Affinage

ATG5

Autophagy protein 5 · UniProt Q9H1Y0

Length
275 aa
Mass
32.4 kDa
Annotated
2026-06-09
100 papers in source corpus 28 papers cited in narrative 28 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATG5 is a core autophagy effector that, after covalent conjugation to ATG12, assembles with ATG16L1 into a large (~800 kDa) E3-like complex on the autophagic isolation membrane to drive LC3/ATG8 lipidation and autophagosome formation (PMID:11266458, PMID:12665549, PMID:37062893). The pathway is evolutionarily conserved from yeast APG5, where it is essential for starvation-induced autophagy (PMID:8921905), to mammals, where the ATG12–ATG5 conjugate and the ATG16L1 oligomer co-localize to the elongating isolation membrane and are required for LC3 targeting and membrane elongation (PMID:11266458, PMID:11897782, PMID:12665549). In reconstitution, the purified ATG12–ATG5–ATG16L1 complex accelerates LC3/GABARAP lipidation and tethers vesicles while restraining inter-vesicular fusion, positioning it as the regulator of phagophore expansion (PMID:37062893); conjugation of ATG12 to ATG5 is dispensable for membrane targeting but required for elongation (PMID:11266458). ATG5 activity is gated by post-translational control: HACE1 directs K63-linked ubiquitination driving proteasomal degradation, USP22 removes K27/K48 chains at Lys118 to stabilize the protein, and calpain cleaves ATG5 to impair autophagic flux under ischemic stress (PMID:40126194, PMID:35900990, PMID:36562207). Beyond canonical autophagy, ATG5 acts independently of the conjugation machinery in several settings: it engages alternative E3-like partners such as TECPR1 to drive ATG16L1-independent LC3 lipidation at damaged lysosomes (PMID:37381828), translocates to the nucleus to bind survivin and trigger mitotic catastrophe after DNA damage (PMID:23945651), recognizes phosphorylated dimerized BST2/tetherin at the plasma membrane to initiate an LC3C-associated pathway against HIV-1 (PMID:37155854), and restrains type I interferon-driven NET release and CXCL2 secretion in neutrophils during M. tuberculosis infection (PMID:40374743). ATG5-dependent autophagy further shapes cell-fate and immune outcomes by degrading SOCS2 to license JAK2-STAT3-driven astrocyte differentiation (PMID:25227738), suppressing NF-κB and NLRP3 inflammasome signaling (PMID:30874544, PMID:35900990), and controlling lysosomal exocytosis and extracellular-vesicle secretion via an ATG12–ATG3–ALIX axis (PMID:37054706). A homozygous missense ATG5 mutation that impairs ATG12 conjugation and autophagy flux causes congenital ataxia with intellectual disability in humans (PMID:26812546).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1996 High

    Established that the ATG5 gene product is genetically required for autophagy, defining its foundational loss-of-function phenotype.

    Evidence Yeast APG5 null mutant with complementation and microscopic scoring of autophagic bodies under nitrogen starvation

    PMID:8921905

    Open questions at the time
    • No molecular mechanism for how APG5 acts on membranes
    • Mammalian relevance not yet shown
  2. 1998 Medium

    Identified the human ortholog, extending the autophagy role to mammalian cells.

    Evidence cDNA cloning of human ATG5 with sequence homology and Northern blot expression analysis

    PMID:9563500

    Open questions at the time
    • Functional validation in human cells indirect
    • No partner or complex identified
  3. 2001 High

    Resolved where and when ATG5 acts, showing the ATG12–ATG5 conjugate marks the elongating isolation membrane and is needed for LC3 targeting.

    Evidence GFP-ATG5 live imaging, ATG5-knockout mouse ES cells, immunofluorescence and electron microscopy

    PMID:11266458

    Open questions at the time
    • Catalytic mechanism of LC3 conjugation not defined
    • Role of conjugation versus targeting partially separated
  4. 2002 High

    Defined the higher-order complex architecture by showing ATG16 oligomerization assembles a multimeric ATG12–ATG5–ATG16 complex essential for activity.

    Evidence In vivo oligomerization control system, size-exclusion chromatography, autophagy assays in yeast

    PMID:11897782

    Open questions at the time
    • Mammalian complex stoichiometry not addressed
    • How oligomerization couples to lipidation unknown
  5. 2003 High

    Identified ATG16L1 as the mammalian partner forming the ~800 kDa complex and mapped ATG5-dependent membrane targeting.

    Evidence Co-immunoprecipitation, size-exclusion chromatography, immunofluorescence and domain-deletion analysis in mouse cells

    PMID:12665549

    Open questions at the time
    • WD-domain function unresolved at this stage
    • Catalytic basis of E3-like activity not shown
  6. 2009 High

    Revealed that autophagosomes can form without ATG5 via an LC3-lipidation-independent, Rab9-dependent alternative pathway, distinguishing canonical from alternative macroautophagy.

    Evidence ATG5- and ATG7-knockout mouse cells, electron microscopy, LC3 lipidation assays, in vivo erythroid maturation

    PMID:19794493

    Open questions at the time
    • Molecular machinery of the alternative pathway incomplete
    • Physiological triggers selecting each pathway unclear
  7. 2013 High

    Uncovered an autophagy-independent nuclear function in which ATG5 binds survivin to trigger mitotic catastrophe after DNA damage.

    Evidence Nuclear fractionation, ATG5–survivin co-IP, pharmacological autophagy inhibition, patient carcinoma immunohistochemistry

    PMID:23945651

    Open questions at the time
    • Signal driving ATG5 nuclear translocation unknown
    • Structural basis of ATG5–survivin binding undefined
  8. 2016 High

    Linked ATG5 directly to human disease, showing a conjugation-impairing missense mutation causes congenital ataxia with intellectual disability.

    Evidence Human genetics, autophagy flux and ATG12–ATG5 conjugation assays in patient cells, yeast and Drosophila models

    PMID:26812546

    Open questions at the time
    • Tissue-specific basis of neurological phenotype unresolved
    • Whether non-autophagic ATG5 roles contribute not tested
  9. 2016 High

    Connected ATG5-dependent autophagy to cell-cycle control and differentiation through autophagy-competence-dependent rescue and substrate degradation.

    Evidence Conditional knockout mice, ATG5 K130R autophagy-incompetent mutant rescue, SOCS2/STAT3 epistasis, flow cytometry and immunofluorescence

    PMID:25227738 PMID:27304991

    Open questions at the time
    • Direct mechanism coupling autophagy to G2/M arrest unclear
    • Generality across tissues not established
  10. 2017 Medium

    Identified upstream regulators (RACK1, GTP-RAB37) and a transcriptional pathway (p73-DAPK2) that promote ATG5 complex assembly and stimulus-specific autophagy.

    Evidence Co-immunoprecipitation, GTP/GDP and binding-deficient mutants, knockdown, LC3 lipidation and APL cell assays

    PMID:27325703 PMID:28978663 PMID:29229996

    Open questions at the time
    • Single-lab interaction studies
    • Hierarchy among these regulators unknown
  11. 2018 High

    Separated canonical autophagy from non-canonical pathways by domain dissection and revealed ATG5's role in immune-synapse organization.

    Evidence ATG16L1 domain-deletion mouse knockins, conditional B-cell ATG5 KO, immunofluorescence, ATG16L1–PCM1 co-IP and antigen-presentation assays

    PMID:30196744 PMID:30403914

    Open questions at the time
    • Molecular link between complex and centrosome relocalization incomplete
    • WD-domain LAP mechanism not fully defined
  12. 2019 High

    Demonstrated ATG5-dependent autophagy restrains inflammatory and lipid-handling programs in tubular and dendritic cells.

    Evidence Conditional KO mice, ATG5–p65 co-IP, ATG5 K130R mutant, CD36 blockade and T-cell priming assays

    PMID:30874544 PMID:30900506

    Open questions at the time
    • Whether p65 is an autophagy substrate or binding partner not resolved
    • Mechanism of CD36 regulation incomplete
  13. 2022 Medium

    Defined post-translational stability control of ATG5 through opposing ubiquitination by HACE1 and deubiquitination by USP22, coupling ATG5 levels to inflammasome and chemotherapy responses.

    Evidence Co-IP, ubiquitination site mapping (K63; K118 with K27/K48 chains), ChIP, knockdown/knockout and inflammasome assays

    PMID:35900990 PMID:40126194

    Open questions at the time
    • Single-lab site-mapping studies
    • Interplay between competing modifications in vivo unclear
  14. 2023 High

    Reconstituted the E3-like complex's biochemical activity and uncovered ATG16L1-independent and conjugation-independent functions at lysosomes and the plasma membrane.

    Evidence In vitro reconstitution with purified complex and liposome tethering/lipid-mixing assays; TECPR1–ATG12–ATG5 co-IP with double KO; ATG5–BST2 co-IP with phospho/dimerization and conjugation-deficient mutants; ATG12–ATG3–ALIX co-IP across ATG KO lines

    PMID:37054706 PMID:37062893 PMID:37155854 PMID:37381828

    Open questions at the time
    • Structural switch between tethering and fusion not defined
    • Selection between ATG16L1 and TECPR1 routes context-dependent and incompletely mapped
  15. 2024 Medium

    Extended ATG5's autophagic and non-autophagic roles to spermine metabolism, lipophagy-driven ferroptosis, and calpain-regulated cardiac injury.

    Evidence Co-IP with SMOX and perilipin3, knockdown/knockout models, spermine and lipidomic measurements, diabetic I/R model with ATG5/LAMP2 overexpression

    PMID:36562207 PMID:38775007 PMID:39636725

    Open questions at the time
    • Single-lab interaction studies
    • Direct versus indirect basis of metabolic effects unresolved
  16. 2025 High

    Established an autophagy-independent neutrophil function in which ATG5 suppresses type I interferon-driven NET release and CXCL2-mediated swarming during infection.

    Evidence Atg5fl/fl-LysM-Cre conditional KO mice, in vivo and in vitro M. tuberculosis infection, PAD4 citrullination, NET and CXCL2 assays

    PMID:40374743

    Open questions at the time
    • Molecular target of ATG5 in the IFN/PAD4 axis unidentified
    • Whether this requires ATG5 conjugation not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single protein partitions between its canonical conjugation-dependent E3-like role and its multiple conjugation- and ATG16L1-independent functions remains the central open question.
  • No unifying structural model for partner switching (ATG16L1 vs TECPR1 vs survivin vs BST2)
  • Signals dictating nuclear versus membrane versus complex localization unknown
  • Relative in vivo contribution of non-canonical functions to disease unquantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0016740 transferase activity 2
Localization
GO:0005764 lysosome 2 GO:0031410 cytoplasmic vesicle 2 GO:0005634 nucleus 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-9612973 Autophagy 4 R-HSA-1640170 Cell Cycle 2 R-HSA-5653656 Vesicle-mediated transport 1
Partners
ATG12ATG16L1BST2DAPK2RAB37RACK1SMOXTECPR1
Complex memberships
ATG12–ATG3–ALIX complexATG12–ATG5–ATG16L1 E3-like complexTECPR1–ATG12–ATG5 alternative conjugation complex

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 APG5 (yeast ortholog of ATG5) is required for autophagy in Saccharomyces cerevisiae; null mutant cells fail to sequester autophagic bodies in the vacuole under nitrogen starvation, demonstrating that APG5 function is essential specifically under nutrient-starvation conditions. Yeast null mutant construction, complementation of autophagy-defective phenotype, microscopic analysis of autophagic bodies Gene High 8921905
1998 Human ATG5 (hAPG5) was cloned and shown to share significant homology with yeast APG5, identifying it as the mammalian ortholog involved in autophagy; protein expression is regulated at the translational level. cDNA cloning from human expression library, sequence homology analysis, Northern blot FEBS letters Medium 9563500
2001 The ATG12–ATG5 conjugate localizes to the isolation membrane throughout its elongation process and is required for autophagosome formation; the covalent modification of ATG5 with ATG12 is not required for membrane targeting of ATG5 but is essential for isolation membrane elongation. ATG12–ATG5 is also required for targeting of the mammalian ATG8 homolog LC3 to isolation membranes. GFP-tagged ATG5 live imaging, ATG5-deficient mouse embryonic stem cells (genetic knockout), immunofluorescence, electron microscopy The Journal of cell biology High 11266458
2002 In yeast, the APG12–APG5 conjugate and APG16 form an ~350 kDa multimeric complex; this complex formation, mediated by APG16 homo-oligomerization, is essential for autophagic activity. In vivo oligomerization control system, size-exclusion chromatography, autophagy activity assays in yeast The Journal of biological chemistry High 11897782
2003 Mouse ATG16L (Apg16L) is a novel WD-repeat protein that interacts with ATG5 (and with additional ATG16L monomers) to form an ~800 kDa complex containing the ATG12–ATG5 conjugate; this complex associates with the autophagic isolation membrane. Membrane targeting of ATG16L requires ATG5 but not ATG12. The WD-repeat domain is not required for ATG5 binding or ATG16L oligomerization. Co-immunoprecipitation, size-exclusion chromatography, immunofluorescence localization, domain-deletion analysis Journal of cell science High 12665549
2009 Mouse cells lacking ATG5 or ATG7 can still form autophagosomes/autolysosomes and perform autophagy-mediated protein degradation under certain stresses via an alternative macroautophagy pathway. This ATG5/ATG7-independent alternative autophagy does not involve LC3 lipidation but is Rab9-dependent, and autophagosomes are generated by fusion of isolation membranes with vesicles from the trans-Golgi and late endosomes. ATG5-knockout and ATG7-knockout mouse cells, electron microscopy, LC3 lipidation assays, Rab9 dependency analysis, in vivo erythroid maturation studies Nature High 19794493
2013 ATG5 translocates to the nucleus in response to DNA-damaging agents (etoposide, cisplatin) where it physically interacts with survivin, displacing elements of the chromosomal passenger complex and causing chromosome misalignment and mitotic catastrophe independently of autophagy. Nuclear fractionation, co-immunoprecipitation (ATG5–survivin interaction), pharmacological autophagy inhibition, immunohistochemistry in patient carcinoma tissues Nature communications High 23945651
2014 ATG5-mediated autophagy promotes astrocyte differentiation in the developing mouse cortex by degrading the inhibitory protein SOCS2, thereby activating the JAK2-STAT3 pathway; the differentiation defect from ATG5 loss can be rescued by SOCS2 knockdown or STAT3 overexpression. In vivo conditional knockout, in vitro ATG5 overexpression and knockdown, epistasis rescue experiments (SOCS2 KD, STAT3 OE), immunofluorescence EMBO reports High 25227738
2016 A homozygous missense mutation in ATG5 in human patients causes congenital ataxia with mental retardation; patient cells display decreased autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous yeast mutation reduces autophagy 30–50%, and flies expressing the mutant human ATG5 exhibit severe movement disorder. Human genetics (homozygous patient mutation), autophagy flux assay in patient cells, ATG12–ATG5 conjugation assay, yeast homologous mutation, Drosophila substitution experiments eLife High 26812546
2016 Proximal tubule-specific deletion of ATG5 in mice causes marked G2/M cell cycle arrest and severe renal fibrosis; overexpression of wild-type ATG5, but not the autophagy-incompetent ATG5 K130R mutant, rescues G2/M arrest, demonstrating that ATG5 regulates cell cycle progression in an autophagy-dependent manner. Conditional knockout mice (UUO model), primary tubular cell culture, ATG5 K130R mutant rescue experiment, flow cytometry cell-cycle analysis, Western blot Autophagy High 27304991
2016 RACK1 (GNB2L1) is a novel ATG5-interacting protein; RACK1–ATG5 interaction is stimulated by canonical autophagy inducers (starvation, mTOR inhibition) and is required for autophagy activation, as RACK1 knockdown or prevention of its binding to ATG5 by mutagenesis blocks autophagy. Co-immunoprecipitation, mutagenesis preventing RACK1–ATG5 binding, RACK1 knockdown, multiple independent interaction techniques The Journal of biological chemistry Medium 27325703
2017 RAB37, when GTP-bound, directly binds ATG5 and promotes formation of the ATG5–ATG12–ATG16L1 complex on the isolation membrane, facilitating LC3B lipidation and autophagosome formation; GDP-stabilized RAB37 impairs this interaction. Co-immunoprecipitation, mutation analysis (GTP/GDP forms), LC3B lipidation assay, autophagosome formation assay, ATG16L1 interaction assay Cell death and differentiation Medium 29229996
2017 DAPK2 interacts with ATG5 and this interaction is essential for ATRA-induced autophagy in APL cells; TP73-mediated transcription of DAPK2 drives the p73-DAPK2-ATG5 pathway for autophagy. In contrast, DAPK2 mediates ATO-induced apoptosis independently of ATG5. Co-immunoprecipitation (DAPK2–ATG5 interaction), DAPK2 and TP73 siRNA knockdown, pathway epistasis, APL cell treatment assays Journal of leukocyte biology Medium 28978663
2018 ATG5 is required for BCR polarization, centrosome relocalization to the immune synapse, and actin nucleation in B cells after BCR stimulation; the ATG12–ATG5–ATG16L1 complex interacts with the centrosome-associated protein PCM1, which is required for BCR polarization and MHC class II antigen presentation of particulate antigens. ATG5-conditional B cell knockout mice, immunofluorescence (BCR polarization, centrosome, actin), co-immunoprecipitation (ATG16L1–PCM1), T cell priming assays Autophagy Medium 30196744
2018 The ATG5-binding and coiled-coil domains of ATG16L1 are sufficient for canonical autophagy and tissue homeostasis in mice, whereas the WD domain of ATG16L1 is specifically required for LC3-associated phagocytosis (LAP) but not for canonical autophagy. Domain-deletion mouse models (WD-domain deletion, coiled-coil E230 deletion), autophagy cargo assays (LC3, p62), tissue histology, SQSTM1 inclusion analysis Autophagy High 30403914
2019 ATG5-mediated autophagy in proximal tubular epithelial cells suppresses NF-κB signaling: ATG5 co-immunoprecipitates with NF-κB p65, and ATG5 (but not autophagy-incompetent ATG5 K130R mutant) reduces angiotensin II-induced phosphorylation and nuclear translocation of p65, thereby reducing pro-inflammatory cytokine production. Conditional tubule-specific ATG5 KO mice, co-immunoprecipitation (ATG5–p65), immunofluorescence colocalization, siRNA knockdown, ATG5 K130R mutant, UUO in vivo model Cell death & disease High 30874544
2019 ATG5 regulates CD36 expression and MHC class II antigen presentation in dendritic cells: ATG5 deletion leads to elevated CD36 expression and excessive lipid accumulation, causing increased phagocytosis of apoptotic tumor cells but reduced CD4+ T cell priming. Dendritic cell-specific ATG5 conditional knockout mice, CD36 blockade experiments, T cell priming assays, lipid accumulation assays Autophagy Medium 30900506
2020 Calpain-mediated proteolytic cleavage of ATG5 (and LAMP2) during diabetic myocardial ischemia-reperfusion injury impairs autophagic flux; calpain inhibition restores ATG5 levels and co-overexpression of ATG5 and LAMP2 reduces myocardial injury and normalizes autophagic flux. STZ-induced diabetic mouse I/R model, calpain inhibition, co-overexpression of ATG5+LAMP2, Western blot, LC3/p62 flux assays Journal of cellular and molecular medicine Medium 36562207
2022 USP22 stabilizes ATG5 by removing K27- and K48-linked ubiquitin chains at Lys118, thereby preventing ATG5 degradation and promoting ATG5-mediated autophagy to suppress NLRP3 inflammasome activation. Co-immunoprecipitation, ubiquitination site mapping (K118), USP22 knockdown/knockout, NLRP3 inflammasome activation assays, in vivo inflammation models Autophagy Medium 35900990
2022 A hydrocarbon-stapled peptide derived from ATG16L1 binds ATG5 with high affinity, resists proteolysis, and inhibits autophagy in cells by disrupting the ATG5–ATG16L1 protein-protein interaction. Stapled peptide synthesis, binding affinity assay, proteolysis resistance assay, cell-based autophagy inhibition assay Journal of the American Chemical Society Medium 36107218
2023 ATG5, in the absence of other canonical autophagy ATGs, prevents lysosomal exocytosis and excessive secretion of extracellular vesicles; loss of ATG5 (but not other canonical ATGs) promotes lysosomal disrepair. An alternative conjugation complex, ATG12–ATG3, sequesters ESCRT protein ALIX in ATG5 KO cells, impairing membrane repair and exosome secretion. In murine neutrophils, ATG5 loss causes excessive degranulation. ATG5 and other ATG knockout human cell lines, lysosomal exocytosis assay, extracellular vesicle secretion assay, ATG12–ATG3–ALIX co-immunoprecipitation, murine Atg5fl/fl LysM-Cre neutrophil degranulation assay Developmental cell High 37054706
2023 TECPR1 forms an alternative E3-like conjugation complex with the ATG12–ATG5 conjugate at damaged lysosomes that regulates ATG16L1-independent unconventional LC3 lipidation; TECPR1 recruitment to damaged membranes occurs via its N-terminal dysferlin domain and precedes lysophagy induction. Double knockout of ATG16L1 and TECPR1 abolishes LC3 lipidation and impairs lysosomal recovery. Co-immunoprecipitation (TECPR1–ATG12–ATG5 complex), domain deletion analysis (dysferlin domain), ATG16L1/TECPR1 double knockout, LC3 lipidation assays, lysosomal damage recovery assay EMBO reports High 37381828
2023 ATG5 specifically recognizes cysteine-linked homodimerized, phosphorylated BST2/tetherin that is tethering HIV-1 virions at the plasma membrane; ATG5 and BST2 form a complex independently of Vpu and ahead of LC3C recruitment, initiating an LC3C-associated pathway. ATG12 conjugation to ATG5 is dispensable for this BST2 interaction. Co-immunoprecipitation (ATG5–BST2 complex), BST2 phosphorylation/dimerization mutants, Vpu-independent complex formation assay, ATG12–ATG5 conjugation-deficient mutant analysis, LC3C recruitment assay Proceedings of the National Academy of Sciences of the United States of America High 37155854
2023 The ATG12–ATG5–ATG16L1 complex (E3) increases and accelerates LC3/GABARAP lipidation and promotes vesicle tethering but inhibits LC3/GABARAP-induced inter-vesicular lipid mixing/fusion, suggesting the complex regulates phagophore expansion by modulating tethering versus fusion activities. In vitro reconstitution with purified ATG12–ATG5–ATG16L1 complex, liposome-based LC3 lipidation assay, vesicle tethering and lipid mixing assays Autophagy High 37062893
2025 ATG5 in neutrophils suppresses type I interferon-induced PAD4-mediated histone citrullination and NET release, and suppresses type I IFN-induced CXCL2 secretion and neutrophil swarming during M. tuberculosis infection; this function is autophagy-independent. Atg5fl/fl-LysM-Cre conditional KO mice, in vivo and in vitro Mtb infection, PAD4 citrullination assay, NET release assay, CXCL2 secretion assay, type I IFN pathway analysis Nature microbiology High 40374743
2022 HACE1 E3 ubiquitin ligase promotes K63-linked ubiquitination of ATG5, leading to its proteasomal degradation; HMBOX1 transcriptionally upregulates HACE1, thereby reducing ATG5 protein levels and inhibiting autophagy to sensitize colorectal cancer cells to 5-fluorouracil. Mass-spectrometry proteomics, co-immunoprecipitation, ubiquitination site mapping (K63), ChIP assay (HMBOX1 on HACE1 promoter), in vivo xenograft, single-cell RNA sequencing Autophagy Medium 40126194
2024 ATG5 interacts with SMOX (spermine oxidase) under physiological conditions and during TGF-β1-induced fibrogenesis, preserving cellular spermine levels; ATG5 downregulation increases SMOX expression and reduces spermine, promoting renal senescence and fibrosis. Co-immunoprecipitation (ATG5–SMOX), ATG5 knockdown in tubular epithelial cells, SMOX genetic knockout mice, spermine measurement, fibrosis assays in vivo Advanced science Medium 38775007
2024 ATG5 mediates lipophagy in corneal epithelial cells under hyperosmotic stress by interacting with perilipin3 (confirmed by co-immunoprecipitation and immunofluorescence); this lipophagy increases free fatty acid levels and lipid peroxidation, driving ferroptosis. ATG5 inhibition ameliorates corneal damage and suppresses ferroptosis in a dry eye mouse model. Co-immunoprecipitation (ATG5–perilipin3), immunofluorescence colocalization, siRNA-mediated ATG5 inhibition in vivo (cholesterol-modified siRNA), lipidomics, ferroptosis marker assays, transmission electron microscopy Investigative ophthalmology & visual science Medium 39636725

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Dissection of autophagosome formation using Apg5-deficient mouse embryonic stem cells. The Journal of cell biology 1190 11266458
2009 Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 932 19794493
2003 Mouse Apg16L, a novel WD-repeat protein, targets to the autophagic isolation membrane with the Apg12-Apg5 conjugate. Journal of cell science 631 12665549
2006 A critical role for the autophagy gene Atg5 in T cell survival and proliferation. The Journal of experimental medicine 532 17190837
2002 Formation of the approximately 350-kDa Apg12-Apg5.Apg16 multimeric complex, mediated by Apg16 oligomerization, is essential for autophagy in yeast. The Journal of biological chemistry 370 11897782
2019 m6A mRNA methylation controls autophagy and adipogenesis by targeting Atg5 and Atg7. Autophagy 321 31451060
2018 Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases. Frontiers in immunology 239 30386331
2011 Genetic association of PRDM1-ATG5 intergenic region and autophagy with systemic lupus erythematosus in a Chinese population. Annals of the rheumatic diseases 187 21622776
2016 Atg5-mediated autophagy deficiency in proximal tubules promotes cell cycle G2/M arrest and renal fibrosis. Autophagy 175 27304991
2016 Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay. eLife 174 26812546
2009 Identification of Atg5-dependent transcriptional changes and increases in mitochondrial mass in Atg5-deficient T lymphocytes. Autophagy 162 19276668
2021 GLS-driven glutamine catabolism contributes to prostate cancer radiosensitivity by regulating the redox state, stemness and ATG5-mediated autophagy. Theranostics 144 34335968
2017 Molecular mechanisms and physiological roles of Atg5/Atg7-independent alternative autophagy. Proceedings of the Japan Academy. Series B, Physical and biological sciences 142 28603209
2022 Exosomal LOC85009 inhibits docetaxel resistance in lung adenocarcinoma through regulating ATG5-induced autophagy. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 137 36641841
2019 ATG5 and ATG7 induced autophagy interplays with UPR via PERK signaling. Cell communication and signaling : CCS 136 31060556
2019 ATG5-mediated autophagy suppresses NF-κB signaling to limit epithelial inflammatory response to kidney injury. Cell death & disease 133 30874544
2013 ATG5 regulates plasma cell differentiation. Autophagy 128 23327930
2013 ATG5 is induced by DNA-damaging agents and promotes mitotic catastrophe independent of autophagy. Nature communications 128 23945651
2009 Atg5 regulates phenethyl isothiocyanate-induced autophagic and apoptotic cell death in human prostate cancer cells. Cancer research 128 19336571
2009 Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis. Autophagy 126 19066443
2020 Autophagy core protein ATG5 is required for elongating spermatid development, sperm individualization and normal fertility in male mice. Autophagy 107 32677505
2009 Atg5-independent sequestration of ubiquitinated mycobacteria. PLoS pathogens 105 19436699
2019 Autophagy protein ATG5 regulates CD36 expression and anti-tumor MHC class II antigen presentation in dendritic cells. Autophagy 95 30900506
2019 Sodium butyrate causes α-synuclein degradation by an Atg5-dependent and PI3K/Akt/mTOR-related autophagy pathway. Experimental cell research 92 31836471
2016 TRIM31 promotes Atg5/Atg7-independent autophagy in intestinal cells. Nature communications 89 27216961
1996 Structural and functional analyses of APG5, a gene involved in autophagy in yeast. Gene 84 8921905
2018 The ATG5-binding and coiled coil domains of ATG16L1 maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3-associated phagocytosis. Autophagy 83 30403914
2017 RAB37 interacts directly with ATG5 and promotes autophagosome formation via regulating ATG5-12-16 complex assembly. Cell death and differentiation 81 29229996
2017 Aging-related Atg5 defect impairs neutrophil extracellular traps formation. Immunology 80 28375544
2022 ATG5: A central autophagy regulator implicated in various human diseases. Cell biochemistry and function 76 36062813
1998 Homology between a human apoptosis specific protein and the product of APG5, a gene involved in autophagy in yeast. FEBS letters 71 9563500
2022 USP22 suppresses the NLRP3 inflammasome by degrading NLRP3 via ATG5-dependent autophagy. Autophagy 69 35900990
2014 Autophagy-related gene Atg5 is essential for astrocyte differentiation in the developing mouse cortex. EMBO reports 58 25227738
2023 TRIM45 aggravates microglia pyroptosis via Atg5/NLRP3 axis in septic encephalopathy. Journal of neuroinflammation 55 38037161
2023 An ATG12-ATG5-TECPR1 E3-like complex regulates unconventional LC3 lipidation at damaged lysosomes. EMBO reports 54 37381828
2011 Expression pattern and functions of autophagy-related gene atg5 in zebrafish organogenesis. Autophagy 54 22082871
2021 Highly enriched exosomal lncRNA OIP5-AS1 regulates osteosarcoma tumor angiogenesis and autophagy through miR-153 and ATG5. American journal of translational research 53 34150009
2020 lncRNA ZNF649-AS1 Induces Trastuzumab Resistance by Promoting ATG5 Expression and Autophagy. Molecular therapy : the journal of the American Society of Gene Therapy 48 32735773
2023 ATG5 provides host protection acting as a switch in the atg8ylation cascade between autophagy and secretion. Developmental cell 46 37054706
2017 IL-17A induces autophagy and promotes microglial neuroinflammation through ATG5 and ATG7 in intracerebral hemorrhage. Journal of neuroimmunology 46 28778418
2022 Autophagy inhibits cancer stemness in triple-negative breast cancer via miR-181a-mediated regulation of ATG5 and/or ATG2B. Molecular oncology 44 35029026
2011 Expressional and mutational analyses of ATG5 gene in prostate cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 43 21995634
2021 Cadmium promotes breast cancer cell proliferation, migration and invasion by inhibiting ACSS2/ATG5-mediated autophagy. Environmental pollution (Barking, Essex : 1987) 42 33486244
2018 ATG5 is required for B cell polarization and presentation of particulate antigens. Autophagy 42 30196744
2013 Tumor suppressor gene PDCD4 negatively regulates autophagy by inhibiting the expression of autophagy-related gene ATG5. Autophagy 42 23486359
2019 Endothelial-Specific Deficiency of ATG5 (Autophagy Protein 5) Attenuates Ischemia-Related Angiogenesis. Arteriosclerosis, thrombosis, and vascular biology 41 31070476
2016 RACK1 Is an Interaction Partner of ATG5 and a Novel Regulator of Autophagy. The Journal of biological chemistry 40 27325703
2015 Atg5 siRNA inhibits autophagy and enhances norcantharidin-induced apoptosis in hepatocellular carcinoma. International journal of oncology 38 26240015
2022 ATG5 Knockdown Attenuates Ischemia‒Reperfusion Injury by Reducing Excessive Autophagy-Induced Ferroptosis. Translational stroke research 37 36522583
2021 LncRNA CCAT1 Upregulates ATG5 to Enhance Autophagy and Promote Gastric Cancer Development by Absorbing miR-140-3p. Digestive diseases and sciences 36 34417924
2018 TP53 is required for BECN1- and ATG5-dependent cell death induced by sphingosine kinase 1 inhibition. Autophagy 36 29368980
2019 miR-20a inhibits hypoxia-induced autophagy by targeting ATG5/FIP200 in colorectal cancer. Molecular carcinogenesis 35 30883936
2023 ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease. Autophagy 33 37915255
2021 Circadian clock regulates granulosa cell autophagy through NR1D1-mediated inhibition of ATG5. American journal of physiology. Cell physiology 33 34936504
2023 Deubiquitinase USP13 regulates glycolytic reprogramming and progression in osteosarcoma by stabilizing METTL3/m6A/ATG5 axis. International journal of biological sciences 32 37151889
2023 Exosomal circTGFBR2 promotes hepatocellular carcinoma progression via enhancing ATG5 mediated protective autophagy. Cell death & disease 31 37474520
2016 Atg5-dependent autophagy plays a protective role against methylmercury-induced cytotoxicity. Toxicology letters 31 27667695
2015 Gene-gene interaction of ATG5, ATG7, BLK and BANK1 in systemic lupus erythematosus. International journal of rheumatic diseases 31 26420661
2022 FTO-dependent N(6)-Methyladenosine regulates the progression of endometriosis via the ATG5/PKM2 Axis. Cellular signalling 28 35839979
2019 Plasma ATG5 is increased in Alzheimer's disease. Scientific reports 28 30894637
2024 Inhibition of ACSS2 triggers glycolysis inhibition and nuclear translocation to activate SIRT1/ATG5/ATG2B deacetylation axis, promoting autophagy and reducing malignancy and chemoresistance in ovarian cancer. Metabolism: clinical and experimental 26 39362518
2021 miR-30a-5p suppresses lung squamous cell carcinoma via ATG5 - mediated autophagy. Aging 25 34253689
2022 Apicoplast biogenesis mediated by ATG8 requires the ATG12-ATG5-ATG16L and SNAP29 complexes in Toxoplasma gondii. Autophagy 24 36095096
2021 ATG5 promotes eosinopoiesis but inhibits eosinophil effector functions. Blood 24 33598715
2019 Microrna-130a Downregulates HCV Replication through an atg5-Dependent Autophagy Pathway. Cells 24 30974864
2023 Berberine attenuates liver fibrosis by autophagy inhibition triggering apoptosis via the miR-30a-5p/ATG5 axis. Experimental cell research 21 37062521
2022 Targeting the ATG5-ATG16L1 Protein-Protein Interaction with a Hydrocarbon-Stapled Peptide Derived from ATG16L1 for Autophagy Inhibition. Journal of the American Chemical Society 21 36107218
2021 MiR-30c-5p/ATG5 Axis Regulates the Progression of Parkinson's Disease. Frontiers in cellular neuroscience 21 34113238
2020 miR-30d-5p suppresses proliferation and autophagy by targeting ATG5 in renal cell carcinoma. FEBS open bio 21 33145996
2017 Stat3-Atg5 signal axis inducing autophagy to alleviate hepatic ischemia-reperfusion injury. Journal of cellular biochemistry 21 29143976
2018 ATG5 overexpression is neuroprotective and attenuates cytoskeletal and vesicle-trafficking alterations in axotomized motoneurons. Cell death & disease 19 29799519
2024 The Spermine Oxidase/Spermine Axis Coordinates ATG5-Mediated Autophagy to Orchestrate Renal Senescence and Fibrosis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 38775007
2019 HIF1α promotes prostate cancer progression by increasing ATG5 expression. Animal cells and systems 18 31700698
2023 ATG5 selectively engages virus-tethered BST2/tetherin in an LC3C-associated pathway. Proceedings of the National Academy of Sciences of the United States of America 17 37155854
2021 ATG5 in microglia does not contribute vitally to autoimmune neuroinflammation in mice. Autophagy 17 33522362
2020 Atg5-mediated autophagy controls apoptosis/anoikis via p53/Rb pathway in naked mole-rat fibroblasts. Biochemical and biophysical research communications 17 32451084
2024 Quercetin promotes ATG5-mediating autophagy-dependent ferroptosis in gastric cancer. Journal of molecular histology 16 38441713
2024 Atg5-Mediated Lipophagy Induces Ferroptosis in Corneal Epithelial Cells in Dry Eye Disease. Investigative ophthalmology & visual science 16 39636725
2022 Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12 Prevents Gut Dysbiosis and Inflammation. Journal of Crohn's & colitis 16 34374750
2020 LC3 and ATG5 overexpression and neuronal cell death in the prefrontal cortex of postmortem chronic methamphetamine users. Journal of chemical neuroanatomy 16 32416129
2017 Distinct TP73-DAPK2-ATG5 pathway involvement in ATO-mediated cell death versus ATRA-mediated autophagy responses in APL. Journal of leukocyte biology 16 28978663
2015 Obatoclax induces Beclin 1- and ATG5-dependent apoptosis and autophagy in adenoid cystic carcinoma cells. Oral diseases 16 25482163
2020 Proteaphagy in Mammalian Cells Can Function Independent of ATG5/ATG7. Molecular & cellular proteomics : MCP 15 32299840
2025 Atg5 deficiency in basophils improves metabolism in lupus mice by regulating gut microbiota dysbiosis. Cell communication and signaling : CCS 14 39844180
2020 ATG5 regulates mesenchymal stem cells differentiation and mediates chemosensitivity in acute myeloid leukemia. Biochemical and biophysical research communications 14 32098672
2018 Autophagy gene ATG5 knockdown upregulates apoptotic cell death during Candida albicans infection in human vaginal epithelial cells. American journal of reproductive immunology (New York, N.Y. : 1989) 14 30303264
2025 HMBOX1 reverses autophagy mediated 5-fluorouracil resistance through promoting HACE1-induced ubiquitination and degradation of ATG5 in colorectal cancer. Autophagy 13 40126194
2022 Experimental diabetes exacerbates autophagic flux impairment during myocardial I/R injury through calpain-mediated cleavage of Atg5/LAMP2. Journal of cellular and molecular medicine 13 36562207
2022 Bortezomib abrogates temozolomide-induced autophagic flux through an ATG5 dependent pathway. Frontiers in cell and developmental biology 13 36619857
2022 Trehalose promotes functional recovery of keratinocytes under oxidative stress and wound healing via ATG5/ATG7. Burns : journal of the International Society for Burn Injuries 13 36759218
2015 Detecting Genetic Associations between ATG5 and Lupus Nephritis by trans-eQTL. Journal of immunology research 13 26509176
2025 ATG5 suppresses type I IFN-dependent neutrophil effector functions during Mycobacterium tuberculosis infection in mice. Nature microbiology 12 40374743
2023 Vesicle tethering and fusion promoted by LC3/GABARAP proteins is modulated by the ATG12-ATG5-ATG16L1 complex. Autophagy 12 37062893
2023 Loss of Atg5 in Sertoli cells enhances the susceptibility of cadmium-impaired testicular spermatogenesis in mice. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 12 37506864
2020 Heme Induces BECN1/ATG5-Mediated Autophagic Cell Death via ER Stress in Neurons. Neurotoxicity research 12 32840757
2020 MicroRNA-7 inhibits hepatocellular carcinoma cell invasion and metastasis by regulating Atg5-mediated autophagy. Translational cancer research 12 35117763
2024 Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis. Cell communication and signaling : CCS 11 38594728
2019 Knockout of Atg5 inhibits proliferation and promotes apoptosis of DF-1 cells. In vitro cellular & developmental biology. Animal 11 31025250
2025 The Role of WIPI2, ATG16L1 and ATG12-ATG5 in Selective and Nonselective Autophagy. Journal of molecular biology 10 40221132
2020 Phosphorylation of ULK1 serine 746 dictates ATG5-independent autophagy. Autophagy 10 32544365

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