id: Q8WUM4 gene_symbol: PDCD6IP product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- PDCD6IP encodes ALIX/AIP1, a Bro1-domain ESCRT accessory adaptor that links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III. ALIX supports MVB/late-endosomal cargo sorting, exosome biogenesis with the syndecan-syntenin pathway, basal autophagic flux and endolysosomal trafficking through ATG12-ATG3-associated regulation, and CEP55-dependent midbody cytokinesis. Viral budding is a well-supported pathogen-exploitation context, while endogenous ALIX roles center on ESCRT adaptor activity in endolysosomal, exosome, and cytokinetic membrane-remodeling pathways. alternative_products: - name: '1' id: Q8WUM4-1 - name: '2' id: Q8WUM4-2 sequence_note: VSP_044860 - name: '3' id: Q8WUM4-3 sequence_note: VSP_057190, VSP_057191 existing_annotations: - term: id: GO:0000281 label: mitotic cytokinesis evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: 'Supported endogenous ALIX cytokinesis/midbody function: mitotic cytokinesis.' action: ACCEPT reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - term: id: GO:0005576 label: extracellular region evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: extracellular region.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: cytoplasm.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005813 label: centrosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: centrosome.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: cytosol.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005923 label: bicellular tight junction evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: bicellular tight junction.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0042470 label: melanosome evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: melanosome.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0090543 label: Flemming body evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: 'Supported ALIX midbody/Flemming body localization: Flemming body.' action: ACCEPT reason: ALIX targets the Flemming body/midbody during cytokinesis through CEP55-dependent recruitment. supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17196169 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17350572 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17853893 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18256029 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18434552 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18511562 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18940611 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19706535 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20176808 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:20670214 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21889351 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21911577 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21988832 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22484091 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22641034 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23088713 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25118280 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25686249 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:26496610 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31413325 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37100772 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:37219487 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0005813 label: centrosome evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: centrosome.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0042470 label: melanosome evidence_type: EXP original_reference_id: PMID:17081065 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: melanosome.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0016236 label: macroautophagy evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Supported ALIX basal autophagy/endolysosomal function: macroautophagy.' action: ACCEPT reason: ATG12-ATG3 and ALIX evidence supports basal autophagic flux and late-endosome function, making macroautophagy a PN-relevant ALIX core context. supported_by: - reference_id: PMID:25686249 supporting_text: Alix is functionally required for efficient basal, but not starvation-induced, autophagy - reference_id: PMID:25686249 supporting_text: Alix deficiency specifically impairs basal autophagy - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Murrow et al. support basal autophagy and endolysosomal trafficking. - term: id: GO:0097734 label: extracellular exosome biogenesis evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome biogenesis.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0061952 label: midbody abscission evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Supported endogenous ALIX cytokinesis/midbody function: midbody abscission.' action: ACCEPT reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - term: id: GO:0000281 label: mitotic cytokinesis evidence_type: IDA original_reference_id: PMID:18641129 qualifier: involved_in review: summary: 'Supported endogenous ALIX cytokinesis/midbody function: mitotic cytokinesis.' action: ACCEPT reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18641129 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0046755 label: viral budding evidence_type: IDA original_reference_id: PMID:18641129 qualifier: involved_in review: summary: 'Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding.' action: KEEP_AS_NON_CORE reason: ALIX can be recruited by viral late domains and supports selected viral budding pathways, but this infection context should not replace endogenous MVB/exosome/cytokinesis/autophagy core functions. supported_by: - reference_id: PMID:14519844 supporting_text: interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX - reference_id: UniProt:Q8WUM4 supporting_text: Involved in HIV-1 virus budding - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Viral budding is well supported as a pathogen-exploitation context. - term: id: GO:0051260 label: protein homooligomerization evidence_type: IDA original_reference_id: PMID:18641129 qualifier: involved_in review: summary: 'Supported specific ALIX molecular interaction/assembly function: protein homooligomerization.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0090543 label: Flemming body evidence_type: IDA original_reference_id: PMID:18641129 qualifier: located_in review: summary: 'Supported ALIX midbody/Flemming body localization: Flemming body.' action: ACCEPT reason: ALIX targets the Flemming body/midbody during cytokinesis through CEP55-dependent recruitment. supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25667979 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0000915 label: actomyosin contractile ring assembly evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: actomyosin contractile ring assembly.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0042641 label: actomyosin evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: actomyosin.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0045199 label: maintenance of epithelial cell apical/basal polarity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: maintenance of epithelial cell apical/basal polarity.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0070830 label: bicellular tight junction assembly evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: bicellular tight junction assembly.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0090559 label: regulation of membrane permeability evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: regulation of membrane permeability.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0036258 label: multivesicular body assembly evidence_type: NAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported ALIX MVB/ESCRT function: multivesicular body assembly.' action: ACCEPT reason: ALIX links cargo/adaptors to CHMP4/ESCRT-III and supports MVB formation/sorting. supported_by: - reference_id: UniProt:Q8WUM4 supporting_text: Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) - reference_id: UniProt:Q8WUM4 supporting_text: Adapter for a subset of ESCRT-III proteins, such as CHMP4 - reference_id: PMID:12860994 supporting_text: CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1 - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: ALIX links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: NAS original_reference_id: PMID:20588296 qualifier: involved_in review: summary: 'Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: ALIX can be recruited by viral late domains and supports selected viral budding pathways, but this infection context should not replace endogenous MVB/exosome/cytokinesis/autophagy core functions. supported_by: - reference_id: PMID:14519844 supporting_text: interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX - reference_id: UniProt:Q8WUM4 supporting_text: Involved in HIV-1 virus budding - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Viral budding is well supported as a pathogen-exploitation context. - term: id: GO:1903561 label: extracellular vesicle evidence_type: HDA original_reference_id: PMID:24769233 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: extracellular vesicle.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0006997 label: nucleus organization evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in negated: true review: summary: 'Retain existing negated PDCD6IP annotation: NOT nucleus organization.' action: ACCEPT reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records - term: id: GO:0007080 label: mitotic metaphase chromosome alignment evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in negated: true review: summary: 'Retain existing negated PDCD6IP annotation: NOT mitotic metaphase chromosome alignment.' action: ACCEPT reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records - term: id: GO:0010824 label: regulation of centrosome duplication evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: regulation of centrosome duplication.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:1901673 label: regulation of mitotic spindle assembly evidence_type: IMP original_reference_id: PMID:20616062 qualifier: involved_in negated: true review: summary: 'Retain existing negated PDCD6IP annotation: NOT regulation of mitotic spindle assembly.' action: ACCEPT reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records - term: id: GO:0070971 label: endoplasmic reticulum exit site evidence_type: IMP original_reference_id: PMID:16957052 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: endoplasmic reticulum exit site.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0048306 label: calcium-dependent protein binding evidence_type: IPI original_reference_id: PMID:23924735 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0090611 label: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway evidence_type: IMP original_reference_id: PMID:22547407 qualifier: involved_in review: summary: 'The ALIX/PAR1 MVB sorting biology is correct but the GO term is obsolete: obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway.' action: MODIFY reason: Replace this obsolete ubiquitin-independent protein-catabolism term with current MVB sorting / late endosome-to-lysosome transport wording. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Modify the obsolete ubiquitin-independent MVB protein-catabolism term to current MVB sorting/endolysosomal sorting wording proposed_replacement_terms: - id: GO:0071985 label: multivesicular body sorting pathway - id: GO:1902774 label: late endosome to lysosome transport - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:22660413 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:1903551 label: regulation of extracellular exosome assembly evidence_type: IMP original_reference_id: PMID:24105262 qualifier: involved_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: regulation of extracellular exosome assembly.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:1903543 label: positive regulation of exosomal secretion evidence_type: IMP original_reference_id: PMID:22660413 qualifier: involved_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: positive regulation of exosomal secretion.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:1903553 label: positive regulation of extracellular exosome assembly evidence_type: IMP original_reference_id: PMID:22660413 qualifier: involved_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: positive regulation of extracellular exosome assembly.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0031871 label: proteinase activated receptor binding evidence_type: IPI original_reference_id: PMID:22547407 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: proteinase activated receptor binding.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0039702 label: viral budding via host ESCRT complex evidence_type: IGI original_reference_id: PMID:24107264 qualifier: involved_in review: summary: 'Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding via host ESCRT complex.' action: KEEP_AS_NON_CORE reason: ALIX can be recruited by viral late domains and supports selected viral budding pathways, but this infection context should not replace endogenous MVB/exosome/cytokinesis/autophagy core functions. supported_by: - reference_id: PMID:14519844 supporting_text: interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX - reference_id: UniProt:Q8WUM4 supporting_text: Involved in HIV-1 virus budding - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Viral budding is well supported as a pathogen-exploitation context. - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:23092844 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0005925 label: focal adhesion evidence_type: HDA original_reference_id: PMID:21423176 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: focal adhesion.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:16501490 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:21276792 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0016020 label: membrane evidence_type: HDA original_reference_id: PMID:19946888 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: membrane.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14519844 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: protein homodimerization activity.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0042803 label: protein homodimerization activity evidence_type: IPI original_reference_id: PMID:14505570 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: protein homodimerization activity.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0001772 label: immunological synapse evidence_type: IDA original_reference_id: PMID:19706535 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: immunological synapse.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19199708 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:12860994 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. - term: id: GO:0070062 label: extracellular exosome evidence_type: IDA original_reference_id: PMID:15326289 qualifier: located_in review: summary: 'Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome.' action: ACCEPT reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. supported_by: - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-3159232 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: cytosol.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9688832 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: cytosol.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9948266 qualifier: located_in review: summary: 'Plausible broad or peripheral ALIX/PDCD6IP context: cytosol.' action: KEEP_AS_NON_CORE reason: This annotation reflects broad localization, similarity-based epithelial/tight-junction biology, or a secondary ALIX context rather than the core ESCRT adaptor roles in MVB/exosome/cytokinesis/autophagy. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Keep broad or peripheral locations/processes such as cytoplasm/cytosol, extracellular region, centrosome, melanosome, tight junction, focal adhesion, immunological synapse, ER exit site, membrane, actomyosin/tight-junction polarity, and centrosome duplication as non-core - term: id: GO:0048306 label: calcium-dependent protein binding evidence_type: IPI original_reference_id: PMID:18256029 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0048306 label: calcium-dependent protein binding evidence_type: IPI original_reference_id: PMID:19520058 qualifier: enables review: summary: 'Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding.' action: ACCEPT reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:11883939 qualifier: enables review: summary: 'Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding.' action: MARK_AS_OVER_ANNOTATED reason: The interactions are real but GO:0005515 loses the biologically meaningful ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain contexts. supported_by: - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: The meaningful interactions are ALIX-CHMP4, ALIX-TSG101, ALIX-CEP55, ALIX-PAR1, ALIX-syntenin/syndecan, ALIX-ATG12-ATG3, ALIX-PDCD6, and viral late-domain binding, not generic protein binding. references: - 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:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: PMID:11883939 title: ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner. findings: [] - id: PMID:12860994 title: The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. findings: [] - id: PMID:14505570 title: The protein network of HIV budding. findings: [] - id: PMID:14519844 title: Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins. findings: [] - id: PMID:15326289 title: Identification and proteomic profiling of exosomes in human urine. findings: [] - id: PMID:16501490 title: Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery. findings: [] - id: PMID:16957052 title: The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. findings: [] - id: PMID:17081065 title: Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. findings: [] - id: PMID:17196169 title: ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner. findings: [] - id: PMID:17350572 title: Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. findings: [] - id: PMID:17853893 title: Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. findings: [] - id: PMID:18256029 title: 'Identification of Alix-type and Non-Alix-type ALG-2-binding sites in human phospholipid scramblase 3: differential binding to an alternatively spliced isoform and amino acid-substituted mutants.' findings: [] - id: PMID:18434552 title: The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis. findings: [] - id: PMID:18511562 title: ALIX-CHMP4 interactions in the human ESCRT pathway. findings: [] - id: PMID:18641129 title: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release. findings: [] - id: PMID:18940611 title: 'Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism.' findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19199708 title: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). findings: [] - id: PMID:19520058 title: Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101. findings: [] - id: PMID:19706535 title: Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse. findings: [] - id: PMID:19946888 title: Defining the membrane proteome of NK cells. findings: [] - id: PMID:20176808 title: TEX14 interacts with CEP55 to block cell abscission. findings: [] - id: PMID:20588296 title: 'Membrane budding and scission by the ESCRT machinery: it''s all in the neck.' findings: [] - id: PMID:20616062 title: Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance. findings: [] - id: PMID:20670214 title: Identification and biophysical assessment of the molecular recognition mechanisms between the human haemopoietic cell kinase Src homology domain 3 and ALG-2-interacting protein X. findings: [] - id: PMID:21276792 title: Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells. findings: [] - id: PMID:21423176 title: "Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for \u03B2-Pix in negative regulation\ \ of focal adhesion maturation." findings: [] - id: PMID:21889351 title: The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release. findings: [] - id: PMID:21911577 title: A physical interaction network of dengue virus and human proteins. findings: [] - id: PMID:21988832 title: Toward an understanding of the protein interaction network of the human liver. findings: [] - id: PMID:22484091 title: Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B. findings: [] - id: PMID:22547407 title: ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. findings: [] - id: PMID:22641034 title: Structural recognition mechanisms between human Src homology domain 3 (SH3) and ALG-2-interacting protein X (Alix). findings: [] - id: PMID:22660413 title: Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. findings: [] - id: PMID:23088713 title: Protein interactions of the transcription factor Hoxa1. findings: [] - id: PMID:23092844 title: Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:23924735 title: VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I. findings: [] - id: PMID:24105262 title: Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. findings: [] - id: PMID:24107264 title: ESCRT requirements for EIAV budding. findings: [] - id: PMID:24769233 title: 'Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.' findings: [] - id: PMID:25118280 title: Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal targeting of CD4 receptor. findings: [] - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:25667979 title: Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2. findings: [] - id: PMID:25686249 title: ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function. findings: [] - id: PMID:26496610 title: A human interactome in three quantitative dimensions organized by stoichiometries and abundances. findings: [] - id: PMID:31413325 title: HENA, heterogeneous network-based data set for Alzheimer's disease. findings: [] - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' findings: [] - id: PMID:37100772 title: Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs. findings: [] - id: PMID:37219487 title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions. findings: [] - id: Reactome:R-HSA-3159232 title: Recruitment Of HIV Virion Budding Machinery findings: [] - id: Reactome:R-HSA-9688832 title: MLKL binds PDCD6IP and SDCBP findings: [] - id: Reactome:R-HSA-9948266 title: NS3 binds PDCD6IP findings: [] - id: UniProt:Q8WUM4 title: UniProtKB entry Q8WUM4 (PDCD6IP/ALIX) findings: - statement: ALIX is a multifunctional ESCRT adaptor involved in MVB cargo sorting, exosome biogenesis, cytokinesis, and viral budding contexts. supporting_text: Adapter for a subset of ESCRT-III proteins, such as CHMP4 - id: file:human/PDCD6IP/PDCD6IP-notes.md title: PDCD6IP review notes findings: - statement: PDCD6IP/ALIX core function is ESCRT adaptor activity, not undifferentiated protein binding. supporting_text: The core biological picture is not undifferentiated binding core_functions: - description: ALIX/PDCD6IP acts as a Bro1-domain ESCRT adaptor that binds cargo/adaptor motifs and recruits CHMP4/ESCRT-III, supporting MVB assembly/sorting, PAR1 MVB-lysosomal sorting, exosome biogenesis/assembly/secretion, and basal autophagy/endolysosomal trafficking. molecular_function: id: GO:0031871 label: proteinase activated receptor binding directly_involved_in: - id: GO:0036258 label: multivesicular body assembly - id: GO:0097734 label: extracellular exosome biogenesis - id: GO:1903551 label: regulation of extracellular exosome assembly - id: GO:1903543 label: positive regulation of exosomal secretion - id: GO:1903553 label: positive regulation of extracellular exosome assembly - id: GO:0016236 label: macroautophagy locations: - id: GO:0070062 label: extracellular exosome supported_by: - reference_id: UniProt:Q8WUM4 supporting_text: Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) - reference_id: UniProt:Q8WUM4 supporting_text: Adapter for a subset of ESCRT-III proteins, such as CHMP4 - reference_id: PMID:12860994 supporting_text: CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1 - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: ALIX links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III - reference_id: PMID:22660413 supporting_text: Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs - reference_id: UniProt:Q8WUM4 supporting_text: Regulates exosome biogenesis in concert with SDC1/4 and SDCBP - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Baietti et al. support the exosome role - reference_id: PMID:25686249 supporting_text: Alix is functionally required for efficient basal, but not starvation-induced, autophagy - reference_id: PMID:25686249 supporting_text: Alix deficiency specifically impairs basal autophagy - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Murrow et al. support basal autophagy and endolysosomal trafficking. - description: ALIX self-association and CEP55/ESCRT interactions target it to the Flemming body/midbody, where it supports ESCRT-dependent completion of cytokinesis and midbody abscission. molecular_function: id: GO:0042803 label: protein homodimerization activity directly_involved_in: - id: GO:0000281 label: mitotic cytokinesis - id: GO:0061952 label: midbody abscission - id: GO:0051260 label: protein homooligomerization locations: - id: GO:0090543 label: Flemming body supported_by: - reference_id: PMID:18641129 supporting_text: Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release - reference_id: UniProt:Q8WUM4 supporting_text: Required for completion of cytokinesis - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: Morita et al. support the cytokinesis/midbody role. - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported - description: ALIX has specific calcium-dependent interaction biology through PDCD6/ALG-2 and related ESCRT adaptor contacts; these interactions are meaningful when curated specifically rather than as generic protein binding. molecular_function: id: GO:0048306 label: calcium-dependent protein binding supported_by: - reference_id: PMID:22547407 supporting_text: ALIX binds to a YPX3L motif of PAR1 - reference_id: UniProt:Q8WUM4 supporting_text: Interacts with PDCD6 in a calcium-dependent manner - reference_id: UniProt:Q8WUM4 supporting_text: Self-associates - reference_id: file:human/PDCD6IP/PDCD6IP-notes.md supporting_text: specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported proposed_new_terms: [] suggested_questions: - question: Can ALIX GO annotations separate endogenous MVB/exosome/cytokinesis/autophagy roles from pathogen-hijacked viral budding without losing the shared ESCRT membrane-remodeling mechanism? - question: Should ALIX-PAR1 ubiquitin-independent sorting be represented by a current non-obsolete GO term more specific than generic MVB sorting? - question: Which of the many ALIX interaction annotations should be recast as specific cargo/adaptor-binding activities rather than GO:0005515 protein binding? suggested_experiments: - description: Use endogenous ALIX depletion/rescue with Bro1, V-domain, PRD, CEP55-binding, CHMP4-binding, and PDCD6-binding mutants while measuring PAR1 degradation, exosome release, basal autophagy flux, and cytokinesis completion in parallel. hypothesis: Distinct ALIX domains will separate MVB/exosome/autophagy functions from midbody cytokinesis while preserving the common CHMP4/ESCRT-III adaptor mechanism. - description: Re-annotate major ALIX interactors by testing whether specific interactions are required for a defined ESCRT output rather than only co-immunoprecipitation or interactome detection. hypothesis: Most GO:0005515 records will resolve into a smaller set of specific adaptor/cargo-binding functions or non-core physical interactions.