PDCD6IP

UniProt ID: Q8WUM4
Organism: Homo sapiens
Review Status: COMPLETE
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Gene 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.

Existing Annotations Review

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.
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.

Core Functions

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:
proteinase activated receptor binding
Directly Involved In:
multivesicular body assembly extracellular exosome biogenesis regulation of extracellular exosome assembly positive regulation of exosomal secretion positive regulation of extracellular exosome assembly macroautophagy
Cellular Locations:
extracellular exosome
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
  • 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
  • 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.

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:
protein homodimerization activity
Directly Involved In:
mitotic cytokinesis midbody abscission protein homooligomerization
Cellular Locations:
Flemming body
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.
  • 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

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:
calcium-dependent protein binding
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

References

GO_REF:0000024
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000117
Electronic Gene Ontology annotations created by ARBA machine learning models
PMID:11883939
ALG-2 interacts with the amino-terminal domain of annexin XI in a Ca(2+)-dependent manner.
PMID:12860994
The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting.
PMID:14505570
The protein network of HIV budding.
PMID:14519844
Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins.
PMID:15326289
Identification and proteomic profiling of exosomes in human urine.
PMID:16501490
Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery.
PMID:16957052
The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A.
PMID:17081065
Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.
PMID:17196169
ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner.
PMID:17350572
Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding.
PMID:17853893
Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis.
PMID:18256029
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.
PMID:18434552
The Bro1-related protein HD-PTP/PTPN23 is required for endosomal cargo sorting and multivesicular body morphogenesis.
PMID:18511562
ALIX-CHMP4 interactions in the human ESCRT pathway.
PMID:18641129
Differential requirements for Alix and ESCRT-III in cytokinesis and HIV-1 release.
PMID:18940611
Structural basis for Ca2+ -dependent formation of ALG-2/Alix peptide complex: Ca2+/EF3-driven arginine switch mechanism.
PMID:19056867
Large-scale proteomics and phosphoproteomics of urinary exosomes.
PMID:19199708
Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT).
PMID:19520058
Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that bridges Alix and TSG101.
PMID:19706535
Galectin-3 negatively regulates TCR-mediated CD4+ T-cell activation at the immunological synapse.
PMID:19946888
Defining the membrane proteome of NK cells.
PMID:20176808
TEX14 interacts with CEP55 to block cell abscission.
PMID:20588296
Membrane budding and scission by the ESCRT machinery: it's all in the neck.
PMID:20616062
Human ESCRT-III and VPS4 proteins are required for centrosome and spindle maintenance.
PMID:20670214
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.
PMID:21276792
Morphologic and proteomic characterization of exosomes released by cultured extravillous trophoblast cells.
PMID:21423176
Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation.
PMID:21889351
The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release.
PMID:21911577
A physical interaction network of dengue virus and human proteins.
PMID:21988832
Toward an understanding of the protein interaction network of the human liver.
PMID:22484091
Two distinct binding modes define the interaction of Brox with the C-terminal tails of CHMP5 and CHMP4B.
PMID:22547407
ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting.
PMID:22641034
Structural recognition mechanisms between human Src homology domain 3 (SH3) and ALG-2-interacting protein X (Alix).
PMID:22660413
Syndecan-syntenin-ALIX regulates the biogenesis of exosomes.
PMID:23088713
Protein interactions of the transcription factor Hoxa1.
PMID:23092844
Monitoring the Rab27 associated exosome pathway using nanoparticle tracking analysis.
PMID:23533145
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
PMID:23924735
VPS37 isoforms differentially modulate the ternary complex formation of ALIX, ALG-2, and ESCRT-I.
PMID:24105262
Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles.
PMID:24107264
ESCRT requirements for EIAV budding.
PMID:24769233
Proteomic analysis of cerebrospinal fluid extracellular vesicles: a comprehensive dataset.
PMID:25118280
Interaction of HIV-1 Nef protein with the host protein Alix promotes lysosomal targeting of CD4 receptor.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:25667979
Structural analysis of the complex between penta-EF-hand ALG-2 protein and Sec31A peptide reveals a novel target recognition mechanism of ALG-2.
PMID:25686249
ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function.
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
PMID:31413325
HENA, heterogeneous network-based data set for Alzheimer's disease.
PMID:31515488
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
PMID:35271311
OpenCell: Endogenous tagging for the cartography of human cellular organization.
PMID:37100772
Large-scale phage-based screening reveals extensive pan-viral mimicry of host short linear motifs.
PMID:37219487
Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.
Reactome:R-HSA-3159232
Recruitment Of HIV Virion Budding Machinery
Reactome:R-HSA-9688832
MLKL binds PDCD6IP and SDCBP
Reactome:R-HSA-9948266
NS3 binds PDCD6IP
UniProt:Q8WUM4
UniProtKB entry Q8WUM4 (PDCD6IP/ALIX)
  • ALIX is a multifunctional ESCRT adaptor involved in MVB cargo sorting, exosome biogenesis, cytokinesis, and viral budding contexts.
    "Adapter for a subset of ESCRT-III proteins, such as CHMP4"
file:human/PDCD6IP/PDCD6IP-notes.md
PDCD6IP review notes
  • PDCD6IP/ALIX core function is ESCRT adaptor activity, not undifferentiated protein binding.
    "The core biological picture is not undifferentiated binding"

Suggested Questions for Experts

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?

Suggested Experiments

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.

📚 Additional Documentation

Notes

(PDCD6IP-notes.md)

PDCD6IP notes

Review focus

PDCD6IP encodes ALIX/AIP1, a Bro1-domain ESCRT accessory/adaptor protein. The key curation issue is that GOA contains many generic protein-binding records and many pathway contexts. The core biological picture is not undifferentiated binding: ALIX links cargo/adaptors and membrane-remodeling sites to CHMP4/ESCRT-III, supporting MVB/late-endosomal sorting, exosome biogenesis, midbody cytokinesis, membrane repair, and selected viral-budding pathways.

Direct evidence

  • UniProt summarizes ALIX as a multifunctional ESCRT-associated adaptor: a "Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB)" and an "Adapter for a subset of ESCRT-III proteins, such as CHMP4" [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"].
  • Katoh et al. identified the ALIX-CHMP4 connection in the endocytic/MVB pathway and concluded that "CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1" PMID:12860994.
  • Dores et al. support cargo-specific MVB/lysosomal sorting: activated PAR1 sorts into MVB ILVs through an ALIX/ESCRT-III pathway independent of receptor ubiquitination, and "ALIX binds to a YPX3L motif of PAR1 and recruits ESCRT-III to mediate MVB/lysosomal sorting" PMID:22547407.
  • Baietti et al. support the exosome role: syntenin interacts with ALIX and "Syntenin exosomes depend on the availability of heparan sulphate, syndecans, ALIX and ESCRTs" PMID:22660413.
  • Morita et al. support the cytokinesis/midbody role. The abstract states that the "ESCRT-III-binding protein Alix is recruited to the midbody of dividing cells through binding Cep55" and that interfering with Alix/Cep55/ESCRT-III/TSG101 strongly inhibits cytokinesis PMID:18641129.
  • Viral budding is well supported as a pathogen-exploitation context. Earlier HIV/EIAV work found that "interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX" and that EIAV YPDL-type L-domain function depends on AIP-1/ALIX PMID:14519844.
  • Murrow et al. support basal autophagy and endolysosomal trafficking. They found that ATG12-ATG3 interacts with ALIX and controls ALIX-mediated late endosome distribution, exosome biogenesis, and viral budding; they also state that "Alix is functionally required for efficient basal, but not starvation-induced, autophagy" PMID:25686249.

Annotation decisions

  • Accept as core: MVB assembly / MVB-lysosomal sorting, exosome biogenesis/assembly/secretion, macroautophagy or basal autophagic flux where tied to ALIX/ATG12-ATG3 endolysosomal function, cytokinesis/midbody abscission/Flemming body, and specific molecular functions such as calcium-dependent protein binding, proteinase activated receptor binding, and homodimerization when supported.
  • Keep viral budding as non-core rather than the primary function. It is a strong microbial-infection/pathogen-hijacking context, but the endogenous ALIX roles are ESCRT adaptor functions in MVB/exosome/cytokinesis/autophagy.
  • Mark GO:0005515 protein binding as over-annotated. 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.
  • Retain the NOT annotations for nucleus organization, metaphase chromosome alignment, and mitotic spindle assembly as negated/non-core records; they should not be converted into positive PDCD6IP functions.
  • 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 unless directly tied to the core ESCRT adaptor functions.
  • Modify the obsolete ubiquitin-independent MVB protein-catabolism term to current MVB sorting/endolysosomal sorting wording while preserving the PAR1/ALIX-specific biology.

Description cleanup note

The YAML description field was revised to keep it as a standalone biological summary. Project-specific curation framing moved here instead.

  • Moved out of the YAML description: the prior wording framed the endogenous proteostasis-network core as ALIX-mediated ESCRT adaptor activity in endolysosomal/exosome and cytokinetic membrane-remodeling pathways.

Pn Notes

(PDCD6IP-pn-notes.md)

PDCD6IP PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q8WUM4
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-pr-1217 (PR 1217)
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • 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.
  • Existing/core annotation action counts: ACCEPT: 28; KEEP_AS_NON_CORE: 25; MARK_AS_OVER_ANNOTATED: 32; MODIFY: 1

PN Consistency Summary

  • Consistency: Largely consistent. The PN note (ALIX/ATG12-ATG3 recruits ESCRT-III for autophagosome closure) aligns with the review, which ACCEPTs GO:0016236 macroautophagy (ISS) on the strength of PMID:25686249 (ALIX required for basal autophagic flux). The autophagy-closure framing is supported. The leaf being no_mapping (heterogeneous members) is consistent with the review not asserting an autophagy-specific ESCRT-III-localization MF for ALIX.
  • PN story / NEW pressure: PN projects GO:0000045 autophagosome assembly (more_specific_than_existing_goa — GOA/review have the broader GO:0016236 macroautophagy). For ALIX this is more defensible than for the MVB12 subunits because the gene-specific basal-autophagy evidence (PMID:25686249) exists, but the cited support is for basal autophagic flux/late-endosome function rather than phagophore sealing specifically. Conclusion: GO:0000045 is a plausible candidate (not pure over-reach), but the review's macroautophagy ACCEPT already captures the role; adding autophagosome assembly should be expert-gated, not auto-propagated.
  • Evidence alignment: Shared: PMID:25686249 (ATG12-ATG3–ALIX) is a PN reference and the review's macroautophagy anchor. PN also cites closure-regulator and exosome/autophagy reviews; review independently supports MVB/exosome/cytokinesis (PMID:12860994, PMID:22660413, PMID:18641129). Good overlap on the autophagy link.
  • Verdict: Consistent; PN autophagosome-assembly projection is a reasonable candidate but the curated macroautophagy ACCEPT already covers it. No edits required.

Full Consistency Review

  • UniProt: Q8WUM4 · batch: proteostasis-pr-1217 · review status: COMPLETE
  • PN placement: ALP|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex ; PN-node mapping: leaf no_mapping (members mix endosomal-sorting + SNARE genes); "Sealing" group mapped / ok_for_propagation / GO:0000045 autophagosome assembly; class context_only GO:0016236. Projected: GO:0000045 (more_specific_than_existing_goa).
  • Consistency: Largely consistent. The PN note (ALIX/ATG12-ATG3 recruits ESCRT-III for autophagosome closure) aligns with the review, which ACCEPTs GO:0016236 macroautophagy (ISS) on the strength of PMID:25686249 (ALIX required for basal autophagic flux). The autophagy-closure framing is supported. The leaf being no_mapping (heterogeneous members) is consistent with the review not asserting an autophagy-specific ESCRT-III-localization MF for ALIX.
  • PN story / NEW pressure: PN projects GO:0000045 autophagosome assembly (more_specific_than_existing_goa — GOA/review have the broader GO:0016236 macroautophagy). For ALIX this is more defensible than for the MVB12 subunits because the gene-specific basal-autophagy evidence (PMID:25686249) exists, but the cited support is for basal autophagic flux/late-endosome function rather than phagophore sealing specifically. Conclusion: GO:0000045 is a plausible candidate (not pure over-reach), but the review's macroautophagy ACCEPT already captures the role; adding autophagosome assembly should be expert-gated, not auto-propagated.
  • Mapping strategy: Node scoping is sound. The no_mapping leaf correctly avoids over-claiming; the "Sealing" group projecting GO:0000045 is acceptable as candidate for ALIX given basal-autophagy evidence, but should remain more_specific candidate rather than displacing the curated macroautophagy call.
  • Evidence alignment: Shared: PMID:25686249 (ATG12-ATG3–ALIX) is a PN reference and the review's macroautophagy anchor. PN also cites closure-regulator and exosome/autophagy reviews; review independently supports MVB/exosome/cytokinesis (PMID:12860994, PMID:22660413, PMID:18641129). Good overlap on the autophagy link.
  • Verdict: Consistent; PN autophagosome-assembly projection is a reasonable candidate but the curated macroautophagy ACCEPT already covers it. No edits required.

PN Dossier Context

  • review_batch: proteostasis-pr-1217
  • review_yaml: genes/human/PDCD6IP/PDCD6IP-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Autophagy-Lysosome Pathway | Autophagosome closure maturation and lysosome fusion | Sealing of autophagophore membrane | Localization of the ESCRT-III complex

  • UniProt: Q8WUM4
  • In branches: ALP
  • Notes: Binds to ATG13-ATG3 complexes to recruit ESCRT-III for autophagosome closure
  • PN references (titles):
    • Cells | Free Full-Text | Key Regulators of Autophagosome Closure (mdpi.com)
    • Synergies in exosomes and autophagy pathways for cellular homeostasis and metastasis of tumor cells | Cell & Bioscience | Full Text (biomedcentral.com)
    • ATG12–ATG3 interacts with Alix to promote basal autophagic flux and late endosome function | Nature Cell Biology
  • PN-node mapping records (path + ancestors):
    • [type] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane|Localization of the ESCRT-III complex
      status=no_mapping scope= GO=[]
      rationale: This PN leaf groups factors that affect ESCRT-III localization during sealing, but the current member set mixes endosomal sorting and SNARE trafficking genes rather than one clean shared autophagy-specific GO term.
    • [group] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0000045 autophagosome assembly]
      rationale: This group captures autophagophore closure/sealing, a late step in autophagosome assembly. Autophagosome assembly is the safer process target than autophagosome-lysosome fusion.
    • [class] Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion
      status=context_only scope=too_broad_to_propagate GO=[GO:0016236 macroautophagy]
      rationale: This class is a late macroautophagy context, but the subtree mixes docking, fusion, localization, membrane-composition, and unknown late-stage roles. The class-level relation is useful for display while propagation is restricted to narrower mechanism nodes.
    • [branch] Autophagy-Lysosome Pathway
      status=no_mapping scope= GO=[]
      rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (1)

  • GO:0000045 autophagosome assembly | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=Autophagy-Lysosome Pathway|Autophagosome closure maturation and lysosome fusion|Sealing of autophagophore membrane

Note

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

📄 View Raw YAML

 
id: 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.