ULK1 is an ATP-dependent serine/threonine kinase that coordinates canonical macroautophagy initiation with nutrient and energy signaling. It forms the ULK1 complex with ATG13, RB1CC1/FIP200 and ATG101, and phosphorylates components of this complex and downstream machinery, including AMBRA1, BECN1, ATG14, ATG9A and ATG4B. Nutrient-sensitive mTORC1 and AMPK inputs, feedback phosphorylation, self-association and membrane recruitment regulate its activity. ULK1 exchanges between cytosolic and recycling-endosomal pools and early autophagic membranes, where LIR-mediated interactions and palmitoylation support recruitment. Its complex coassembles with PI3KC3-C1 during initiation. Conditional functions include selective autophagy, RIPK1-dependent death signaling and neuronal growth-cone trafficking that regulates axon extension and branching.
Definition: A protein-containing supercomplex formed by coassembly of the mammalian ULK1 kinase complex with class III phosphatidylinositol 3-kinase complex I. The ordered interface involves FIP200, ATG13 and the ULK1 C-terminal domain on one side and VPS15, ATG14 and BECN1 on the other; the complete component complexes also contain ATG101 and VPS34.
Justification: PMID:40442316 directly characterizes coassembly by structural and biochemical experiments. A specific term could distinguish the assembled signaling unit from its component ULK1 and PI3KC3-C1 complexes. The broad existing PI3K-complex annotation is retained with this boundary explained; neither the indirect interface nor absence of a dedicated term disproves the assembly. The proposed kinase-activation mechanism remains a structural interpretation.
Parent term: protein-containing complex
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: ULK1 acts in the cytoplasm and its associated membrane compartments. Reason: The broad location is supported by target microscopy and the cytoplasmic autophagy-initiation mechanism. More specific cytosolic, endosomal and autophagic-membrane pools coexist; their presence does not make the parent location an over-annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002805221 · PTN002805221 SUPPORTS TRANSFER The PAINT IBD is grounded in experimental descendant evidence including human ULK1 itself. Target biology supports this conserved assertion; broader scope or additional specific terms is not a propagation failure. Supporting Evidence: PMID:17595159 Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive |
| GO:0000045 autophagosome assembly | IBA GO_REF:0000033 | ACCEPT | Summary: Autophagosome assembly, supported by two IDA experiments and by IBA. Reason: ULK1 phosphorylates components of the autophagy-initiation system, coordinating PI3KC3-C1 activation and membrane assembly. This is direct execution and regulation of canonical autophagosome biogenesis; it does not assert that every selective-autophagy route universally requires ULK1. |
| GO:0000423 mitophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitophagy, a selective subtype downstream of the initiation step. Reason: The inherited mitophagy role is consistent with deployment of ULK machinery in mitochondrial sequestration. ULK1 contributes phosphorylation/assembly work, rather than being consumed as cargo. This is retained as a conditional selective-autophagy role without asserting that all mitophagy or macroautophagy routes require ULK1. |
| GO:0010506 regulation of autophagy | IBA GO_REF:0000033 | ACCEPT | Summary: ULK1 regulates autophagy through substrate phosphorylation and feedback signaling. Reason: mTOR/AMPK inputs and ULK1 phosphorylation of autophagy machinery control initiation and flux. A broad regulation term does not require equal positive and negative effects and is appropriate to the core kinase mechanism. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000681272 · PTN000681272 SUPPORTS TRANSFER The PAINT IBD is grounded in experimental descendant evidence including human ULK1 itself. Target biology supports this conserved assertion; broader scope or additional specific terms is not a propagation failure. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0042594 response to starvation | IBA GO_REF:0000033 | ACCEPT | Summary: Response to starvation, supported by IBA across ULK1, ULK2, fly Atg1 and yeast ATG1. Reason: Starvation activates conserved Atg1/ULK autophagy machinery. Human nutrient-withdrawal experiments support the inherited response, while paralog usage and regulatory details can differ among organisms. |
| GO:0061709 reticulophagy | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Reticulophagy, propagated from fly Atg1 and yeast Atg1. Reason: The PAINT Atg1/ULK assertion supports participation in selective ER turnover. ULK1 can execute initiation machinery recruited in this context without serving as the ER cargo receptor. The conditional role is retained as noncore; different ER degradation routes can have different requirements. |
| GO:0000407 phagophore assembly site | IBA GO_REF:0000033 | ACCEPT | Summary: Phagophore assembly site, supported by IDA, IBA and an SL propagation. Reason: Where ULK1 concentrates on autophagy induction and the structure term the four GO:0034045 assertions on this gene reduce to. Core. |
| GO:0005776 autophagosome | IBA GO_REF:0000033 | ACCEPT | Summary: ULK1 associates with autophagosomal structures during autophagy. Reason: Target microscopy and LIR-dependent recruitment in PMID:22885598 Fig. 4C–E place human ULK1 on GABARAP/LC3/WIPI2-positive structures. The paper explicitly allows a mixture of autophagosomes, phagophores and omegasomes, so this supports conditional autophagosomal association without asserting permanent residence on every mature closed organelle. Early initiation activity and a retained membrane child do not refute this broader annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000681272 · PTN000681272 SUPPORTS TRANSFER The PAINT IBD is grounded in experimental descendant evidence including human ULK1 itself. Target biology supports this conserved assertion; broader scope or additional specific terms is not a propagation failure. Supporting Evidence: PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals PMID:22885598 These structures most likely represent autophagosomes, but may also include phagophores and omegasomes. |
| GO:0004674 protein serine/threonine kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0034045 phagophore assembly site membrane | IBA GO_REF:0000033 | MODIFY | Summary: ULK1 associates with the phagophore membrane through regulated peripheral recruitment. Reason: Live QuickGO marks GO:0034045 obsolete and provides GO:7770114 phagophore membrane. Preserve the membrane claim with that current term. Original PMID:18936157 describes CTD-dependent membrane association; PMID:22885598 establishes LIR-mediated targeting and PMID:39169022 shows palmitoylation-dependent anchoring. The previous absence-of-a-membrane-binding-domain argument was factually wrong; a soluble kinase can bind a membrane. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000681273 · PTN000681273 SUPPORTS TRANSFER The source membrane localization is supported by human ULK1 experimental evidence. The change updates the obsolete GO destination to current phagophore membrane without rejecting the inherited localization. Proposed replacements: phagophore membrane Supporting Evidence: PMID:39169022 These data support the essential role of ULK1 palmitoylation in anchoring the entire ULK1 complex to the membrane PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000681272 · PTN000681272 SUPPORTS TRANSFER The PAINT IBD is grounded in experimental descendant evidence including human ULK1 itself. Target biology supports this conserved assertion; broader scope or additional specific terms is not a propagation failure. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0034727 piecemeal microautophagy of the nucleus | IBA GO_REF:0000033 | UNDECIDED | Summary: Conservation of the specific nuclear microautophagy route remains unresolved. Reason: PAINT PTN000681273 has a genuine GO:0034727 IBD seeded by yeast ATG1 (SGD:S000003148). The current definition is degradation of a cell nucleus by microautophagy, not a categorical taxon restriction to yeast. Human nuclear macroautophagy or general ULK1 dependence would not establish this specific microautophagic route; conversely, absence of yeast-style NVJ proteins does not demonstrate target loss. Route-specific comparative adjudication is required. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000681273 · PTN000681273 UNRESOLVED The ancestral nuclear-microautophagy assertion and yeast experimental source are genuine. No target-specific loss is established, but generic nucleophagy does not by itself confirm conservation of microautophagic topology. |
| GO:0048671 negative regulation of collateral sprouting | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Negative regulation of collateral sprouting, propagated from mouse Ulk1 and Ulk2. Reason: Narrower and less commonly used than the other neuronal terms but drawn from the same two mouse orthologs. The neuronal terms are anchored at different PANTHER nodes from the autophagy terms, which is the expected pattern rather than a warning sign - PAINT places each function at the depth where the curator judged it to have arisen, and a neuronal role confined to the ULK1/ULK2 clade would properly sit shallower than the catalytic and autophagy assertions. Non-core because it is a tissue-restricted deployment, not because the inference is doubtful. Supporting Evidence: PMID:17389358 RNAi-mediated knockdown of Ulk1 and/or Ulk2 resulted in impaired endocytosis of nerve growth factor (NGF), excessive axon arborization, and severely stunted axon elongation. |
| GO:0048675 axon extension | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Axon extension, propagated from mouse Ulk1 and Ulk2. Reason: A more specific statement of the neurite phenotype, from genuine orthologs rather than distant family members. Non-core, alongside GO:0031175. Supporting Evidence: PMID:17389358 RNAi-mediated knockdown of Ulk1 and/or Ulk2 resulted in impaired endocytosis of nerve growth factor (NGF), excessive axon arborization, and severely stunted axon elongation. |
| GO:0000407 phagophore assembly site | IEA GO_REF:0000044 | ACCEPT | Summary: Phagophore assembly site, supported by IDA, IBA and an SL propagation. Reason: Where ULK1 concentrates on autophagy induction and the structure term the four GO:0034045 assertions on this gene reduce to. Core. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: ULK1 is an ATP-dependent protein kinase. Reason: The conserved serine/threonine kinase activity and direct substrate-phosphorylation assays support this broader molecular function. A more specific kinase annotation does not make the parent assertion incorrect. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding, from the InterPro kinase-domain mapping. Reason: A protein kinase binds ATP as its phosphate donor. Automatic, but a safe and necessary consequence of the catalytic activity. Core. |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0006914 autophagy | IEA GO_REF:0000117 | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0007165 signal transduction | IEA GO_REF:0000002 | ACCEPT | Summary: ULK1 transmits nutrient and stress signals to autophagic machinery. Reason: The direct mTORC1–ULK1 regulatory interaction and ULK1 phosphorylation of autophagy components establish signal transduction, beyond an inference from the presence of any kinase domain. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0007409 axonogenesis | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: The ULK1/UNC-51 family supports axon formation and extension. Reason: Mouse ULK1/ULK2 experiments in PMID:17389358 connect endocytic NGF/TrkA regulation to axon growth and branching, while PMID:18007665 implicates ULK1 in neurite remodeling. The electronic evidence route and overlap with more specific neuronal terms are not reasons to reject the conserved developmental role. Supporting Evidence: PMID:17389358 RNAi-mediated knockdown of Ulk1 and/or Ulk2 resulted in impaired endocytosis of nerve growth factor (NGF), excessive axon arborization, and severely stunted axon elongation. |
| GO:0010506 regulation of autophagy | IEA GO_REF:0000002 | ACCEPT | Summary: ULK1 regulates autophagy through substrate phosphorylation and feedback signaling. Reason: mTOR/AMPK inputs and ULK1 phosphorylation of autophagy machinery control initiation and flux. A broad regulation term does not require equal positive and negative effects and is appropriate to the core kinase mechanism. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0034045 phagophore assembly site membrane | IEA GO_REF:0000117 | MODIFY | Summary: ULK1 associates with the phagophore membrane through regulated peripheral recruitment. Reason: Live QuickGO marks GO:0034045 obsolete and provides GO:7770114 phagophore membrane. Preserve the membrane claim with that current term. Original PMID:18936157 describes CTD-dependent membrane association; PMID:22885598 establishes LIR-mediated targeting and PMID:39169022 shows palmitoylation-dependent anchoring. The previous absence-of-a-membrane-binding-domain argument was factually wrong; a soluble kinase can bind a membrane. Proposed replacements: phagophore membrane Supporting Evidence: PMID:39169022 These data support the essential role of ULK1 palmitoylation in anchoring the entire ULK1 complex to the membrane PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals |
| GO:0106310 protein serine kinase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0005515 protein binding | IPI PMID:17389358 Unc-51-like kinase 1/2-mediated endocytic processes regulate... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:19597335 Atg101, a novel mammalian autophagy protein interacting with... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:21072212 The association of AMPK with ULK1 regulates autophagy. | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:22613832 TBC1D14 regulates autophagosome formation via Rab11- and ULK... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:23392225 FIP200 regulates targeting of Atg16L1 to the isolation membr... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:24290141 Structural basis of the autophagy-related LC3/Atg13 LIR comp... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:25438055 AMBRA1 links autophagy to cell proliferation and tumorigenes... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:25686248 Huntingtin functions as a scaffold for selective macroautoph... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:26593251 Targeting PDK1 with dichloroacetophenone to inhibit acute my... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:27334615 The C9orf72 protein interacts with Rab1a and the ULK1 comple... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:29950492 The C9orf72-interacting protein Smcr8 is a negative regulato... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:32707033 Kinase Interaction Network Expands Functional and Disease Ro... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:33422265 ORF3a of the COVID-19 virus SARS-CoV-2 blocks HOPS complex-m... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:33450483 The papain-like protease of coronaviruses cleaves ULK1 to di... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0042802 identical protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | ACCEPT | Summary: ULK1 self-association contributes to its regulated activation. Reason: PMID:23524951 links ULK1 ubiquitylation, self-association and autophagic function. PMID:40442316 provides a structural mechanism that recruits two ULK1 molecules on the FIP200 scaffold. Retain this experimentally supported interaction as part of core activation without treating the proposed trans-autophosphorylation geometry as fully proven. Supporting Evidence: PMID:23524951 and its subsequent stabilization, self-association and function. |
| GO:0042802 identical protein binding | IPI PMID:23524951 mTOR inhibits autophagy by controlling ULK1 ubiquitylation, ... | ACCEPT | Summary: ULK1 self-association contributes to its regulated activation. Reason: PMID:23524951 links ULK1 ubiquitylation, self-association and autophagic function. PMID:40442316 provides a structural mechanism that recruits two ULK1 molecules on the FIP200 scaffold. Retain this experimentally supported interaction as part of core activation without treating the proposed trans-autophosphorylation geometry as fully proven. Supporting Evidence: PMID:23524951 and its subsequent stabilization, self-association and function. |
| GO:0005515 protein binding | IPI PMID:22354037 Genome-wide siRNA screen reveals amino acid starvation-induc... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway | TAS Reactome:R-HSA-5357905 | KEEP AS NON CORE | Summary: ULK1 regulates TNF-induced death signaling through RIPK1 phosphorylation. Reason: The Reactome pathway placement is consistent with direct substrate evidence in PMID:32320653: ULK1 phosphorylates RIPK1 and reduces necrosome assembly and TNF-induced cell death. This conditional signaling function is retained alongside the core autophagy role. Supporting Evidence: PMID:32320653 ULK1-dependent phosphorylation of RIPK1 reduces complex IIb/necrosome assembly and tumor necrosis factor (TNF)-induced cell death |
| GO:0016236 macroautophagy | TAS Reactome:R-HSA-1632852 | ACCEPT | Summary: Macroautophagy, the pathway ULK1 initiates. Reason: The most upstream and central player in initiation of macroautophagy in mammals. Core. Supporting Evidence: PMID:40442316 The Unc-51-like kinase protein kinase complex (ULK1C) is the most upstream and central player in the initiation of macroautophagy in mammals. |
| GO:0016236 macroautophagy | TAS Reactome:R-HSA-8934903 | ACCEPT | Summary: Macroautophagy, the pathway ULK1 initiates. Reason: The most upstream and central player in initiation of macroautophagy in mammals. Core. Supporting Evidence: PMID:40442316 The Unc-51-like kinase protein kinase complex (ULK1C) is the most upstream and central player in the initiation of macroautophagy in mammals. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:32320653 The Autophagy-Initiating Kinase ULK1 Controls RIPK1-Mediated... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-5675868 | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-8876446 | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | TAS Reactome:R-HSA-8948146 | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0000045 autophagosome assembly | IDA PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the aut... | ACCEPT | Summary: Autophagosome assembly, supported by two IDA experiments and by IBA. Reason: ULK1 phosphorylates components of the autophagy-initiation system, coordinating PI3KC3-C1 activation and membrane assembly. This is direct execution and regulation of canonical autophagosome biogenesis; it does not assert that every selective-autophagy route universally requires ULK1. |
| GO:0000407 phagophore assembly site | IDA PMID:19597335 Atg101, a novel mammalian autophagy protein interacting with... | ACCEPT | Summary: Phagophore assembly site, supported by IDA, IBA and an SL propagation. Reason: Where ULK1 concentrates on autophagy induction and the structure term the four GO:0034045 assertions on this gene reduce to. Core. |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:21795849 ULK1 inhibits the kinase activity of mTORC1 and cell prolife... | KEEP AS NON CORE | Summary: Negative regulation of cell population proliferation, directly observed. Reason: A cell-level consequence of sustained autophagy rather than a molecular function of the kinase. Retained because it is directly supported, marked non-core. |
| GO:0016236 macroautophagy | NAS PMID:40442316 Structure and activation of the human autophagy-initiating U... | ACCEPT | Summary: Macroautophagy, the pathway ULK1 initiates. Reason: The most upstream and central player in initiation of macroautophagy in mammals. Core. Supporting Evidence: PMID:40442316 The Unc-51-like kinase protein kinase complex (ULK1C) is the most upstream and central player in the initiation of macroautophagy in mammals. |
| GO:0035032 phosphatidylinositol 3-kinase complex, class III | IPI PMID:40442316 Structure and activation of the human autophagy-initiating U... | KEEP AS NON CORE | Summary: ULK1 is associated with class III PI3K in a structurally defined autophagy-initiation supercomplex. Reason: Full PMID:40442316 demonstrates physical coassembly of ULK1C with PI3KC3-C1 through FIP200–VPS15/ATG14/BECN1 contacts. GO:0035032 is defined broadly as a class-III catalytic/regulatory PI3K complex and permits additional adaptors. Retain the broad experimentally grounded assembly association while distinguishing ULK1C from the canonical VPS34/VPS15/BECN1/ATG14 tetramer. Lack of a direct ULK1–VPS34 interface does not disprove membership in the larger assembly. A specific supercomplex term would describe the boundary more precisely. Supporting Evidence: PMID:40442316 We also show that ULK1C and PI3KC3-C1 form a physical supercomplex |
| GO:1903059 regulation of protein lipidation | IDA PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the aut... | ACCEPT | Summary: ULK1 regulates ATG8 lipidation and processing during autophagosome formation. Reason: The source PMID:19225151 supports initiation-linked lipidation control, and full PMID:28821708 provides a specific mechanism: ULK1 phosphorylates ATG4B at Ser316 and inhibits its LC3-processing activity. Thus this is not only an unspecified downstream dependency; kinase-mediated control of lipidation/de-lipidation machinery contributes to the core autophagy mechanism. Endogenous site regulation and timing remain qualifications noted by the authors. Supporting Evidence: PMID:28821708 ULK1 inhibits LC3 processing through direct phosphorylation and inhibition of ATG4B. |
| GO:1990316 Atg1/ULK1 kinase complex | IPI PMID:19597335 Atg101, a novel mammalian autophagy protein interacting with... | ACCEPT | Summary: Atg1/ULK1 kinase complex. The complex ULK1 names and is the catalytic subunit of. Reason: ULK1 is the catalytic subunit of the mammalian initiation complex with ATG13, RB1CC1/FIP200 and ATG101. The stable complex is supported by PMID:19597335 and PMID:19211835. The 2025 core structure excludes flexible peripheral domains and reveals a rearrangement during PI3KC3-C1 coassembly, rather than redefining the complete native subunit list. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0106310 protein serine kinase activity | EXP PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0106310 protein serine kinase activity | EXP PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0106310 protein serine kinase activity | EXP PMID:28821708 A reversible phospho-switch mediated by ULK1 regulates the a... | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0106310 protein serine kinase activity | EXP PMID:31123703 Autophagy induction in atrophic muscle cells requires ULK1 a... | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0106310 protein serine kinase activity | EXP PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa... | ACCEPT | Summary: Protein serine kinase activity, the specific residue-level statement of the same activity. Reason: Five independent EXP experiments plus the RHEA reaction mapping. More precise than GO:0004674 in naming the acceptor residue, and directly matched by the GO:0018105 peptidyl-serine phosphorylation process annotation. Core. |
| GO:0005737 cytoplasm | IDA PMID:29487085 The deubiquitinating enzyme USP20 stabilizes ULK1 and promot... | ACCEPT | Summary: ULK1 acts in the cytoplasm and its associated membrane compartments. Reason: The broad location is supported by target microscopy and the cytoplasmic autophagy-initiation mechanism. More specific cytosolic, endosomal and autophagic-membrane pools coexist; their presence does not make the parent location an over-annotation. Supporting Evidence: PMID:17595159 Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive |
| GO:0033554 cellular response to stress | IDA PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | KEEP AS NON CORE | Summary: Cellular response to stress, the broad parent of the starvation and nutrient terms. Reason: A broad term, but not a redundant one. GO:0042594 and GO:0031669 name the specific stimulus and are both annotated to this gene, yet neither is a descendant of this term - GO:0042594 sits under GO:0006950 response to stress rather than under the cellular branch, and GO:0031669 sits under the response-to-extracellular-stimulus branch - so neither states this claim more precisely and this row is not discharged by them. Retained on its own IDA as the only stress-response assertion this gene carries, but too general to be core. Non-core. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0000421 autophagosome membrane | IDA PMID:22885598 Binding of the Atg1/ULK1 kinase to the ubiquitin-like protei... | ACCEPT | Summary: ULK1 has a supported autophagosomal membrane-associated pool. Reason: Full PMID:22885598 maps LIR-dependent human ULK1 recruitment to ATG8-positive autophagic structures. The microscopy includes precursor structures and does not prove exclusive mature-autophagosome residence, but it supports the curated conditional membrane association. The early phagophore role does not exclude it. Supporting Evidence: PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals |
| GO:0034045 phagophore assembly site membrane | IDA PMID:22885598 Binding of the Atg1/ULK1 kinase to the ubiquitin-like protei... | MODIFY | Summary: ULK1 associates with the phagophore membrane through regulated peripheral recruitment. Reason: Live QuickGO marks GO:0034045 obsolete and provides GO:7770114 phagophore membrane. Preserve the membrane claim with that current term. Original PMID:18936157 describes CTD-dependent membrane association; PMID:22885598 establishes LIR-mediated targeting and PMID:39169022 shows palmitoylation-dependent anchoring. The previous absence-of-a-membrane-binding-domain argument was factually wrong; a soluble kinase can bind a membrane. Proposed replacements: phagophore membrane Supporting Evidence: PMID:39169022 These data support the essential role of ULK1 palmitoylation in anchoring the entire ULK1 complex to the membrane PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals |
| GO:1903349 omegasome membrane | IDA PMID:22885598 Binding of the Atg1/ULK1 kinase to the ubiquitin-like protei... | ACCEPT | Summary: ULK1 associates with early autophagic structures that include omegasomes. Reason: Full PMID:22885598 reports ULK1 on WIPI2/ATG8-positive structures and explicitly includes omegasomes in their interpretation. The compartment complements phagophore and autophagosome locations; membrane association is also independently supported by palmitoylation-dependent anchoring. Supporting Evidence: PMID:22885598 These structures most likely represent autophagosomes, but may also include phagophores and omegasomes. PMID:39169022 These data support the essential role of ULK1 palmitoylation in anchoring the entire ULK1 complex to the membrane |
| GO:0006914 autophagy | IDA PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0010508 positive regulation of autophagy | IDA PMID:29487085 The deubiquitinating enzyme USP20 stabilizes ULK1 and promot... | ACCEPT | Summary: ULK1 promotes autophagy in the tested initiation pathway. Reason: The cited experiments support ULK1-dependent activation of autophagic machinery. The broad positive-regulation term is biologically correct and need not be replaced merely to combine it with the separately annotated macroautophagy branch. Structural cofactors can also regulate pathways; catalytic status is not an exclusive prerequisite. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0005737 cytoplasm | IC PMID:35670107 TRIM27 cooperates with STK38L to inhibit ULK1-mediated autop... | ACCEPT | Summary: ULK1 acts in the cytoplasm and its associated membrane compartments. Reason: The broad location is supported by target microscopy and the cytoplasmic autophagy-initiation mechanism. More specific cytosolic, endosomal and autophagic-membrane pools coexist; their presence does not make the parent location an over-annotation. Supporting Evidence: PMID:17595159 Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive |
| GO:0010508 positive regulation of autophagy | IDA PMID:35670107 TRIM27 cooperates with STK38L to inhibit ULK1-mediated autop... | ACCEPT | Summary: ULK1 promotes autophagy in the tested initiation pathway. Reason: The cited experiments support ULK1-dependent activation of autophagic machinery. The broad positive-regulation term is biologically correct and need not be replaced merely to combine it with the separately annotated macroautophagy branch. Structural cofactors can also regulate pathways; catalytic status is not an exclusive prerequisite. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:28821708 A reversible phospho-switch mediated by ULK1 regulates the a... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:20921139 The dynamic interaction of AMBRA1 with the dynein motor comp... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:31123703 Autophagy induction in atrophic muscle cells requires ULK1 a... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0016241 regulation of macroautophagy | IDA PMID:20921139 The dynamic interaction of AMBRA1 with the dynein motor comp... | ACCEPT | Summary: ULK1 regulates macroautophagy through phosphorylation of AMBRA1. Reason: Full PMID:20921139 shows ULK1-dependent AMBRA1 phosphorylation and release of the BECN1–VPS34 machinery from dynein, enabling ER recruitment. This supports regulation of macroautophagy; a direction-neutral parent does not assert bidirectionality. Other ULK1 feedback and ATG4B mechanisms also make a blanket positive-only characterization inaccurate. Supporting Evidence: PMID:20921139 ULK1 phosphorylates AMBRA1, releasing the autophagy core complex from dynein. |
| GO:0006914 autophagy | IGI PMID:28389568 Hepatitis C virus triggers Golgi fragmentation and autophagy... | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0000045 autophagosome assembly | IDA PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | ACCEPT | Summary: Autophagosome assembly, supported by two IDA experiments and by IBA. Reason: ULK1 phosphorylates components of the autophagy-initiation system, coordinating PI3KC3-C1 activation and membrane assembly. This is direct execution and regulation of canonical autophagosome biogenesis; it does not assert that every selective-autophagy route universally requires ULK1. |
| GO:0005515 protein binding | IPI PMID:28890335 The ER-Localized Transmembrane Protein EPG-3/VMP1 Regulates ... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:31806350 The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulat... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0051020 GTPase binding | IPI PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | KEEP AS NON CORE | Summary: GTPase binding, the parent of the small GTPase binding term, from the IRGM interaction. Reason: Full PMID:25891078 establishes interaction with the immunity-related GTPase IRGM, which organizes ULK1/BECN1 autophagy complexes during antimicrobial responses. This partner-specific interaction is retained as a conditional regulatory association. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0010508 positive regulation of autophagy | IDA PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | ACCEPT | Summary: ULK1 promotes autophagy in the tested initiation pathway. Reason: The cited experiments support ULK1-dependent activation of autophagic machinery. The broad positive-regulation term is biologically correct and need not be replaced merely to combine it with the separately annotated macroautophagy branch. Structural cofactors can also regulate pathways; catalytic status is not an exclusive prerequisite. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0018105 peptidyl-serine phosphorylation | IDA PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | ACCEPT | Summary: Peptidyl-serine phosphorylation, the process counterpart of the serine kinase activity. Reason: Directly observed and specific to the residue actually modified. Core. |
| GO:0010508 positive regulation of autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: ULK1 promotes autophagy in the tested initiation pathway. Reason: The cited experiments support ULK1-dependent activation of autophagic machinery. The broad positive-regulation term is biologically correct and need not be replaced merely to combine it with the separately annotated macroautophagy branch. Structural cofactors can also regulate pathways; catalytic status is not an exclusive prerequisite. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0005515 protein binding | IPI PMID:28561066 WIPI3 and WIPI4 β-propellers are scaffolds for LKB1-AMPK-TSC... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:25891078 IRGM governs the core autophagy machinery to conduct antimic... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0005515 protein binding | IPI PMID:28195531 Multiplex image-based autophagy RNAi screening identifies SM... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0006914 autophagy | ISS GO_REF:0000024 | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0006914 autophagy | IMP PMID:17595159 siRNA screening of the kinome identifies ULK1 as a multidoma... | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0006914 autophagy | IDA PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | ACCEPT | Summary: ULK1 executes and regulates autophagy through protein phosphorylation. Reason: The conserved kinase and human perturbation experiments support this broad process. More specific macroautophagy and assembly annotations complement it; multiple independent source assertions do not inflate or invalidate the biology. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-8948136 | KEEP AS NON CORE | Summary: Mitochondrial outer membrane, from two Reactome mitophagy reactions. Reason: ULK1 is recruited to damaged mitochondria during PINK1/Parkin mitophagy, so the location is real in that context. Asserted by author statement and tied to a selective pathway rather than the core function. Non-core. |
| GO:0005741 mitochondrial outer membrane | TAS Reactome:R-HSA-8948146 | KEEP AS NON CORE | Summary: Mitochondrial outer membrane, from two Reactome mitophagy reactions. Reason: ULK1 is recruited to damaged mitochondria during PINK1/Parkin mitophagy, so the location is real in that context. Asserted by author statement and tied to a selective pathway rather than the core function. Non-core. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-1632857 | ACCEPT | Summary: Endoplasmic reticulum membrane, the compartment the omegasome is part of. Reason: Consistent with the directly observed omegasome membrane annotation - omegasomes are ER subdomains. Core as the compartment where initiation happens, though GO:1903349 is the more informative statement. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5679205 | ACCEPT | Summary: Endoplasmic reticulum membrane, the compartment the omegasome is part of. Reason: Consistent with the directly observed omegasome membrane annotation - omegasomes are ER subdomains. Core as the compartment where initiation happens, though GO:1903349 is the more informative statement. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5679239 | ACCEPT | Summary: Endoplasmic reticulum membrane, the compartment the omegasome is part of. Reason: Consistent with the directly observed omegasome membrane annotation - omegasomes are ER subdomains. Core as the compartment where initiation happens, though GO:1903349 is the more informative statement. |
| GO:0055037 recycling endosome | TAS Reactome:R-HSA-8854759 | ACCEPT | Summary: ULK1 acts at recycling endosomes involved in autophagosome membrane supply. Reason: Full PMID:22613832 directly places endogenous ULK1 on transferrin-receptor-positive recycling endosomes and links this pool to starvation-induced membrane delivery. The pool is part of core autophagy-associated trafficking rather than an incidental localization. Supporting Evidence: PMID:22613832 ULK1 localizes to TfnR-positive REs |
| GO:0005515 protein binding | IPI PMID:26347139 TRIM-mediated precision autophagy targets cytoplasmic regula... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005515 protein binding | IPI PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0031333 negative regulation of protein-containing complex assembly | IDA PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an... | KEEP AS NON CORE | Summary: Negative regulation of protein-containing complex assembly, from the FLCN study. Reason: Full PMID:25126726 tests ULK1-dependent modulation of FLCN/FNIP/GABARAP association, with FLCN phosphosite analysis. Retain this contextual complex-assembly regulation without dismissing the evidence because the process term is broad or claiming an unidentified disassembly mechanism. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672008 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5675868 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5679239 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8876446 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5665868 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672010 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5673768 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5675790 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5683925 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005515 protein binding | IPI PMID:24603492 TBC1D5 and the AP2 complex regulate ATG9 trafficking and ini... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0005776 autophagosome | IDA PMID:22456507 Dynamic and transient interactions of Atg9 with autophagosom... | ACCEPT | Summary: ULK1 associates with autophagosomal structures during autophagy. Reason: Target microscopy and LIR-dependent recruitment in PMID:22885598 Fig. 4C–E place human ULK1 on GABARAP/LC3/WIPI2-positive structures. The paper explicitly allows a mixture of autophagosomes, phagophores and omegasomes, so this supports conditional autophagosomal association without asserting permanent residence on every mature closed organelle. Early initiation activity and a retained membrane child do not refute this broader annotation. Supporting Evidence: PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals PMID:22885598 These structures most likely represent autophagosomes, but may also include phagophores and omegasomes. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672011 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5672817 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8948136 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9819106 | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0031267 small GTPase binding | IPI PMID:22613832 TBC1D14 regulates autophagosome formation via Rab11- and ULK... | UNDECIDED | Summary: The cited interaction is clear, but its small-GTPase specificity is unresolved. Reason: Full PMID:22613832 maps ULK1 binding to TBC1D14, a Rab-binding TBC-domain effector, and separately maps TBC1D14 binding to Rab11. TBC1D14 is not itself a small monomeric GTPase, the ligand required by GO:0031267. Colocalization or association in a ternary trafficking assembly does not establish a direct ULK1–Rab contact. Preserve source-specific uncertainty rather than extrapolating this mismatch to all possible ULK1–GTPase interactions. Supporting Evidence: PMID:22613832 A yeast two-hybrid assay revealed an interaction between TBC1D14 and ULK1 PMID:22613832 TBC1D14 binds activated Rab11 but is not a GAP for Rab11 |
| GO:0004674 protein serine/threonine kinase activity | IDA PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0005515 protein binding | IPI PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0034045 phagophore assembly site membrane | IDA PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | MODIFY | Summary: ULK1 associates with the phagophore membrane through regulated peripheral recruitment. Reason: Live QuickGO marks GO:0034045 obsolete and provides GO:7770114 phagophore membrane. Preserve the membrane claim with that current term. Original PMID:18936157 describes CTD-dependent membrane association; PMID:22885598 establishes LIR-mediated targeting and PMID:39169022 shows palmitoylation-dependent anchoring. The previous absence-of-a-membrane-binding-domain argument was factually wrong; a soluble kinase can bind a membrane. Proposed replacements: phagophore membrane Supporting Evidence: PMID:39169022 These data support the essential role of ULK1 palmitoylation in anchoring the entire ULK1 complex to the membrane PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals |
| GO:0042594 response to starvation | ISS GO_REF:0000024 | ACCEPT | Summary: Response to starvation, supported by IBA across ULK1, ULK2, fly Atg1 and yeast ATG1. Reason: Starvation activates conserved Atg1/ULK autophagy machinery. Human nutrient-withdrawal experiments support the inherited response, while paralog usage and regulatory details can differ among organisms. |
| GO:0046777 protein autophosphorylation | IDA PMID:18936157 Kinase-inactivated ULK proteins inhibit autophagy via their ... | ACCEPT | Summary: Protein autophosphorylation, directly observed. Reason: ULK1 autophosphorylation is supported by PMID:18936157. The 2025 structure suggests how FIP200-dependent recruitment of two ULK1 molecules could facilitate activation; it does not directly resolve the kinase domains or itself prove the proposed trans-autophosphorylation reaction. Supporting Evidence: PMID:40442316 The FIP200:ATG13:ULK1 core of ULK1C undergoes a rearrangement from 2:1:1 to 2:2:2 stoichiometry in the presence of PI3KC3-C1. |
| GO:0031669 cellular response to nutrient levels | ISS GO_REF:0000024 | ACCEPT | Summary: Cellular response to nutrient levels. ULK1 is the node where nutrient signals enter autophagy. Reason: mTORC1 phosphorylates and inhibits ULK1 when nutrients are plentiful and releases it when they are not, and AMPK acts on the same protein from the energy-status side. Being the substrate of that switch is not incidental to ULK1's function; it is why the kinase sits where it does in the pathway. Core. |
| GO:1990316 Atg1/ULK1 kinase complex | IPI PMID:19211835 Nutrient-dependent mTORC1 association with the ULK1-Atg13-FI... | ACCEPT | Summary: Atg1/ULK1 kinase complex. The complex ULK1 names and is the catalytic subunit of. Reason: ULK1 is the catalytic subunit of the mammalian initiation complex with ATG13, RB1CC1/FIP200 and ATG101. The stable complex is supported by PMID:19597335 and PMID:19211835. The 2025 core structure excludes flexible peripheral domains and reveals a rearrangement during PI3KC3-C1 coassembly, rather than redefining the complete native subunit list. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0005515 protein binding | IPI PMID:19211835 Nutrient-dependent mTORC1 association with the ULK1-Atg13-FI... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
| GO:0044877 protein-containing complex binding | IPI PMID:19211835 Nutrient-dependent mTORC1 association with the ULK1-Atg13-FI... | ACCEPT | Summary: ULK1 binds mTORC1 through RPTOR in nutrient-sensitive autophagy regulation. Reason: Full PMID:19211835 directly establishes the mTORC1–ULK1-complex interaction and nutrient dependence. This complex-binding event is integral to regulation of the core kinase and is more informative than unspecified protein binding. Supporting Evidence: PMID:19211835 mTORC1 directly interacts with ULK1 and phosphorylates ULK1 and Atg13. |
| GO:0004674 protein serine/threonine kinase activity | NAS PMID:9693035 Human ULK1, a novel serine/threonine kinase related to UNC-5... | ACCEPT | Summary: Protein serine/threonine kinase activity. ULK1's defining activity, supported by an EXP and eight independent IDA experiments. Reason: ULK1 is the initiating kinase of macroautophagy. It phosphorylates ATG13, RB1CC1, ATG9A, BECN1 and ATG14 among others, and its catalytic output is what converts an upstream nutrient signal into assembly of the downstream machinery. Core. |
| GO:0005737 cytoplasm | NAS PMID:9693035 Human ULK1, a novel serine/threonine kinase related to UNC-5... | ACCEPT | Summary: ULK1 acts in the cytoplasm and its associated membrane compartments. Reason: The broad location is supported by target microscopy and the cytoplasmic autophagy-initiation mechanism. More specific cytosolic, endosomal and autophagic-membrane pools coexist; their presence does not make the parent location an over-annotation. Supporting Evidence: PMID:17595159 Full-length ULK1 localized to cytoplasmic structures, some of which were GFP-LC3-positive |
| GO:0005776 autophagosome | IDA PMID:17595159 siRNA screening of the kinome identifies ULK1 as a multidoma... | ACCEPT | Summary: ULK1 associates with autophagosomal structures during autophagy. Reason: Target microscopy and LIR-dependent recruitment in PMID:22885598 Fig. 4C–E place human ULK1 on GABARAP/LC3/WIPI2-positive structures. The paper explicitly allows a mixture of autophagosomes, phagophores and omegasomes, so this supports conditional autophagosomal association without asserting permanent residence on every mature closed organelle. Early initiation activity and a retained membrane child do not refute this broader annotation. Supporting Evidence: PMID:22885598 Atg8 recruits Atg1/ULK1 to autophagosome-like structures in yeast and mammals PMID:22885598 These structures most likely represent autophagosomes, but may also include phagophores and omegasomes. |
| GO:0005829 cytosol | IDA PMID:11146101 Interaction of the Unc-51-like kinase and microtubule-associ... | ACCEPT | Summary: ULK1 has a cytosolic pool that exchanges with autophagic membranes. Reason: Cytosolic localization is integral to nutrient-sensitive complex recruitment and signaling. Recruitment to membranes does not erase this pool, and repeated Reactome or evidence assertions do not invalidate the location. Supporting Evidence: PMID:11146101 In HeLa cells, endogenous ULK1 and tagged GABARAP showed punctate structures in the cytosol, and were colocalized. |
| GO:0006468 protein phosphorylation | NAS PMID:9693035 Human ULK1, a novel serine/threonine kinase related to UNC-5... | ACCEPT | Summary: ULK1 catalyzes protein phosphorylation. Reason: Its conserved kinase domain and multiple direct substrate assays support this broad process. More specific residue and autophosphorylation annotations complement the parent assertion rather than invalidate it. Supporting Evidence: PMID:19225151 ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. |
| GO:0008104 intracellular protein localization | IMP PMID:16940348 Starvation and ULK1-dependent cycling of mammalian Atg9 betw... | ACCEPT | Summary: ULK1 controls ATG9A trafficking during autophagosome biogenesis. Reason: PMID:16940348 directly tests starvation-dependent ATG9 redistribution and its loss after ULK1 depletion. Together with the established kinase-dependent assembly mechanism, this supports intracellular protein localization as a core trafficking role; the broader term is not erroneous simply because the cargo is known. Supporting Evidence: PMID:16940348 siRNA-mediated depletion of the putative mammalian homologue of Atg1p, ULK1, inhibits this starvation-induced redistribution. |
| GO:0031175 neuron projection development | IMP PMID:18007665 Identification of new kinase clusters required for neurite o... | KEEP AS NON CORE | Summary: Neuron projection development, supported by IMP. The best-evidenced of this gene's five neuronal annotations. Reason: The human-kinase RNAi screen PMID:18007665 implicates ULK1 in neurite remodeling, complementing mouse ULK1/ULK2 growth-cone and NGF-endocytosis experiments in PMID:17389358. Retain the neuronal context as noncore without requiring proof that every neuronal effect is independent of autophagy or treating other evidence codes as disposable. |
| GO:0005515 protein binding | IPI PMID:11146101 Interaction of the Unc-51-like kinase and microtubule-associ... | REMOVE | Summary: The reported interaction is retained as evidence, but generic protein binding is uninformative. Reason: The cited interaction evidence can inform complex membership or a demonstrated regulatory/adaptor mechanism. Generic protein binding does not identify that function; removing this annotation does not reject the measured interaction or assign an untested mechanism to every interactor. |
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Download this section (compressed HTML)Q: Is the Atg1-dependent nuclear microautophagy route conserved in mammalian cells, and which experiments distinguish it from nuclear macroautophagy?
Q: Does the source PMID:22613832 demonstrate direct ULK1 binding to a small GTPase beyond its separately demonstrated TBC1D14 interaction?
Q: How does ULK1 palmitoylation coordinate LIR-mediated recruitment, self-association and release from autophagic membranes?
Q: Which neuronal trafficking effects require ULK1 kinase activity independently of autophagic degradation, and which are shared with ULK2?
Experiment: Separation-of-function analysis of ULK1 in neurons: compare kinase-dead ULK1, an autophagy-null background, and unc-51-derived point mutants for axon extension and neurite outgrowth, to determine whether the neuronal annotations describe an autophagy-independent activity.
Experiment: Quantitative phosphoproteomics after acute ULK1 activation with a chemical-genetic allele, to enumerate direct substrates and give the twenty-seven protein binding annotations a directional replacement grounded in which partners are actually phosphorylated.
Experiment: Measure assembly and kinase activity of the ULK1C:PI3KC3-C1 supercomplex under nutrient-replete and starvation conditions, testing the proposed coupling between FIP200-mediated ULK1 recruitment and trans-autophosphorylation.
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