, ATG3 knockdown/knockout, cell death assays, mitochondrial mass measurements Cell High 20723759
2010 Atg3 directly interacts with Atg8 through the WEDL sequence (a canonical Atg8-family interacting motif, AIM), which is required for transfer of Atg8 from the Atg8~Atg3 thioester intermediate to PE but not for thioester intermediate formation; the AIM is necessary for the Cvt pathway but not starvation-induced autophagy. NMR, in vitro lipidation assays, mutational analysis, in vivo autophagy assays The Journal of biological chemistry High 20615880
2011 Atg7 is a noncanonical homodimeric E1 enzyme that recruits Atg3 via its unique N-terminal domain (Atg7NTD) binding a flexible region (Atg3FR); crystal structures of Atg7NTD-Atg3FR complex and Atg7 C-terminal domain reveal that Atg8 is transferred in trans from the catalytic cysteine of one Atg7 protomer to Atg3 bound to the N-terminal domain of the opposite Atg7 protomer within the homodimer. X-ray crystallography, SAXS, crosslinking, biochemical transfer assays Molecular cell High 22055190
2012 Atg3 is cleaved by caspase-8 during receptor-mediated cell death (TRAIL/TNF-α); caspase-8 directly targets a specific cleavage site on Atg3, and mutation of this site abolishes cleavage both in vitro and in vivo. Atg3 cleavage inactivates autophagy during apoptosis, and overexpression of non-cleavable Atg3 reestablishes autophagic activity. In vitro caspase cleavage assay, site-directed mutagenesis, caspase inhibitors, cell death assays Apoptosis High 22644571
2012 Crystallographic and mutational analyses of yeast (Atg7-Atg3)2 complexes reveal noncanonical, multisite E1-E2 recognition: Atg7's unique N-terminal domain recruits the 'backside' flexible element of Atg3, while Atg3's 'frontside' active site is presented to the catalytic cysteine of the opposite Atg7 protomer. X-ray crystallography, site-directed mutagenesis, biochemical assays Nature structural & molecular biology High 23142976
2013 The Atg12-Atg5 conjugate acts as an E3 enzyme for Atg3 by rearranging its catalytic site: Atg3 uses a threonine residue (instead of the typical asparagine) and its catalytic cysteine is suppressed in the resting state; Atg12-Atg5 induces reorientation of the cysteine toward the threonine, enhancing Atg3 conjugase activity. Biochemical reconstitution, structural analysis, site-directed mutagenesis Nature structural & molecular biology High 23503366
2013 The E3-binding site on human Atg3 overlaps with the E1 (Atg7)-binding site, making E1 and E3 binding mutually exclusive; short peptides from this region inhibit LC3 lipidation in vitro, implying Atg3 cycles between E1-bound and E3-bound states during the lipidation cascade. Bioinformatic identification, peptide competition assay, in vitro LC3 lipidation assay Protein science Medium 24186333
2013 Crystal structure of the minimal ATG12-ATG5-ATG16L1 E3 complex with an ATG3 fragment reveals that 13 residues of ATG3 form a short β-strand and α-helix on an ATG12 surface exclusive to ATG12; four critical residues make contacts with ATG12 and are required for E3 interaction and LC3 lipidation. X-ray crystallography, mutational analysis, LC3 lipidation assays Proceedings of the National Academy of Sciences of the United States of America High 24191030
2014 Atg3 contains an N-terminal amphipathic helix (AH) that senses membrane curvature/lipid-packing defects; lipidation of LC3/GABARAP by Atg3 occurs only on membranes with local lipid-packing defects. Tuning the hydrophobicity of this AH promotes or inhibits lipidation in vitro and in Atg3-knockout rescue experiments. In vitro lipidation reconstitution, mutagenesis of amphipathic helix, rescue experiments in Atg3-KO cells Nature cell biology High 24747438
2015 ATG12-ATG3 interacts with the ESCRT-associated protein Alix (PDCD6IP); this interaction controls late endosome distribution, exosome biogenesis, and viral budding, and is required for basal (but not starvation-induced) autophagic flux. Co-immunoprecipitation, loss-of-function experiments, endolysosomal trafficking assays, exosome quantification Nature cell biology High 25686249
2015 The N-terminal amino acid residues of Atg3 (specifically, Leu6 and surrounding residues) are essential for Atg8-PE conjugation and for interaction with the substrate PE. In vivo and in vitro mutagenesis, Atg8-PE conjugation assay FEBS letters Medium 19285500
2015 Atg3 localizes to the pre-autophagosomal structure (PAS) and isolation membrane (IM) in yeast; mutations in the AIM of Atg3 impair PAS/IM localization and result in inefficient isolation membrane expansion. Live-cell fluorescence imaging of GFP-tagged Atg3, co-localization with Atg8, mutational analysis FEBS letters Medium 25680528
2015 Atg3-GFP localizes to the isolation membrane during autophagy in S. cerevisiae, as shown by colocalization with Atg8 at autophagic structures, providing direct cellular evidence that Atg8-PE conjugation occurs on the isolation membrane. Live-cell fluorescence imaging of functional GFP-tagged Atg3, fine-localization analysis The Journal of biological chemistry Medium 25645919
2017 Acetylation of Atg3 at K19/K48 promotes its binding to PE-containing liposomes and to the endoplasmic reticulum, thereby promoting Atg8 lipidation; demonstrated using semisynthetically produced homogeneous diacetylated Atg3 in in vitro reconstitution. Semisynthesis via native chemical ligation, in vitro lipidation reconstitution, liposome binding assay Nature communications High 28327644
2017 PTK2 (FAK) phosphorylates ATG3 at tyrosine 203 in response to DNA-damaging agents, leading to ATG3 degradation; phospho-Y203 ATG3 was confirmed by phospho-specific antibody, PTK2 inhibitor, and siRNA. ATG3 also has an autophagy-independent function: it promotes DNA damage-induced mitotic catastrophe by binding to BAG3. Mass spectrometry, mutagenesis (Y203E/Y203F), phospho-specific antibody, kinase inhibitor, siRNA, Co-IP Autophagy High 28103122
2018 eIF5A is required for efficient translation of ATG3; a specific amino acid motif in ATG3 causes eIF5A dependency for its translation, and loss of eIF5A reduces ATG3 protein levels, LC3B lipidation, and autophagosome formation. High-throughput screen, western blotting, polysome profiling, C. elegans genetic validation EMBO reports Medium 29712776
2019 An element in Atg3 termed E123IR (E1, E2, and E3-interacting region) acts as an allosteric switch: in the absence of cascade partners, E123IR makes intramolecular interactions that restrain Atg3's catalytic loop; binding of E1 (Atg7) or E3 directly removes this brace to conformationally activate Atg3 for Atg8 lipidation. NMR, X-ray crystallography, biochemical assays, genetic yeast experiments Nature communications High 31399562
2021 An N-terminal conserved region of human ATG3 couples membrane curvature sensing (via the amphipathic helix) to catalytic activity of the C-terminal core; mutations in this communication region reduce or abolish LC3-PE conjugation in vitro and in vivo, and alter the membrane-bound conformation as shown by NMR. NMR, in vitro conjugation assay, mutagenesis, rescue in Atg3-KO cells Nature communications High 33446636
2021 ATG3 has an autophagy-independent role in lipid metabolism: hepatic knockdown of ATG3 reduces JNK1 activity, increases SIRT1 and CPT1a, and improves mitochondrial fatty acid oxidation, ameliorating steatosis independently of autophagic function. Genetic knockdown in mice and human hepatocytes, proteomic analysis, metabolic assays, epistasis with SIRT1/CPT1a knockdown Journal of hepatology Medium 34555423
2023 Molecular dynamics simulations and experiments show the amphipathic α-helix of ATG3 (AHATG3) has low hydrophobicity and less bulky residues, which regulate dynamics and accessibility of the ATG3~LC3 thioester bond to lipids; AHATG3 governs transient membrane association of ATG3 and remodels the lipid bilayer required for LC3 lipidation. Molecular dynamics simulations, mutagenesis, live-cell imaging, in vitro lipidation assays Science advances High 37352354
2023 The C-terminal catalytic regions of human ATG3 are conformationally dynamic and directly interact with the phagophore membrane in collaboration with the N-terminal curvature-sensitive helix; these multifaceted membrane interactions target the catalytic center to the membrane surface and promote LC3-PE conjugation. NMR, in vitro conjugation assay, mutagenesis, cellular autophagy assays Nature communications High 37679347
2023 A noncanonical LIR motif in the flexible region of human ATG3 binds to the backside of LC3 via a β-sheet conformation; this LIRATG3 is required for ATG3~LC3 thioester formation and subsequent LC3 lipidation, as demonstrated by CRISPR-enabled in cellulo studies and X-ray crystallography of the ATG3-LIR peptide/LC3 complex. X-ray crystallography, activity-based probes, CRISPR mutagenesis, thioester formation assay ACS central science High 37252361
2024 LC3 lipidation proceeds via a three-step docking mechanism: (i) WIPI2 recruits the ATG12-ATG5-ATG16L1/ATG3 complex via phosphatidylinositol 3-phosphate; (ii) helix α2 of ATG16L1 docks to the membrane; (iii) a membrane-interacting surface of ATG3 is engaged; PE lipids concentrate around the ATG3~LC3 thioester bond, with two conserved histidines implicated in the catalytic transfer. Molecular dynamics simulations, in vitro reconstitution, cellular assays Science advances Medium 38324698
2025 HDAC6 interacts with ATG3, deacetylates it, and also ubiquitinates ATG3 at lysine 272 via its E3 ligase activity, leading to ATG3 proteasomal degradation and regulation of autophagy; K272 is the target of both deacetylation and ubiquitination by HDAC6. Co-immunoprecipitation, site-directed mutagenesis, ubiquitination assay, western blotting Cell death and differentiation Medium 40739328
2025 Crystal structure of GABARAP~ATG3 isopeptide conjugate reveals a non-covalent backside interaction between GABARAP and the ATG3 E2 catalytic domain; this interface overlaps with the LIR-binding site on GABARAP. NMR confirms the interaction in solution, and mutagenesis of the E2 backside interface impairs PE conjugation. An intramolecular contact between the ATG3 flexible region and catalytic core suppresses conjugation activity in the apo state. X-ray crystallography, NMR, mutagenesis, PE conjugation assay, AlphaFold modeling Biochemistry High 40628661
2015 NMR data precisely define the region of the flexible region of human ATG3 that interacts with ATG7 (RIA7), showing it partially overlaps with the E3-interacting region, explaining mutual exclusivity of E1 and E3 binding to ATG3; critical residues for E1 interaction and GABARAP transfer were identified by mutagenesis. NMR, mutational analysis, GABARAP transfer assay Biochemical and biophysical research communications Medium 26043688

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. Nature cell biology 258 25686249
2010 ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death. Cell 241 20723759
2014 Lipidation of the LC3/GABARAP family of autophagy proteins relies on a membrane-curvature-sensing domain in Atg3. Nature cell biology 213 24747438
2015 Cytoplastic Glyceraldehyde-3-Phosphate Dehydrogenases Interact with ATG3 to Negatively Regulate Autophagy and Immunity in Nicotiana benthamiana. The Plant cell 153 25829441
2013 Uba1 functions in Atg7- and Atg3-independent autophagy. Nature cell biology 153 23873149
2011 Atg8 transfer from Atg7 to Atg3: a distinctive E1-E2 architecture and mechanism in the autophagy pathway. Molecular cell 145 22055190
2012 Cleavage of Atg3 protein by caspase-8 regulates autophagy during receptor-activated cell death. Apoptosis : an international journal on programmed cell death 138 22644571
2016 The long noncoding RNA HOTAIR activates autophagy by upregulating ATG3 and ATG7 in hepatocellular carcinoma. Molecular bioSystems 135 27301338
2013 Atg12-Atg5 conjugate enhances E2 activity of Atg3 by rearranging its catalytic site. Nature structural & molecular biology 128 23503366
2007 The crystal structure of Atg3, an autophagy-related ubiquitin carrier protein (E2) enzyme that mediates Atg8 lipidation. The Journal of biological chemistry 122 17227760
2018 Mycobacterium tuberculosis-induced miR-155 subverts autophagy by targeting ATG3 in human dendritic cells. PLoS pathogens 109 29300789
2019 LncRNA NEAT1 promotes autophagy via regulating miR-204/ATG3 and enhanced cell resistance to sorafenib in hepatocellular carcinoma. Journal of cellular physiology 101 31549407
2011 Autophagy protein Atg3 is essential for maintaining mitochondrial integrity and for normal intracellular development of Toxoplasma gondii tachyzoites. PLoS pathogens 94 22144900
2012 Noncanonical E2 recruitment by the autophagy E1 revealed by Atg7-Atg3 and Atg7-Atg10 structures. Nature structural & molecular biology 93 23142976
2017 Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3. Oncotarget 90 28423647
2010 Autophagy-related protein 8 (Atg8) family interacting motif in Atg3 mediates the Atg3-Atg8 interaction and is crucial for the cytoplasm-to-vacuole targeting pathway. The Journal of biological chemistry 90 20615880
2013 Structural basis of ATG3 recognition by the autophagic ubiquitin-like protein ATG12. Proceedings of the National Academy of Sciences of the United States of America 86 24191030
2016 ATG3-dependent autophagy mediates mitochondrial homeostasis in pluripotency acquirement and maintenance. Autophagy 84 27575019
2018 Effect of the LncRNA GAS5-MiR-23a-ATG3 Axis in Regulating Autophagy in Patients with Breast Cancer. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 80 30007957
2018 eIF5A is required for autophagy by mediating ATG3 translation. EMBO reports 78 29712776
2014 The E2-like conjugation enzyme Atg3 promotes binding of IRG and Gbp proteins to Chlamydia- and Toxoplasma-containing vacuoles and host resistance. PloS one 77 24466199
2019 Long non-coding RNA PVT1 promotes autophagy as ceRNA to target ATG3 by sponging microRNA-365 in hepatocellular carcinoma. Gene 72 30794914
2022 A novel long noncoding RNA SP100-AS1 induces radioresistance of colorectal cancer via sponging miR-622 and stabilizing ATG3. Cell death and differentiation 65 35978049
2019 Long Noncoding RNA KCNQ1OT1 Promotes the Progression of Non-Small Cell Lung Cancer via Regulating miR-204-5p/ATG3 Axis. OncoTargets and therapy 57 31849486
2018 RETRACTED: Long noncoding RNA RMRP upregulation aggravates myocardial ischemia-reperfusion injury by sponging miR-206 to target ATG3 expression. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 56 30551524
2009 The amino-terminal region of Atg3 is essential for association with phosphatidylethanolamine in Atg8 lipidation. FEBS letters 51 19285500
2021 Binding Features and Functions of ATG3. Frontiers in cell and developmental biology 46 34235149
2015 ATG12-ATG3 connects basal autophagy and late endosome function. Autophagy 46 25998418
2006 Atg8L/Apg8L is the fourth mammalian modifier of mammalian Atg8 conjugation mediated by human Atg4B, Atg7 and Atg3. The FEBS journal 46 16704426
2012 Structural characterization and inhibition of the Plasmodium Atg8-Atg3 interaction. Journal of structural biology 44 22982544
2014 Identification of an Atg8-Atg3 protein-protein interaction inhibitor from the medicines for Malaria Venture Malaria Box active in blood and liver stage Plasmodium falciparum parasites. Journal of medicinal chemistry 40 24786226
2019 A switch element in the autophagy E2 Atg3 mediates allosteric regulation across the lipidation cascade. Nature communications 38 31399562
2021 Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function. Journal of hepatology 37 34555423
2019 ATG3, a Target of miR-431-5p, Promotes Proliferation and Invasion of Colon Cancer via Promoting Autophagy. Cancer management and research 37 31849517
2017 A semisynthetic Atg3 reveals that acetylation promotes Atg3 membrane binding and Atg8 lipidation. Nature communications 37 28327644
2014 Identification of Atg3 as an intrinsically disordered polypeptide yields insights into the molecular dynamics of autophagy-related proteins in yeast. Autophagy 37 24879155
2012 Combination erlotinib-cisplatin and Atg3-mediated autophagy in erlotinib resistant lung cancer. PloS one 37 23119048
2017 Human ATG3 binding to lipid bilayers: role of lipid geometry, and electric charge. Scientific reports 35 29142222
2015 Localization of Atg3 to autophagy-related membranes and its enhancement by the Atg8-family interacting motif to promote expansion of the membranes. FEBS letters 34 25680528
2018 Knockdown of Long Non-Coding RNA GAS5 Increases miR-23a by Targeting ATG3 Involved in Autophagy and Cell Viability. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 32 30078013
2013 Structures of Atg7-Atg3 and Atg7-Atg10 reveal noncanonical mechanisms of E2 recruitment by the autophagy E1. Autophagy 32 23388412
2021 An N-terminal conserved region in human Atg3 couples membrane curvature sensitivity to conjugase activity during autophagy. Nature communications 30 33446636
2023 Multifaceted membrane interactions of human Atg3 promote LC3-phosphatidylethanolamine conjugation during autophagy. Nature communications 29 37679347
2024 Three-step docking by WIPI2, ATG16L1, and ATG3 delivers LC3 to the phagophore. Science advances 27 38324698
2011 Vaccinia virus leads to ATG12–ATG3 conjugation and deficiency in autophagosome formation. Autophagy 27 22024753
2015 Visualization of Atg3 during autophagosome formation in Saccharomyces cerevisiae. The Journal of biological chemistry 25 25645919
2015 Upregulation of ATG3 contributes to autophagy induced by the detachment of intestinal epithelial cells from the extracellular matrix, but promotes autophagy-independent apoptosis of the attached cells. Autophagy 25 26061804
2021 Platinum complexes inhibit HER-2 enriched and triple-negative breast cancer cells metabolism to suppress growth, stemness and migration by targeting PKM/LDHA and CCND1/BCL2/ATG3 signaling pathways. European journal of medicinal chemistry 24 34293698
2011 Atg3-mediated lipidation of Atg8 is involved in encystation of Acanthamoeba. The Korean journal of parasitology 24 21738264
2021 VDR/Atg3 Axis Regulates Slit Diaphragm to Tight Junction Transition via p62-Mediated Autophagy Pathway in Diabetic Nephropathy. Diabetes 23 34376476
2021 Cancer-Derived Exosomal miR-651 as a Diagnostic Marker Restrains Cisplatin Resistance and Directly Targets ATG3 for Cervical Cancer. Disease markers 23 34567283
2016 MicroRNA-495 regulates starvation-induced autophagy by targeting ATG3. FEBS letters 21 26910393
2014 Depletion of autophagy-related genes ATG3 and ATG5 in Tenebrio molitor leads to decreased survivability against an intracellular pathogen, Listeria monocytogenes. Archives of insect biochemistry and physiology 21 25403020
2023 Unique amphipathic α helix drives membrane insertion and enzymatic activity of ATG3. Science advances 20 37352354
2020 Let-7c-3p Regulates Autophagy under Oxidative Stress by Targeting ATG3 in Lens Epithelial Cells. BioMed research international 20 32258130
2016 Atg3 Overexpression Enhances Bortezomib-Induced Cell Death in SKM-1 Cell. PloS one 20 27391105
2021 Propofol protects cardiomyocytes from hypoxia/reoxygenation injury via regulating MALAT1/miR-206/ATG3 axis. Journal of biochemical and molecular toxicology 19 34383354
2013 Binding to E1 and E3 is mutually exclusive for the human autophagy E2 Atg3. Protein science : a publication of the Protein Society 19 24186333
2016 Virtual Screening and Experimental Validation Identify Novel Inhibitors of the Plasmodium falciparum Atg8-Atg3 Protein-Protein Interaction. ChemMedChem 18 26748931
2018 Atg12-Atg3 Coordinates Basal Autophagy, Endolysosomal Trafficking, and Exosome Release. Molecular & cellular oncology 17 30263931
2017 PTK2-mediated degradation of ATG3 impedes cancer cells susceptible to DNA damage treatment. Autophagy 17 28103122
2023 Semisynthetic LC3 Probes for Autophagy Pathways Reveal a Noncanonical LC3 Interacting Region Motif Crucial for the Enzymatic Activity of Human ATG3. ACS central science 14 37252361
2021 ATG3 Is Important for the Chorion Ultrastructure During Oogenesis in the Insect Vector Rhodnius prolixus. Frontiers in physiology 14 33613326
2019 Autophagy Related Gene (ATG3) is a Key Regulator for Cell Growth, Development, and Virulence of Fusarium oxysporum. Genes 14 31466418
2018 Salinomycin-induced autophagy blocks apoptosis via the ATG3/AKT/mTOR signaling axis in PC-3 cells. Life sciences 14 29966607
2018 Characterization of Plasmodium Atg3-Atg8 Interaction Inhibitors Identifies Novel Alternative Mechanisms of Action in Toxoplasma gondii. Antimicrobial agents and chemotherapy 13 29158278
2021 Autophagy Inhibition by ATG3 Knockdown Remits Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury and Inflammation in Brain Microvascular Endothelial Cells. Neurochemical research 12 34379294
2019 Allosteric regulation through a switch element in the autophagy E2, Atg3. Autophagy 12 31690182
2023 Identifying a selective inhibitor of autophagy that targets ATG12-ATG3 protein-protein interaction. Autophagy 11 37184247
2021 Knockdown of long non-coding RNA RMRP protects cerebral ischemia-reperfusion injury via the microRNA-613/ATG3 axis and the JAK2/STAT3 pathway. The Kaohsiung journal of medical sciences 10 33560543
2021 Multiple structural rearrangements mediated by high-plasticity regions in Atg3 are key for efficient conjugation of Atg8 to PE during autophagy. Autophagy 10 34338142
2021 Metabolic Rewiring Is Essential for AML Cell Survival to Overcome Autophagy Inhibition by Loss of ATG3. Cancers 10 34885250
2018 Structure-based drug design, synthesis and biological assays of P. falciparum Atg3-Atg8 protein-protein interaction inhibitors. Journal of computer-aided molecular design 10 29383466
2018 EIF5A mediates autophagy via translation of ATG3. Autophagy 10 29973124
2018 Characterization of the molecular mechanism of the autophagy-related Atg8-Atg3 protein interaction in Toxoplasma gondii. The Journal of biological chemistry 9 30026233
2015 Identification and characterization of the linear region of ATG3 that interacts with ATG7 in higher eukaryotes. Biochemical and biophysical research communications 9 26043688
2023 Redox-mediated activation of ATG3 promotes ATG8 lipidation and autophagy progression in Chlamydomonas reinhardtii. Plant physiology 8 37772945
2018 ERK-mediated autophagy promotes inactivated Sendai virus (HVJ-E)-induced apoptosis in HeLa cells in an Atg3-dependent manner. Cancer cell international 8 30534001
2014 Lentiviral vector-mediate ATG3 overexpression inhibits growth and promotes apoptosis of human SKM-1 cells. Molecular biology reports 8 24420857
2025 Betaine inhibits the stem cell-like properties of hepatocellular carcinoma by activating autophagy via SAM/m6A/YTHDF1-mediated enhancement on ATG3 stability. Theranostics 7 39897540
2021 miR-651-3p Enhances the Sensitivity of Hepatocellular Carcinoma to Cisplatin via Targeting ATG3-Mediated Cell Autophagy. Journal of oncology 7 34457004
2021 Long non-coding RNA ANRIL mitigates neonatal hypoxic-ischemic brain damage via targeting the miR-378b/ATG3 axis. American journal of translational research 7 34786084
2019 The combination of lonafarnib and sorafenib induces cyclin D1 degradation via ATG3-mediated autophagic flux in hepatocellular carcinoma cells. Aging 7 31409760
2024 Curcumin enhances ATG3-dependent autophagy and inhibits metastasis in cervical carcinoma. Cell division 6 39609925
2022 Silencing the Autophagy-Related Genes ATG3 and ATG9 Promotes SRBSDV Propagation and Transmission in Sogatella furcifera. Insects 6 35447836
2006 Crystallization and preliminary X-ray analysis of Atg3. Acta crystallographica. Section F, Structural biology and crystallization communications 5 17012800
2021 Identification of novel Atg3-Atg8 inhibitors using virtual screening for autophagy modulation. Bioorganic chemistry 4 34147881
2023 Japanese Flounder pol-miR-155 Is Involved in Edwardsiella tarda Infection via ATG3. Genes 3 37239318
2012 Role of ATG3 in the parasite Toxoplasma gondii: autophagy in an early branching eukaryote. Autophagy 3 22361579
2025 Role of Atg3, Atg5 and Atg12 in the crosstalk between apoptosis and autophagy in the posterior silk gland of Bombyx mori. Insect molecular biology 2 39910402
2025 Histone deacetylase 6 deacetylates and ubiquitinates ATG3 to regulate autophagy. Cell death and differentiation 2 40739328
2025 Draper-ATG3 Interaction Positively Regulates Autophagy to Mediate Silk Gland Degradation in Bombyx mori. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 40953285
2024 Structure-activity relationship study of small-molecule inhibitor of Atg12-Atg3 protein-protein interaction. Bioorganic & medicinal chemistry letters 2 39218407
2025 ATG-3 limits Orsay virus infection in C. elegans through regulation of collagen pathways. bioRxiv : the preprint server for biology 1 39868230
2024 Menthol induces extracellular vesicle regulation of apoptosis via ATG3 and caspase-3 in acute leukemic cells. Heliyon 1 39021955
2021 NMR resonance assignments of human Atg3 in aqueous solution and bicelles. Biomolecular NMR assignments 1 34296398
2025 Structural Insights into the GABARAP-ATG3 Backside Interaction and Apo ATG3 Conformation. Biochemistry 0 40628661
2025 Targeting the ATG12-ATG3 protein-protein interaction: From structural insights to therapeutic opportunities in autophagy modulation. Pathology, research and practice 0 40763565
2024 Structural Analyses of a GABARAP~ATG3 Conjugate Uncover a Novel Non-covalent Ubl-E2 Backside Interaction. bioRxiv : the preprint server for biology 0 39185234
2023 ATG3 proteins possess a unique amphipathic α-helix essential for the Atg8/LC3 lipidation reaction. Autophagy 0 37679935