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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000281 mitotic cytokinesis | IBA GO_REF:0000033 | ACCEPT | Summary: Supported endogenous ALIX cytokinesis/midbody function: mitotic cytokinesis. Reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. Supporting Evidence: PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release UniProt:Q8WUM4 Required for completion of cytokinesis file:human/PDCD6IP/PDCD6IP-notes.md Morita et al. support the cytokinesis/midbody role. |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: extracellular region. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005737 cytoplasm | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: cytoplasm. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: centrosome. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005829 cytosol | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: cytosol. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005923 bicellular tight junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: bicellular tight junction. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: melanosome. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0090543 Flemming body | IEA GO_REF:0000044 | ACCEPT | Summary: Supported ALIX midbody/Flemming body localization: Flemming body. Reason: ALIX targets the Flemming body/midbody during cytokinesis through CEP55-dependent recruitment. Supporting Evidence: PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release UniProt:Q8WUM4 Required for completion of cytokinesis file:human/PDCD6IP/PDCD6IP-notes.md Morita et al. support the cytokinesis/midbody role. |
| GO:0005515 protein binding | IPI PMID:17196169 ALG-2 directly binds Sec31A and localizes at endoplasmic ret... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:17350572 Structural and biochemical studies of ALIX/AIP1 and its role... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:17853893 Human ESCRT and ALIX proteins interact with proteins of the ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:18256029 Identification of Alix-type and Non-Alix-type ALG-2-binding ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:18434552 The Bro1-related protein HD-PTP/PTPN23 is required for endos... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:18511562 ALIX-CHMP4 interactions in the human ESCRT pathway. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:18940611 Structural basis for Ca2+ -dependent formation of ALG-2/Alix... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:19706535 Galectin-3 negatively regulates TCR-mediated CD4+ T-cell act... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:20176808 TEX14 interacts with CEP55 to block cell abscission. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:20670214 Identification and biophysical assessment of the molecular r... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:21889351 The Phe105 loop of Alix Bro1 domain plays a key role in HIV-... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:21911577 A physical interaction network of dengue virus and human pro... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:22484091 Two distinct binding modes define the interaction of Brox wi... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:22641034 Structural recognition mechanisms between human Src homology... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:23088713 Protein interactions of the transcription factor Hoxa1. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:25118280 Interaction of HIV-1 Nef protein with the host protein Alix ... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:25686249 ATG12-ATG3 interacts with Alix to promote basal autophagic f... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:26496610 A human interactome in three quantitative dimensions organiz... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:31413325 HENA, heterogeneous network-based data set for Alzheimer's d... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0005813 centrosome | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: centrosome. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0042470 melanosome | EXP PMID:17081065 Proteomic and bioinformatic characterization of the biogenes... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: melanosome. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0016236 macroautophagy | ISS GO_REF:0000024 | ACCEPT | Summary: Supported ALIX basal autophagy/endolysosomal function: macroautophagy. Reason: ATG12-ATG3 and ALIX evidence supports basal autophagic flux and late-endosome function, making macroautophagy a PN-relevant ALIX core context. Supporting Evidence: PMID:25686249 Alix is functionally required for efficient basal, but not starvation-induced, autophagy PMID:25686249 Alix deficiency specifically impairs basal autophagy file:human/PDCD6IP/PDCD6IP-notes.md Murrow et al. support basal autophagy and endolysosomal trafficking. |
| GO:0097734 extracellular exosome biogenesis | ISS GO_REF:0000024 | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome biogenesis. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0061952 midbody abscission | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Supported endogenous ALIX cytokinesis/midbody function: midbody abscission. Reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. Supporting Evidence: PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release UniProt:Q8WUM4 Required for completion of cytokinesis file:human/PDCD6IP/PDCD6IP-notes.md Morita et al. support the cytokinesis/midbody role. |
| GO:0000281 mitotic cytokinesis | IDA PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine... | ACCEPT | Summary: Supported endogenous ALIX cytokinesis/midbody function: mitotic cytokinesis. Reason: ALIX is recruited to the midbody through CEP55 and is required for completion of cytokinesis/midbody abscission. Supporting Evidence: PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release UniProt:Q8WUM4 Required for completion of cytokinesis file:human/PDCD6IP/PDCD6IP-notes.md Morita et al. support the cytokinesis/midbody role. |
| GO:0005515 protein binding | IPI PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0046755 viral budding | IDA PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine... | KEEP AS NON CORE | Summary: Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding. 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. Supporting Evidence: PMID:14519844 interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX UniProt:Q8WUM4 Involved in HIV-1 virus budding file:human/PDCD6IP/PDCD6IP-notes.md Viral budding is well supported as a pathogen-exploitation context. |
| GO:0051260 protein homooligomerization | IDA PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: protein homooligomerization. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0090543 Flemming body | IDA PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokine... | ACCEPT | Summary: Supported ALIX midbody/Flemming body localization: Flemming body. Reason: ALIX targets the Flemming body/midbody during cytokinesis through CEP55-dependent recruitment. Supporting Evidence: PMID:18641129 Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release UniProt:Q8WUM4 Required for completion of cytokinesis file:human/PDCD6IP/PDCD6IP-notes.md Morita et al. support the cytokinesis/midbody role. |
| GO:0005515 protein binding | IPI PMID:25667979 Structural analysis of the complex between penta-EF-hand ALG... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0000915 actomyosin contractile ring assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: actomyosin contractile ring assembly. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0042641 actomyosin | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: actomyosin. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0045199 maintenance of epithelial cell apical/basal polarity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: maintenance of epithelial cell apical/basal polarity. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0070830 bicellular tight junction assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: bicellular tight junction assembly. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0090559 regulation of membrane permeability | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: regulation of membrane permeability. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0036258 multivesicular body assembly | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | ACCEPT | Summary: Supported ALIX MVB/ESCRT function: multivesicular body assembly. Reason: ALIX links cargo/adaptors to CHMP4/ESCRT-III and supports MVB formation/sorting. Supporting Evidence: UniProt:Q8WUM4 Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) UniProt:Q8WUM4 Adapter for a subset of ESCRT-III proteins, such as CHMP4 PMID:12860994 CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1 PMID:22547407 ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting file:human/PDCD6IP/PDCD6IP-notes.md ALIX links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III |
| GO:0039702 viral budding via host ESCRT complex | NAS PMID:20588296 Membrane budding and scission by the ESCRT machinery: it's a... | KEEP AS NON CORE | Summary: Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding via host ESCRT complex. 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. Supporting Evidence: PMID:14519844 interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX UniProt:Q8WUM4 Involved in HIV-1 virus budding file:human/PDCD6IP/PDCD6IP-notes.md Viral budding is well supported as a pathogen-exploitation context. |
| GO:1903561 extracellular vesicle | HDA PMID:24769233 Proteomic analysis of cerebrospinal fluid extracellular vesi... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: extracellular vesicle. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0006997 nucleus organization | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Retain existing negated PDCD6IP annotation: NOT nucleus organization. Reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records |
| GO:0007080 mitotic metaphase chromosome alignment | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Retain existing negated PDCD6IP annotation: NOT mitotic metaphase chromosome alignment. Reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records |
| GO:0010824 regulation of centrosome duplication | IMP PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: regulation of centrosome duplication. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:1901673 regulation of mitotic spindle assembly | IMP NOT PMID:20616062 Human ESCRT-III and VPS4 proteins are required for centrosom... | ACCEPT | Summary: Retain existing negated PDCD6IP annotation: NOT regulation of mitotic spindle assembly. Reason: This is an explicit NOT annotation and should not be interpreted as a positive PDCD6IP cell-cycle/nuclear function. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records |
| GO:0070971 endoplasmic reticulum exit site | IMP PMID:16957052 The Ca2+-binding protein ALG-2 is recruited to endoplasmic r... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: endoplasmic reticulum exit site. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0048306 calcium-dependent protein binding | IPI PMID:23924735 VPS37 isoforms differentially modulate the ternary complex f... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0090611 obsolete ubiquitin-independent protein catabolic process via the multivesicular body sorting pathway | IMP PMID:22547407 ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubi... | MODIFY | 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. Reason: Replace this obsolete ubiquitin-independent protein-catabolism term with current MVB sorting / late endosome-to-lysosome transport wording. Proposed replacements: multivesicular body sorting pathway late endosome to lysosome transport Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting file:human/PDCD6IP/PDCD6IP-notes.md Modify the obsolete ubiquitin-independent MVB protein-catabolism term to current MVB sorting/endolysosomal sorting wording |
| GO:0005515 protein binding | IPI PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:1903551 regulation of extracellular exosome assembly | IMP PMID:24105262 Analysis of ESCRT functions in exosome biogenesis, compositi... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: regulation of extracellular exosome assembly. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:1903543 positive regulation of exosomal secretion | IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: positive regulation of exosomal secretion. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:1903553 positive regulation of extracellular exosome assembly | IMP PMID:22660413 Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: positive regulation of extracellular exosome assembly. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0031871 proteinase activated receptor binding | IPI PMID:22547407 ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubi... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: proteinase activated receptor binding. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0039702 viral budding via host ESCRT complex | IGI PMID:24107264 ESCRT requirements for EIAV budding. | KEEP AS NON CORE | Summary: Supported but non-core pathogen-exploitation ALIX viral-budding context: viral budding via host ESCRT complex. 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. Supporting Evidence: PMID:14519844 interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX UniProt:Q8WUM4 Involved in HIV-1 virus budding file:human/PDCD6IP/PDCD6IP-notes.md Viral budding is well supported as a pathogen-exploitation context. |
| GO:0070062 extracellular exosome | IDA PMID:23092844 Monitoring the Rab27 associated exosome pathway using nanopa... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: focal adhesion. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0070062 extracellular exosome | IDA PMID:16501490 Collection, storage, preservation, and normalization of huma... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0070062 extracellular exosome | IDA PMID:21276792 Morphologic and proteomic characterization of exosomes relea... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: membrane. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005515 protein binding | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0042803 protein homodimerization activity | IPI PMID:14519844 Divergent retroviral late-budding domains recruit vacuolar p... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: protein homodimerization activity. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0005515 protein binding | IPI PMID:14505570 The protein network of HIV budding. | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0042803 protein homodimerization activity | IPI PMID:14505570 The protein network of HIV budding. | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: protein homodimerization activity. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0001772 immunological synapse | IDA PMID:19706535 Galectin-3 negatively regulates TCR-mediated CD4+ T-cell act... | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: immunological synapse. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0005515 protein binding | IPI PMID:12860994 The ALG-2-interacting protein Alix associates with CHMP4b, a... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
| GO:0070062 extracellular exosome | IDA PMID:15326289 Identification and proteomic profiling of exosomes in human ... | ACCEPT | Summary: Supported ALIX exosome/extracellular-vesicle function or location: extracellular exosome. Reason: ALIX functions with syntenin/syndecans and ESCRTs in exosome biogenesis/assembly/secretion, and extracellular exosome localization is consistent with this core role. Supporting Evidence: PMID:22660413 Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs UniProt:Q8WUM4 Regulates exosome biogenesis in concert with SDC1/4 and SDCBP file:human/PDCD6IP/PDCD6IP-notes.md Baietti et al. support the exosome role |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3159232 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: cytosol. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9688832 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: cytosol. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9948266 | KEEP AS NON CORE | Summary: Plausible broad or peripheral ALIX/PDCD6IP context: cytosol. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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 |
| GO:0048306 calcium-dependent protein binding | IPI PMID:18256029 Identification of Alix-type and Non-Alix-type ALG-2-binding ... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0048306 calcium-dependent protein binding | IPI PMID:19520058 Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent ad... | ACCEPT | Summary: Supported specific ALIX molecular interaction/assembly function: calcium-dependent protein binding. Reason: This term is more informative than generic protein binding and is supported by ALIX-specific PAR1, PDCD6/calcium, or self-association evidence. Supporting Evidence: PMID:22547407 ALIX binds to a YPX3L motif of PAR1 UniProt:Q8WUM4 Interacts with PDCD6 in a calcium-dependent manner UniProt:Q8WUM4 Self-associates file:human/PDCD6IP/PDCD6IP-notes.md specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported |
| GO:0005515 protein binding | IPI PMID:11883939 ALG-2 interacts with the amino-terminal domain of annexin XI... | MARK AS OVER ANNOTATED | Summary: Generic protein binding is over-annotated for ALIX/PDCD6IP: protein binding. 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. Supporting Evidence: file:human/PDCD6IP/PDCD6IP-notes.md 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. |
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Download this section (compressed HTML)Q: Can ALIX GO annotations separate endogenous MVB/exosome/cytokinesis/autophagy roles from pathogen-hijacked viral budding without losing the shared ESCRT membrane-remodeling mechanism?
Q: Should ALIX-PAR1 ubiquitin-independent sorting be represented by a current non-obsolete GO term more specific than generic MVB sorting?
Q: Which of the many ALIX interaction annotations should be recast as specific cargo/adaptor-binding activities rather than GO:0005515 protein binding?
Experiment: 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.
Experiment: 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.
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