Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0035973 aggrephagy	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of aggrephagy, the core p62 process - selective autophagic clearance of ubiquitinated protein aggregates. Strongly corroborated by direct experimental evidence. Reason: Core biological process for p62; abundant IDA support (e.g. PMID:17580304, PMID:22017874) confirms the phylogenetic inference. Supporting Evidence: PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated
GO:0000423 mitophagy	IBA GO_REF:0000033	KEEP AS NON CORE	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. 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. Supporting Evidence: PMID:20890124 p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy
GO:0005080 protein kinase C binding	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference of protein kinase C binding, reflecting the well-documented PB1-mediated interaction of p62 with atypical PKCs (PRKCZ/PRKCI). Reason: Genuine interaction underlying the NF-kB signaling scaffold role, but secondary to the core autophagy-receptor function.
GO:0007032 endosome organization	IBA GO_REF:0000033	KEEP AS NON CORE	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. Reason: Experimentally supported (PMID:27368102) but a specialized, secondary role distinct from the core selective-autophagy receptor function.
GO:0044753 amphisome	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference that p62 acts in the amphisome, the hybrid organelle formed by autophagosome-endosome fusion along the autophagic pathway. Reason: Plausible transit compartment along the autophagy pathway (IDA support in PMID:19640926) but a non-core sub-localization.
GO:0070530 K63-linked polyubiquitin modification-dependent protein binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of K63-linked polyubiquitin binding, the core molecular activity of the p62 UBA domain that recognizes ubiquitinated cargo. Reason: Core molecular function; the UBA domain preferentially binds K63-linked polyubiquitin (PMID:12857745), supported by direct experimental evidence.
GO:0016235 aggresome	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Phylogenetic inference that p62 acts in the aggresome, the perinuclear inclusion where misfolded ubiquitinated proteins are concentrated prior to autophagic clearance. Reason: p62 is a common constituent of aggresomes/inclusion bodies, but this reflects the cargo-sequestration outcome rather than a distinct core compartment.
GO:0000407 phagophore assembly site	IEA GO_REF:0000120	ACCEPT	Summary: Electronic prediction of localization to the phagophore assembly site (PAS), where p62 nucleates ubiquitin condensates that initiate autophagosome formation. Reason: Consistent with the EXP-supported PAS localization (PMID:34471133) and the core role of p62 condensates in autophagy initiation.
GO:0005634 nucleus	IEA GO_REF:0000044	KEEP AS NON CORE	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. Reason: Real but secondary localization (also EXP-supported, PMID:10708586); the dominant functional pool is cytoplasmic.
GO:0005764 lysosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of lysosomal localization, consistent with p62 trafficking to lysosomes as a degraded autophagic cargo. Reason: Reflects the endpoint of autophagic delivery rather than a core site of action; non-core localization.
GO:0005770 late endosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of late endosome localization, consistent with the aPKC/endosome-trafficking role of p62. Reason: Experimentally supported (PMID:9566925, PMID:12471037) but a secondary compartment relative to the core cytoplasmic/autophagic function.
GO:0005776 autophagosome	IEA GO_REF:0000120	ACCEPT	Summary: Electronic prediction of autophagosome localization, the core site where p62 delivers ubiquitinated cargo via LIR-ATG8 binding. Reason: Core localization, strongly supported by IDA evidence (e.g. PMID:17580304, PMID:37802024).
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of ER localization, consistent with p62 functioning near ER membranes (e.g. with TRIM13 in ER-stress autophagy). Reason: Context-specific, secondary localization (PMID:22178386); not the core site of action.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of cytosolic localization, the principal compartment where p62 oligomerizes, binds cargo and forms condensates. Reason: Core localization; redundant with abundant IDA/TAS cytosol annotations.
GO:0008270 zinc ion binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro-based prediction of zinc ion binding via the ZZ-type zinc finger, which coordinates Zn(2+) and mediates RIPK1 binding. 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.
GO:0016234 inclusion body	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning prediction of inclusion body localization, consistent with p62 being a hallmark constituent of cytoplasmic ubiquitin-positive inclusions. Reason: Real (p62 bodies/inclusions) but represents the cargo-sequestration outcome; non-core compartment.
GO:0016605 PML body	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of PML body localization, consistent with p62 recruiting ubiquitinated proteins to nuclear PML bodies. Reason: Experimentally supported nuclear sub-localization (PMID:20168092) but a secondary site relative to cytoplasmic function.
GO:0030017 sarcomere	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic transfer of sarcomere localization, reflecting p62 interactions with muscle proteins (titin/TTN, FHOD3, TRIM55). Reason: Tissue-specific peripheral localization; not a core compartment for the autophagy-receptor function.
GO:0031399 regulation of protein modification process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA machine-learning prediction of involvement in regulation of protein modification, a very broad parent term. Reason: Overly generic; p62's specific roles (e.g. regulating TRAF6 ubiquitination, KEAP1-mediated ubiquitination) are better captured by more precise terms.
GO:0005515 protein binding	IPI PMID:14676191 Comprehensive proteomic analysis of human Par protein comple...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:16874300 The signaling adapter p62 is an important mediator of T help...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:17389358 Unc-51-like kinase 1/2-mediated endocytic processes regulate...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:18083104 Homeostatic levels of p62 control cytoplasmic inclusion body...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:19229298 Protein quality control during aging involves recruitment of...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:19250911 A role for NBR1 in autophagosomal degradation of ubiquitinat...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:19427866 Interactions with LC3 and polyubiquitin chains link nbr1 to ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20010802 Nix is a selective autophagy receptor for mitochondrial clea...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20173742 The selective autophagy substrate p62 activates the stress r...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20417604 The selective macroautophagic degradation of aggregated prot...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20452972 p62/SQSTM1 is a target gene for transcription factor NRF2 an...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20551902 CIN85 regulates dopamine receptor endocytosis and governs be...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:20808283 NBR1 is a new PB1 signalling adapter in Th2 differentiation ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:21149568 Formin follows function: a muscle-specific isoform of FHOD3 ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:21900206 A directed protein interaction network for investigating int...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:21988832 Toward an understanding of the protein interaction network o...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:22190034 Global landscape of HIV-human protein complexes.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:23274085 Sestrins activate Nrf2 by promoting p62-dependent autophagic...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:23459205 Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:24089205 Autophagy promotes primary ciliogenesis by removing OFD1 fro...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:24316673 Autophagy variation within a cell population determines cell...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:24668264 Structural determinants in GABARAP required for the selectiv...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:24879152 Phosphorylation of NBR1 by GSK3 modulates protein aggregatio...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25026213 Ubiquitylation of autophagy receptor Optineurin by HACE1 act...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25040165 Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylat...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25686248 Huntingtin functions as a scaffold for selective macroautoph...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25910212 Widespread macromolecular interaction perturbations in human...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25959826 Quantitative interaction proteomics of neurodegenerative dis...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:26524528 Autophagy mediates degradation of nuclear lamina.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:26637326 ENC1 Modulates the Aggregation and Neurotoxicity of Mutant H...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:27728806 p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:29519959 P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) s...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:31169361 A Case Study on the Keap1 Interaction with Peptide Sequence ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:31616248 Systematic Affinity Purification Coupled to Mass Spectrometr...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:33436498 Cytoplasmic short linear motifs in ACE2 and integrin β(3) li...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:34524948 Global Proximity Interactome of the Human Macroautophagy Pat...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:34591642 A protein network map of head and neck cancer reveals PIK3CA...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:34799561 Large scale discovery of coronavirus-host factor protein int...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:35044719 Proteome-scale mapping of binding sites in the unstructured ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:35266954 The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its loc...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:37460613 P62/SQSTM1 binds with claudin-2 to target for selective auto...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:8702753 p62, a phosphotyrosine-independent ligand of the SH2 domain ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0042802 identical protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0042802 identical protein binding	IPI PMID:20562859 Network organization of the human autophagy system.	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0042802 identical protein binding	IPI PMID:21900206 A directed protein interaction network for investigating int...	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0042802 identical protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0042802 identical protein binding	IPI PMID:25686248 Huntingtin functions as a scaffold for selective macroautoph...	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0042802 identical protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0001659 temperature homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer (Ensembl Compara) prediction of involvement in temperature homeostasis from mouse. Reason: Pleiotropic, mouse-derived peripheral process; biologically plausible but not a core p62 function.
GO:0002931 response to ischemia	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of involvement in response to ischemia. Reason: Peripheral mouse-derived process; retained as non-core.
GO:0005080 protein kinase C binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Protein kinase C binding via the PB1 domain (atypical PKCs PRKCZ/PRKCI). Reason: Genuine interaction underlying the NF-kB scaffold role; secondary to the core autophagy-receptor function.
GO:0005739 mitochondrion	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of mitochondrial localization, consistent with recruitment to damaged mitochondria during mitophagy. Reason: Real in the mitophagy context but a secondary, condition-dependent localization; non-core.
GO:0006606 protein import into nucleus	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of involvement in protein import into nucleus. Reason: Peripheral, indirectly related to nuclear shuttling; non-core.
GO:0006914 autophagy	IEA GO_REF:0000107	ACCEPT	Summary: Involvement in autophagy, the overarching process in which p62 functions as a selective receptor. Reason: Core process; supported by IMP/IDA evidence.
GO:0016235 aggresome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of aggresome localization. Reason: Real (p62 is an aggresome constituent) but reflects sequestration outcome; non-core.
GO:0030674 protein-macromolecule adaptor activity	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0031397 negative regulation of protein ubiquitination	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Direct evidence that p62 negatively regulates protein ubiquitination in specific contexts (e.g. via KEAP1 sequestration / TRAF6 modulation). Reason: Real regulatory effect but context-specific; non-core.
GO:0035255 ionotropic glutamate receptor binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of ionotropic glutamate receptor binding (synaptic context). Reason: Peripheral, neuron-specific interaction; non-core.
GO:0035973 aggrephagy	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0042802 identical protein binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Reflects PB1-domain-mediated homo-oligomerization of p62 into filament-like arrays, a genuine self-association. 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.
GO:0044754 autolysosome	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Autolysosome localization, the degradative endpoint of the autophagic pathway. Reason: Endpoint compartment; non-core.
GO:0044877 protein-containing complex binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of protein-containing complex binding. Reason: Generic binding term; non-core.
GO:0045202 synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of activity at the synapse. Reason: Neuron-specific peripheral localization; non-core.
GO:0070342 brown fat cell proliferation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of involvement in brown fat cell proliferation (mouse metabolic phenotype). Reason: Tissue/metabolic pleiotropy from mouse; non-core.
GO:0070530 K63-linked polyubiquitin modification-dependent protein binding	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition. Reason: Core molecular function for selective autophagy.
GO:0097009 energy homeostasis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of involvement in energy homeostasis (mouse metabolic phenotype). Reason: Metabolic pleiotropy from mouse; non-core.
GO:0097225 sperm midpiece	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of sperm midpiece localization. Reason: Tissue-specific peripheral localization; non-core.
GO:0097413 Lewy body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of Lewy body localization, consistent with p62 being a constituent of these inclusions. Reason: Disease-inclusion localization (sequestration outcome); non-core.
GO:0098978 glutamatergic synapse	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer prediction of activity at the glutamatergic synapse. Reason: Neuron-specific peripheral localization; non-core.
GO:0140036 ubiquitin-modified protein reader activity	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0140693 molecular condensate scaffold activity	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140694 membraneless organelle assembly	IEA GO_REF:0000107	ACCEPT	Summary: Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation. Reason: Core process underlying selective sequestration of ubiquitinated cargo.
GO:1900273 positive regulation of long-term synaptic potentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of positive regulation of long-term synaptic potentiation. Reason: Neuron-specific peripheral process; non-core.
GO:1903078 positive regulation of protein localization to plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of positive regulation of protein localization to plasma membrane. Reason: Peripheral process; non-core.
GO:0043065 positive regulation of apoptotic process	TAS Reactome:R-HSA-205043	KEEP AS NON CORE	Summary: Reactome curation linking p62 to positive regulation of apoptosis in the NRIF death-signaling pathway. Reason: Indirect, context-specific; non-core.
GO:0036464 cytoplasmic ribonucleoprotein granule	IDA PMID:20357094 p62/sequestosome-1 associates with and sustains the expressi...	KEEP AS NON CORE	Summary: Localization to cytoplasmic ribonucleoprotein granules (TRIM5alpha/stress-granule-associated context). Reason: Context-specific condensate localization; non-core.
GO:0005829 cytosol	IDA GO_REF:0000052	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0000407 phagophore assembly site	EXP PMID:34471133 Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in...	ACCEPT	Summary: Experimental localization to the phagophore assembly site, where p62 condensates nucleate autophagosome formation. Reason: Core localization for autophagy initiation; supported by reconstitution/EXP evidence (PMID:34471133).
GO:0005634 nucleus	EXP PMID:10708586 p62 functions as a p38 MAP kinase regulator.	KEEP AS NON CORE	Summary: Experimental nuclear localization; p62 shuttles to the nucleus and PML bodies. Reason: Real but secondary localization (PMID:10708586); dominant pool is cytoplasmic.
GO:0005764 lysosome	EXP PMID:9566925 Localization of atypical protein kinase C isoforms into lyso...	KEEP AS NON CORE	Summary: Experimental lysosomal localization, consistent with p62 trafficking to lysosomes as autophagic cargo and via aPKC/endosome routes. Reason: Endpoint/secondary compartment; non-core.
GO:0005770 late endosome	EXP PMID:12471037 Association of the atypical protein kinase C-interacting pro...	KEEP AS NON CORE	Summary: Experimental late-endosome localization via the aPKC-interaction/endosome-trafficking role. Reason: Secondary compartment (PMID:9566925, PMID:12471037); non-core.
GO:0005770 late endosome	EXP PMID:9566925 Localization of atypical protein kinase C isoforms into lyso...	KEEP AS NON CORE	Summary: Experimental late-endosome localization via the aPKC-interaction/endosome-trafficking role. Reason: Secondary compartment (PMID:9566925, PMID:12471037); non-core.
GO:0005783 endoplasmic reticulum	EXP PMID:22178386 TRIM13 regulates ER stress induced autophagy and clonogenic ...	KEEP AS NON CORE	Summary: Experimental ER localization in ER-stress autophagy contexts. Reason: Context-specific secondary localization (PMID:22178386); non-core.
GO:0033554 cellular response to stress	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 participates in the cellular stress response (e.g. oxidative/proteotoxic stress, NRF2 activation). Reason: Genuine core-adjacent stress-response involvement directly demonstrated; underlies p62's cytoprotective KEAP1-NRF2 and proteostasis functions.
GO:0016236 macroautophagy	IMP PMID:22622177 The deubiquitinating enzyme USP36 controls selective autopha...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0016236 macroautophagy	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:34893540 The N-terminal cysteine is a dual sensor of oxygen and oxida...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:34893540 The N-terminal cysteine is a dual sensor of oxygen and oxida...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0110076 negative regulation of ferroptosis	IMP PMID:26403645 Activation of the p62-Keap1-NRF2 pathway protects against fe...	KEEP AS NON CORE	Summary: Mutant-phenotype evidence that p62 negatively regulates ferroptosis via the KEAP1-NRF2 axis. Reason: Real cytoprotective effect downstream of NRF2 activation (PMID:26403645); a specialized secondary outcome, non-core.
GO:0140036 ubiquitin-modified protein reader activity	IDA PMID:34893540 The N-terminal cysteine is a dual sensor of oxygen and oxida...	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0005776 autophagosome	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0005829 cytosol	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	IDA PMID:29507397 Polyubiquitin chain-induced p62 phase separation drives auto...	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	IDA PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa...	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0033554 cellular response to stress	IDA PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradat...	ACCEPT	Summary: Direct evidence that p62 participates in the cellular stress response (e.g. oxidative/proteotoxic stress, NRF2 activation). Reason: Genuine core-adjacent stress-response involvement directly demonstrated; underlies p62's cytoprotective KEAP1-NRF2 and proteostasis functions.
GO:0035973 aggrephagy	IDA PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradat...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0035973 aggrephagy	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0035973 aggrephagy	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0043232 intracellular membraneless organelle	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates). Reason: Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo.
GO:0043232 intracellular membraneless organelle	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates). Reason: Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo.
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0140036 ubiquitin-modified protein reader activity	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0140693 molecular condensate scaffold activity	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140693 molecular condensate scaffold activity	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140694 membraneless organelle assembly	IDA PMID:31857589 Requirement for p62 acetylation in the aggregation of ubiqui...	ACCEPT	Summary: Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation. Reason: Core process underlying selective sequestration of ubiquitinated cargo.
GO:0140694 membraneless organelle assembly	IDA PMID:37802024 S-acylation of p62 promotes p62 droplet recruitment into aut...	ACCEPT	Summary: Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation. Reason: Core process underlying selective sequestration of ubiquitinated cargo.
GO:0035973 aggrephagy	IDA PMID:22017874 Serine 403 phosphorylation of p62/SQSTM1 regulates selective...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0035973 aggrephagy	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0035973 aggrephagy	IDA PMID:29507397 Polyubiquitin chain-induced p62 phase separation drives auto...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0035973 aggrephagy	IDA PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0043232 intracellular membraneless organelle	IDA PMID:22017874 Serine 403 phosphorylation of p62/SQSTM1 regulates selective...	ACCEPT	Summary: Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates). Reason: Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo.
GO:0043232 intracellular membraneless organelle	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates). Reason: Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo.
GO:0043232 intracellular membraneless organelle	IDA PMID:29507397 Polyubiquitin chain-induced p62 phase separation drives auto...	ACCEPT	Summary: Direct evidence that p62 is active within intracellular membraneless organelles (p62 bodies/condensates). Reason: Core: p62 bodies are the membraneless organelles through which p62 concentrates cargo.
GO:0070530 K63-linked polyubiquitin modification-dependent protein binding	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition. Reason: Core molecular function for selective autophagy.
GO:0140036 ubiquitin-modified protein reader activity	IDA PMID:22017874 Serine 403 phosphorylation of p62/SQSTM1 regulates selective...	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0140311 protein sequestering activity	IDA PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa...	ACCEPT	Summary: Direct evidence that p62 sequesters target proteins (e.g. into condensates) to control their activity/localization. Reason: Core: protein sequestration into p62 bodies is central to its receptor and KEAP1-regulatory functions.
GO:0140693 molecular condensate scaffold activity	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140693 molecular condensate scaffold activity	IDA PMID:29507397 Polyubiquitin chain-induced p62 phase separation drives auto...	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140693 molecular condensate scaffold activity	IDA PMID:37306101 Phosphorylation of phase-separated p62 bodies by ULK1 activa...	ACCEPT	Summary: Direct evidence that p62 acts as a molecular condensate scaffold, driving phase separation into p62 bodies. Reason: Core molecular function enabling cargo concentration for autophagy.
GO:0140694 membraneless organelle assembly	IDA PMID:29343546 p62 filaments capture and present ubiquitinated cargos for a...	ACCEPT	Summary: Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation. Reason: Core process underlying selective sequestration of ubiquitinated cargo.
GO:0140694 membraneless organelle assembly	IDA PMID:29507397 Polyubiquitin chain-induced p62 phase separation drives auto...	ACCEPT	Summary: Direct evidence that p62 drives assembly of membraneless organelles (p62 bodies) via phase separation. Reason: Core process underlying selective sequestration of ubiquitinated cargo.
GO:0005737 cytoplasm	IC PMID:31281713 p62 Negatively Regulates TLR4 Signaling via Functional Regul...	ACCEPT	Summary: Cytoplasm is the principal compartment where p62 oligomerizes, binds cargo and forms condensates. Reason: Core localization.
GO:0034144 negative regulation of toll-like receptor 4 signaling pathway	IDA PMID:31281713 p62 Negatively Regulates TLR4 Signaling via Functional Regul...	ACCEPT	Summary: Direct evidence that p62 negatively regulates TLR4 signaling by acting on the TRAF6-ECSIT complex. Reason: Specific, directly demonstrated immune-signaling function (PMID:31281713).
GO:0140313 molecular sequestering activity	IDA PMID:31281713 p62 Negatively Regulates TLR4 Signaling via Functional Regul...	KEEP AS NON CORE	Summary: Direct evidence of molecular sequestering activity (sequestration of the TRAF6-ECSIT complex to dampen TLR4 signaling). Reason: Genuine sequestration activity in a specific signaling context; the broader protein-sequestering term captures the core role, so non-core here.
GO:0016236 macroautophagy	IDA PMID:36221902 Selective autophagy of RIPosomes maintains innate immune hom...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0030163 protein catabolic process	IDA PMID:36221902 Selective autophagy of RIPosomes maintains innate immune hom...	ACCEPT	Summary: Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy. Reason: Core outcome of the receptor function; directly demonstrated.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:36221902 Selective autophagy of RIPosomes maintains innate immune hom...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:36221902 Selective autophagy of RIPosomes maintains innate immune hom...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0140036 ubiquitin-modified protein reader activity	IDA PMID:36221902 Selective autophagy of RIPosomes maintains innate immune hom...	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0005776 autophagosome	IDA PMID:30612879 The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammaso...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0016236 macroautophagy	IDA PMID:30612879 The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammaso...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0016236 macroautophagy	IDA PMID:32715615 Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS ...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0030163 protein catabolic process	IDA PMID:30612879 The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammaso...	ACCEPT	Summary: Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy. Reason: Core outcome of the receptor function; directly demonstrated.
GO:0030163 protein catabolic process	IDA PMID:32715615 Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS ...	ACCEPT	Summary: Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy. Reason: Core outcome of the receptor function; directly demonstrated.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:30612879 The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammaso...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:32715615 Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS ...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:30612879 The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammaso...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:32715615 Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS ...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0030163 protein catabolic process	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	Summary: Direct evidence that p62 drives catabolism of its cargo proteins via selective autophagy. Reason: Core outcome of the receptor function; directly demonstrated.
GO:0035591 signaling adaptor activity	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	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). Reason: Core scaffolding/adaptor molecular function; directly demonstrated (PMID:27498865).
GO:0071211 protein targeting to vacuole involved in autophagy	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	Summary: Direct evidence that p62 targets proteins to the vacuole/lysosome via autophagy. Reason: Core: this is the cargo-delivery outcome of the p62 receptor function.
GO:0140036 ubiquitin-modified protein reader activity	IDA PMID:27498865 TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p6...	ACCEPT	Summary: Direct evidence that p62 acts as a ubiquitin-modified protein reader, recognizing ubiquitinated cargo. Reason: Core molecular function of the selective autophagy receptor.
GO:0005515 protein binding	IPI PMID:26458771 Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis thro...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0010508 positive regulation of autophagy	IDA PMID:28871090 TRIM23 mediates virus-induced autophagy via activation of TB...	ACCEPT	Summary: Direct evidence that p62 positively regulates autophagy (e.g. via TBK1/TRIM23 activation). Reason: Core-adjacent positive regulation of autophagy; directly demonstrated (PMID:28871090).
GO:0038023 signaling receptor activity	IDA PMID:28871090 TRIM23 mediates virus-induced autophagy via activation of TB...	KEEP AS NON CORE	Summary: p62 reported to act as a signaling receptor (TRIM23/TBK1 virus-induced autophagy). Reason: 'Signaling receptor activity' overstates p62's adaptor/scaffold role; the condensate-scaffold/adaptor terms are more accurate, so non-core.
GO:0000425 pexophagy	IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo...	ACCEPT	Summary: Direct evidence that p62 mediates pexophagy by bridging ROS-induced ubiquitinated PEX5 to autophagosomes. Reason: Core selective-autophagy function applied to peroxisomes; directly demonstrated (PMID:26344566).
GO:0030674 protein-macromolecule adaptor activity	IDA PMID:26344566 ATM functions at the peroxisome to induce pexophagy in respo...	ACCEPT	Summary: Direct evidence that p62 acts as a protein-macromolecule adaptor bridging ubiquitinated cargo to the ATG8/autophagosome machinery. Reason: Core molecular function of p62 as a selective autophagy receptor.
GO:0005829 cytosol	TAS Reactome:R-HSA-9759169	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9759172	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9766532	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9766645	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9766656	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9766677	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9766687	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9759154	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005776 autophagosome	IDA PMID:25365221 Spastic paraplegia proteins spastizin and spatacsin mediate ...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0043130 ubiquitin binding	TAS Reactome:R-HSA-205008	ACCEPT	Summary: Direct evidence that p62 binds ubiquitin via its UBA domain. Reason: Core molecular function underlying cargo recognition.
GO:0005515 protein binding	IPI PMID:31006538 Intrinsically Disordered Protein TEX264 Mediates ER-phagy.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0006914 autophagy	IDA PMID:20452972 p62/SQSTM1 is a target gene for transcription factor NRF2 an...	ACCEPT	Summary: Involvement in autophagy, the overarching process in which p62 functions as a selective receptor. Reason: Core process; supported by IMP/IDA evidence.
GO:0031397 negative regulation of protein ubiquitination	IDA PMID:20452972 p62/SQSTM1 is a target gene for transcription factor NRF2 an...	KEEP AS NON CORE	Summary: Direct evidence that p62 negatively regulates protein ubiquitination in specific contexts (e.g. via KEAP1 sequestration / TRAF6 modulation). Reason: Real regulatory effect but context-specific; non-core.
GO:0005776 autophagosome	IDA PMID:22948227 MAPK15/ERK8 stimulates autophagy by interacting with LC3 and...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0035973 aggrephagy	IPI PMID:28404643 The BEACH-containing protein WDR81 coordinates p62 and LC3C ...	ACCEPT	Summary: Direct evidence that p62 mediates aggrephagy - selective autophagic clearance of ubiquitinated protein aggregates. Reason: Core biological process; the defining selective-autophagy activity of p62.
GO:0070530 K63-linked polyubiquitin modification-dependent protein binding	IDA PMID:28404643 The BEACH-containing protein WDR81 coordinates p62 and LC3C ...	ACCEPT	Summary: Direct evidence that p62 binds K63-linked polyubiquitin via its UBA domain - the chain-type preference central to cargo recognition. Reason: Core molecular function for selective autophagy.
GO:0005515 protein binding	IPI PMID:28404643 The BEACH-containing protein WDR81 coordinates p62 and LC3C ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0035255 ionotropic glutamate receptor binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of ionotropic glutamate receptor binding (synaptic context). Reason: Peripheral, neuron-specific interaction; non-core.
GO:1900273 positive regulation of long-term synaptic potentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of positive regulation of long-term synaptic potentiation. Reason: Neuron-specific peripheral process; non-core.
GO:1903078 positive regulation of protein localization to plasma membrane	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Ortholog-transfer/ISS prediction of positive regulation of protein localization to plasma membrane. Reason: Peripheral process; non-core.
GO:0005515 protein binding	IPI PMID:25422469 Disruption of FAT10-MAD2 binding inhibits tumor progression.	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005776 autophagosome	IDA PMID:24954904 WIPI2 links LC3 conjugation with PI3P, autophagosome formati...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0007032 endosome organization	IDA PMID:27368102 An ER-Associated Pathway Defines Endosomal Architecture for ...	KEEP AS NON CORE	Summary: Direct evidence that ubiquitinated p62 organizes endosomes as a perinuclear molecular bridge. Reason: Specialized secondary role (PMID:27368102); non-core relative to selective autophagy.
GO:0019899 enzyme binding	IPI PMID:27368102 An ER-Associated Pathway Defines Endosomal Architecture for ...	KEEP AS NON CORE	Summary: Enzyme binding (interaction with RNF26 ligase activity in endosome organization). Reason: Generic binding term; the specific adaptor/ubiquitin-ligase-binding roles are more informative.
GO:0031625 ubiquitin protein ligase binding	IDA PMID:27368102 An ER-Associated Pathway Defines Endosomal Architecture for ...	KEEP AS NON CORE	Summary: Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26). Reason: Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:27368102 An ER-Associated Pathway Defines Endosomal Architecture for ...	KEEP AS NON CORE	Summary: Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26). Reason: Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function.
GO:1905719 protein localization to perinuclear region of cytoplasm	IDA PMID:27368102 An ER-Associated Pathway Defines Endosomal Architecture for ...	KEEP AS NON CORE	Summary: Direct evidence that p62 promotes protein localization to the perinuclear region (endosome-organization role). Reason: Specialized secondary role (PMID:27368102); non-core.
GO:0016236 macroautophagy	IMP PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0000423 mitophagy	IGI PMID:20457763 Disease-causing mutations in parkin impair mitochondrial ubi...	KEEP AS NON CORE	Summary: Genetic-interaction evidence for involvement in mitophagy of depolarized mitochondria. Reason: Real but secondary role; p62 contributes to mitophagy (clustering) yet is dispensable for the clearance step (PMID:20890124).
GO:0098780 response to mitochondrial depolarisation	IGI PMID:20457763 Disease-causing mutations in parkin impair mitochondrial ubi...	KEEP AS NON CORE	Summary: Genetic-interaction evidence for involvement in response to mitochondrial depolarization (mitophagy context). Reason: Secondary mitophagy-associated process; non-core.
GO:0005515 protein binding	IPI PMID:27103069 Loss of C9ORF72 impairs autophagy and synergizes with polyQ ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005776 autophagosome	IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0044753 amphisome	IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi...	KEEP AS NON CORE	Summary: Amphisome localization along the autophagy pathway (autophagosome-endosome fusion intermediate). Reason: Transit compartment (PMID:19640926); non-core.
GO:0044754 autolysosome	IDA PMID:19640926 LRRK2 regulates autophagic activity and localizes to specifi...	KEEP AS NON CORE	Summary: Autolysosome localization, the degradative endpoint of the autophagic pathway. Reason: Endpoint compartment; non-core.
GO:0005515 protein binding	IPI PMID:26347139 TRIM-mediated precision autophagy targets cytoplasmic regula...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:25126726 FLCN, a novel autophagy component, interacts with GABARAP an...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0031625 ubiquitin protein ligase binding	IPI PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s...	KEEP AS NON CORE	Summary: Ubiquitin protein ligase binding (interactions with TRIM E3 ligases and RNF26). Reason: Genuine interactions enabling selective autophagy of specific substrates; secondary to the core ubiquitin-reader function.
GO:0061635 regulation of protein complex stability	IDA PMID:25127057 TRIM proteins regulate autophagy and can target autophagic s...	KEEP AS NON CORE	Summary: Direct evidence for regulation of protein complex stability (TRIM5 autophagy targeting context). Reason: Context-specific regulatory role; non-core.
GO:0010821 regulation of mitochondrion organization	NAS PMID:20890124 p62/SQSTM1 is required for Parkin-induced mitochondrial clus...	KEEP AS NON CORE	Summary: Author statement on regulation of mitochondrion organization (Parkin-induced clustering). Reason: Reflects the clustering role in mitophagy; secondary, non-core.
GO:0000422 autophagy of mitochondrion	NAS PMID:20098416 PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p6...	KEEP AS NON CORE	Summary: Author statement that p62 is involved in autophagy of mitochondrion (mitophagy). Reason: Supporting role in mitophagy; p62 mediates clustering of damaged mitochondria but is dispensable for clearance, so non-core.
GO:0005737 cytoplasm	IDA PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	ACCEPT	Summary: Cytoplasm is the principal compartment where p62 oligomerizes, binds cargo and forms condensates. Reason: Core localization.
GO:0005776 autophagosome	IDA PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0016234 inclusion body	IDA PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	KEEP AS NON CORE	Summary: p62 localizes to inclusion bodies, the ubiquitin-positive cytoplasmic aggregates it helps form. Reason: Reflects cargo-sequestration outcome; non-core compartment.
GO:0016605 PML body	IDA PMID:20168092 p62/SQSTM1 and ALFY interact to facilitate the formation of ...	KEEP AS NON CORE	Summary: p62 localizes to nuclear PML bodies, recruiting ubiquitinated proteins there. Reason: Secondary nuclear sub-localization (PMID:20168092); non-core.
GO:0005829 cytosol	TAS Reactome:R-HSA-193641	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-193684	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-193694	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-193703	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-193705	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-204947	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-205008	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-209566	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-507719	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-5205649	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-5205663	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-5205673	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9664855	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9664880	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9664881	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9664892	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9759157	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9759158	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0005829 cytosol	TAS Reactome:R-HSA-9761900	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: High-throughput proteomic detection of p62 in urinary exosomes. Reason: Likely incidental detection in secreted vesicles; non-core localization.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-204947	KEEP AS NON CORE	Summary: Reactome curation placing p62 in the nucleoplasm in the NRIF death-signaling context. Reason: Indirect/context-specific nuclear localization; non-core.
GO:0005515 protein binding	IPI PMID:20357094 p62/sequestosome-1 associates with and sustains the expressi...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradat...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005776 autophagosome	IDA PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradat...	ACCEPT	Summary: Autophagosome localization, the core organelle where p62 delivers and is degraded with ubiquitinated cargo via LIR-ATG8 binding. Reason: Core site of action; directly demonstrated across multiple IDA studies (e.g. PMID:17580304, PMID:37802024).
GO:0006914 autophagy	IMP PMID:17580304 p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradat...	ACCEPT	Summary: Involvement in autophagy, the overarching process in which p62 functions as a selective receptor. Reason: Core process; supported by IMP/IDA evidence.
GO:0005515 protein binding	IPI PMID:22178386 TRIM13 regulates ER stress induced autophagy and clonogenic ...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:22421968 TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-fa...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0005515 protein binding	IPI PMID:8618896 Phosphotyrosine-independent binding of a 62-kDa protein to t...	KEEP AS NON CORE	Summary: Records a physical interaction captured as bare 'protein binding'. Per curation guidelines this term is uninformative about the actual molecular function. 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.
GO:0046578 regulation of Ras protein signal transduction	NAS PMID:8618896 Phosphotyrosine-independent binding of a 62-kDa protein to t...	KEEP AS NON CORE	Summary: Author statement on regulation of Ras signal transduction (early RASA1/Lck-binding work). Reason: Historical/weak; non-core.
GO:0016236 macroautophagy	ISS GO_REF:0000024	ACCEPT	Summary: Direct/mutant-phenotype evidence that p62 functions in macroautophagy as a selective cargo receptor. Reason: Core biological process; strongly supported across multiple IDA/IMP studies.
GO:0006914 autophagy	TAS PMID:19816510 Essential role of the unfolded protein response regulator GR...	ACCEPT	Summary: Involvement in autophagy, the overarching process in which p62 functions as a selective receptor. Reason: Core process; supported by IMP/IDA evidence.
GO:0005080 protein kinase C binding	IPI PMID:14676191 Comprehensive proteomic analysis of human Par protein comple...	KEEP AS NON CORE	Summary: Protein kinase C binding via the PB1 domain (atypical PKCs PRKCZ/PRKCI). Reason: Genuine interaction underlying the NF-kB scaffold role; secondary to the core autophagy-receptor function.
GO:0006511 ubiquitin-dependent protein catabolic process	TAS PMID:8702753 p62, a phosphotyrosine-independent ligand of the SH2 domain ...	KEEP AS NON CORE	Summary: Author statement linking p62 to ubiquitin-dependent protein catabolism (early polyubiquitin-binding work). Reason: Correct but generic; the specific autophagic targeting/catabolic terms are more informative.
GO:0030971 receptor tyrosine kinase binding	TAS PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	KEEP AS NON CORE	Summary: Author statement on receptor tyrosine kinase binding (TrkA/NTRK1). Reason: Genuine RTK interaction underlying NGF/NF-kB signaling; secondary, non-core.
GO:0043122 regulation of canonical NF-kappaB signal transduction	IMP PMID:12857745 Structure of the ubiquitin-associated domain of p62 (SQSTM1)...	ACCEPT	Summary: Mutant-phenotype evidence that p62 regulates canonical NF-kB signaling (UBA-domain-dependent ubiquitin binding). Reason: Well-established signaling-scaffold function; directly demonstrated (PMID:12857745).
GO:0043130 ubiquitin binding	IDA PMID:12857745 Structure of the ubiquitin-associated domain of p62 (SQSTM1)...	ACCEPT	Summary: Direct evidence that p62 binds ubiquitin via its UBA domain. Reason: Core molecular function underlying cargo recognition.
GO:0005829 cytosol	TAS PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	ACCEPT	Summary: Cytosol is the core compartment of p62 oligomerization, cargo binding and condensate formation. Reason: Core localization; many redundant TAS/IDA copies.
GO:0008104 intracellular protein localization	TAS PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	KEEP AS NON CORE	Summary: Author statement on a role in intracellular protein localization (early aPKC/endosome targeting work). Reason: Broad/historical; non-core.
GO:0016197 endosomal transport	TAS PMID:12857745 Structure of the ubiquitin-associated domain of p62 (SQSTM1)...	KEEP AS NON CORE	Summary: Author statement on endosomal transport (NF-kB/TRAF6 signaling context). Reason: Secondary trafficking role; non-core.
GO:0019901 protein kinase binding	IDA PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	KEEP AS NON CORE	Summary: Protein kinase binding (e.g. atypical PKCs, ULK1, MAP2K5) underlying p62 signaling scaffolds. Reason: Genuine but generic interaction class; secondary to the core function.
GO:0035556 intracellular signal transduction	TAS PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	KEEP AS NON CORE	Summary: Author statement on involvement in intracellular signal transduction (Lck/NF-kB scaffolding). Reason: Broad signaling role; non-core.
GO:0042169 SH2 domain binding	IDA PMID:8650207 Molecular cloning of a phosphotyrosine-independent ligand of...	KEEP AS NON CORE	Summary: SH2 domain binding - the original phosphotyrosine-independent Lck SH2-domain ligand activity. Reason: Historical/defining-but-peripheral interaction; non-core.
GO:0045944 positive regulation of transcription by RNA polymerase II	TAS PMID:12857745 Structure of the ubiquitin-associated domain of p62 (SQSTM1)...	KEEP AS NON CORE	Summary: Reactome curation linking p62 to positive regulation of Pol II transcription (NRIF pathway). Reason: Indirect transcriptional effect; non-core.

Core Functions

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:

ubiquitin-modified protein reader activity

Directly Involved In:

aggrephagy protein targeting to vacuole involved in autophagy

Cellular Locations:

cytosol autophagosome

Supporting Evidence:

PMID:17580304
p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated
PMID:29343546
p62 filaments capture and present ubiquitinated cargos for autophagy

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:

molecular condensate scaffold activity

Directly Involved In:

membraneless organelle assembly aggrephagy

Supporting Evidence:

PMID:29507397
Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation

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:

protein sequestering activity

Directly Involved In:

cellular response to stress

Supporting Evidence:

PMID:20452972
p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive

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:

signaling adaptor activity

Directly Involved In:

regulation of canonical NF-kappaB signal transduction

Supporting Evidence:

PMID:31281713
p62 Negatively Regulates TLR4 Signaling via Functional Regulation of the TRAF6-ECSIT

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10708586

p62 functions as a p38 MAP kinase regulator.

PMID:12471037

Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve growth factor receptor TrkA regulates receptor trafficking and Erk5 signaling.

PMID:12857745

Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone.

PMID:14676191

Comprehensive proteomic analysis of human Par protein complexes reveals an interconnected protein network.

PMID:16169070

A human protein-protein interaction network: a resource for annotating the proteome.

PMID:16189514

Towards a proteome-scale map of the human protein-protein interaction network.

PMID:16874300

The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation.

PMID:17389358

Unc-51-like kinase 1/2-mediated endocytic processes regulate filopodia extension and branching of sensory axons.

PMID:17580304

p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.

PMID:18083104

Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:19229298

Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3.

PMID:19250911

A role for NBR1 in autophagosomal degradation of ubiquitinated substrates.

PMID:19427866

Interactions with LC3 and polyubiquitin chains link nbr1 to autophagic protein turnover.

PMID:19615732

Defining the human deubiquitinating enzyme interaction landscape.

PMID:19640926

LRRK2 regulates autophagic activity and localizes to specific membrane microdomains in a novel human genomic reporter cellular model.

PMID:19816510

Essential role of the unfolded protein response regulator GRP78/BiP in protection from neuronal apoptosis.

PMID:20010802

Nix is a selective autophagy receptor for mitochondrial clearance.

PMID:20098416

PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1.

PMID:20168092

p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy.

PMID:20173742

The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1.

PMID:20357094

p62/sequestosome-1 associates with and sustains the expression of retroviral restriction factor TRIM5alpha.

PMID:20417604

The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy.

PMID:20452972

p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription.

PMID:20457763

Disease-causing mutations in parkin impair mitochondrial ubiquitination, aggregation, and HDAC6-dependent mitophagy.

PMID:20551902

CIN85 regulates dopamine receptor endocytosis and governs behaviour in mice.

PMID:20562859

Network organization of the human autophagy system.

PMID:20808283

NBR1 is a new PB1 signalling adapter in Th2 differentiation and allergic airway inflammation in vivo.

PMID:20890124

p62/SQSTM1 is required for Parkin-induced mitochondrial clustering but not mitophagy; VDAC1 is dispensable for both.

PMID:21149568

Formin follows function: a muscle-specific isoform of FHOD3 is regulated by CK2 phosphorylation and promotes myofibril maintenance.

PMID:21900206

A directed protein interaction network for investigating intracellular signal transduction.

PMID:21988832

Toward an understanding of the protein interaction network of the human liver.

PMID:22017874

Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins.

PMID:22178386

TRIM13 regulates ER stress induced autophagy and clonogenic ability of the cells.

PMID:22190034

Global landscape of HIV-human protein complexes.

PMID:22421968

TP53INP1, a tumor suppressor, interacts with LC3 and ATG8-family proteins through the LC3-interacting region (LIR) and promotes autophagy-dependent cell death.

PMID:22622177

The deubiquitinating enzyme USP36 controls selective autophagy activation by ubiquitinated proteins.

PMID:22948227

MAPK15/ERK8 stimulates autophagy by interacting with LC3 and GABARAP proteins.

PMID:23274085

Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage.

PMID:23459205

Ubiquilin4 is an adaptor protein that recruits Ubiquilin1 to the autophagy machinery.

PMID:24089205

Autophagy promotes primary ciliogenesis by removing OFD1 from centriolar satellites.

PMID:24189400

Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.

PMID:24316673

Autophagy variation within a cell population determines cell fate through selective degradation of Fap-1.

PMID:24668264

Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures.

PMID:24879152

Phosphorylation of NBR1 by GSK3 modulates protein aggregation.

PMID:24954904

WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1.

PMID:25026213

Ubiquitylation of autophagy receptor Optineurin by HACE1 activates selective autophagy for tumor suppression.

PMID:25040165

Sestrin2 promotes Unc-51-like kinase 1 mediated phosphorylation of p62/sequestosome-1.

PMID:25126726

FLCN, a novel autophagy component, interacts with GABARAP and is regulated by ULK1 phosphorylation.

PMID:25127057

TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.

PMID:25365221

Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25422469

Disruption of FAT10-MAD2 binding inhibits tumor progression.

PMID:25686248

Huntingtin functions as a scaffold for selective macroautophagy.

PMID:25910212

Widespread macromolecular interaction perturbations in human genetic disorders.

PMID:25959826

Quantitative interaction proteomics of neurodegenerative disease proteins.

PMID:26344566

ATM functions at the peroxisome to induce pexophagy in response to ROS.

PMID:26347139

TRIM-mediated precision autophagy targets cytoplasmic regulators of innate immunity.

PMID:26403645

Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells.

PMID:26458771

Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor-TRAF6 signaling.

PMID:26524528

Autophagy mediates degradation of nuclear lamina.

PMID:26637326

ENC1 Modulates the Aggregation and Neurotoxicity of Mutant Huntingtin Through p62 Under ER Stress.

PMID:27103069

Loss of C9ORF72 impairs autophagy and synergizes with polyQ Ataxin-2 to induce motor neuron dysfunction and cell death.

PMID:27368102

An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport.

PMID:27498865

TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy.

PMID:27728806

p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer.

PMID:28404643

The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy.

PMID:28871090

TRIM23 mediates virus-induced autophagy via activation of TBK1.

PMID:29343546

p62 filaments capture and present ubiquitinated cargos for autophagy.

PMID:29507397

Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation.

PMID:29519959

P62/SQSTM1 is a novel leucine-rich repeat kinase 2 (LRRK2) substrate that enhances neuronal toxicity.

PMID:30612879

The Crohn's Disease Risk Factor IRGM Limits NLRP3 Inflammasome Activation by Impeding Its Assembly and by Mediating Its Selective Autophagy.

PMID:31006538

Intrinsically Disordered Protein TEX264 Mediates ER-phagy.

PMID:31169361

A Case Study on the Keap1 Interaction with Peptide Sequence Epitopes Selected by the Peptidomic mRNA Display.

PMID:31281713

p62 Negatively Regulates TLR4 Signaling via Functional Regulation of the TRAF6-ECSIT Complex.

PMID:31515488

Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.

PMID:31616248

Systematic Affinity Purification Coupled to Mass Spectrometry Identified p62 as Part of the Cannabinoid Receptor CB2 Interactome.

PMID:31857589

Requirement for p62 acetylation in the aggregation of ubiquitylated proteins under nutrient stress.

PMID:31980649

Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRAS(G13D).

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32715615

Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response.

PMID:32814053

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

PMID:33436498

Cytoplasmic short linear motifs in ACE2 and integrin β(3) link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34471133

Reconstitution defines the roles of p62, NBR1 and TAX1BP1 in ubiquitin condensate formation and autophagy initiation.

PMID:34524948

Global Proximity Interactome of the Human Macroautophagy Pathway.

PMID:34591642

A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.

PMID:34799561

Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities.

PMID:34893540

The N-terminal cysteine is a dual sensor of oxygen and oxidative stress.

PMID:35044719

Proteome-scale mapping of binding sites in the unstructured regions of the human proteome.

PMID:35266954

The E3 ligase TRIM1 ubiquitinates LRRK2 and controls its localization, degradation, and toxicity.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

PMID:36221902

Selective autophagy of RIPosomes maintains innate immune homeostasis during bacterial infection.

PMID:37219487

Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.

PMID:37306101

Phosphorylation of phase-separated p62 bodies by ULK1 activates a redox-independent stress response.

PMID:37460613

P62/SQSTM1 binds with claudin-2 to target for selective autophagy in stressed intestinal epithelium.

PMID:37802024

S-acylation of p62 promotes p62 droplet recruitment into autophagosomes in mammalian autophagy.

PMID:39009827

Proteome-scale characterisation of motif-based interactome rewiring by disease mutations.

PMID:8618896

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.

PMID:8650207

Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain.

PMID:8702753

p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins.

PMID:9566925

Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62.

Reactome:R-HSA-193641

IKK-beta is recruited

Reactome:R-HSA-193684

p62 recruits an atypical PKC

Reactome:R-HSA-193694

p62 is recruited and forms a complex with TRAF6

Reactome:R-HSA-193703

IKKbeta is activated

Reactome:R-HSA-193705

IKKbeta phosphorylates IkB causing NF-kB to dissociate

Reactome:R-HSA-204947

Polyubiquitinated NRIF migrates to the nucleus

Reactome:R-HSA-205008

Polyubiquitinated NRIF binds to p62 (Sequestosome)

Reactome:R-HSA-205043

NRIF signals cell death from the nucleus

Reactome:R-HSA-209566

TRAF6 is auto-ubiquitinated

Reactome:R-HSA-507719

p62:MEKK3 binds to TRAF6

Reactome:R-HSA-5205649

p62 links damaged mitochondria to LC3

Reactome:R-HSA-5205663

LC3 binds the autophagosome membrane Atg5-Atg12 complex

Reactome:R-HSA-5205673

p62 binds ubiquitinated mitochondrial substrates

Reactome:R-HSA-9664855

MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1

Reactome:R-HSA-9664880

MAP1LC3B binds ATM dimer:Ub-p-PEX5:SQSTM1:NBR1

Reactome:R-HSA-9664881

NBR1 binds ATM:Ub-p-PEX5:SQSTM1

Reactome:R-HSA-9664892

SQSTM1 binds ATM dimer:Ub-p-PEX5

Reactome:R-HSA-9759154

TRIM21 ubiquitinates SQSTM1

Reactome:R-HSA-9759157

NFE2L2-dependent SQSTM1 gene expression

Reactome:R-HSA-9759158

SQSTM1 oligomerizes

Reactome:R-HSA-9759169

p-S349 SQSTM1 oligomer binds KEAP1:CUL3:RBX1

Reactome:R-HSA-9759172

KEAP1:CUL3:RBX1 ubiquitinates p-S349 SQSTM1 oligomer

Reactome:R-HSA-9761900

HBV X protein binds SQSTM1 oligomer

Reactome:R-HSA-9766532

SQSTM1 oligomer is phosphorylated

Reactome:R-HSA-9766645

CUL3:RBX1 ubiquitinates KEAP1

Reactome:R-HSA-9766656

RBX1:CUL3 dissociates from forming autophagosome

Reactome:R-HSA-9766677

MAP1LC3B binds KEAP1 and SQSTM1

Reactome:R-HSA-9766687

SESN1,SESN1 bind SQSTM1 and KEAP1

Suggested Experiments

Experiment: 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.

Experiment: 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.

Deep Research

Falcon

(SQSTM1-deep-research-falcon.md)

Research Report: Human **SQSTM1 / p62 (Sequestosome-1)** — Functional Annotation (UniProt **Q13501**) Falcon Edison Scientific Literature 34 citations 2 artifacts 2026-06-14T16:05:00.242550

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000025 The requested information can be found in Figures 1 and 5 of the document. Figure 1 provides a schematic representation of the p62/ (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Human SQSTM1 / p62 (Sequestosome-1) — Functional Annotation (UniProt Q13501)

0) Target verification (critical identity check)

The requested target is human SQSTM1 (Sequestosome-1; p62), and recent primary literature explicitly ties p62 structural annotation to AlphaFold model AF-Q13501-F1, consistent with UniProt accession Q13501 (human). (masato2024sequestosome1(sqstm1p62)as pages 8-11)

1) Key concepts and definitions (current understanding)

1.1 What SQSTM1/p62 is

SQSTM1/p62 is a multifunctional adaptor/scaffold protein best understood as a selective autophagy receptor that couples ubiquitinated cargo to autophagosomal membranes through binding to ATG8-family proteins (LC3/GABARAP), promoting lysosomal degradation of aggregates and other cargo. (gibertini2023proteinaggregatesand pages 18-19, alcober‐boquet2024thepb1and pages 1-2)

1.2 “Selective autophagy receptor” for SQSTM1/p62

In selective autophagy (e.g., aggrephagy), receptors bind both:
- ubiquitin chains on cargo (cargo recognition), and
- LC3/GABARAP on phagophores/autophagosomes (membrane tethering).

Recent experimental work directly quantifies p62–LC3B interaction in vitro and shows that p62 contains multiple domains that regulate the exposure of its LC3-binding region, reinforcing the concept that p62 is not merely a static tether but a regulated receptor. (alcober‐boquet2024thepb1and pages 9-10, alcober‐boquet2024thepb1and pages 1-2)

1.3 Condensates (“p62 bodies”) as a functional organizing principle

Current models emphasize that p62 can assemble into higher-order bodies/condensates that concentrate ubiquitinated cargo and recruit additional factors; these structures are dynamic and their associated protein neighborhoods remodel under proteotoxic and aggregation stress. (rondonortiz2024proximitylabelingreveals pages 1-2)

2) Molecular mechanisms: domains, motifs, and binding partners

2.1 Core domain architecture and regulated LC3 engagement

A recent mechanistic study using full-length recombinant human p62 shows that PB1 and ZZ domains regulate whether the LIR is accessible to bind LC3B (a proposed “LIR-sequence Accessibility Mechanism (LAM)”). (alcober‐boquet2024thepb1and pages 1-2)

A figure-level schematic in the same work depicts the domain architecture (PB1, ZZ, LIR, KIR, UBA) and the LAM concept for regulated LIR exposure. (alcober‐boquet2024thepb1and media 41957107, alcober‐boquet2024thepb1and media e0bee45a)

2.2 LIR motif (LC3/GABARAP binding): quantitative biochemical evidence (2024)

In an AlphaScreen assay with purified proteins, 7 nM His-Trx-p62 plus 3.5 nM GST–LC3B produced a strong interaction signal (60,861 ± 2,473 AU) over background (1,573 ± 108 AU). Addition of an LIR peptide competitor displaced binding to approximately background (~1,714 ± 104 AU). The assay Z′ of 0.87 indicates a high-quality, robust assay—useful both mechanistically and for screening approaches targeting the p62–LC3 interface. (alcober‐boquet2024thepb1and pages 9-10)

2.3 PB1 and ZZ domains: regulation and pharmacologic modulation (2024)

The PB1 and ZZ domains modulate LC3B binding by controlling LIR exposure; notably, a phosphomimetic mutation in the ZZ domain (Thr138Glu) increases LC3B binding, and a small-molecule ZZ binder can also enhance the p62–LC3B interaction, supporting the idea that p62’s autophagy receptor activity is drug-modulatable at the level of domain conformation. (alcober‐boquet2024thepb1and pages 1-2)

2.4 UBA domain (ubiquitin binding) and ubiquitination sites relevant to function

Recent work situates the UBA domain as the ubiquitin-recognition module of p62 and highlights that ubiquitination of p62 itself can be functionally important. In stress-granule biology, p62 ubiquitination sites K420 and K435 are functionally implicated: wild-type p62 (but not K420R or K435R mutants) rescues ubiquitination-dependent phenotypes in a model where NS1-BP regulates p62 ubiquitination and stress-granule clearance. (jeon2024ns1bindingprotein pages 1-2)

2.5 KIR motif: linking p62 to KEAP1–NRF2 antioxidant signaling

p62 contains a KEAP1-interacting region (KIR) that connects selective autophagy/proteostasis to oxidative-stress defense by enabling KEAP1 sequestration and degradation, thereby promoting NRF2 activation. Domain descriptions in recent interactome work list KIR explicitly and capture KEAP1 as a proximal protein to SQSTM1 in living cells. (rondonortiz2024proximitylabelingreveals pages 1-2)

3) Pathways and systems-level roles (recent developments prioritized)

3.1 AMPK–p62–NRF2 coupling during metabolic stress (Autophagy, 2024)

A 2024 study reports that metabolic stress induces increased SQSTM1/p62 expression and phosphorylation, and that p62 is required for KEAP1 degradation and NRF2 activation, while also facilitating lysosome-associated assembly of an AXIN–STK11/LKB1–AMPK complex. The authors describe a double-positive feedback loop between AMPK and SQSTM1/p62, and identify p62 phosphorylation at S24 and S226 as critical for activation of AMPK and NRF2. (choi2024metabolicstressinduces pages 20-21)

3.2 Stress granule clearance (“granulophagy”): a 2024 mechanistic link to p62 ubiquitination

A 2024 Nature Communications study identifies NS1-BP as a regulator of stress granule (SG) dynamics/clearance through inhibition of p62 ubiquitination and facilitation of GABARAP recruitment to SGs. NS1-BP knockout increases p62 ubiquitination, promotes p62 autophagic degradation, and alters SG morphology/dynamics. Importantly, p62 ubiquitination site mutants (K420R, K435R) fail to restore key phenotypes, implicating specific p62 ubiquitination events in SG homeostasis. (jeon2024ns1bindingprotein pages 1-2, jeon2024ns1bindingprotein pages 10-11)

3.3 Condensate/interactome remodeling under proteotoxic stress and tau aggregation (JBC, 2024)

A 2024 TurboID proximity-labeling study quantifies the dynamic neighborhood of SQSTM1 bodies:
- 236 unique proximity proteins were recovered, with an overlapping subset of 83 proteins linked to autophagy/catabolic processes. (rondonortiz2024proximitylabelingreveals pages 1-2)
- Under proteasome inhibition, 51 proteins were enriched in the p62 neighborhood using Log2FC > 0.58 and FDR < 0.05, consistent with stress-driven remodeling of SQSTM1 bodies. (rondonortiz2024proximitylabelingreveals pages 5-6)
- Exposure to recombinant P301S tau fibrils altered the SQSTM1-proximal proteome, with 24 proteins changing at 24 h and 98 proteins changing at 48 h (Log2FC > 0.58, p < 0.05; n = 4). (rondonortiz2024proximitylabelingreveals pages 6-10)
These data support a modern view of p62 as a dynamic hub whose molecular environment changes in response to protein aggregation and proteostasis disruption. (rondonortiz2024proximitylabelingreveals pages 5-6, rondonortiz2024proximitylabelingreveals pages 6-10, rondonortiz2024proximitylabelingreveals pages 1-2)

4) Subcellular localization and where p62 acts

p62 is primarily cytosolic, where it forms bodies/condensates and engages LC3/GABARAP-positive autophagic membranes. Proximity-labeling evidence also notes p62 is detectable in the nucleus and may support a nucleus-to-cytosol shuttling function for ubiquitinylated nuclear proteins, aligning with its adaptor role in proteostasis. (rondonortiz2024proximitylabelingreveals pages 1-2)

5) Current applications and real-world implementations

5.1 Clinical genetics and prevention trial in SQSTM1 mutation carriers (Paget disease of bone)

The ZiPP program provides an instructive real-world implementation of SQSTM1 genetic screening + imaging + preventive pharmacotherapy.

Trial design/application:
- A 2024 randomized trial enrolled 222 SQSTM1 pathogenic-variant carriers to receive a single 5 mg zoledronic acid infusion or placebo with median follow-up 84 months (and 81% completing the study). (phillips2024randomisedtrialof pages 1-2)

Key quantitative outcomes (2024):
- Baseline lesions: 21/222 (9.5%) had Paget-like lesions on bone scan at entry. (phillips2024prophylacticzoledronicacid pages 7-8)
- New lesions: 0/90 zoledronic acid vs 2/90 (2.2%) placebo; OR 0.41 (95% CI 0.00–3.43), p = 0.25 (underpowered primary endpoint due to few events). (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024randomisedtrialof pages 1-2)
- Composite “poor outcome” (new/unchanged/progressing lesions): 0 zoledronic acid vs 8 placebo; OR 0.08 (95% CI 0.00–0.42), p = 0.003. (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024randomisedtrialof pages 1-2)
- Lesion disappearance among baseline lesions: 13/15 (86.6%) zoledronic acid vs 1/29 (3.4%) placebo; p < 0.0001. (phillips2024prophylacticzoledronicacid pages 7-8)
- Bone turnover markers: significant reductions reported for CTX and PINP (p < 0.0001) and BAP (p = 0.0003) in zoledronic acid vs placebo. (phillips2024prophylacticzoledronicacid pages 7-8)
- PDB-related skeletal events: 3 (zoledronic acid) vs 13 (placebo). (phillips2024prophylacticzoledronicacid pages 42-43)

Together, these results support a translational pipeline in which SQSTM1 genotyping identifies at-risk individuals and a standard antiresorptive therapy (zoledronic acid) can favorably modify early imaging and biochemical phenotypes of SQSTM1-associated Paget disease. (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024randomisedtrialof pages 1-2, phillips2024prophylacticzoledronicacid pages 42-43)

5.2 Tooling and reagent standardization (research implementation)

A 2024 benchmarking study evaluates commercial antibodies for sequestosome-1/p62 across Western blot, immunoprecipitation, and immunofluorescence using knockout controls, supporting reproducibility in p62 biology (reagent selection is a practical implementation component for functional studies and translational biomarker work). (paper metadata retrieved; not used as evidence in excerpts)

6) Expert opinions and authoritative synthesis (what experts emphasize now)

6.1 p62 as a regulated receptor, not just a passive adaptor

The 2024 biochemical and structural/regulatory framing (LAM) emphasizes that p62’s LC3 engagement is regulated by intramolecular/domain-level mechanisms (PB1/ZZ-dependent control of LIR exposure) and potentially pharmacologically tunable. (alcober‐boquet2024thepb1and pages 1-2, alcober‐boquet2024thepb1and media 41957107, alcober‐boquet2024thepb1and media e0bee45a)

6.2 p62 as a hub connecting proteostasis, redox defense, and stress response

Recent mechanistic papers place p62 at interfaces between selective autophagy, ubiquitin handling, and oxidative-stress signaling (KEAP1–NRF2), with additional links to lysosome-associated AMPK activation during metabolic stress. (choi2024metabolicstressinduces pages 20-21, rondonortiz2024proximitylabelingreveals pages 1-2)

6.3 Condensates/phase organization as a framework for understanding p62 function

The 2024 TurboID study’s quantitative interactome remodeling and enrichment of stress/RNA-binding proteins under proteasome inhibition or tau aggregation supports a viewpoint that p62 bodies act as organizational hubs whose local proteome changes with stress and disease-associated aggregation. (rondonortiz2024proximitylabelingreveals pages 5-6, rondonortiz2024proximitylabelingreveals pages 6-10, rondonortiz2024proximitylabelingreveals pages 1-2)

7) Relevant statistics and data (recent studies)

Key quantitative highlights from recent (2024) studies include:
- p62–LC3B binding assay: 60,861 ± 2,473 AU signal; displaced to ~1,714 ± 104 AU by LIR peptide; Z′ = 0.87. (alcober‐boquet2024thepb1and pages 9-10)
- TurboID proximity proteomics: 236 proximity proteins; 83 overlapping autophagy/catabolism-associated; MG132 enriched 51 proteins at Log2FC > 0.58 and FDR < 0.05; tau fibrils changed 24 proteins at 24 h and 98 at 48 h (Log2FC > 0.58, p < 0.05). (rondonortiz2024proximitylabelingreveals pages 5-6, rondonortiz2024proximitylabelingreveals pages 6-10, rondonortiz2024proximitylabelingreveals pages 1-2)
- ZiPP RCT in SQSTM1 carriers: 222 participants; 21/222 baseline lesions; lesion disappearance 86.6% vs 3.4%; ORs for new lesions (0.41) and poor outcome (0.08) with corresponding CIs/p-values; fewer PDB-related skeletal events (3 vs 13). (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024randomisedtrialof pages 1-2, phillips2024prophylacticzoledronicacid pages 42-43)

8) Summary functional annotation statement (for database-style use)

SQSTM1/p62 (UniProt Q13501) is a predominantly cytosolic (also nucleus-detectable) selective autophagy receptor and signaling adaptor that binds ubiquitinylated cargo (UBA) and LC3/GABARAP (LIR), assembling cargo into higher-order bodies and recruiting autophagic membranes for lysosomal degradation; its autophagosome engagement is regulated by PB1/ZZ-dependent control of LIR exposure and is coupled to cellular stress-response pathways including KEAP1–NRF2 antioxidant signaling and lysosome-associated AMPK activation during metabolic stress. (rondonortiz2024proximitylabelingreveals pages 1-2, alcober‐boquet2024thepb1and pages 9-10, choi2024metabolicstressinduces pages 20-21, alcober‐boquet2024thepb1and pages 1-2)

Evidence summary table

The following table compiles the most directly supported domain-to-function links and 2024 quantitative findings.

Feature (domain/motif or process)	Mechanistic role	Key evidence (including quantitative numbers when available)	Recent source (first author, journal, publication month/year)	URL/DOI
Identity / target verification	UniProt Q13501 corresponds to human SQSTM1/p62 (sequestosome-1); AlphaFold model AF-Q13501-F1 is used for domain mapping in recent literature, matching the requested human protein.	Recent p62 structural work explicitly cites AF-Q13501-F1 for p62 domain/residue mapping, consistent with UniProt Q13501 and the human SQSTM1/p62 annotation. (masato2024sequestosome1(sqstm1p62)as pages 8-11)	Masato, Cell Death & Disease, Jun 2024	https://doi.org/10.1038/s41419-024-06763-x
PB1 domain	N-terminal oligomerization/polymerization module that helps build p62 bodies/condensates, supports aggregate capture, and regulates accessibility of the LC3-binding LIR; also implicated in signaling scaffolds.	2024 in vitro work showed PB1 contributes to regulation of LC3B binding via a proposed LIR-sequence Accessibility Mechanism (LAM). In proteomics/interactome studies, PB1 was required for interaction with aggregation-prone K18-tau; removal abrogated binding. PB1 is also listed among core domains in recent reviews/tables of p62 function. (alcober‐boquet2024thepb1and pages 1-2, rondonortiz2024proximitylabelingreveals pages 10-11, gibertini2023proteinaggregatesand pages 8-9)	Alcober-Boquet, Protein Science, Dec 2024; Rondón-Ortiz, JBC, Sep 2024	https://doi.org/10.1002/pro.4840; https://doi.org/10.1016/j.jbc.2024.107621
ZZ domain	Regulatory zinc-finger module that modulates p62 conformation and promotes/exposes the LIR for LC3B engagement; also a signaling/drug-targeting interface.	Alcober-Boquet et al. identified ZZ-dependent control of LC3B interaction; a phosphomimetic Thr138Glu mutant increased LC3B binding, and a small-molecule ZZ binder also enhanced binding, supporting pharmacologic tunability of p62–LC3 interaction. (alcober‐boquet2024thepb1and pages 1-2, alcober‐boquet2024thepb1and pages 10-11)	Alcober-Boquet, Protein Science, Dec 2024	https://doi.org/10.1002/pro.4840
LIR motif	Canonical LC3/GABARAP-binding motif that tethers p62-bound cargo to autophagosomal membranes during selective autophagy.	Direct p62–LC3B interaction was quantified in AlphaScreen assays: 7 nM His-Trx-p62 + 3.5 nM GST-LC3B produced 60,861 ± 2,473 AU versus background 1,573 ± 108 AU; an LIR peptide competitor reduced signal to ~1,714 ± 104 AU; assay Z' = 0.87, showing robust measurable LIR-dependent binding. (alcober‐boquet2024thepb1and pages 9-10, alcober‐boquet2024thepb1and pages 1-2)	Alcober-Boquet, Protein Science, Dec 2024	https://doi.org/10.1002/pro.4840
KIR motif	KEAP1-interacting region that enables p62 to sequester/degrade KEAP1 and thereby activate NRF2-dependent antioxidant transcription.	Recent mechanistic synthesis describes p62 as a scaffold in KEAP1–NRF2 signaling; Choi et al. further show stress-induced SQSTM1 is required for KEAP1 degradation and NRF2 activation, placing the KIR-containing region at the core of this signaling function. Domain architecture tables and recent interactome work also explicitly list KIR. (alcober‐boquet2024thepb1and pages 1-2, choi2024metabolicstressinduces pages 20-21, rondonortiz2024proximitylabelingreveals pages 1-2)	Choi, Autophagy, Jul 2024; Rondón-Ortiz, JBC, Sep 2024	https://doi.org/10.1080/15548627.2024.2374692; https://doi.org/10.1016/j.jbc.2024.107621
UBA domain	C-terminal ubiquitin-binding module that recognizes ubiquitinated cargo for aggrephagy/selective autophagy; also participates in regulated ubiquitination of p62 itself.	Recent summaries and experiments identify UBA as the ubiquitin-recognition module of p62. In NS1-BP/stress-granule work, p62 lysines K420 and K435 were functionally important for ubiquitination-dependent phenotypes; in other recent studies UBA-dependent interactions were required for some proximity-labeled partners. (gibertini2023proteinaggregatesand pages 8-9, jeon2024ns1bindingprotein pages 1-2, rondonortiz2024proximitylabelingreveals pages 5-6)	Jeon, Nature Communications, Dec 2024; Rondón-Ortiz, JBC, Sep 2024	https://doi.org/10.1038/s41467-024-55446-w; https://doi.org/10.1016/j.jbc.2024.107621
Selective autophagy receptor / aggrephagy	p62 bridges ubiquitinated proteins/aggregates to LC3/GABARAP-positive autophagosomes and helps organize cargo into higher-order assemblies/condensates.	Multiple recent sources describe p62 as a selective autophagy receptor/adaptor that binds ubiquitinylated cargo and ATG8-family proteins. Human SQSTM1 is also reported to form bodies/condensates and scaffold aggregate handling. (gibertini2023proteinaggregatesand pages 18-19, rondonortiz2024proximitylabelingreveals pages 1-2, choi2024metabolicstressinduces pages 20-21)	Gibertini, IJMS, May 2023; Rondón-Ortiz, JBC, Sep 2024; Choi, Autophagy, Jul 2024	https://doi.org/10.3390/ijms24098456; https://doi.org/10.1016/j.jbc.2024.107621; https://doi.org/10.1080/15548627.2024.2374692
p62–LC3B binding regulation (LAM model)	PB1/ZZ domains regulate whether the LIR is exposed or occluded, tuning autophagosome engagement.	Figure-level evidence and biochemical assays support a LIR-sequence Accessibility Mechanism (LAM) in which PB1 and ZZ regulate LIR exposure; the 2024 paper provides both a domain schematic and a mechanistic model for how modification or ligand binding can increase LC3 access. (alcober‐boquet2024thepb1and media 41957107, alcober‐boquet2024thepb1and media e0bee45a, alcober‐boquet2024thepb1and pages 1-2)	Alcober-Boquet, Protein Science, Dec 2024	https://doi.org/10.1002/pro.4840
Cellular localization	Predominantly cytosolic but also present in nucleus; forms cytoplasmic bodies/condensates and associates with autophagosomes, aggregates, and stress-related structures.	Recent proximity-labeling work states SQSTM1 is mainly cytosolic, also detected in the nucleus, and may shuttle ubiquitinylated nuclear proteins to the cytosol; multiple studies describe SQSTM1 bodies/condensates and recruitment to aggregates. (rondonortiz2024proximitylabelingreveals pages 1-2)	Rondón-Ortiz, JBC, Sep 2024	https://doi.org/10.1016/j.jbc.2024.107621
Condensates / interactome remodeling	p62 bodies act as dynamic hubs whose protein neighborhood changes with proteotoxic stress and tau aggregation.	TurboID::SQSTM1 proteomics identified 236 unique proximity proteins and an overlapping subset of 83 linked to autophagy/catabolic processes. Under MG132, 51 proteins were enriched using Log2FC > 0.58 and FDR < 0.05. Tau fibrils changed 24 proteins at 24 h and 98 proteins at 48 h (Log2FC > 0.58, p < 0.05; n = 4). (rondonortiz2024proximitylabelingreveals pages 1-2, rondonortiz2024proximitylabelingreveals pages 5-6, rondonortiz2024proximitylabelingreveals pages 6-10)	Rondón-Ortiz, JBC, Sep 2024	https://doi.org/10.1016/j.jbc.2024.107621
AMPK–p62–NRF2 feedback loop	Under metabolic stress, p62 both activates and is induced by AMPK/lysosomal stress pathways, creating a positive feedback loop that promotes KEAP1 degradation, NRF2 signaling, and antioxidant defense.	Choi et al. report a “double-positive feedback loop” between AMPK and SQSTM1/p62: metabolic stress increased p62 expression/phosphorylation; p62 promoted autophagic KEAP1 degradation and facilitated AXIN–STK11–AMPK complex formation on lysosomes; phosphorylation at S24 and S226 was critical for AMPK and NRF2 activation. (choi2024metabolicstressinduces pages 20-21)	Choi, Autophagy, Jul 2024	https://doi.org/10.1080/15548627.2024.2374692
Stress granules / granulophagy via NS1-BP	p62 helps target stress granules for autophagic clearance; NS1-BP restrains p62 ubiquitination and supports GABARAP recruitment to stress granules.	In NS1-BP knockout cells, p62 ubiquitination increased and p62 underwent autophagic degradation; WT p62, but not K420R or K435R mutants, restored ubiquitination-dependent phenotypes. NS1-BP loss altered stress-granule number/size/dynamics and reduced contact between ubiquitinated p62 aggregates and stress granules. (jeon2024ns1bindingprotein pages 1-2, jeon2024ns1bindingprotein pages 10-11)	Jeon, Nature Communications, Dec 2024	https://doi.org/10.1038/s41467-024-55446-w
Disease relevance / Paget disease of bone (clinical translation)	Germline SQSTM1 mutations are a major risk factor for Paget disease of bone; preventive treatment strategies are now being tested in mutation carriers.	In the ZiPP program, SQSTM1 mutation carriers were prospectively screened and treated. Background estimates in the trial report note ~80% penetrance by the seventh decade in carriers from familial PDB settings. (phillips2024prophylacticzoledronicacid pages 23-25, phillips2024prophylacticzoledronicacid pages 7-8)	Phillips, Efficacy and Mechanism Evaluation, Jun 2024; Phillips, Ann Rheum Dis, Apr 2024	https://doi.org/10.3310/ftkc2007; https://doi.org/10.1136/ard-2023-224990
ZiPP RCT: trial population and baseline disease burden	Real-world implementation of SQSTM1 genetic testing plus radionuclide scanning in relatives at risk for Paget disease.	1,307 people were offered SQSTM1 testing, 750 were tested, 350 (46.7%) were mutation-positive, and 222 enrolled in the RCT. Median follow-up was 84 months; 180/222 (81%) completed the study. Baseline PDB lesions were present in 21/222 (9.5%); arm-specific baseline prevalence was 8.1% (ZA) vs 10.8% (placebo). (phillips2024prophylacticzoledronicacid pages 15-17, phillips2024randomisedtrialof pages 1-2, phillips2024prophylacticzoledronicacid pages 7-8)	Phillips, EME, Jun 2024; Phillips, Ann Rheum Dis, Apr 2024	https://doi.org/10.3310/ftkc2007; https://doi.org/10.1136/ard-2023-224990
ZiPP RCT: prevention/progression outcomes	A single 5 mg zoledronic acid infusion favorably modified early SQSTM1-associated Paget lesions, though the primary endpoint was underpowered due to few new lesions.	New lesions: 0/90 in ZA vs 2/90 (2.2%) in placebo; OR 0.41 (95% CI 0.00–3.43), p = 0.25. Composite poor outcome: 0 in ZA vs 8 in placebo; OR 0.08 (95% CI 0.00–0.42), p = 0.003. At study end, lesions remained in 1/111 ZA vs 11/111 placebo participants. (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024randomisedtrialof pages 1-2, phillips2024prophylacticzoledronicacid pages 39-41)	Phillips, EME, Jun 2024; Phillips, Ann Rheum Dis, Apr 2024	https://doi.org/10.3310/ftkc2007; https://doi.org/10.1136/ard-2023-224990
ZiPP RCT: lesion-level efficacy and biomarkers	Demonstrates measurable lesion regression and suppression of bone turnover in SQSTM1 carriers, supporting biomarker-guided preventive intervention.	Existing-lesion disappearance was 13/15 (86.6%) with ZA vs 1/29 (3.4%) with placebo, p < 0.0001. In the lesion-level analysis, ZA baseline lesions = 15: 13 disappeared, 2 diminished, 0 new lesions; placebo baseline lesions = 25 with 1 disappeared, 12 reduced, 8 stable, 4 increased, ending with 26 lesions. Bone-turnover markers CTX and PINP fell with p < 0.0001 and BAP with p = 0.0003 in ZA vs placebo. PDB-related skeletal events were 3 with ZA vs 13 with placebo. (phillips2024prophylacticzoledronicacid pages 7-8, phillips2024prophylacticzoledronicacid pages 42-43)	Phillips, EME, Jun 2024	https://doi.org/10.3310/ftkc2007

Table: This table summarizes the core functional annotation of human SQSTM1/p62 (UniProt Q13501), combining domain-level mechanism, recent molecular studies, and 2024 clinical trial data. It is designed to support a concise, evidence-based narrative on p62 function, localization, signaling, and translational relevance.

Key figure(s) supporting domain architecture and the LIR accessibility model

The domain schematic and LAM model figure panels were retrieved from the 2024 Protein Science paper. (alcober‐boquet2024thepb1and media 41957107, alcober‐boquet2024thepb1and media e0bee45a)

References

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(gibertini2023proteinaggregatesand pages 8-9): Sara Gibertini, Alessandra Ruggieri, Marta Cheli, and Lorenzo Maggi. Protein aggregates and aggrephagy in myopathies. International Journal of Molecular Sciences, 24:8456, May 2023. URL: https://doi.org/10.3390/ijms24098456, doi:10.3390/ijms24098456. This article has 16 citations.
(alcober‐boquet2024thepb1and pages 10-11): Lucia Alcober‐Boquet, Tabea Zang, Larissa Pietsch, Evelyn Suess, Markus Hartmann, Ewgenij Proschak, Lissy Z. F. Gross, Mariana Sacerdoti, Stefan Zeuzem, Vladimir V. Rogov, Alejandro E. Leroux, Albrecht Piiper, and Ricardo M. Biondi. The pb1 and the zz domain of the autophagy receptor p62/sqstm1 regulate the interaction of p62/sqstm1 with the autophagosome protein lc3b. Protein Science, Dec 2024. URL: https://doi.org/10.1002/pro.4840, doi:10.1002/pro.4840. This article has 27 citations and is from a peer-reviewed journal.
(phillips2024prophylacticzoledronicacid pages 23-25): Jonathan Phillips, Deepak Subedi, Steff C Lewis, Catriona Keerie, and Stuart H Ralston. Prophylactic zoledronic acid therapy to prevent or modify paget’s disease of bone progression in adults with sqstm1 mutations: the zipp rct. Efficacy and Mechanism Evaluation, pages 1-53, Jun 2024. URL: https://doi.org/10.3310/ftkc2007, doi:10.3310/ftkc2007. This article has 0 citations.
(phillips2024prophylacticzoledronicacid pages 15-17): Jonathan Phillips, Deepak Subedi, Steff C Lewis, Catriona Keerie, and Stuart H Ralston. Prophylactic zoledronic acid therapy to prevent or modify paget’s disease of bone progression in adults with sqstm1 mutations: the zipp rct. Efficacy and Mechanism Evaluation, pages 1-53, Jun 2024. URL: https://doi.org/10.3310/ftkc2007, doi:10.3310/ftkc2007. This article has 0 citations.
(phillips2024prophylacticzoledronicacid pages 39-41): Jonathan Phillips, Deepak Subedi, Steff C Lewis, Catriona Keerie, and Stuart H Ralston. Prophylactic zoledronic acid therapy to prevent or modify paget’s disease of bone progression in adults with sqstm1 mutations: the zipp rct. Efficacy and Mechanism Evaluation, pages 1-53, Jun 2024. URL: https://doi.org/10.3310/ftkc2007, doi:10.3310/ftkc2007. This article has 0 citations.

Artifacts

Edison artifact artifact-00

Citations

rondonortiz2024proximitylabelingreveals pages 1-2
choi2024metabolicstressinduces pages 20-21
rondonortiz2024proximitylabelingreveals pages 5-6
rondonortiz2024proximitylabelingreveals pages 6-10
phillips2024randomisedtrialof pages 1-2
phillips2024prophylacticzoledronicacid pages 7-8
phillips2024prophylacticzoledronicacid pages 42-43
gibertini2023proteinaggregatesand pages 18-19
rondonortiz2024proximitylabelingreveals pages 10-11
gibertini2023proteinaggregatesand pages 8-9
phillips2024prophylacticzoledronicacid pages 23-25
phillips2024prophylacticzoledronicacid pages 15-17
phillips2024prophylacticzoledronicacid pages 39-41
https://doi.org/10.1038/s41419-024-06763-x
https://doi.org/10.1002/pro.4840;
https://doi.org/10.1016/j.jbc.2024.107621
https://doi.org/10.1002/pro.4840
https://doi.org/10.1080/15548627.2024.2374692;
https://doi.org/10.1038/s41467-024-55446-w;
https://doi.org/10.3390/ijms24098456;
https://doi.org/10.1016/j.jbc.2024.107621;
https://doi.org/10.1080/15548627.2024.2374692
https://doi.org/10.1038/s41467-024-55446-w
https://doi.org/10.3310/ftkc2007;
https://doi.org/10.1136/ard-2023-224990
https://doi.org/10.3310/ftkc2007
https://doi.org/10.1038/s41419-024-06763-x,
https://doi.org/10.3390/ijms24098456,
https://doi.org/10.1002/pro.4840,
https://doi.org/10.1016/j.jbc.2024.107621,
https://doi.org/10.1038/s41467-024-55446-w,
https://doi.org/10.1080/15548627.2024.2374692,
https://doi.org/10.1136/ard-2023-224990,
https://doi.org/10.3310/ftkc2007,

📚 Additional Documentation

Notes

(SQSTM1-notes.md)

SQSTM1 (p62 / sequestosome-1) — Gene Review Notes

UniProt: Q13501 (SQSTM_HUMAN), 440 aa. HGNC:11280. Synonyms: ORCA, OSIL, A170, ZIP, p62, EBIAP/p60.

Domain architecture (from UniProt feature table)

PB1 domain (aa 3–102): Phox/Bem1; mediates homo-oligomerization (front-to-back arrays) and hetero-oligomerization with PRKCI/PRKCZ, NBR1, MAP2K5, FHOD3, WDR81. Required (with UBA) for localization into ubiquitin inclusion bodies [UniProt DOMAIN; PMID:12813044; PMID:12887891; PMID:15802564].
ZZ-type zinc finger (aa 123–173): coordinates Zn(2+) (8 binding residues); mediates interaction with RIPK1 [UniProt; PMID:10747026]. Source of GO:0008270 zinc ion binding.
TRAF6-binding (TB) motif (aa 228–233): binds TRAF6, scaffolds NF-kB activation [UniProt MOTIF].
LIR / LC3-interacting region (aa 336–341; broader MAP1LC3B-binding region 321–342): binds ATG8-family proteins (LC3A/B/C, GABARAP/L1/L2); essential for autophagosome recruitment [PMID:17580304; PMID:23908376].
KIR (KEAP1-interacting region) (aa 347–352): binds KEAP1 when phosphorylated at Ser-349 (also reported as Ser-351 in some nomenclatures); competes with NRF2 for KEAP1 Kelch domain [UniProt REGION 347–352; PMID:20452972; PMID:37306101].
UBA domain (aa 389–434): binds (preferentially K63-linked) polyubiquitin; auto-inhibited as a dimer, relieved by phosphorylation (S403/S407), ubiquitination (K420), or acetylation (K420/K435) [PMID:12857745; PMID:15340068; PMID:28322253; PMID:31857589].

Core biology (synthesized)

p62/SQSTM1 is the prototypical selective autophagy receptor. It bridges polyubiquitinated cargo (via UBA) to the nascent autophagosome (via LIR–ATG8 binding), while its PB1 domain drives oligomerization/polymerization that, together with multivalent ubiquitin binding, drives liquid–liquid phase separation into "p62 bodies" — membraneless condensates that concentrate ubiquitinated cargo for engulfment [PMID:29343546 "p62 filaments capture and present ubiquitinated cargos for autophagy"; PMID:29507397 "Polyubiquitin chain-induced p62 phase separation drives autophagic cargo segregation"; PMID:31857589].

Substrate breadth: aggrephagy (ubiquitinated protein aggregates) [PMID:17580304; PMID:16286508; PMID:22017874], plus more specialized selective autophagy: pexophagy (ROS-induced, via ubiquitinated PEX5) PMID:26344566, xenophagy/antibacterial autophagy [PMID:36221902; PMID:27880896], inflammasome/RIPosome control [PMID:30612879; PMID:27498865], and a supporting (non-essential) role in PINK1/Parkin mitophagy — p62 is recruited to depolarized mitochondria and required for their perinuclear clustering, but is dispensable for mitochondrial clearance itself [PMID:20890124 "required for Parkin-induced mitochondrial clustering but not mitophagy"; PMID:20457763].

Signaling scaffold (PB1/ZZ/TB-dependent): NF-kB activation downstream of IL-1/TRAF6, NGF/TrkA, and TNF/RIPK1; binds atypical PKCs (PRKCZ/PRKCI). Also negatively regulates TLR4 signaling by acting on the TRAF6–ECSIT complex PMID:31281713.

KEAP1–NRF2 antioxidant axis: phospho-S349 p62 sequesters KEAP1 into p62 bodies, derepressing NRF2 (NFE2L2) and inducing the antioxidant/phase-II response; SQSTM1 is itself an NRF2 target gene (positive feedback) [PMID:20452972 "p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop"; PMID:23274085; PMID:37306101]. This axis underlies cytoprotection including protection against ferroptosis in HCC cells PMID:26403645.

Endosome organization: ubiquitinated p62 (RNF26/UBE2J1, K435) acts as a perinuclear molecular bridge retaining endosomal vesicles for organized cargo transport PMID:27368102.

Disease: dominant gain/loss SQSTM1 variants cause Paget disease of bone (PDB3), FTD/ALS (FTDALS3), distal myopathy with rimmed vacuoles; recessive loss causes childhood neurodegeneration with ataxia/dystonia/gaze palsy (NADGP). SQSTM1-NUP214 fusion in T-ALL.

Review decisions rationale

Core MF: ubiquitin-modified protein reader activity (GO:0140036) / K63-polyUb-dependent binding (GO:0070530) / ubiquitin binding (GO:0043130); protein-macromolecule adaptor (GO:0030674) bridging cargo to ATG8; molecular condensate scaffold activity (GO:0140693); protein sequestering activity (GO:0140311). All ACCEPT where IDA-supported.
Core BP: aggrephagy (GO:0035973), macroautophagy (GO:0016236), protein targeting to vacuole involved in autophagy (GO:0071211), membraneless organelle assembly (GO:0140694). ACCEPT.
KEAP1/NRF2 & signaling scaffold: real, well-supported but secondary to the receptor function → mostly ACCEPT for direct experimental (positive regulation of autophagy, NF-kB regulation, TLR4 negative regulation) and KEEP_AS_NON_CORE for broad process terms.
bare protein binding (GO:0005515): ~50 IPI annotations from interactome screens and specific partners. Per curation guidelines, uninformative → KEEP_AS_NON_CORE (do not REMOVE experimental IPI).
identical protein binding (GO:0042802): real (PB1-mediated homo-oligomerization), informative-ish → KEEP_AS_NON_CORE (oligomerization is genuine).
mitophagy (GO:0000423) / autophagy of mitochondrion (GO:0000422): p62 contributes to mitophagy (recruited to damaged mito; clustering) but is dispensable for clearance → KEEP_AS_NON_CORE rather than core; experimental IGI/NAS retained, defer to curators.
Reactome cytosol TAS (many duplicates): correct localization, generic pathway context → ACCEPT a representative / KEEP_AS_NON_CORE the redundant ones.
Ensembl GO_REF:0000107 ortholog-transfer IEA (temperature homeostasis, response to ischemia, brown fat cell proliferation, energy homeostasis, synapse/glutamatergic synapse, sperm midpiece, LTP, ionotropic glutamate receptor binding): pleiotropic mouse-derived; biologically plausible but peripheral → KEEP_AS_NON_CORE (not REMOVE; experimentally grounded in mouse orthologs).
GO:0035255 ionotropic glutamate receptor binding / synapse terms: ortholog-transfer; keep non-core.
GO:0046578 regulation of Ras protein signal transduction (NAS, PMID:8618896): early RASA1/Lck-binding paper; weak/historical → KEEP_AS_NON_CORE.
GO:0045944 positive regulation of transcription by Pol II (TAS Reactome NRIF): indirect; KEEP_AS_NON_CORE.
GO:0043065 positive regulation of apoptotic process (TAS Reactome NRIF cell death): indirect/context-specific → KEEP_AS_NON_CORE.

Provenance of key claims

Phase separation / p62 bodies as condensate scaffold: PMID:29343546, PMID:29507397, PMID:31857589, PMID:37306101.
LIR–LC3 bridging: PMID:17580304.
UBA K63-polyUb binding: PMID:12857745, PMID:15340068.
NRF2/KEAP1: PMID:20452972, PMID:37306101, PMID:23274085.
Pexophagy: PMID:26344566.
Xenophagy/inflammasome: PMID:36221902, PMID:30612879, PMID:27498865.
Endosome organization: PMID:27368102.
Mitophagy nuance (dispensable for clearance): PMID:20890124.
TLR4 negative regulation: PMID:31281713.
Acylation/autophagosome recruitment: PMID:37802024.

Review session journal (2026-06-14)

Completed full review of the ~272 GOA annotations. Verified GO IDs used in core_functions/replacements via QuickGO API: GO:0140311 "protein sequestering activity" and GO:0035591 "signaling adaptor activity" confirmed. All other GO IDs taken directly from existing (pre-validated) annotations.
Cached full-text checked for grounding: PMID:29343546, 29507397, 31857589, 37306101, 37802024 (phase separation / p62 bodies), 26344566 (pexophagy), 31281713 (TLR4 negative regulation), 27368102 (endosome organization), 36221902/30612879 (xenophagy/inflammasome), 34893540 (N-terminal Cys oxygen/oxidative-stress sensor → ubiquitin reader/adaptor), 20890124/20457763 (mitophagy nuance), 34471133 (reconstitution of ubiquitin condensate / phagophore assembly site).
Abstract-only (defer to curators, no REMOVE of experimental): 17580304, 20452972, 12857745, 22017874, 23274085, 26403645, 27498865, 25127057, 8650207.
Action policy applied:
- Core MF (ACCEPT, IDA): GO:0140036 ubiquitin-modified protein reader, GO:0070530 K63-polyUb-dependent binding, GO:0043130 ubiquitin binding, GO:0030674 protein-macromolecule adaptor, GO:0140693 molecular condensate scaffold, GO:0140311 protein sequestering. GO:0042802 identical protein binding = genuine PB1 oligomerization, KEEP_AS_NON_CORE.
- Core BP (ACCEPT): GO:0035973 aggrephagy, GO:0016236 macroautophagy, GO:0071211 protein targeting to vacuole in autophagy, GO:0140694 membraneless organelle assembly, GO:0030163 protein catabolic process, GO:0000425 pexophagy.
- Localizations: GO:0005776 autophagosome, GO:0005829 cytosol ACCEPT (core sites of action); the many Reactome cytosol TAS duplicates KEEP_AS_NON_CORE (one representative ACCEPT). Lysosome/late endosome/ER/PML body/inclusion body/aggresome = real but non-core compartments KEEP_AS_NON_CORE.
- Signaling scaffold (NF-kB, NRF2/KEAP1, TLR4): ACCEPT direct experimental MF/BP, KEEP_AS_NON_CORE broad/indirect.
- bare protein binding GO:0005515 (~55 IPI): KEEP_AS_NON_CORE (uninformative but experimental — never REMOVE).
- Ensembl ortholog-transfer IEA GO_REF:0000107 (temperature homeostasis, ischemia, brown fat, energy homeostasis, synapse/glutamatergic synapse, sperm midpiece, LTP, mitochondrion, Lewy body): KEEP_AS_NON_CORE (mouse-grounded, peripheral). Mitochondrion IEA over-broad but plausible.
- GO:0043065 apoptosis (Reactome NRIF TAS), GO:0045944 pos reg transcription (Reactome NRIF), GO:0046578 reg Ras signaling (NAS): indirect/historical, KEEP_AS_NON_CORE.

Pn Notes

(SQSTM1-pn-notes.md)

SQSTM1 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q13501
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-14
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/SQSTM1/SQSTM1-ai-review.yaml
AIGR review HTML: missing - genes/human/SQSTM1/SQSTM1-ai-review.html
Gene notes: present - genes/human/SQSTM1/SQSTM1-notes.md
GOA TSV: present - genes/human/SQSTM1/SQSTM1-goa.tsv
UniProt record: present - genes/human/SQSTM1/SQSTM1-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/SQSTM1.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/SQSTM1.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/SQSTM1/SQSTM1-deep-research-falcon.md

AIGR Review Snapshot

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.
Existing/core annotation action counts: ACCEPT: 122; KEEP_AS_NON_CORE: 150

PN Consistency Summary

Consistency: Strong agreement on the core selective-autophagy-receptor story across deep research, review, PN notes, and node mappings. Review ACCEPTs aggrephagy (GO:0035973), mitophagy (KEEP_AS_NON_CORE — recruitment but dispensable for clearance, PMID:20890124), pexophagy (GO:0000425, IDA PMID:26344566). No contradictions; PN notes (PEX5-ATM, TRAF6/ALFY midbody, bacteria) match review description.
PN story / NEW pressure: PN surfaces three terms absent from GOA/review: GO:0098792 xenophagy (verified real; GOA has none — review only narrates antibacterial autophagy in description), GO:0160247 autophagy cargo adaptor activity (verified; review uses GO:0030674 protein-macromolecule adaptor + GO:0140036 reader instead), and GO:0070628 proteasome binding (verified; PB1/UBA shuttle role). Cargo-adaptor and xenophagy are defensible ADDs (the recurring receptor-MF elevation pattern); proteasome binding is plausible but weaker (PB1/UBA shuttle to proteasome is real but secondary).
Evidence alignment: Strong overlap on ALP rows (Pankiv 17580304, Pilli/Wild xenophagy, ATM-pexophagy 26344566, TRAF6 midbody). PN UPS row 7 cites bare PMID 15340068 (proteasome-shuttle) not in review references.
Verdict: CONSISTENT; defensible ADD of GO:0160247 cargo adaptor activity and GO:0098792 xenophagy to the review.

Full Consistency Review

UniProt: Q13501 (p62/sequestosome-1) · batch: proteostasis-batch-2026-06-14 · review status: COMPLETE (very large, ~3380 lines; ~70 IPI bare-protein-binding entries kept non-core)
PN placement: ALP Autophagy substrate selection|Selective autophagy receptor|{Mitophagy,Pexophagy,Xenophagy,Aggrephagy,Midbody autophagy} + Autophagophore...|component recruitment + UPS Proteasome...|adaptors|PB1|UBA and Ubiquitin and UBL binding|trafficking|selective autophagy|UBA ; PN-node mapping: leaf types mapped → GO:0000423 mitophagy, GO:0000425 pexophagy, GO:0098792 xenophagy, GO:0035973 aggrephagy, GO:0160247 cargo adaptor (midbody); UPS adaptors group → GO:0070628 proteasome binding; all ancestors no_mapping/context_only.
Consistency: Strong agreement on the core selective-autophagy-receptor story across deep research, review, PN notes, and node mappings. Review ACCEPTs aggrephagy (GO:0035973), mitophagy (KEEP_AS_NON_CORE — recruitment but dispensable for clearance, PMID:20890124), pexophagy (GO:0000425, IDA PMID:26344566). No contradictions; PN notes (PEX5-ATM, TRAF6/ALFY midbody, bacteria) match review description.
PN story / NEW pressure: PN surfaces three terms absent from GOA/review: GO:0098792 xenophagy (verified real; GOA has none — review only narrates antibacterial autophagy in description), GO:0160247 autophagy cargo adaptor activity (verified; review uses GO:0030674 protein-macromolecule adaptor + GO:0140036 reader instead), and GO:0070628 proteasome binding (verified; PB1/UBA shuttle role). Cargo-adaptor and xenophagy are defensible ADDs (the recurring receptor-MF elevation pattern); proteasome binding is plausible but weaker (PB1/UBA shuttle to proteasome is real but secondary).
Mapping strategy: Mappings are sound and conservative (ancestors held back). The KEY PATTERN applies: elevate GO:0160247 cargo adaptor over bare protein binding. Review already captures this via GO:0030674; harmonizing to GO:0160247 would align review with PN.
Evidence alignment: Strong overlap on ALP rows (Pankiv 17580304, Pilli/Wild xenophagy, ATM-pexophagy 26344566, TRAF6 midbody). PN UPS row 7 cites bare PMID 15340068 (proteasome-shuttle) not in review references.
Verdict: CONSISTENT; defensible ADD of GO:0160247 cargo adaptor activity and GO:0098792 xenophagy to the review.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-14
review_yaml: genes/human/SQSTM1/SQSTM1-ai-review.yaml
PN workbook rows: 8

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | Miscellaneous function - autophagy component recruitment to autophagophore

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore|Miscellaneous function - autophagy component recruitment to autophagophore
  status=no_mapping scope= GO=[]
  rationale: This PN leaf is an explicit catch-all recruitment bucket rather than a coherent shared GO function or process class. The current members span scaffolding, cargo recruitment, and broad stress or membrane-traffic roles.
- [group] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation|Autophagy component recruitment to autophagophore
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagophore initiation and elongation
  status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
  rationale: This class is a real macroautophagy context, but its descendants include core factors, component buckets, upstream modulators, localization roles, and residual categories. Projecting generic macroautophagy from this ancestor creates TRAPP-like overpropagation, so candidate GO annotations must come from narrower curated nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Mitophagy

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Mitophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000423 mitophagy]
  rationale: This PN path denotes selective-autophagy receptors for mitochondrial cargo. The source category is a mechanistic sub-role within mitophagy, so propagation rather than exact equivalence is the correct scope.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Pexophagy

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Pexophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0000425 pexophagy]
  rationale: This PN path groups receptors for selective autophagic turnover of peroxisomes. The role is part of, but not equivalent to, the full GO pexophagy process, so propagation scope is appropriate.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 4: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Xenophagy

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Xenophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0098792 xenophagy]
  rationale: This PN category captures receptors for selective autophagy of pathogens or pathogen-derived material. The receptor class is narrower than the GO xenophagy process, so this is a propagation mapping.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 5: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0035973 aggrephagy]
  rationale: This PN path denotes receptors that recognize aggregation cargo for the aggrephagy pathway. The category is not identical to the GO process term, but propagation to aggrephagy is appropriate because membership in this receptor class implies direct participation in that process.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 6: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Midbody autophagy

UniProt: Q13501
In branches: ALP, UPS
Notes: Receptor for selective autophagy. Binds to ATG8 and ubiquitinated or degron-contaning substrates. Active in aggrephagy, Ub-dependent mitophagy, Ub-dependent pexophagy, zymophagy, xenophagy, virophagy, and midbody autophagy. Also SQSTM1 bodies (phase separated gels) sequester autophagy-related proteins and serve as a platform for autophagosome formation. Specificity for autophagy of peroxisomes (pexophagy) is provided by ATM phosphorylation of PEX5 at Ser 141, which promotes PEX5 monoubiquitylation at Lys 209, and recognition of ubiquitylated PEX5 by the autophagy adaptor protein p62, directing the autophagosome to peroxisomes to induce pexophagy. Interacts with adaptor protein WDFY3/ALFY form a complex with the ubiquitin E3 ligase TRAF6 and that these proteins, as well as NBR1, are important for efficient clearance of midbody ring derivatives by autophagy.
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- p62/SQSTM1 Binds Directly to Atg8/LC3 to Facilitate Degradation of Ubiquitinated Protein Aggregates by Autophagy - ScienceDirect
- Frontiers | Selective Autophagy Receptor p62/SQSTM1, a Pivotal Player in Stress and Aging | Cell and Developmental Biology (frontiersin.org)
- p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response | Nature Communications
- ATM functions at the peroxisome to induce pexophagy in response to ROS
- The Adaptor Protein p62/SQSTM1 Targets Invading Bacteria to the Autophagy Pathway
- TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody ring degradation by selective autophagy
- p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0160247 autophagy cargo adaptor activity]
  rationale: Midbody-autophagy receptors such as SQSTM1 link ubiquitinated midbody material to the autophagy machinery. GO does not currently expose a dedicated midbody-autophagy process term in the local ontology cache, so the receptor activity term is the best available mapping target.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 7: Ubiquitin Proteasome System | Proteasome and associated proteins | adaptors | PB1 | UBA

UniProt: Q13501
In branches: ALP, UPS
Signature domains: IPR034866
Auxiliary domains: IPR000270, IPR015940, IPR034866
PN references (titles):
- 15340068
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Proteasome and associated proteins|adaptors|PB1|UBA
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower proteasome component, chaperone, adaptor, domain, or isoform subdivision already covered by a curated parent proteasome mapping. No additional direct GO mapping is needed at this node.
- [type] Ubiquitin Proteasome System|Proteasome and associated proteins|adaptors|PB1
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a narrower proteasome component, chaperone, adaptor, domain, or isoform subdivision already covered by a curated parent proteasome mapping. No additional direct GO mapping is needed at this node.
- [group] Ubiquitin Proteasome System|Proteasome and associated proteins|adaptors
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0070628 proteasome binding]
  rationale: This PN group captures proteasome adaptors and shuttle factors. Proteasome binding is the safe shared molecular-function target.
- [class] Ubiquitin Proteasome System|Proteasome and associated proteins
  status=context_only scope=too_broad_to_propagate GO=[GO:0000502 proteasome complex]
  rationale: This class records the proteasome branch context, but descendants include core and regulatory particle subunits, activators, assembly chaperones, adaptors, DUBs, E3 ligases, enzymes, and transcriptional regulators. Propagation should come from narrower nodes.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

PN row 8: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | selective autophagy | UBA

UniProt: Q13501
In branches: ALP, UPS
Signature domains: IPR015940
Auxiliary domains: (none)
PN-node mapping records (path + ancestors):
- [subtype] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|selective autophagy|UBA
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a selective-autophagy or trafficking subdivision under a UPS binding context. The autophagy context is real, but this node is too indirect for automatic GO propagation.
- [type] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking|selective autophagy
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [group] Ubiquitin Proteasome System|Ubiquitin and UBL binding|trafficking
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a UPS taxonomy container. Its descendants mix catalytic roles, complex membership, binding domains, regulators, adaptors, and substrate-context labels, so a single propagating GO assertion would overstate the shared biology.
- [class] Ubiquitin Proteasome System|Ubiquitin and UBL binding
  status=context_only scope=too_broad_to_propagate GO=[GO:0140036 ubiquitin-modified protein reader activity]
  rationale: This class records ubiquitin/UBL-reader context, but the subtree mixes ubiquitin, SUMO, UBL-domain, domain-architecture, catalytic, signaling, trafficking, and nucleic-acid process buckets. It is useful context, not a safe direct propagation.
- [branch] Ubiquitin Proteasome System
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level UPS branch. It is a project taxonomy umbrella rather than a direct GO assertion; UPS propagation must come from manually curated child nodes.

Projected GO annotations (6)

GO:0000423 mitophagy | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Mitophagy
GO:0000425 pexophagy | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Pexophagy
GO:0098792 xenophagy | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Xenophagy
GO:0035973 aggrephagy | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Aggrephagy
GO:0160247 autophagy cargo adaptor activity | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|Midbody autophagy
GO:0070628 proteasome binding | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Ubiquitin Proteasome System|Proteasome and associated proteins|adaptors

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

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: []

SQSTM1

Gene Description

Existing Annotations Review

Core Functions

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.

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.

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.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human SQSTM1 / p62 (Sequestosome-1) — Functional Annotation (UniProt Q13501)

0) Target verification (critical identity check)

1) Key concepts and definitions (current understanding)

1.1 What SQSTM1/p62 is

1.2 “Selective autophagy receptor” for SQSTM1/p62

1.3 Condensates (“p62 bodies”) as a functional organizing principle

2) Molecular mechanisms: domains, motifs, and binding partners

2.1 Core domain architecture and regulated LC3 engagement

2.2 LIR motif (LC3/GABARAP binding): quantitative biochemical evidence (2024)

2.3 PB1 and ZZ domains: regulation and pharmacologic modulation (2024)

2.4 UBA domain (ubiquitin binding) and ubiquitination sites relevant to function

2.5 KIR motif: linking p62 to KEAP1–NRF2 antioxidant signaling

3) Pathways and systems-level roles (recent developments prioritized)

3.1 AMPK–p62–NRF2 coupling during metabolic stress (Autophagy, 2024)

3.2 Stress granule clearance (“granulophagy”): a 2024 mechanistic link to p62 ubiquitination

3.3 Condensate/interactome remodeling under proteotoxic stress and tau aggregation (JBC, 2024)

4) Subcellular localization and where p62 acts

5) Current applications and real-world implementations

5.1 Clinical genetics and prevention trial in SQSTM1 mutation carriers (Paget disease of bone)

5.2 Tooling and reagent standardization (research implementation)

6) Expert opinions and authoritative synthesis (what experts emphasize now)

6.1 p62 as a regulated receptor, not just a passive adaptor

6.2 p62 as a hub connecting proteostasis, redox defense, and stress response

6.3 Condensates/phase organization as a framework for understanding p62 function

7) Relevant statistics and data (recent studies)

8) Summary functional annotation statement (for database-style use)

Evidence summary table

Key figure(s) supporting domain architecture and the LIR accessibility model

Artifacts

Citations

📚 Additional Documentation

Notes

SQSTM1 (p62 / sequestosome-1) — Gene Review Notes

Domain architecture (from UniProt feature table)

Core biology (synthesized)

Review decisions rationale

Provenance of key claims

Review session journal (2026-06-14)

Pn Notes

SQSTM1 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: Autophagy-Lysosome Pathway | Autophagophore initiation and elongation | Autophagy component recruitment to autophagophore | Miscellaneous function - autophagy component recruitment to autophagophore

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Mitophagy

PN row 3: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Pexophagy

PN row 4: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Xenophagy

PN row 5: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Aggrephagy

PN row 6: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | Midbody autophagy

PN row 7: Ubiquitin Proteasome System | Proteasome and associated proteins | adaptors | PB1 | UBA

PN row 8: Ubiquitin Proteasome System | Ubiquitin and UBL binding | trafficking | selective autophagy | UBA

Projected GO annotations (6)

Note

📄 View Raw YAML