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ATG13

Autophagy-related protein 13 · UniProt O75143

Length
517 aa
Mass
56.6 kDa
Annotated
2026-04-28
97 papers in source corpus 38 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATG13 is a central scaffolding subunit of the autophagy initiation complex (ULK1–ATG13–FIP200–ATG101) that integrates nutrient-sensing signals to control phagophore nucleation, expansion, and termination. Its intrinsically disordered C-terminal region bridges the tandem MIT domain of ULK1 and both UBL domains of the FIP200 dimer (1:1:2 stoichiometry), while its N-terminal HORMA domain heterodimerizes with ATG101 and directly recruits ATG9A vesicles, PI3-kinase (via Atg14), WIPI2/3, and LC3 family proteins to coordinate membrane delivery and lipid kinase activation at the phagophore assembly site (PMID:40552710, PMID:25737544, PMID:23509291, PMID:24290141, PMID:34369648). ATG13 activity is tightly regulated by inhibitory mTORC1 phosphorylation at Ser-258, activating dephosphorylation by PP2A, stimulatory CDK1 phosphorylation during mitosis, AMPK- and ERK-dependent phosphorylation, and linear ubiquitination by LUBAC, with Hsp90–Cdc37-stabilized ULK1 phosphorylating ATG13 to release it for mitochondrial recruitment during mitophagy (PMID:26801615, PMID:27973551, PMID:32516310, PMID:32543267, PMID:21855797). ATG13 also functions partly independently of ULK1/2: its interaction with FIP200 is indispensable for autophagy even when ULK1 and ULK2 are both ablated, and the ATG13–ATG101 dimer regulates ATG9A trafficking independently of ULK1 binding (PMID:22024743, PMID:34369648).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2004 High

    The question of what upstream complex controls autophagosome membrane trafficking was addressed by showing that the Atg1–Atg13 complex governs retrograde retrieval of Atg9 vesicles from the PAS, establishing ATG13 as a regulator of membrane dynamics at the initiation site.

    Evidence Yeast atg mutant genetic epistasis with fluorescence imaging of Atg9/Atg23 trafficking

    PMID:14723849

    Open questions at the time
    • Mechanism by which Atg13 promotes Atg9 retrieval was unknown
    • Whether mammalian ATG13 has the same trafficking role was untested
  2. 2005 High

    How Atg13 connects to the scaffolding platform was resolved by demonstrating that Atg17 associates with the Atg1 complex through Atg13, and this bridging interaction is required for normal Atg1 kinase activity and autophagosome size.

    Evidence Yeast two-hybrid, Co-IP, Atg17-C24R point mutant with reduced Atg13 binding, in vitro kinase assay

    PMID:15743910

    Open questions at the time
    • Mammalian FIP200 (Atg17 counterpart) interaction with ATG13 was not yet mapped
    • Stoichiometry of the complex was unknown
  3. 2009 High

    The mammalian ULK1–ATG13–FIP200 complex was identified as a stable ~3-MDa assembly regulated by mTORC1 phosphorylation, with ATG13 and FIP200 required for ULK1 kinase stimulation, protein stability, and pre-autophagosome targeting, establishing ATG13 as the core adaptor of the mammalian autophagy initiation machinery.

    Evidence Reciprocal Co-IP, gel filtration, in vitro ULK1 kinase assay reconstitution, siRNA knockdown, phosphorylation assays across multiple labs

    PMID:19211835 PMID:19258318

    Open questions at the time
    • Direct mTOR phosphorylation sites on ATG13 were unmapped
    • How ATG13 stimulates ULK1 kinase activity mechanistically was unclear
  4. 2009 High

    ATG101 was identified as a direct ATG13-binding partner that stabilizes ATG13 protein levels and is required for autophagy, expanding the initiation complex to a four-subunit assembly.

    Evidence Reciprocal Co-IP, siRNA knockdown with LC3 puncta assay, discovered independently by two labs

    PMID:19287211 PMID:19597335

    Open questions at the time
    • Structural basis of ATG13–ATG101 interaction was unknown
    • Whether ATG101 has functions beyond ATG13 stabilization was unclear
  5. 2009 High

    Parallel kinase inputs beyond TOR were identified: PKA phosphorylates Atg13 at distinct sites from TOR in yeast, regulating Atg13 PAS localization, and Drosophila Atg13 modulates both Atg1 autophagic activity and TOR-dependent growth signaling.

    Evidence In vitro PKA kinase assay with phosphosite mapping; Drosophila genetic knockout with phosphorylation analysis

    PMID:19225150 PMID:19805182

    Open questions at the time
    • Whether PKA regulation is conserved in mammals was untested
    • Full complement of Atg13 phosphosites was unknown
  6. 2010 High

    Direct TORC1 phosphorylation of Atg13 was mapped to eight serine residues, and expression of unphosphorylatable Atg13-8SA was sufficient to bypass TORC1 and induce autophagy under nutrient-rich conditions, proving Atg13 dephosphorylation is the key TORC1-regulated switch.

    Evidence In vitro TORC1 kinase assay, Atg13-8SA phosphomutant in yeast with PAS formation and autophagy assay

    PMID:20383061

    Open questions at the time
    • Specific mammalian mTOR phosphosites on ATG13 were still unmapped
    • Phosphatase(s) responsible for activating dephosphorylation were unidentified
  7. 2011 High

    Three key advances refined ATG13's mechanistic roles: (1) ATG13 promotes Atg1 homodimerization and activation-loop autophosphorylation independently of Atg17; (2) Hsp90–Cdc37 stabilizes ULK1 which phosphorylates ATG13 to release it for mitochondrial recruitment during mitophagy; (3) ATG13 is indispensable for autophagy even when both ULK1 and ULK2 are deleted, revealing a ULK-independent function dependent on FIP200 binding.

    Evidence Co-IP of Atg1 homodimer with in vitro kinase assay (yeast); Hsp90/Cdc37 siRNA with mitophagy assay; ATG13-deficient and ULK1/2 double-KO cells with autophagy readouts

    PMID:21712380 PMID:21855797 PMID:22024743

    Open questions at the time
    • Molecular basis of ATG13's ULK-independent function was unclear
    • Whether ATG13 phosphorylation by ULK1 directly triggers mitochondrial recruitment was not resolved
  8. 2013 High

    Structural characterization revealed that the ATG13 N-terminus adopts a HORMA fold (2.3 Å crystal structure) required for PI3-kinase recruitment via Atg14, and a separate crystal structure showed ATG13 engages LC3 isoforms through a LIR motif, establishing dual interaction surfaces on ATG13 for downstream effector recruitment.

    Evidence X-ray crystallography of Atg13 HORMA domain and of LC3A/LC3C–ATG13 LIR complexes, with mutagenesis validated in yeast and mammalian cells

    PMID:23509291 PMID:24290141

    Open questions at the time
    • How the HORMA domain contacts Atg9 vesicles was unknown
    • Whether the LIR motif functions in initiation or later steps was unclear
  9. 2015 High

    The HORMA domain was shown to directly bind Atg9 for vesicle recruitment to the PAS; the ATG13–ATG101 HORMA heterodimer structure was solved revealing a Mad2-like conformational switch with a sequestered WF finger; and the extreme C-terminal peptide of ATG13 was mapped as the minimal ULK1-binding motif, though a ULK1-binding-deficient ATG13 retained partial autophagic activity.

    Evidence Pulldown and Y2H for Atg9 binding with HORMA mutants in yeast; crystal structure of human ATG13–ATG101 complex; KO reconstitution with binding-deficient ATG13 variants

    PMID:25737544 PMID:26213203 PMID:26299944

    Open questions at the time
    • How ATG101 WF finger exposure is regulated was unknown
    • Structural basis of ATG13 IDR contacts with FIP200 was not resolved
  10. 2016 High

    mTOR was shown to directly phosphorylate mammalian ATG13 at Ser-258, with AMPK modulating Ser-224, while PP2A phosphatases were identified as the activating counterpart that dephosphorylates Atg13 after TORC1 inactivation in yeast; the Atg13 IDR was found to bridge two Atg17 molecules driving supramolecular self-assembly that accelerates Atg1 autophosphorylation and Atg9 vesicle recruitment.

    Evidence In vitro mTOR kinase assay with phosphosite mutagenesis in ATG13-KO cells; yeast PP2A deletion genetics with Atg13-8SA rescue; crystallography, NMR, and high-speed AFM of Atg13–Atg17 supramolecular assembly

    PMID:26801615 PMID:27404361 PMID:27973551

    Open questions at the time
    • Complete set of mammalian ATG13 phosphosites was not mapped
    • How PP2A is recruited to ATG13 was not determined
  11. 2018 High

    Stoichiometric analysis revealed Atg1 is present at twice the level of Atg13 on autophagic puncta, and the Atg13-free Atg1 EAT domain mediates Atg8-dependent membrane association required for phagophore expansion, demonstrating that ATG13 regulates not only initiation but also the transition to expansion through partial dissociation.

    Evidence ITC, crystal structure-guided mutagenesis, quantitative and superresolution microscopy in yeast

    PMID:29540529

    Open questions at the time
    • Whether mammalian ULK1 has analogous Atg13-free membrane functions was untested
    • Mechanism of Atg13 release from Atg1 during expansion was unclear
  12. 2019 High

    The Atg13 C-terminal IDR was found to directly bind phospholipid membranes via electrostatic and hydrophobic interactions, with membrane binding mutually exclusive with Vac8 binding, adding direct lipid engagement to ATG13's scaffolding functions.

    Evidence ITC, liposome pulldown, CD spectroscopy, mutagenesis with yeast autophagy assays

    PMID:31352862

    Open questions at the time
    • Whether mammalian ATG13 IDR binds membranes directly was not tested
    • How the switch between membrane and Vac8 binding is regulated was unclear
  13. 2020 High

    New regulatory inputs were discovered: LUBAC linearly ubiquitinates ATG13 and OTULIN deubiquitinates it to control autophagosome maturation; CDK1/cyclin B phosphorylates ATG13 during mitosis to promote mitotic autophagy and cell cycle progression.

    Evidence Co-IP ubiquitination assay with OTULIN/RNF31 KD; mass spectrometry phosphosite mapping with CDK1 in vitro kinase assay, ULK1/ATG13 double-KO with xenograft model

    PMID:32516310 PMID:32543267

    Open questions at the time
    • Specific linear ubiquitination sites on ATG13 were not mapped
    • Whether CDK1 phosphorylation of ATG13 is relevant outside cancer cells was untested
  14. 2021 High

    The ATG13–ATG101 dimer was shown to interact with ATG9A independently of ULK1, controlling ATG9A distribution at p62/ubiquitin condensates; separately, Atg1-mediated re-phosphorylation of Atg13 (counteracted by PP2C) was identified as the signal for autophagy termination, and ERK1/2 was shown to phosphorylate ATG13 during glucose starvation to promote protective autophagy.

    Evidence BioID proximity proteomics and split-mVenus with ATG13/ATG101 KO reconstitution; yeast genetic screen with Atg13 phosphorylation analysis; ERK-ATG13 Co-IP with phosphomutant rescue

    PMID:33536246 PMID:33682133 PMID:34369648

    Open questions at the time
    • Whether ATG13–ATG101 directly contacts ATG9A lipid scramblase domain was unknown
    • Mammalian autophagy termination mechanism involving ATG13 re-phosphorylation was not established
  15. 2022 High

    Connections to DNA damage signaling and meiosis were established: Mec1 (ATR ortholog) directly binds Atg13 via mapped interaction regions and is recruited to the PAS for glucose starvation-induced autophagy, while Cdc14 phosphatase dephosphorylates Atg13 during meiotic anaphase to drive sporulation-coupled autophagy.

    Evidence Yeast two-hybrid and Co-IP with domain mapping for Mec1–Atg13; Cdc14 localization imaging with Atg13 phosphorylation analysis and sporulation assays

    PMID:35238874 PMID:36574691

    Open questions at the time
    • Whether ATR–ATG13 interaction is conserved in mammals was not tested
    • Mec1 substrates at the PAS were not identified
  16. 2024 High

    Comprehensive phosphoproteomics of yeast Atg13 identified 48 in vivo phosphosites, establishing that balanced dynamic phosphorylation/dephosphorylation is required for autophagy, and that Atg11 cooperates with Atg1 in phase separation of the PAS during nitrogen starvation; separately, YBX3 was identified as an RNA-binding protein that stabilizes ATG13 mRNA via its 3′ UTR.

    Evidence Mass spectrometry with phosphomimetic/deficient mutants and phase separation analysis in yeast; RIP and 3′ UTR reporter assay in human cells

    PMID:38233718 PMID:39414370

    Open questions at the time
    • Mammalian ATG13 phosphosite landscape is incomplete
    • Whether phase separation of the initiation complex occurs in mammalian cells was not tested
  17. 2025 High

    The molecular architecture of the core ULK1–ATG13–FIP200 complex was resolved: ATG13 IDR contacts both FIP200 UBL domains via two phenylalanines and the ULK1 MIT domain, establishing 1:1:2 stoichiometry with each pairwise interaction additively required for flux.

    Evidence AlphaFold prediction validated by ITC, pulldown, point mutagenesis, and cellular autophagy flux assay

    PMID:40552710

    Open questions at the time
    • Full-length complex structure at atomic resolution is still lacking
    • How conformational dynamics of the IDR are regulated by phosphorylation in this context was not addressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) the complete mammalian ATG13 phosphosite landscape and how combinatorial phosphorylation patterns encode signal-specific autophagy responses; (2) the structural basis of ATG13 HORMA domain interaction with mammalian ATG9A; (3) whether ATG13-driven phase separation of the initiation complex occurs in mammalian cells; (4) the mechanism by which linear ubiquitination of ATG13 regulates autophagosome maturation versus initiation.
  • No full-length cryo-EM structure of the complete ULK1–ATG13–FIP200–ATG101 complex
  • Mammalian ATG13 phosphosite-specific functions are largely uncharacterized
  • Role of ATG13 in selective autophagy pathways beyond mitophagy is poorly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 2 GO:0008289 lipid binding 1
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-9612973 Autophagy 13 R-HSA-162582 Signal Transduction 5 R-HSA-1640170 Cell Cycle 1
Partners
ATG101ATG14ATG9AFIP200HOIPLC3BOTULINULK1
Complex memberships
ATG13-ATG101 HORMA heterodimerULK1-ATG13-FIP200-ATG101 complex

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 ATG13 forms a stable ~3-MDa complex with ULK1 and FIP200; mTORC1 is incorporated into this complex through ULK1 in a nutrient-dependent manner and phosphorylates both ULK1 and ATG13, suppressing autophagy. Co-immunoprecipitation, gel filtration, immunofluorescence localization, siRNA knockdown, phosphorylation assays Molecular biology of the cell High 19211835
2009 ATG13 and FIP200 individually enhance ULK1 kinase activity, and both together are required for maximal stimulation; ATG13 and FIP200 are critical for correct localization of ULK1 to the pre-autophagosome and for ULK1 protein stability. In vitro reconstituted ULK1 kinase assay, co-immunoprecipitation, siRNA knockdown, immunofluorescence The Journal of biological chemistry High 19258318
2009 ATG101 is a novel mammalian ATG13-binding protein that associates with the ULK1-ATG13-FIP200 complex most likely through direct interaction with ATG13; ATG101 is required for autophagy and stabilizes ATG13 and ULK1 basal phosphorylation. Co-immunoprecipitation, siRNA knockdown, GFP-ATG101 localization, LC3 puncta assay Autophagy High 19287211 19597335
2004 The Atg1-Atg13 signaling complex governs retrograde transport (retrieval) of Atg9 and Atg23 from the pre-autophagosomal structure (PAS); Atg1 kinase activity is specifically required for retrograde transport of Atg23. Yeast genetics, fluorescence microscopy of Atg9/Atg23 trafficking, atg mutant analysis Developmental cell High 14723849
2005 Atg17 physically associates with the Atg1-Atg13 complex through Atg13; Atg17-Atg13 complex formation is required for normal Atg1 kinase activity and normal autophagosome size. Two-hybrid analysis, co-immunoprecipitation, atg17 point mutant (C24R) with reduced Atg13 affinity, Atg1 kinase assay Molecular biology of the cell High 15743910
2008 The C-terminal domain (CTD) of ULK1 contains a distinct region that interacts with ATG13; ATG13 is required for autophagy and Atg9 trafficking during autophagy in mammalian cells. Domain mapping, co-immunoprecipitation, siRNA knockdown of ATG13, Atg9 trafficking assay Molecular and cellular biology Medium 18936157
2009 In Drosophila, Atg13 stimulates both the autophagic activity of Atg1 and its inhibition of cell growth/TOR signaling; Atg1 and Atg13 are phosphorylated in a TOR- and Atg1 kinase-dependent manner, and increased Atg13 levels disrupt TOR trafficking. Drosophila genetic knockout, co-immunoprecipitation, phosphorylation analysis, autophagy assays Molecular biology of the cell High 19225150
2009 In yeast, both Tor kinase and PKA independently phosphorylate Atg13 at distinct sites; PKA phosphorylation regulates Atg13 localization to the PAS, controlling autophagy induction. In vitro kinase assays with purified PKA, phosphosite mapping, fluorescence microscopy of Atg13-PAS localization in yeast mutants Proceedings of the National Academy of Sciences of the United States of America High 19805182
2011 Hsp90-Cdc37 chaperone complex stabilizes and activates ULK1, which in turn phosphorylates ATG13 to release it from ULK1; released ATG13 is then recruited to damaged mitochondria, and this pathway is required for efficient mitophagy. Co-immunoprecipitation, siRNA knockdown of Hsp90/Cdc37, phosphorylation assays, mitophagy assay (mitochondrial clearance) Molecular cell High 21855797
2013 The N-terminal domain of Atg13 adopts a HORMA fold (2.3-Å crystal structure) similar to C-Mad2; this HORMA domain is required for recruitment of PI3-kinase subunit Atg14 to initiate autophagy, but is not required for Atg1 interaction or Atg13 recruitment to the PAS. Two conserved Arg residues essential for autophagy form a putative phosphate sensor. X-ray crystallography, yeast mutant functional assays, Atg14 localization by fluorescence microscopy Proceedings of the National Academy of Sciences of the United States of America High 23509291
2013 Human ATG13 interacts with LC3 isoforms (LC3A, LC3B, LC3C) via a LIR motif; crystal structures of LC3A/LC3C complexed with the ATG13 LIR reveal that Lys49 of LC3 acts as a gatekeeper regulating LIR binding affinity. X-ray crystallography of LC3-ATG13 LIR complexes, binding assays, LC3A Lys49 mutation reducing LC3 puncta in cells Structure (London, England : 1993) High 24290141
2015 The N-terminal HORMA domain of Atg13 directly binds Atg9, and this interaction recruits Atg9 vesicles to the PAS; HORMA domain mutants unable to bind Atg9 show severe defects in starvation-induced autophagy and loss of Atg9 PAS localization. Pulldown assay, yeast two-hybrid, fluorescence microscopy of Atg9 localization, autophagy flux assay with HORMA point mutants in yeast Proceedings of the National Academy of Sciences of the United States of America High 25737544
2015 Crystal structure of human ATG13 HORMA domain in complex with full-length ATG101 HORMA reveals a heterodimer conserved with the Mad2 conformational heterodimer; the WF finger of ATG101 is sequestered in a hydrophobic pocket suggesting regulated exposure, and conserved hydrophobic pockets suggest additional interaction sites. X-ray crystallography of human ATG13-ATG101 complex Structure (London, England : 1993) High 26299944
2015 ATG13 binding to ULK1/2 is mediated by an extremely short peptide motif at the C-terminus of ATG13, which is mandatory for ULK1 recruitment into the high-molecular-mass autophagy initiation complex; a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity. Domain mapping, co-immunoprecipitation, ATG13 knockout cells reconstituted with binding-deficient variants, autophagy flux assay Autophagy High 26213203
2016 mTOR directly phosphorylates ATG13 on Ser-258, while Ser-224 is modulated by the AMPK pathway; expression of unphosphorylatable ATG13 in knockout cells enhances ULK1 kinase activity and accelerates starvation-induced ATG13/ULK1 translocation and autophagy. In vitro mTOR kinase assay, phosphosite mutagenesis, ATG13 knockout cell reconstitution, autophagy flux assay, live imaging of translocation The Journal of biological chemistry High 26801615
2016 Atg13 has a large intrinsically disordered region (IDR) that uses two distinct binding regions to interact with two separate Atg17 molecules, bridging multiple Atg1 complexes; this supramolecular self-assembly accelerates Atg1 autophosphorylation, Atg9 vesicle recruitment, and Atg9 phosphorylation by Atg1. X-ray crystallography, NMR, pulldown assays, yeast genetic functional assays, in vitro reconstitution of complex assembly, high-speed AFM Developmental cell High 27404361
2016 In yeast, PP2A phosphatases (PP2A-Cdc55 and PP2A-Rts1) are required for Atg13 dephosphorylation after TORC1 inactivation; loss of PP2A impairs Atg13 dephosphorylation, Atg1 kinase activation, PAS formation, and autophagy induction, all of which are rescued by non-phosphorylatable Atg13. Yeast PP2A deletion genetics, phosphorylation state analysis by western blot, Atg1 kinase assay, PAS formation assay, autophagy flux assay, rescue with Atg13-8SA mutant PloS one High 27973551
2011 ATG13 is indispensable for autophagy induction in mammalian cells, and ATG13 function strictly depends on FIP200 binding; simultaneously knocking out ULK1 and ULK2 does not abolish autophagy, indicating ATG13 has a ULK1/2-independent function acting in concert with FIP200. ATG13-deficient cells, ULK1/ULK2 double knockout, autophagy induction assays, binding domain analysis by co-immunoprecipitation Autophagy High 22024743
2018 The dynamic Atg13-free conformation of the Atg1 EAT domain is required for phagophore expansion; Atg1 is present at twice the stoichiometry of Atg13 on autophagic puncta, and the EAT domain functions in Atg13-independent membrane association via Atg8 for phagophore expansion. Isothermal titration calorimetry, crystal structure-guided mutagenesis, quantitative and superresolution microscopy, stoichiometry analysis in yeast Molecular biology of the cell High 29540529
2019 The C-terminus IDR of yeast Atg13 directly binds phospholipid membranes via electrostatic interactions with positively charged residues and hydrophobic insertion of a Phe residue; Atg13 binding to phospholipids and to Vac8 is mutually exclusive, and both are required for efficient autophagy. Lipid-binding assays (ITC, liposome pulldown), circular dichroism, mutagenesis, yeast autophagy flux assays Autophagy High 31352862
2020 ATG13 is subject to linear ubiquitination by the LUBAC complex (via RNF31/HOIP); excessive ubiquitinated ATG13 accumulates at the phagophore when deubiquitinase OTULIN is depleted, blocking autophagosome maturation. Co-immunoprecipitation, siRNA knockdown of RNF31 and OTULIN, ubiquitination assay, LC3 puncta and autophagy flux assays Autophagy Medium 32543267
2020 ULK1 and ATG13 are phosphorylated by CDK1/cyclin B during mitosis; CDK1-induced ULK1-ATG13 phosphorylation promotes mitotic autophagy and cell cycle progression; double knockout of ULK1 and ATG13 blocks cell cycle progression and reduces cancer cell proliferation in vitro and in vivo. Mass spectrometry phosphosite identification, site-directed mutagenesis, CDK1 in vitro kinase assay, ULK1/ATG13 double KO with cell cycle analysis, mouse xenograft model PLoS biology High 32516310
2020 ATG13 dynamics during autophagy were characterized by live imaging: in nonselective autophagy ATG13 translocations approximate a normal distribution, whereas during mitophagy ATG13 undergoes multiple translocations proportional to the diameter of targeted mitochondrial fragments, consistent with successive phagophore nucleation events. Live fluorescence imaging, mathematical modeling, wortmannin perturbation Autophagy Medium 32320309
2021 ATG9A interacts with the ATG13-ATG101 dimer independently of ULK1; deletion of ATG13 or ATG101 causes aberrant accumulation of ATG9A at stalled p62/ubiquitin clusters, which is rescued by a ULK1 binding-deficient ATG13 mutant. BioID proximity proteomics, split-mVenus complementation, ATG13/ATG101 KO and reconstitution, confocal imaging of ATG9A distribution EMBO reports High 34369648
2021 Vacuolar membrane protein Tag1 and Atg1-Atg13 activity regulate autophagy termination during persistent starvation; re-phosphorylation of Atg13 by Atg1 kinase (antagonized by PP2C phosphatases) drives PAS dispersal and terminates autophagy. Yeast genetic screen, Atg13 phosphorylation state analysis, PAS imaging, atg1 kinase and PP2C mutant analysis Journal of cell science Medium 33536246
2022 In yeast, Mec1 (ATM/ATR-related kinase) directly binds Atg13 via a Mec1-Binding Region (MBR) on Atg13 and an Atg13-Binding Region (ABR) on Mec1; this interaction recruits Mec1 puncta to the PAS and is required for glucose starvation-induced autophagy. Yeast two-hybrid, co-immunoprecipitation, domain mapping by mutagenesis, fluorescence microscopy of PAS localization, autophagy flux assay Proceedings of the National Academy of Sciences of the United States of America High 36574691
2022 In yeast, Cdc14 phosphatase dephosphorylates Atg13 in anaphase I and II upon its nucleolar release to the cytoplasm, stimulating Atg1 kinase activity and autophagy; genetically enhanced autophagy via Atg13 dephosphorylation increases meiotic kinetics and sporulation efficiency. Yeast genetics, Cdc14 localization imaging, Atg13 phosphorylation state analysis, Atg1 kinase assay, sporulation assays The Journal of cell biology High 35238874
2022 LPS induces p38 MAPK-dependent proteasomal degradation of ATG13 in hepatic stellate cells (LX2); ATG13 knockdown inhibits autophagy and promotes inflammatory responses, identifying ATG13 as a mediator between the autophagy and proteasome pathways. siRNA knockdown, co-immunoprecipitation for ubiquitination, p38 MAPK inhibitor treatment, ELISA for inflammatory cytokines, western blot Mediators of inflammation Medium 36148140
2023 PM2.5 exposure promotes m6A methylation of Atg13 mRNA at site 767 through downregulation of ALKBH5, enhancing ATG13-mediated ULK complex activity and autophagy-driven NF-κB/NLRP3 inflammation in lung epithelial cells. ALKBH5 knockout mouse model, m6A site mapping, western blot of ULK complex components, NF-κB/NLRP3 pathway analysis Journal of hazardous materials Medium 37295326
2024 Comprehensive phosphoproteomic analysis of yeast Atg13 identifies 48 in vivo phosphorylation sites; dynamic dephosphorylation/phosphorylation of Atg13 is required for balanced autophagy, and Atg11 contributes to bulk autophagy during nitrogen starvation by driving phase separation of the PAS together with Atg1. Mass spectrometry phosphosite mapping, phosphomimetic and phospho-deficient mutants, yeast genetic epistasis, autophagy flux assays, phase separation analysis EMBO reports High 38233718
2025 The intrinsically disordered region of ATG13 directly contacts the bases of both UBL domains of the FIP200 dimer via two phenylalanines, and also binds the tandem MIT domain of ULK1, establishing a 1:1:2 stoichiometry of the ULK1-ATG13-FIP200 core complex; each pairwise interaction is additively required for autophagic flux. AlphaFold structural prediction, validated by point mutations and in vitro direct binding assays (pulldown, ITC), co-immunoprecipitation in cells, autophagy flux assay eLife High 40552710
2025 The ATG13:ATG101 HORMA dimer forms a tight complex with the PI3P-binding proteins WIPI3 and WIPI2; this complex aligns with the membrane so that ATG101's WF finger inserts into the membrane, and the PVP motif of the ULK1 IDR docks onto the ATG13:ATG101 surface to bring the ULK1 kinase domain near the membrane for substrate phosphorylation. WIPI3-ATG13 engagement is required for ATG16L1 phosphorylation by ULK1, ATG13 puncta formation, and bulk autophagic flux. Biochemical reconstitution, molecular dynamics simulations, molecular modeling, cell-based ATG13 puncta and flux assays, in vitro ULK1 phosphorylation of ATG16L1 bioRxivpreprint High bio_10.1101_2025.11.07.687251
2025 ULK1 kinase phosphorylates ATG101, triggering its homo-dimerization and conformational change (metamorphosis) that dramatically accelerates ATG101 association with ATG13 and ATG9A; this ATG101 activation has persistent memory (hours after dephosphorylation) and creates a positive feedback cascade for assembly of the ATG9A-ATG13-ATG101 initiation complex. In vitro kinetics assays, phosphorylation by ULK1, interaction kinetics measurement, homo-dimerization assay, cell-based autophagy assays bioRxivpreprint Medium bio_10.1101_2025.06.27.661946
2024 The RNA-binding protein YBX3 interacts with and stabilizes ATG13 mRNA via its 3' UTR, increasing ATG13 protein expression; YBX3 depletion reduces ATG13 transcript levels in multiple human cell lines. RNA immunoprecipitation (RIP), 3' UTR reporter assay, siRNA knockdown with western blot and mRNA quantification FEBS letters Medium 39414370
2021 ERK1/2 associates with ATG13 and FIP200 upon glucose starvation in renal cells; phospho-defective ATG13 mutants at ERK consensus sites block starvation-induced autophagy and increase cell death, while phospho-mimetic ATG13 mutants induce autophagy and protect cells from hypoglycemia. Co-immunoprecipitation of ERK1/2 with ATG13, phospho-defective/mimetic mutagenesis, autophagy flux assay, cell viability assay Journal of cellular physiology Medium 33682133
2010 Yeast TORC1 directly phosphorylates Atg13 on at least eight Ser residues; expression of unphosphorylatable Atg13-8SA bypasses TORC1 to induce autophagy in vegetatively growing cells, accompanied by Atg1 complex formation, Atg1 activation, and PAS organization. In vitro TORC1 kinase assay with Atg13, phosphosite mapping (8SA mutant), autophagy assay in vegetative yeast, PAS formation assay Autophagy High 20383061
2011 In yeast, Atg13 promotes Atg1 self-association (homodimerization) in an Atg17-independent manner; this Atg1-Atg1 complex is correlated with autophagy induction and is a prerequisite for autophosphorylation of Thr-226 in the Atg1 activation loop, which is required for Atg1 kinase activity. Co-immunoprecipitation of Atg1 homodimer, in vitro kinase assay, heterologous dimerization domain rescue, Thr-226 phosphorylation analysis in yeast mutants The Journal of biological chemistry High 21712380

Source papers

Stage 0 corpus · 97 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Molecular biology of the cell 1647 19211835
2009 ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. The Journal of biological chemistry 1220 19258318
2009 Atg101, a novel mammalian autophagy protein interacting with Atg13. Autophagy 397 19597335
2004 The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Developmental cell 396 14723849
2008 Kinase-inactivated ULK proteins inhibit autophagy via their conserved C-terminal domains using an Atg13-independent mechanism. Molecular and cellular biology 349 18936157
2009 An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Molecular biology of the cell 348 19225150
2009 A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy 338 19287211
2005 Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Molecular biology of the cell 284 15743910
2011 The ATG1/ATG13 protein kinase complex is both a regulator and a target of autophagic recycling in Arabidopsis. The Plant cell 262 21984698
2009 The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proceedings of the National Academy of Sciences of the United States of America 249 19805182
2011 Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Molecular cell 196 21855797
2016 Nutrient-regulated Phosphorylation of ATG13 Inhibits Starvation-induced Autophagy. The Journal of biological chemistry 180 26801615
2016 The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes. Developmental cell 180 27404361
2015 Atg13 HORMA domain recruits Atg9 vesicles during autophagosome formation. Proceedings of the National Academy of Sciences of the United States of America 139 25737544
2020 CircMUC16 promotes autophagy of epithelial ovarian cancer via interaction with ATG13 and miR-199a. Molecular cancer 120 32111227
2011 Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction. Autophagy 116 22024743
2013 A HORMA domain in Atg13 mediates PI 3-kinase recruitment in autophagy. Proceedings of the National Academy of Sciences of the United States of America 107 23509291
2013 Structural basis of the autophagy-related LC3/Atg13 LIR complex: recognition and interaction mechanism. Structure (London, England : 1993) 94 24290141
2015 Structure of the Human Atg13-Atg101 HORMA Heterodimer: an Interaction Hub within the ULK1 Complex. Structure (London, England : 1993) 81 26299944
2020 LUBAC and OTULIN regulate autophagy initiation and maturation by mediating the linear ubiquitination and the stabilization of ATG13. Autophagy 69 32543267
2019 Arabidopsis SINAT Proteins Control Autophagy by Mediating Ubiquitylation and Degradation of ATG13. The Plant cell 68 31732704
2017 Moderate Autophagy Inhibits Vascular Smooth Muscle Cell Senescence to Stabilize Progressed Atherosclerotic Plaque via the mTORC1/ULK1/ATG13 Signal Pathway. Oxidative medicine and cellular longevity 57 28713484
2009 epg-1 functions in autophagy-regulated processes and may encode a highly divergent Atg13 homolog in C. elegans. Autophagy 56 19377305
2016 Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency. Nature genetics 55 27723758
2015 Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity in ATG13-deficient cells. Autophagy 51 26213203
2011 An Atg13 protein-mediated self-association of the Atg1 protein kinase is important for the induction of autophagy. The Journal of biological chemistry 49 21712380
2014 ATG13: just a companion, or an executor of the autophagic program? Autophagy 48 24879146
2020 ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle. PLoS biology 47 32516310
2016 Orchestrated Action of PP2A Antagonizes Atg13 Phosphorylation and Promotes Autophagy after the Inactivation of TORC1. PloS one 47 27973551
2012 The C. elegans ATG101 homolog EPG-9 directly interacts with EPG-1/Atg13 and is essential for autophagy. Autophagy 45 22885670
2014 Arabidopsis ATG11, a scaffold that links the ATG1-ATG13 kinase complex to general autophagy and selective mitophagy. Autophagy 44 24991832
2023 Site-specific Atg13 methylation-mediated autophagy regulates epithelial inflammation in PM2.5-induced pulmonary fibrosis. Journal of hazardous materials 43 37295326
2021 BioID reveals an ATG9A interaction with ATG13-ATG101 in the degradation of p62/SQSTM1-ubiquitin clusters. EMBO reports 42 34369648
2018 Long non-coding RNA HOTTIP affects renal cell carcinoma progression by regulating autophagy via the PI3K/Akt/Atg13 signaling pathway. Journal of cancer research and clinical oncology 41 30511250
2018 Systematic analysis of ATG13 domain requirements for autophagy induction. Autophagy 39 29173006
2022 Elevated ATG13 in serum of patients with ME/CFS stimulates oxidative stress response in microglial cells via activation of receptor for advanced glycation end products (RAGE). Molecular and cellular neurosciences 34 35487443
2022 14-3-3 proteins contribute to autophagy by modulating SINAT-mediated degradation of ATG13. The Plant cell 32 36053201
2018 Histamine deficiency aggravates cardiac injury through miR-206/216b-Atg13 axis-mediated autophagic-dependant apoptosis. Cell death & disease 32 29880830
2024 Novel exosomal circEGFR facilitates triple negative breast cancer autophagy via promoting TFEB nuclear trafficking and modulating miR-224-5p/ATG13/ULK1 feedback loop. Oncogene 29 38280941
2022 Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas. Cell death & disease 26 35220397
2018 LicA induces autophagy through ULK1/Atg13 and ROS pathway in human hepatocellular carcinoma cells. International journal of molecular medicine 25 29484365
2018 Rapamycin induces autophagy to alleviate acute kidney injury following cerebral ischemia and reperfusion via the mTORC1/ATG13/ULK1 signaling pathway. Molecular medicine reports 25 30365078
2023 Exosomal lncRNA GAS5 promotes M1 macrophage polarization in allergic rhinitis via restraining mTORC1/ULK1/ATG13-mediated autophagy and subsequently activating NF-кB signaling. International immunopharmacology 23 37343372
2013 CCCP-Induced LC3 lipidation depends on Atg9 whereas FIP200/Atg13 and Beclin 1/Atg14 are dispensable. Biochemical and biophysical research communications 23 23402761
2021 Circulating Exosomal miR-1-3p from Rats with Myocardial Infarction Plays a Protective Effect on Contrast-Induced Nephropathy via Targeting ATG13 and activating the AKT Signaling Pathway. International journal of biological sciences 20 33867822
2022 Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy. Proceedings of the National Academy of Sciences of the United States of America 19 36574691
2020 ATG13 dynamics in nonselective autophagy and mitophagy: insights from live imaging studies and mathematical modeling. Autophagy 19 32320309
2014 Detection of Saccharomyces cerevisiae Atg13 by western blot. Autophagy 18 24430166
2022 Brucea javanica Oil Emulsion Promotes Autophagy in Ovarian Cancer Cells Through the miR-8485/LAMTOR3/mTOR/ATG13 Signaling Axis. Frontiers in pharmacology 17 35959437
2022 Autophagy regulation of ATG13 and ATG27 on biofilm formation and antifungal resistance in Candida albicans. Biofouling 17 36476055
2019 The carboxy terminus of yeast Atg13 binds phospholipid membrane via motifs that overlap with the Vac8-interacting domain. Autophagy 16 31352862
2018 The dynamic Atg13-free conformation of the Atg1 EAT domain is required for phagophore expansion. Molecular biology of the cell 16 29540529
2017 The molecular mechanism of Atg13 function in autophagy induction: What is hidden behind the data? Autophagy 16 28118060
2018 Rapamycin Alleviates Hormone Imbalance-Induced Chronic Nonbacterial Inflammation in Rat Prostate Through Activating Autophagy via the mTOR/ULK1/ATG13 Signaling Pathway. Inflammation 15 29675586
2021 Vacuolar protein Tag1 and Atg1-Atg13 regulate autophagy termination during persistent starvation in S. cerevisiae. Journal of cell science 14 33536246
2021 IRF1 Inhibits Autophagy-Mediated Proliferation of Colorectal Cancer via Targeting ATG13. Cancer investigation 13 34313498
2010 Prime-numbered Atg proteins act at the primary step in autophagy: unphosphorylatable Atg13 can induce autophagy without TOR inactivation. Autophagy 13 20383061
2022 The emerging roles of ATG1/ATG13 kinase complex in plants. Journal of plant physiology 12 35255243
2022 Beclin1- and Atg13-dependent autophagy activation and morroniside have synergistic effect on osteoblastogenesis. Experimental biology and medicine (Maywood, N.J.) 12 35957534
2022 Cdc14 spatiotemporally dephosphorylates Atg13 to activate autophagy during meiotic divisions. The Journal of cell biology 11 35238874
2020 Functional identification of Bombyx mori Atg13 in autophagy. Archives of insect biochemistry and physiology 11 32515853
2025 The triad interaction of ULK1, ATG13, and FIP200 is required for ULK complex formation and autophagy. eLife 10 40552710
2022 bta-miR-2904 inhibits bovine viral diarrhea virus replication by targeting viral-infection-induced autophagy via ATG13. Archives of virology 10 36576583
2020 Antiviral responses of ATG13 to the infection of peste des petits ruminants virus through activation of interferon response. Gene 10 32531455
2015 Cloning, expression analysis, and RNA interference study of a HORMA domain containing autophagy-related gene 13 (ATG13) from the coleopteran beetle, Tenebrio molitor. Frontiers in physiology 10 26136688
2024 Decoding the function of Atg13 phosphorylation reveals a role of Atg11 in bulk autophagy initiation. EMBO reports 9 38233718
2022 The effect of lactoferrin on ULK1 and ATG13 genes expression in breast cancer cell line MCF7 and bioinformatics studies of protein interaction between lactoferrin and the autophagy initiation complex. Cell biochemistry and biophysics 8 36169801
2021 The ERK1/2-ATG13-FIP200 signaling cascade is required for autophagy induction to protect renal cells from hypoglycemia-induced cell death. Journal of cellular physiology 8 33682133
2020 Klotho-mediated changes in the expression of Atg13 alter formation of ULK1 complex and thus initiation of ER- and Golgi-stress response mediated autophagy. Apoptosis : an international journal on programmed cell death 8 31732843
2021 HSBP1 Is a Novel Interactor of FIP200 and ATG13 That Promotes Autophagy Initiation and Picornavirus Replication. Frontiers in cellular and infection microbiology 7 34869056
2020 The Effect of Shen-Yuan-Dan Capsule on Autophagy-Related Gene Atg13 Promoter Methylation and Genomic Methylation Levels in Atherosclerotic Mice. Acta Cardiologica Sinica 7 32425441
2018 Autophagy-related gene ATG13 is involved in control of xylose alcoholic fermentation in the thermotolerant methylotrophic yeast Ogataea polymorpha. FEMS yeast research 7 29438555
2013 What the N-terminal domain of Atg13 looks like and what it does: a HORMA fold required for PtdIns 3-kinase recruitment. Autophagy 7 23670046
2021 Phospho-regulation and function of ULK1-ATG13 during the cell cycle. Autophagy 6 33666137
2017 Silencing of NRAGE induces autophagy via AMPK/Ulk1/Atg13 signaling pathway in NSCLC cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 6 28639909
2012 Regulator and substrate: dual roles for the ATG1-ATG13 kinase complex during autophagic recycling in Arabidopsis. Autophagy 6 22714291
2025 High Glucose-Induced Senescent Fibroblasts-Derived Exosomal miR-497 Inhibits Wound Healing by Regulating Endothelial Cellular Autophagy via ATG13. Analytical cellular pathology (Amsterdam) 5 39831298
2025 PDGFR-β/Cav1-induced autophagy via mTOR/FIP200/ATG13 activation in cancer-associated fibroblasts promotes the malignant progression of breast cancer. Journal of translational medicine 5 40646615
2023 The role of the HORMA domain proteins ATG13 and ATG101 in initiating autophagosome biogenesis. FEBS letters 5 37567770
2022 Lipopolysaccharide Inhibits Autophagy and Promotes Inflammatory Responses via p38 MAPK-Induced Proteasomal Degradation of Atg13 in Hepatic Stellate Cells. Mediators of inflammation 4 36148140
2021 OBHS impairs the viability of breast cancer via decreasing ERα and Atg13. Biochemical and biophysical research communications 4 34388457
2024 Sodium fluoride-induced autophagy of ameloblast-like cells via the p-ULk1/ATG13/LC3B pathway in vitro. Oral diseases 3 38321366
2023 Exosomal circHIPK3 derived from umbilical cord-derived mesenchymal stem cells enhances skin fibroblast autophagy by blocking miR-20b-5p/ULK1/Atg13 axis. Journal of diabetes investigation 3 37688345
2023 ATG13 is involved in immune response of pathogen invasion in blood clam Tegillarca granosa. Frontiers in veterinary science 2 36937017
2023 Metamorphosis by ATG13 and ATG101 in human autophagy initiation. Autophagy 2 37394799
2022 miR-137 modulates coelomocytes autophagy by targeting Atg13 in the sea cucumber Apostichopus japonicus. Developmental and comparative immunology 2 35772590
2025 Hyperoside suppresses NSCLC progression by inducing ATG13-mediated autophagy and apoptosis. Cellular immunology 1 40250077
2024 The autophagy initiation factor ATG13 mRNA is stabilized by the RNA-binding protein YBX3. FEBS letters 1 39414370
2023 Erratum: Circulating Exosomal miR-1-3p from Rats with Myocardial Infarction Plays a Protective Effect on Contrast-Induced Nephropathy via Targeting ATG13 and activating the AKT Signaling Pathway: Erratum. International journal of biological sciences 1 37928260
2016 An ultrasensitive assay format for detecting ULK1 inhibition by monitoring the phosphorylation status of Atg13. Analytical biochemistry 1 27387056
2026 Genetic depletion of the early autophagy protein ATG13 impairs mitochondrial energy metabolism, augments oxidative stress, induces the polarization of macrophages to the M1 inflammatory mode, and compromises myelin integrity in skeletal muscle. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 0 41591477
2026 Plant Virus and Vector Insect Regulate the Dual Phosphorylation of ATG1-ATG13 To Maintain a Moderate Autophagy for Viral Persistent Propagation. Journal of agricultural and food chemistry 0 41877596
2026 Ferrodoxin 1 (FDX1) drives paclitaxel resistance in ovarian cancer via copper metabolism and ULK1/ATG13-mediated autophagy: overcome by pH/ROS-responsive PPD/PDP@si-FDX1 nanomicelles. Journal of experimental & clinical cancer research : CR 0 42026685
2025 Genetic depletion of early autophagy protein ATG13 impairs mitochondrial energy metabolism, augments oxidative stress, induces the polarization of macrophages to M1 inflammatory mode, and compromises myelin integrity in skeletal muscle. Research square 0 40799759
2025 Inhibition of Atg13-mediated autophagy enhances the anti-osteoclastogenic effect of sirolimus by counteracting its pro-autophagic activity. Differentiation; research in biological diversity 0 40865278
2025 Evolutionary diversification of the autophagy initiation complex: reduced Atg101 dependency and changes in Atg9 binding to Atg13. Autophagy 0 40931865
2025 ULK1/2 Inhibitors that Degrade ATG13 Effectively Target KRAS-Mutant Cancers. bioRxiv : the preprint server for biology 0 41279975