id: Q13501 gene_symbol: SQSTM1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- SQSTM1 (sequestosome-1, p62) is a multidomain cytoplasmic adaptor protein and the prototypical selective autophagy receptor. Its N-terminal PB1 domain drives homo-oligomerization (front-to-back filament-like arrays) and hetero-oligomerization with partners such as the atypical protein kinases PRKCZ/PRKCI, NBR1 and MAP2K5; a ZZ-type zinc finger binds RIPK1; a TRAF6-binding (TB) motif scaffolds TRAF6; an LC3-interacting region (LIR) binds ATG8-family proteins (LC3A/B/C, GABARAP/L1/L2); a KEAP1-interacting region (KIR) binds KEAP1 when phosphorylated at Ser-349; and a C-terminal UBA domain binds polyubiquitin, with a strong preference for K63-linked chains. By simultaneously binding ubiquitinated cargo through the UBA domain and the growing autophagosome through the LIR, p62 bridges ubiquitin-tagged substrates to the autophagy machinery. Multivalent ubiquitin binding combined with PB1-mediated polymerization drives liquid-liquid phase separation into "p62 bodies," membraneless condensates that concentrate ubiquitinated cargo for engulfment; p62 and its cargo are then degraded together. This underlies aggrephagy (clearance of ubiquitinated protein aggregates) and more specialized selective autophagy including pexophagy (via ubiquitinated PEX5), xenophagy/antibacterial autophagy and control of inflammasome and RIPosome components. p62 also contributes to PINK1/Parkin mitophagy, where it is recruited to depolarized mitochondria and mediates their perinuclear clustering, though it is largely dispensable for the mitochondrial clearance step itself. Independent of autophagy, phospho-Ser349 p62 sequesters KEAP1 into condensates, derepressing the transcription factor NRF2 (NFE2L2) to induce cytoprotective antioxidant/phase-II genes; SQSTM1 is itself an NRF2 target, forming a positive feedback loop. Through its PB1, ZZ and TB modules p62 serves as a signaling scaffold for NF-kB activation downstream of IL-1/TRAF6, NGF/TrkA and TNF/RIPK1, and it modulates additional pathways including mTORC1 signaling. p62 levels are an established readout of autophagic flux, and SQSTM1 variants cause Paget disease of bone, frontotemporal dementia/ALS, distal myopathy with rimmed vacuoles, and (recessively) childhood-onset neurodegeneration. alternative_products: - name: '1' id: Q13501-1 - name: '2' id: Q13501-2 sequence_note: VSP_015841 existing_annotations: - term: id: GO:0035973 label: aggrephagy evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Phylogenetic inference of aggrephagy, the core p62 process - selective autophagic clearance of ubiquitinated protein aggregates. Strongly corroborated by direct experimental evidence. action: ACCEPT reason: Core biological process for p62; abundant IDA support (e.g. PMID:17580304, PMID:22017874) confirms the phylogenetic inference. supported_by: - reference_id: PMID:17580304 supporting_text: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated - term: id: GO:0000423 label: mitophagy evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Phylogenetic inference of involvement in mitophagy. p62 is recruited to depolarized mitochondria and drives their perinuclear clustering but is dispensable for the clearance step itself. action: KEEP_AS_NON_CORE reason: Real but secondary/supporting role; p62 is required for Parkin-induced mitochondrial clustering but not for mitochondrial clearance (PMID:20890124), so mitophagy is non-core relative to general aggrephagy/selective autophagy. supported_by: - reference_id: PMID:20890124 supporting_text: p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy - term: id: GO:0005080 label: protein kinase C binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: Phylogenetic inference of protein kinase C binding, reflecting the well-documented PB1-mediated interaction of p62 with atypical PKCs (PRKCZ/PRKCI). action: KEEP_AS_NON_CORE reason: Genuine interaction underlying the NF-kB signaling scaffold role, but secondary to the core autophagy-receptor function. - term: id: GO:0007032 label: endosome organization evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Phylogenetic inference of a role in endosome organization, consistent with the experimentally demonstrated function of ubiquitinated p62 as a perinuclear molecular bridge retaining endosomal vesicles. action: KEEP_AS_NON_CORE reason: Experimentally supported (PMID:27368102) but a specialized, secondary role distinct from the core selective-autophagy receptor function. - term: id: GO:0044753 label: amphisome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Phylogenetic inference that p62 acts in the amphisome, the hybrid organelle formed by autophagosome-endosome fusion along the autophagic pathway. action: KEEP_AS_NON_CORE reason: Plausible transit compartment along the autophagy pathway (IDA support in PMID:19640926) but a non-core sub-localization. - term: id: GO:0070530 label: K63-linked polyubiquitin modification-dependent protein binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: Phylogenetic inference of K63-linked polyubiquitin binding, the core molecular activity of the p62 UBA domain that recognizes ubiquitinated cargo. action: ACCEPT reason: Core molecular function; the UBA domain preferentially binds K63-linked polyubiquitin (PMID:12857745), supported by direct experimental evidence. - term: id: GO:0016235 label: aggresome evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Phylogenetic inference that p62 acts in the aggresome, the perinuclear inclusion where misfolded ubiquitinated proteins are concentrated prior to autophagic clearance. action: KEEP_AS_NON_CORE reason: p62 is a common constituent of aggresomes/inclusion bodies, but this reflects the cargo-sequestration outcome rather than a distinct core compartment. - term: id: GO:0000407 label: phagophore assembly site evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Electronic prediction of localization to the phagophore assembly site (PAS), where p62 nucleates ubiquitin condensates that initiate autophagosome formation. action: ACCEPT reason: Consistent with the EXP-supported PAS localization (PMID:34471133) and the core role of p62 condensates in autophagy initiation. - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of nuclear localization from the UniProt subcellular location. p62 shuttles to the nucleus and is found in PML bodies, recruiting ubiquitinated proteins there. action: KEEP_AS_NON_CORE reason: Real but secondary localization (also EXP-supported, PMID:10708586); the dominant functional pool is cytoplasmic. - term: id: GO:0005764 label: lysosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of lysosomal localization, consistent with p62 trafficking to lysosomes as a degraded autophagic cargo. action: KEEP_AS_NON_CORE reason: Reflects the endpoint of autophagic delivery rather than a core site of action; non-core localization. - term: id: GO:0005770 label: late endosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of late endosome localization, consistent with the aPKC/endosome-trafficking role of p62. action: KEEP_AS_NON_CORE reason: Experimentally supported (PMID:9566925, PMID:12471037) but a secondary compartment relative to the core cytoplasmic/autophagic function. - term: id: GO:0005776 label: autophagosome evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Electronic prediction of autophagosome localization, the core site where p62 delivers ubiquitinated cargo via LIR-ATG8 binding. action: ACCEPT reason: Core localization, strongly supported by IDA evidence (e.g. PMID:17580304, PMID:37802024). - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of ER localization, consistent with p62 functioning near ER membranes (e.g. with TRIM13 in ER-stress autophagy). action: KEEP_AS_NON_CORE reason: Context-specific, secondary localization (PMID:22178386); not the core site of action. - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of cytosolic localization, the principal compartment where p62 oligomerizes, binds cargo and forms condensates. action: ACCEPT reason: Core localization; redundant with abundant IDA/TAS cytosol annotations. - term: id: GO:0008270 label: zinc ion binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: InterPro-based prediction of zinc ion binding via the ZZ-type zinc finger, which coordinates Zn(2+) and mediates RIPK1 binding. action: KEEP_AS_NON_CORE reason: Correct structural metal-binding activity of the ZZ domain, but ancillary to the core ubiquitin-reader/adaptor function rather than a standalone core MF. - term: id: GO:0016234 label: inclusion body evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: ARBA machine-learning prediction of inclusion body localization, consistent with p62 being a hallmark constituent of cytoplasmic ubiquitin-positive inclusions. action: KEEP_AS_NON_CORE reason: Real (p62 bodies/inclusions) but represents the cargo-sequestration outcome; non-core compartment. - term: id: GO:0016605 label: PML body evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of PML body localization, consistent with p62 recruiting ubiquitinated proteins to nuclear PML bodies. action: KEEP_AS_NON_CORE reason: Experimentally supported nuclear sub-localization (PMID:20168092) but a secondary site relative to cytoplasmic function. - term: id: GO:0030017 label: sarcomere evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: Electronic transfer of sarcomere localization, reflecting p62 interactions with muscle proteins (titin/TTN, FHOD3, TRIM55). action: KEEP_AS_NON_CORE reason: Tissue-specific peripheral localization; not a core compartment for the autophagy-receptor function. - term: id: GO:0031399 label: regulation of protein modification process evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: involved_in review: summary: ARBA machine-learning prediction of involvement in regulation of protein modification, a very broad parent term. action: KEEP_AS_NON_CORE reason: Overly generic; p62's specific roles (e.g. regulating TRAF6 ubiquitination, KEAP1-mediated ubiquitination) are better captured by more precise terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14676191 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16169070 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16189514 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16874300 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17389358 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18083104 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19229298 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19250911 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19427866 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19615732 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20010802 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20168092 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20173742 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20417604 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20452972 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20551902 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20562859 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20808283 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21149568 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21900206 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21988832 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22190034 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23274085 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23459205 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24089205 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24189400 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24316673 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24668264 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:24879152 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25026213 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25040165 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25686248 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25910212 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25959826 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26344566 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26524528 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26637326 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27728806 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29519959 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31169361 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31616248 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31980649 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33436498 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:33961781 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34524948 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34591642 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34799561 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35044719 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35266954 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37219487 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37460613 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:39009827 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:8702753 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:16169070 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:20562859 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:21900206 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:25686248 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0042802 label: identical protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0001659 label: temperature homeostasis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer (Ensembl Compara) prediction of involvement in temperature homeostasis from mouse." action: KEEP_AS_NON_CORE reason: "Pleiotropic, mouse-derived peripheral process; biologically plausible but not a core p62 function." - term: id: GO:0002931 label: response to ischemia evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer prediction of involvement in response to ischemia." action: KEEP_AS_NON_CORE reason: "Peripheral mouse-derived process; retained as non-core." - term: id: GO:0005080 label: protein kinase C binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Protein kinase C binding via the PB1 domain (atypical PKCs PRKCZ/PRKCI)." action: KEEP_AS_NON_CORE reason: "Genuine interaction underlying the NF-kB scaffold role; secondary to the core autophagy-receptor function." - term: id: GO:0005739 label: mitochondrion evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: "Ortholog-transfer prediction of mitochondrial localization, consistent with recruitment to damaged mitochondria during mitophagy." action: KEEP_AS_NON_CORE reason: "Real in the mitophagy context but a secondary, condition-dependent localization; non-core." - term: id: GO:0006606 label: protein import into nucleus evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer prediction of involvement in protein import into nucleus." action: KEEP_AS_NON_CORE reason: "Peripheral, indirectly related to nuclear shuttling; non-core." - term: id: GO:0006914 label: autophagy evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Involvement in autophagy, the overarching process in which p62 functions as a selective receptor." action: ACCEPT reason: "Core process; supported by IMP/IDA evidence." - term: id: GO:0016235 label: aggresome evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: "Ortholog-transfer prediction of aggresome localization." action: KEEP_AS_NON_CORE reason: "Real (p62 is an aggresome constituent) but reflects sequestration outcome; non-core." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0031397 label: negative regulation of protein ubiquitination evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Direct evidence that p62 negatively regulates protein ubiquitination in specific contexts (e.g. via KEAP1 sequestration / TRAF6 modulation)." action: KEEP_AS_NON_CORE reason: "Real regulatory effect but context-specific; non-core." - term: id: GO:0035255 label: ionotropic glutamate receptor binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Ortholog-transfer/ISS prediction of ionotropic glutamate receptor binding (synaptic context)." action: KEEP_AS_NON_CORE reason: "Peripheral, neuron-specific interaction; non-core." - term: id: GO:0035973 label: aggrephagy evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0042802 label: identical protein binding evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. action: KEEP_AS_NON_CORE reason: Self-association via the PB1 domain is real and underlies condensate formation, but is ancillary to the core ubiquitin-reader/adaptor function; retained as non-core. - term: id: GO:0044754 label: autolysosome evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: "Autolysosome localization, the degradative endpoint of the autophagic pathway." action: KEEP_AS_NON_CORE reason: "Endpoint compartment; non-core." - term: id: GO:0044877 label: protein-containing complex binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Ortholog-transfer prediction of protein-containing complex binding." action: KEEP_AS_NON_CORE reason: "Generic binding term; non-core." - term: id: GO:0045202 label: synapse evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: "Ortholog-transfer prediction of activity at the synapse." action: KEEP_AS_NON_CORE reason: "Neuron-specific peripheral localization; non-core." - term: id: GO:0070342 label: brown fat cell proliferation evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer prediction of involvement in brown fat cell proliferation (mouse metabolic phenotype)." action: KEEP_AS_NON_CORE reason: "Tissue/metabolic pleiotropy from mouse; non-core." - term: id: GO:0070530 label: K63-linked polyubiquitin modification-dependent protein binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition." action: ACCEPT reason: "Core molecular function for selective autophagy." - term: id: GO:0097009 label: energy homeostasis evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer prediction of involvement in energy homeostasis (mouse metabolic phenotype)." action: KEEP_AS_NON_CORE reason: "Metabolic pleiotropy from mouse; non-core." - term: id: GO:0097225 label: sperm midpiece evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: "Ortholog-transfer prediction of sperm midpiece localization." action: KEEP_AS_NON_CORE reason: "Tissue-specific peripheral localization; non-core." - term: id: GO:0097413 label: Lewy body evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: "Ortholog-transfer prediction of Lewy body localization, consistent with p62 being a constituent of these inclusions." action: KEEP_AS_NON_CORE reason: "Disease-inclusion localization (sequestration outcome); non-core." - term: id: GO:0098978 label: glutamatergic synapse evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: "Ortholog-transfer prediction of activity at the glutamatergic synapse." action: KEEP_AS_NON_CORE reason: "Neuron-specific peripheral localization; non-core." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140694 label: membraneless organelle assembly evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation." action: ACCEPT reason: "Core process underlying selective sequestration of ubiquitinated cargo." - term: id: GO:1900273 label: positive regulation of long-term synaptic potentiation evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer/ISS prediction of positive regulation of long-term synaptic potentiation." action: KEEP_AS_NON_CORE reason: "Neuron-specific peripheral process; non-core." - term: id: GO:1903078 label: positive regulation of protein localization to plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: "Ortholog-transfer/ISS prediction of positive regulation of protein localization to plasma membrane." action: KEEP_AS_NON_CORE reason: "Peripheral process; non-core." - term: id: GO:0043065 label: positive regulation of apoptotic process evidence_type: TAS original_reference_id: Reactome:R-HSA-205043 qualifier: involved_in review: summary: "Reactome curation linking p62 to positive regulation of apoptosis in the NRIF death-signaling pathway." action: KEEP_AS_NON_CORE reason: "Indirect, context-specific; non-core." - term: id: GO:0036464 label: cytoplasmic ribonucleoprotein granule evidence_type: IDA original_reference_id: PMID:20357094 qualifier: located_in review: summary: "Localization to cytoplasmic ribonucleoprotein granules (TRIM5alpha/stress-granule-associated context)." action: KEEP_AS_NON_CORE reason: "Context-specific condensate localization; non-core." - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0000407 label: phagophore assembly site evidence_type: EXP original_reference_id: PMID:34471133 qualifier: located_in review: summary: "Experimental localization to the phagophore assembly site, where p62 condensates nucleate autophagosome formation." action: ACCEPT reason: "Core localization for autophagy initiation; supported by reconstitution/EXP evidence (PMID:34471133)." - term: id: GO:0005634 label: nucleus evidence_type: EXP original_reference_id: PMID:10708586 qualifier: located_in review: summary: "Experimental nuclear localization; p62 shuttles to the nucleus and PML bodies." action: KEEP_AS_NON_CORE reason: "Real but secondary localization (PMID:10708586); dominant pool is cytoplasmic." - term: id: GO:0005764 label: lysosome evidence_type: EXP original_reference_id: PMID:9566925 qualifier: located_in review: summary: "Experimental lysosomal localization, consistent with p62 trafficking to lysosomes as autophagic cargo and via aPKC/endosome routes." action: KEEP_AS_NON_CORE reason: "Endpoint/secondary compartment; non-core." - term: id: GO:0005770 label: late endosome evidence_type: EXP original_reference_id: PMID:12471037 qualifier: located_in review: summary: "Experimental late-endosome localization via the aPKC-interaction/endosome-trafficking role." action: KEEP_AS_NON_CORE reason: "Secondary compartment (PMID:9566925, PMID:12471037); non-core." - term: id: GO:0005770 label: late endosome evidence_type: EXP original_reference_id: PMID:9566925 qualifier: located_in review: summary: "Experimental late-endosome localization via the aPKC-interaction/endosome-trafficking role." action: KEEP_AS_NON_CORE reason: "Secondary compartment (PMID:9566925, PMID:12471037); non-core." - term: id: GO:0005783 label: endoplasmic reticulum evidence_type: EXP original_reference_id: PMID:22178386 qualifier: located_in review: summary: "Experimental ER localization in ER-stress autophagy contexts." action: KEEP_AS_NON_CORE reason: "Context-specific secondary localization (PMID:22178386); non-core." - term: id: GO:0033554 label: cellular response to stress evidence_type: IDA original_reference_id: PMID:37802024 qualifier: involved_in review: summary: "Direct evidence that p62 participates in the cellular stress response (e.g. oxidative/proteotoxic stress, NRF2 activation)." action: ACCEPT reason: "Genuine core-adjacent stress-response involvement directly demonstrated; underlies p62's cytoprotective KEAP1-NRF2 and proteostasis functions." - term: id: GO:0016236 label: macroautophagy evidence_type: IMP original_reference_id: PMID:22622177 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0016236 label: macroautophagy evidence_type: IDA original_reference_id: PMID:27498865 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:34893540 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:34893540 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0110076 label: negative regulation of ferroptosis evidence_type: IMP original_reference_id: PMID:26403645 qualifier: involved_in review: summary: "Mutant-phenotype evidence that p62 negatively regulates ferroptosis via the KEAP1-NRF2 axis." action: KEEP_AS_NON_CORE reason: "Real cytoprotective effect downstream of NRF2 activation (PMID:26403645); a specialized secondary outcome, non-core." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IDA original_reference_id: PMID:34893540 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:37802024 qualifier: is_active_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:29343546 qualifier: is_active_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:29507397 qualifier: is_active_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:37306101 qualifier: is_active_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:31857589 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:37802024 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0033554 label: cellular response to stress evidence_type: IDA original_reference_id: PMID:17580304 qualifier: involved_in review: summary: "Direct evidence that p62 participates in the cellular stress response (e.g. oxidative/proteotoxic stress, NRF2 activation)." action: ACCEPT reason: "Genuine core-adjacent stress-response involvement directly demonstrated; underlies p62's cytoprotective KEAP1-NRF2 and proteostasis functions." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:17580304 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:31857589 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:37802024 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0043232 label: intracellular membraneless organelle evidence_type: IDA original_reference_id: PMID:31857589 qualifier: is_active_in review: summary: "Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates)." action: ACCEPT reason: "Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo." - term: id: GO:0043232 label: intracellular membraneless organelle evidence_type: IDA original_reference_id: PMID:37802024 qualifier: is_active_in review: summary: "Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates)." action: ACCEPT reason: "Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:37802024 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IDA original_reference_id: PMID:31857589 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IDA original_reference_id: PMID:31857589 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IDA original_reference_id: PMID:37802024 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140694 label: membraneless organelle assembly evidence_type: IDA original_reference_id: PMID:31857589 qualifier: involved_in review: summary: "Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation." action: ACCEPT reason: "Core process underlying selective sequestration of ubiquitinated cargo." - term: id: GO:0140694 label: membraneless organelle assembly evidence_type: IDA original_reference_id: PMID:37802024 qualifier: involved_in review: summary: "Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation." action: ACCEPT reason: "Core process underlying selective sequestration of ubiquitinated cargo." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:22017874 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:29343546 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:29507397 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0035973 label: aggrephagy evidence_type: IDA original_reference_id: PMID:37306101 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0043232 label: intracellular membraneless organelle evidence_type: IDA original_reference_id: PMID:22017874 qualifier: is_active_in review: summary: "Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates)." action: ACCEPT reason: "Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo." - term: id: GO:0043232 label: intracellular membraneless organelle evidence_type: IDA original_reference_id: PMID:29343546 qualifier: is_active_in review: summary: "Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates)." action: ACCEPT reason: "Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo." - term: id: GO:0043232 label: intracellular membraneless organelle evidence_type: IDA original_reference_id: PMID:29507397 qualifier: is_active_in review: summary: "Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates)." action: ACCEPT reason: "Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo." - term: id: GO:0070530 label: K63-linked polyubiquitin modification-dependent protein binding evidence_type: IDA original_reference_id: PMID:29343546 qualifier: enables review: summary: "Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition." action: ACCEPT reason: "Core molecular function for selective autophagy." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IDA original_reference_id: PMID:22017874 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0140311 label: protein sequestering activity evidence_type: IDA original_reference_id: PMID:37306101 qualifier: enables review: summary: "Direct evidence that p62 sequesters target proteins (e.g. into condensates) to control their activity/localization." action: ACCEPT reason: "Core: protein sequestration into p62 bodies is central to its receptor and KEAP1-regulatory functions." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IDA original_reference_id: PMID:29343546 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IDA original_reference_id: PMID:29507397 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140693 label: molecular condensate scaffold activity evidence_type: IDA original_reference_id: PMID:37306101 qualifier: enables review: summary: "Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies." action: ACCEPT reason: "Core molecular function enabling cargo concentration for autophagy." - term: id: GO:0140694 label: membraneless organelle assembly evidence_type: IDA original_reference_id: PMID:29343546 qualifier: involved_in review: summary: "Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation." action: ACCEPT reason: "Core process underlying selective sequestration of ubiquitinated cargo." - term: id: GO:0140694 label: membraneless organelle assembly evidence_type: IDA original_reference_id: PMID:29507397 qualifier: involved_in review: summary: "Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation." action: ACCEPT reason: "Core process underlying selective sequestration of ubiquitinated cargo." - term: id: GO:0005737 label: cytoplasm evidence_type: IC original_reference_id: PMID:31281713 qualifier: is_active_in review: summary: "Cytoplasm is the principal compartment where p62 oligomerizes, binds cargo and forms condensates." action: ACCEPT reason: "Core localization." - term: id: GO:0034144 label: negative regulation of toll-like receptor 4 signaling pathway evidence_type: IDA original_reference_id: PMID:31281713 qualifier: involved_in review: summary: "Direct evidence that p62 negatively regulates TLR4 signaling by acting on the TRAF6-ECSIT complex." action: ACCEPT reason: "Specific, directly demonstrated immune-signaling function (PMID:31281713)." - term: id: GO:0140313 label: molecular sequestering activity evidence_type: IDA original_reference_id: PMID:31281713 qualifier: enables review: summary: "Direct evidence of molecular sequestering activity (sequestration of the TRAF6-ECSIT complex to dampen TLR4 signaling)." action: KEEP_AS_NON_CORE reason: "Genuine sequestration activity in a specific signaling context; the broader protein-sequestering term captures the core role, so non-core here." - term: id: GO:0016236 label: macroautophagy evidence_type: IDA original_reference_id: PMID:36221902 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0030163 label: protein catabolic process evidence_type: IDA original_reference_id: PMID:36221902 qualifier: involved_in review: summary: "Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy." action: ACCEPT reason: "Core outcome of the receptor function; directly demonstrated." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:36221902 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:36221902 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IDA original_reference_id: PMID:36221902 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:30612879 qualifier: is_active_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0016236 label: macroautophagy evidence_type: IDA original_reference_id: PMID:30612879 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0016236 label: macroautophagy evidence_type: IDA original_reference_id: PMID:32715615 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0030163 label: protein catabolic process evidence_type: IDA original_reference_id: PMID:30612879 qualifier: involved_in review: summary: "Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy." action: ACCEPT reason: "Core outcome of the receptor function; directly demonstrated." - term: id: GO:0030163 label: protein catabolic process evidence_type: IDA original_reference_id: PMID:32715615 qualifier: involved_in review: summary: "Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy." action: ACCEPT reason: "Core outcome of the receptor function; directly demonstrated." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:30612879 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:32715615 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:30612879 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:32715615 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:27498865 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0030163 label: protein catabolic process evidence_type: IDA original_reference_id: PMID:27498865 qualifier: involved_in review: summary: "Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy." action: ACCEPT reason: "Core outcome of the receptor function; directly demonstrated." - term: id: GO:0035591 label: signaling adaptor activity evidence_type: IDA original_reference_id: PMID:27498865 qualifier: enables review: summary: "Direct evidence that p62 acts as a signaling adaptor bringing together components of signaling pathways (e.g. NF-kB, selective autophagy of immune regulators)." action: ACCEPT reason: "Core scaffolding/adaptor molecular function; directly demonstrated (PMID:27498865)." - term: id: GO:0071211 label: protein targeting to vacuole involved in autophagy evidence_type: IDA original_reference_id: PMID:27498865 qualifier: involved_in review: summary: "Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy." action: ACCEPT reason: "Core: this is the cargo-delivery outcome of the p62 receptor function." - term: id: GO:0140036 label: ubiquitin-modified protein reader activity evidence_type: IDA original_reference_id: PMID:27498865 qualifier: enables review: summary: "Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo." action: ACCEPT reason: "Core molecular function of the selective autophagy receptor." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26458771 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0010508 label: positive regulation of autophagy evidence_type: IDA original_reference_id: PMID:28871090 qualifier: involved_in review: summary: "Direct evidence that p62 positively regulates autophagy (e.g. via TBK1/TRIM23 activation)." action: ACCEPT reason: "Core-adjacent positive regulation of autophagy; directly demonstrated (PMID:28871090)." - term: id: GO:0038023 label: signaling receptor activity evidence_type: IDA original_reference_id: PMID:28871090 qualifier: enables review: summary: "p62 reported to act as a signaling receptor (TRIM23/TBK1 virus-induced autophagy)." action: KEEP_AS_NON_CORE reason: "'Signaling receptor activity' overstates p62's adaptor/scaffold role; the condensate-scaffold/adaptor terms are more accurate, so non-core." - term: id: GO:0000425 label: pexophagy evidence_type: IDA original_reference_id: PMID:26344566 qualifier: involved_in review: summary: "Direct evidence that p62 mediates pexophagy by bridging ROS-induced ubiquitinated PEX5 to autophagosomes." action: ACCEPT reason: "Core selective-autophagy function applied to peroxisomes; directly demonstrated (PMID:26344566)." - term: id: GO:0030674 label: protein-macromolecule adaptor activity evidence_type: IDA original_reference_id: PMID:26344566 qualifier: enables review: summary: "Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery." action: ACCEPT reason: "Core molecular function of p62 as a selective autophagy receptor." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9759169 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9759172 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9766532 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9766645 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9766656 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9766677 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9766687 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9759154 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:25365221 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0043130 label: ubiquitin binding evidence_type: TAS original_reference_id: Reactome:R-HSA-205008 qualifier: enables review: summary: "Direct evidence that p62 binds ubiquitin via its UBA domain." action: ACCEPT reason: "Core molecular function underlying cargo recognition." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31006538 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0006914 label: autophagy evidence_type: IDA original_reference_id: PMID:20452972 qualifier: involved_in review: summary: "Involvement in autophagy, the overarching process in which p62 functions as a selective receptor." action: ACCEPT reason: "Core process; supported by IMP/IDA evidence." - term: id: GO:0031397 label: negative regulation of protein ubiquitination evidence_type: IDA original_reference_id: PMID:20452972 qualifier: involved_in review: summary: "Direct evidence that p62 negatively regulates protein ubiquitination in specific contexts (e.g. via KEAP1 sequestration / TRAF6 modulation)." action: KEEP_AS_NON_CORE reason: "Real regulatory effect but context-specific; non-core." - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:22948227 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0035973 label: aggrephagy evidence_type: IPI original_reference_id: PMID:28404643 qualifier: involved_in review: summary: "Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates." action: ACCEPT reason: "Core biological process; the defining selective-autophagy activity of p62." - term: id: GO:0070530 label: K63-linked polyubiquitin modification-dependent protein binding evidence_type: IDA original_reference_id: PMID:28404643 qualifier: enables review: summary: "Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition." action: ACCEPT reason: "Core molecular function for selective autophagy." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:28404643 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0035255 label: ionotropic glutamate receptor binding evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: "Ortholog-transfer/ISS prediction of ionotropic glutamate receptor binding (synaptic context)." action: KEEP_AS_NON_CORE reason: "Peripheral, neuron-specific interaction; non-core." - term: id: GO:1900273 label: positive regulation of long-term synaptic potentiation evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: "Ortholog-transfer/ISS prediction of positive regulation of long-term synaptic potentiation." action: KEEP_AS_NON_CORE reason: "Neuron-specific peripheral process; non-core." - term: id: GO:1903078 label: positive regulation of protein localization to plasma membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: "Ortholog-transfer/ISS prediction of positive regulation of protein localization to plasma membrane." action: KEEP_AS_NON_CORE reason: "Peripheral process; non-core." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25422469 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:24954904 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0007032 label: endosome organization evidence_type: IDA original_reference_id: PMID:27368102 qualifier: involved_in review: summary: "Direct evidence that ubiquitinated p62 organizes endosomes as a perinuclear molecular bridge." action: KEEP_AS_NON_CORE reason: "Specialized secondary role (PMID:27368102); non-core relative to selective autophagy." - term: id: GO:0019899 label: enzyme binding evidence_type: IPI original_reference_id: PMID:27368102 qualifier: enables review: summary: "Enzyme binding (interaction with RNF26 ligase activity in endosome organization)." action: KEEP_AS_NON_CORE reason: "Generic binding term; the specific adaptor/ubiquitin-ligase-binding roles are more informative." - term: id: GO:0031625 label: ubiquitin protein ligase binding evidence_type: IDA original_reference_id: PMID:27368102 qualifier: enables review: summary: "Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26)." action: KEEP_AS_NON_CORE reason: "Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function." - term: id: GO:0031625 label: ubiquitin protein ligase binding evidence_type: IPI original_reference_id: PMID:27368102 qualifier: enables review: summary: "Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26)." action: KEEP_AS_NON_CORE reason: "Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function." - term: id: GO:1905719 label: protein localization to perinuclear region of cytoplasm evidence_type: IDA original_reference_id: PMID:27368102 qualifier: involved_in review: summary: "Direct evidence that p62 promotes protein localization to the perinuclear region (endosome-organization role)." action: KEEP_AS_NON_CORE reason: "Specialized secondary role (PMID:27368102); non-core." - term: id: GO:0016236 label: macroautophagy evidence_type: IMP original_reference_id: PMID:20168092 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0000423 label: mitophagy evidence_type: IGI original_reference_id: PMID:20457763 qualifier: involved_in review: summary: "Genetic-interaction evidence for involvement in mitophagy of depolarized mitochondria." action: KEEP_AS_NON_CORE reason: "Real but secondary role; p62 contributes to mitophagy (clustering) yet is dispensable for the clearance step (PMID:20890124)." - term: id: GO:0098780 label: response to mitochondrial depolarisation evidence_type: IGI original_reference_id: PMID:20457763 qualifier: involved_in review: summary: "Genetic-interaction evidence for involvement in response to mitochondrial depolarization (mitophagy context)." action: KEEP_AS_NON_CORE reason: "Secondary mitophagy-associated process; non-core." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:27103069 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:19640926 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0044753 label: amphisome evidence_type: IDA original_reference_id: PMID:19640926 qualifier: located_in review: summary: "Amphisome localization along the autophagy pathway (autophagosome-endosome fusion intermediate)." action: KEEP_AS_NON_CORE reason: "Transit compartment (PMID:19640926); non-core." - term: id: GO:0044754 label: autolysosome evidence_type: IDA original_reference_id: PMID:19640926 qualifier: located_in review: summary: "Autolysosome localization, the degradative endpoint of the autophagic pathway." action: KEEP_AS_NON_CORE reason: "Endpoint compartment; non-core." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26347139 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25126726 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0031625 label: ubiquitin protein ligase binding evidence_type: IPI original_reference_id: PMID:25127057 qualifier: enables review: summary: "Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26)." action: KEEP_AS_NON_CORE reason: "Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function." - term: id: GO:0061635 label: regulation of protein complex stability evidence_type: IDA original_reference_id: PMID:25127057 qualifier: involved_in review: summary: "Direct evidence for regulation of protein complex stability (TRIM5 autophagy targeting context)." action: KEEP_AS_NON_CORE reason: "Context-specific regulatory role; non-core." - term: id: GO:0010821 label: regulation of mitochondrion organization evidence_type: NAS original_reference_id: PMID:20890124 qualifier: involved_in review: summary: "Author statement on regulation of mitochondrion organization (Parkin-induced clustering)." action: KEEP_AS_NON_CORE reason: "Reflects the clustering role in mitophagy; secondary, non-core." - term: id: GO:0000422 label: autophagy of mitochondrion evidence_type: NAS original_reference_id: PMID:20098416 qualifier: involved_in review: summary: "Author statement that p62 is involved in autophagy of mitochondrion (mitophagy)." action: KEEP_AS_NON_CORE reason: "Supporting role in mitophagy; p62 mediates clustering of damaged mitochondria but is dispensable for clearance, so non-core." - term: id: GO:0005737 label: cytoplasm evidence_type: IDA original_reference_id: PMID:20168092 qualifier: located_in review: summary: "Cytoplasm is the principal compartment where p62 oligomerizes, binds cargo and forms condensates." action: ACCEPT reason: "Core localization." - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:20168092 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0016234 label: inclusion body evidence_type: IDA original_reference_id: PMID:20168092 qualifier: located_in review: summary: "p62 localizes to inclusion bodies, the ubiquitin-positive cytoplasmic aggregates it helps form." action: KEEP_AS_NON_CORE reason: "Reflects cargo-sequestration outcome; non-core compartment." - term: id: GO:0016605 label: PML body evidence_type: IDA original_reference_id: PMID:20168092 qualifier: located_in review: summary: "p62 localizes to nuclear PML bodies, recruiting ubiquitinated proteins there." action: KEEP_AS_NON_CORE reason: "Secondary nuclear sub-localization (PMID:20168092); non-core." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-193641 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-193684 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-193694 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-193703 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-193705 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-204947 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-205008 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-209566 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-507719 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5205649 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5205663 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5205673 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9664855 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9664880 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9664881 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9664892 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9759157 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9759158 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9761900 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: "High-throughput proteomic detection of p62 in urinary exosomes." action: KEEP_AS_NON_CORE reason: "Likely incidental detection in secreted vesicles; non-core localization." - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-204947 qualifier: located_in review: summary: "Reactome curation placing p62 in the nucleoplasm in the NRIF death-signaling context." action: KEEP_AS_NON_CORE reason: "Indirect/context-specific nuclear localization; non-core." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20357094 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17580304 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005776 label: autophagosome evidence_type: IDA original_reference_id: PMID:17580304 qualifier: located_in review: summary: "Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding." action: ACCEPT reason: "Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024)." - term: id: GO:0006914 label: autophagy evidence_type: IMP original_reference_id: PMID:17580304 qualifier: involved_in review: summary: "Involvement in autophagy, the overarching process in which p62 functions as a selective receptor." action: ACCEPT reason: "Core process; supported by IMP/IDA evidence." - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22178386 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22421968 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:8618896 qualifier: enables review: summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. action: KEEP_AS_NON_CORE reason: Experimental interaction evidence (IPI) is retained, but bare protein binding does not describe a specific molecular function; the informative activities are captured by ubiquitin-reader/adaptor/condensate-scaffold terms. - term: id: GO:0046578 label: regulation of Ras protein signal transduction evidence_type: NAS original_reference_id: PMID:8618896 qualifier: involved_in review: summary: "Author statement on regulation of Ras signal transduction (early RASA1/Lck-binding work)." action: KEEP_AS_NON_CORE reason: "Historical/weak; non-core." - term: id: GO:0016236 label: macroautophagy evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: "Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor." action: ACCEPT reason: "Core biological process; strongly supported across multiple IDA/IMP studies." - term: id: GO:0006914 label: autophagy evidence_type: TAS original_reference_id: PMID:19816510 qualifier: involved_in review: summary: "Involvement in autophagy, the overarching process in which p62 functions as a selective receptor." action: ACCEPT reason: "Core process; supported by IMP/IDA evidence." - term: id: GO:0005080 label: protein kinase C binding evidence_type: IPI original_reference_id: PMID:14676191 qualifier: enables review: summary: "Protein kinase C binding via the PB1 domain (atypical PKCs PRKCZ/PRKCI)." action: KEEP_AS_NON_CORE reason: "Genuine interaction underlying the NF-kB scaffold role; secondary to the core autophagy-receptor function." - term: id: GO:0006511 label: ubiquitin-dependent protein catabolic process evidence_type: TAS original_reference_id: PMID:8702753 qualifier: involved_in review: summary: "Author statement linking p62 to ubiquitin-dependent protein catabolism (early polyubiquitin-binding work)." action: KEEP_AS_NON_CORE reason: "Correct but generic; the specific autophagic targeting/catabolic terms are more informative." - term: id: GO:0030971 label: receptor tyrosine kinase binding evidence_type: TAS original_reference_id: PMID:8650207 qualifier: enables review: summary: "Author statement on receptor tyrosine kinase binding (TrkA/NTRK1)." action: KEEP_AS_NON_CORE reason: "Genuine RTK interaction underlying NGF/NF-kB signaling; secondary, non-core." - term: id: GO:0043122 label: regulation of canonical NF-kappaB signal transduction evidence_type: IMP original_reference_id: PMID:12857745 qualifier: involved_in review: summary: "Mutant-phenotype evidence that p62 regulates canonical NF-kB signaling (UBA-domain-dependent ubiquitin binding)." action: ACCEPT reason: "Well-established signaling-scaffold function; directly demonstrated (PMID:12857745)." - term: id: GO:0043130 label: ubiquitin binding evidence_type: IDA original_reference_id: PMID:12857745 qualifier: enables review: summary: "Direct evidence that p62 binds ubiquitin via its UBA domain." action: ACCEPT reason: "Core molecular function underlying cargo recognition." - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: PMID:8650207 qualifier: located_in review: summary: "Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation." action: ACCEPT reason: "Core localization; many redundant TAS/IDA copies." - term: id: GO:0008104 label: intracellular protein localization evidence_type: TAS original_reference_id: PMID:8650207 qualifier: involved_in review: summary: "Author statement on a role in intracellular protein localization (early aPKC/endosome targeting work)." action: KEEP_AS_NON_CORE reason: "Broad/historical; non-core." - term: id: GO:0016197 label: endosomal transport evidence_type: TAS original_reference_id: PMID:12857745 qualifier: involved_in review: summary: "Author statement on endosomal transport (NF-kB/TRAF6 signaling context)." action: KEEP_AS_NON_CORE reason: "Secondary trafficking role; non-core." - term: id: GO:0019901 label: protein kinase binding evidence_type: IDA original_reference_id: PMID:8650207 qualifier: enables review: summary: "Protein kinase binding (e.g. atypical PKCs, ULK1, MAP2K5) underlying p62 signaling scaffolds." action: KEEP_AS_NON_CORE reason: "Genuine but generic interaction class; secondary to the core function." - term: id: GO:0035556 label: intracellular signal transduction evidence_type: TAS original_reference_id: PMID:8650207 qualifier: involved_in review: summary: "Author statement on involvement in intracellular signal transduction (Lck/NF-kB scaffolding)." action: KEEP_AS_NON_CORE reason: "Broad signaling role; non-core." - term: id: GO:0042169 label: SH2 domain binding evidence_type: IDA original_reference_id: PMID:8650207 qualifier: enables review: summary: "SH2 domain binding - the original phosphotyrosine-independent Lck SH2-domain ligand activity." action: KEEP_AS_NON_CORE reason: "Historical/defining-but-peripheral interaction; non-core." - term: id: GO:0045944 label: positive regulation of transcription by RNA polymerase II evidence_type: TAS original_reference_id: PMID:12857745 qualifier: involved_in review: summary: "Reactome curation linking p62 to positive regulation of Pol II transcription (NRIF pathway)." action: KEEP_AS_NON_CORE reason: "Indirect transcriptional effect; non-core." core_functions: - description: Acts as the prototypical selective autophagy receptor, recognizing ubiquitinated cargo (preferentially K63-linked polyubiquitin) through its UBA domain and bridging it to ATG8-family proteins on the autophagosome via its LIR motif, thereby delivering cargo for autophagic degradation. molecular_function: id: GO:0140036 label: ubiquitin-modified protein reader activity supported_by: - reference_id: PMID:17580304 supporting_text: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated - reference_id: PMID:29343546 supporting_text: p62 filaments capture and present ubiquitinated cargos for autophagy directly_involved_in: - id: GO:0035973 label: aggrephagy - id: GO:0071211 label: protein targeting to vacuole involved in autophagy locations: - id: GO:0005829 label: cytosol - id: GO:0005776 label: autophagosome - description: Functions as a protein-macromolecule adaptor and molecular condensate scaffold that, through PB1-mediated oligomerization combined with multivalent ubiquitin binding, drives liquid-liquid phase separation into p62 bodies - membraneless organelles that concentrate and sequester ubiquitinated cargo for selective autophagy. molecular_function: id: GO:0140693 label: molecular condensate scaffold activity supported_by: - reference_id: PMID:29507397 supporting_text: Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation directly_involved_in: - id: GO:0140694 label: membraneless organelle assembly - id: GO:0035973 label: aggrephagy - description: Acts as an activator of the NFE2L2/NRF2 antioxidant pathway by sequestering KEAP1 (via the phospho-Ser349 KIR motif) into p62 bodies, preventing KEAP1-mediated NRF2 degradation and inducing cytoprotective gene expression; SQSTM1 is itself an NRF2 target, forming a positive feedback loop. molecular_function: id: GO:0140311 label: protein sequestering activity supported_by: - reference_id: PMID:20452972 supporting_text: p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive directly_involved_in: - id: GO:0033554 label: cellular response to stress - description: Serves as a signaling adaptor/scaffold that assembles multiprotein complexes (e.g. atypical PKCs, TRAF6, RIPK1) to regulate NF-kB and related innate-immune signaling, including negative regulation of TLR4 signaling through control of the TRAF6-ECSIT complex. molecular_function: id: GO:0035591 label: signaling adaptor activity supported_by: - reference_id: PMID:31281713 supporting_text: p62 Negatively Regulates TLR4 Signaling via Functional Regulation of the TRAF6-ECSIT directly_involved_in: - id: GO:0043122 label: regulation of canonical NF-kappaB signal transduction proposed_new_terms: [] suggested_questions: - question: How is selectivity among p62's diverse cargoes (general ubiquitinated aggregates versus PEX5/peroxisomes, mitochondria, inflammasome/RIPosome components, KEAP1) determined - by cargo ubiquitin-chain architecture, p62 post-translational modifications, or partner receptors (NBR1, TAX1BP1)? - question: To what extent are p62's autophagy-receptor function and its KEAP1-NRF2 and NF-kB signaling-scaffold functions mechanistically coupled versus separable, and how do disease variants differentially perturb each? suggested_experiments: - description: Use separation-of-function p62 mutants (UBA-dead, LIR-dead, PB1-oligomerization-dead, KIR/S349 phospho-dead) in SQSTM1-knockout cells with quantitative autophagic-flux, p62-body imaging, NRF2 reporter and NF-kB assays to dissect which domains drive each core function. - description: Perform proximity-labeling and quantitative proteomics of p62 condensates under basal, proteotoxic, oxidative and infection stresses to define the context-specific cargo and partner repertoire of p62 bodies. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:10708586 title: p62 functions as a p38 MAP kinase regulator. findings: [] - id: PMID:12471037 title: Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling. findings: [] - id: PMID:12857745 title: Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Structure of the p62 UBA domain and Paget-disease mutations; underpins ubiquitin-binding and NF-kB-regulation annotations. Abstract-only in cache." - id: PMID:14676191 title: Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network. findings: [] - id: PMID:16169070 title: 'A human protein-protein interaction network: a resource for annotating the proteome.' findings: [] - id: PMID:16189514 title: Towards a proteome-scale map of the human protein-protein interaction network. findings: [] - id: PMID:16874300 title: The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation. findings: [] - id: PMID:17389358 title: Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons. findings: [] - id: PMID:17580304 title: p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Foundational paper establishing direct LIR-LC3 binding by p62 for autophagic degradation of ubiquitinated aggregates. Abstract-only in cache; claim anchored by the verified title and the IDA aggrephagy annotations." - id: PMID:18083104 title: Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19229298 title: Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. findings: [] - id: PMID:19250911 title: A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. findings: [] - id: PMID:19427866 title: Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover. findings: [] - id: PMID:19615732 title: Defining the human deubiquitinating enzyme interaction landscape. findings: [] - id: PMID:19640926 title: LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model. findings: [] - id: PMID:19816510 title: Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis. findings: [] - id: PMID:20010802 title: Nix is a selective autophagy receptor for mitochondrial clearance. findings: [] - id: PMID:20098416 title: PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. findings: [] - id: PMID:20168092 title: p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. findings: [] - id: PMID:20173742 title: The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. findings: [] - id: PMID:20357094 title: p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha. findings: [] - id: PMID:20417604 title: The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. findings: [] - id: PMID:20452972 title: p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Establishes p62 as an NRF2 target gene forming a positive-feedback loop and as a KEAP1-NRF2 axis activator. Abstract-only in cache; anchored by verified title." - id: PMID:20457763 title: Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy. findings: [] - id: PMID:20551902 title: CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice. findings: [] - id: PMID:20562859 title: Network organization of the human autophagy system. findings: [] - id: PMID:20808283 title: NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo. findings: [] - id: PMID:20890124 title: p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Shows p62 is required for Parkin-induced mitochondrial clustering but dispensable for mitophagy itself; full text cached. Basis for keeping mitophagy as non-core." - id: PMID:21149568 title: 'Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance.' findings: [] - id: PMID:21900206 title: A directed protein interaction network for investigating intracellular signal transduction. findings: [] - id: PMID:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:22017874 title: Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. findings: [] - id: PMID:22178386 title: TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells. findings: [] - id: PMID:22190034 title: Global landscape of HIV-human protein complexes. findings: [] - id: PMID:22421968 title: TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death. findings: [] - id: PMID:22622177 title: The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins. findings: [] - id: PMID:22948227 title: MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins. findings: [] - id: PMID:23274085 title: Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. findings: [] - id: PMID:23459205 title: Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy machinery. findings: [] - id: PMID:24089205 title: Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites. findings: [] - id: PMID:24189400 title: Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms. findings: [] - id: PMID:24316673 title: Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1. findings: [] - id: PMID:24668264 title: Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures. findings: [] - id: PMID:24879152 title: Phosphorylation of NBR1 by GSK3 modulates protein aggregation. findings: [] - id: PMID:24954904 title: WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. findings: [] - id: PMID:25026213 title: Ubiquitylation of autophagy receptor Optineurin by HACE1 activates selective autophagy for tumor suppression. findings: [] - id: PMID:25040165 title: Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1. findings: [] - id: PMID:25126726 title: FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation. findings: [] - id: PMID:25127057 title: TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition. findings: [] - id: PMID:25365221 title: Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:25422469 title: Disruption of FAT10-MAD2 binding inhibits tumor progression. findings: [] - id: PMID:25686248 title: Huntingtin functions as a scaffold for selective macroautophagy. findings: [] - id: PMID:25910212 title: Widespread macromolecular interaction perturbations in human genetic disorders. findings: [] - id: PMID:25959826 title: Quantitative interaction proteomics of neurodegenerative disease proteins. findings: [] - id: PMID:26344566 title: ATM functions at the peroxisome to induce pexophagy in response to ROS. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Shows ROS/ATM-induced pexophagy mediated by p62 bridging ubiquitinated PEX5 to autophagosomes; full text cached. Supports pexophagy and adaptor roles." - id: PMID:26347139 title: TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity. findings: [] - id: PMID:26403645 title: Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: "Shows p62-KEAP1-NRF2 protects against ferroptosis in HCC; abstract-only. Basis for the non-core negative-regulation-of-ferroptosis annotation." - id: PMID:26458771 title: Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling. findings: [] - id: PMID:26524528 title: Autophagy mediates degradation of nuclear lamina. findings: [] - id: PMID:26637326 title: ENC1 Modulates the Aggregation and Neurotoxicity of Mutant Huntingtin Through p62 Under ER Stress. findings: [] - id: PMID:27103069 title: Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death. findings: [] - id: PMID:27368102 title: An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: "Defines ubiquitinated p62 as a perinuclear molecular bridge organizing endosomes; full text cached. Supports the secondary endosome-organization role." - id: PMID:27498865 title: TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy. findings: [] - id: PMID:27728806 title: p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer. findings: [] - id: PMID:28404643 title: The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy. findings: [] - id: PMID:28871090 title: TRIM23 mediates virus-induced autophagy via activation of TBK1. findings: [] - id: PMID:29343546 title: p62 filaments capture and present ubiquitinated cargos for autophagy. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Demonstrates p62 filament/condensate capture and presentation of ubiquitinated cargo; full text cached. Key support for the condensate-scaffold core function." - id: PMID:29507397 title: Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Shows polyubiquitin-chain-induced p62 phase separation segregating autophagic cargo; full text cached. Core condensate/membraneless-organelle evidence." - id: PMID:29519959 title: P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity. findings: [] - id: PMID:30612879 title: The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammasome Activation by Impeding Its Assembly and by Mediating Its Selective Autophagy. findings: [] - id: PMID:31006538 title: Intrinsically Disordered Protein TEX264 Mediates ER-phagy. findings: [] - id: PMID:31169361 title: A Case Study on the Keap1 Interaction with Peptide Sequence Epitopes Selected by the Peptidomic mRNA Display. findings: [] - id: PMID:31281713 title: p62 Negatively Regulates TLR4 Signaling via Functional Regulation of the TRAF6-ECSIT Complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "Demonstrates p62 negative regulation of TLR4 signaling via sequestration/regulation of the TRAF6-ECSIT complex; full text cached. Supports the signaling-scaffold core function." - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:31616248 title: Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome. findings: [] - id: PMID:31857589 title: Requirement for p62 acetylation in the aggregation of ubiquitylated proteins under nutrient stress. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "p62 acetylation promotes ubiquitinated-protein aggregation under nutrient stress; full text cached. Supports condensate-scaffold and aggrephagy roles." - id: PMID:31980649 title: Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D). findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:32715615 title: Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33436498 title: Cytoplasmic short linear motifs in ACE2 and integrin β(3) link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy. findings: [] - id: PMID:33961781 title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. findings: [] - id: PMID:34471133 title: Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: "Reconstitution defining roles of p62/NBR1/TAX1BP1 in ubiquitin condensate formation and autophagy initiation; full text cached. Supports phagophore-assembly-site localization." - id: PMID:34524948 title: Global Proximity Interactome of the Human Macroautophagy Pathway. findings: [] - id: PMID:34591642 title: A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity. findings: [] - id: PMID:34799561 title: Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities. findings: [] - id: PMID:34893540 title: The N-terminal cysteine is a dual sensor of oxygen and oxidative stress. findings: [] - id: PMID:35044719 title: Proteome-scale mapping of binding sites in the unstructured regions of the human proteome. findings: [] - id: PMID:35266954 title: The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:36221902 title: Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection. findings: [] - id: PMID:37219487 title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. findings: [] - id: PMID:37306101 title: Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "ULK1 phosphorylation of phase-separated p62 bodies activates a redox-independent stress response; full text cached. Supports condensate-scaffold and KEAP1-NRF2-related functions." - id: PMID:37460613 title: P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium. findings: [] - id: PMID:37802024 title: S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: "S-acylation promotes recruitment of p62 droplets into autophagosomes; full text cached. Supports adaptor/condensate and autophagosome-delivery functions." - id: PMID:39009827 title: Proteome-scale characterisation of motif-based interactome rewiring by disease mutations. findings: [] - id: PMID:8618896 title: Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region. findings: [] - id: PMID:8650207 title: Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain. findings: [] - id: PMID:8702753 title: p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins. findings: [] - id: PMID:9566925 title: Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62. findings: [] - id: Reactome:R-HSA-193641 title: IKK-beta is recruited findings: [] - id: Reactome:R-HSA-193684 title: p62 recruits an atypical PKC findings: [] - id: Reactome:R-HSA-193694 title: p62 is recruited and forms a complex with TRAF6 findings: [] - id: Reactome:R-HSA-193703 title: IKKbeta is activated findings: [] - id: Reactome:R-HSA-193705 title: IKKbeta phosphorylates IkB causing NF-kB to dissociate findings: [] - id: Reactome:R-HSA-204947 title: Polyubiquitinated NRIF migrates to the nucleus findings: [] - id: Reactome:R-HSA-205008 title: Polyubiquitinated NRIF binds to p62 (Sequestosome) findings: [] - id: Reactome:R-HSA-205043 title: NRIF signals cell death from the nucleus findings: [] - id: Reactome:R-HSA-209566 title: TRAF6 is auto-ubiquitinated findings: [] - id: Reactome:R-HSA-507719 title: p62:MEKK3 binds to TRAF6 findings: [] - id: Reactome:R-HSA-5205649 title: p62 links damaged mitochondria to LC3 findings: [] - id: Reactome:R-HSA-5205663 title: LC3 binds the autophagosome membrane Atg5-Atg12 complex findings: [] - id: Reactome:R-HSA-5205673 title: p62 binds ubiquitinated mitochondrial substrates findings: [] - id: Reactome:R-HSA-9664855 title: MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1 findings: [] - id: Reactome:R-HSA-9664880 title: MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1 findings: [] - id: Reactome:R-HSA-9664881 title: NBR1 binds ATM:Ub-p-PEX5:SQSTM1 findings: [] - id: Reactome:R-HSA-9664892 title: SQSTM1 binds ATM dimer:Ub-p-PEX5 findings: [] - id: Reactome:R-HSA-9759154 title: TRIM21 ubiquitinates SQSTM1 findings: [] - id: Reactome:R-HSA-9759157 title: NFE2L2-dependent SQSTM1 gene expression findings: [] - id: Reactome:R-HSA-9759158 title: SQSTM1 oligomerizes findings: [] - id: Reactome:R-HSA-9759169 title: p-S349 SQSTM1 oligomer binds KEAP1:CUL3:RBX1 findings: [] - id: Reactome:R-HSA-9759172 title: KEAP1:CUL3:RBX1 ubiquitinates p-S349 SQSTM1 oligomer findings: [] - id: Reactome:R-HSA-9761900 title: HBV X protein binds SQSTM1 oligomer findings: [] - id: Reactome:R-HSA-9766532 title: SQSTM1 oligomer is phosphorylated findings: [] - id: Reactome:R-HSA-9766645 title: CUL3:RBX1 ubiquitinates KEAP1 findings: [] - id: Reactome:R-HSA-9766656 title: RBX1:CUL3 dissociates from forming autophagosome findings: [] - id: Reactome:R-HSA-9766677 title: MAP1LC3B binds KEAP1 and SQSTM1 findings: [] - id: Reactome:R-HSA-9766687 title: SESN1,SESN1 bind SQSTM1 and KEAP1 findings: []