PIGY

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment that PIGY is part of the GPI-GnT complex. This is directly supported by the defining experimental work and by UniProt, which lists PIGY as a component of the complex alongside PIGA, PIGC, PIGH, PIGP, PIGQ and DPM2. Reason: Correct and core; PIGY is an established structural component of the GPI-GnT complex. Supporting Evidence: PMID:16162815 Here, we report that human GPI-GnT requires another component, termed PIG-Y, a 71 amino acid protein with two transmembrane domains. file:human/PIGY/PIGY-uniprot.txt Component of the glycosylphosphatidylinositol-N-
GO:0006506 GPI anchor biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) assignment that PIGY is involved in GPI anchor biosynthesis. As part of the GPI-GnT complex, PIGY participates in the first step of GPI biosynthesis. Reason: Correct and core; this is PIGY's central biological role. Supporting Evidence: file:human/PIGY/PIGY-uniprot.txt participates in the first step of GPI biosynthesis
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic (UniProt SubCell keyword mapping) assignment to the ER membrane, consistent with the experimentally determined subcellular location of PIGY as a multi-pass ER membrane protein. Reason: Correct and core; matches experimental IDA and TAS annotations to the same term. Supporting Evidence: file:human/PIGY/PIGY-uniprot.txt Endoplasmic reticulum membrane
GO:0005515 protein binding	IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	MARK AS OVER ANNOTATED	Summary: IPI protein-protein interaction annotation (IntAct/UniProt) recording binding to PIGA (UniProtKB:P37287). The direct PIGY-PIGA interaction is biologically the most important, being the interaction through which PIGY regulates GPI-GnT catalytic activity; however the bare "protein binding" term is uninformative about function. Reason: Per curation guidelines, bare "protein binding" (GO:0005515) conveys no functional information and should not be retained as a core molecular function. The biologically meaningful content (direct interaction with the catalytic subunit PIGA, regulating complex activity) is captured by the contributes_to GO:0017176 annotation and by the complex membership term. The underlying experimental interaction is genuine, so this is over-annotation rather than an incorrect annotation. Supporting Evidence: PMID:16162815 PIG-Y appeared to be directly associated with PIG-A, implying that PIG-Y is the key molecule that regulates GPI-GnT activity by binding directly to the catalytic subunit PIG-A.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: IPI protein-protein interaction annotations (IntAct) from the HuRI human binary interactome map, recording high-throughput yeast two-hybrid interactions of PIGY with TMEM72 (UniProtKB:A0PK05) and ERG28 (UniProtKB:Q9UKR5). These are systematic-screen hits without an established functional relationship to PIGY's role in GPI-GnT. Reason: Bare "protein binding" (GO:0005515) is uninformative per curation guidelines, and these particular interactors derive from a large-scale binary interactome screen rather than GPI-pathway-focused work, with no demonstrated biological significance for PIGY function. Not core. The experimental interaction data are retained in IntAct; this is over-annotation for the purposes of representing gene function. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome
GO:0006506 GPI anchor biosynthetic process	IEA GO_REF:0000041	ACCEPT	Summary: Electronic (UniPathway vocabulary mapping, UPA00196) assignment to GPI anchor biosynthetic process, consistent with PIGY's role in the first step of GPI biosynthesis. Reason: Correct and core; redundant with the IBA and IDA annotations to the same BP term. Supporting Evidence: file:human/PIGY/PIGY-uniprot.txt Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor
GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex	IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	ACCEPT	Summary: ComplexPortal IPI annotation (CPX-6502) placing PIGY as part of the GPI-GnT complex, based on the co-precipitation / reconstitution work that identified PIGY as the seventh component. Reason: Correct and core; experimentally supported complex membership. Supporting Evidence: PMID:16162815 human GPI-GnT requires another component, termed PIG-Y
GO:0005789 endoplasmic reticulum membrane	IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	ACCEPT	Summary: Experimental (IDA, ComplexPortal) localisation of PIGY to the ER membrane, where the GPI-GnT complex initiates GPI biosynthesis. Reason: Correct and core; this is the established site of action of PIGY and the GPI-GnT complex. Supporting Evidence: file:human/PIGY/PIGY-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0017176 phosphatidylinositol N-acetylglucosaminyltransferase activity	IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	ACCEPT	Summary: Experimental (IDA) annotation with the contributes_to qualifier, capturing that PIGY is required for the phosphatidylinositol N-acetylglucosaminyltransferase activity of the GPI-GnT complex. PIGY is not itself the catalytic subunit (that is PIGA); it binds directly to PIGA and regulates the complex's activity, so contributes_to is the appropriate qualifier. Reason: Correct and represents PIGY's core molecular contribution. The contributes_to qualifier correctly reflects that PIGY is a required non-catalytic subunit of the enzyme complex rather than an independent catalyst. Supporting Evidence: PMID:16162815 PIG-Y is the key molecule that regulates GPI-GnT activity by binding directly to the catalytic subunit PIG-A
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-162730	ACCEPT	Summary: Traceable author statement (Reactome) localising the GlcNAc-PI-forming reaction and its catalysing complex, including PIGY, to the ER membrane. Reason: Correct and core; consistent with the experimental IDA and IEA ER membrane annotations. Supporting Evidence: Reactome:R-HSA-162730 The first step of GPI synthesis is the transfer of N-acetylglucosamine from cytosolic UDP-N-acetylglucosamine to phosphatidyl inositol (PI) in the endoplasmic reticulum membrane.
GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex	IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	ACCEPT	Summary: Experimental (IDA, MGI) annotation placing PIGY as part of the GPI-GnT complex, from the study that identified PIGY as the seventh required component of the complex. Reason: Correct and core; experimentally established complex membership. Supporting Evidence: PMID:16162815 A complex of six components was formed without PIG-Y.
GO:0005886 plasma membrane	IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	MARK AS OVER ANNOTATED	Summary: Experimental (IDA, MGI) localisation to the plasma membrane. PIGY is an ER-resident GPI-GnT subunit; its established site of function is the ER membrane, and UniProt records only the ER membrane as its subcellular location. A plasma membrane assignment is inconsistent with an ER GPI-biosynthesis subunit and most likely reflects an overexpression/tag-driven readout in the original study. Reason: The functionally relevant, well-established location of PIGY is the ER membrane (multiple IDA/IEA/TAS annotations and UniProt). Plasma membrane localisation does not fit PIGY's role in the ER-localised GPI-GnT complex. Because this is an experimental annotation whose full text is not available in the cache, it is not removed but flagged as an over-annotation / non-core location. Supporting Evidence: file:human/PIGY/PIGY-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0006506 GPI anchor biosynthetic process	IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth...	ACCEPT	Summary: Experimental (IDA, MGI) annotation that PIGY acts upstream of or within GPI anchor biosynthesis, based on the demonstration that the PIGY-null Daudi cell line is severely defective in surface expression of GPI-anchored proteins. Reason: Correct and core; loss of PIGY abolishes GPI-GnT function and hence GPI-anchor biosynthesis. Supporting Evidence: PMID:16162815 The Burkitt lymphoma cell line Daudi, severely defective in the surface expression of GPI-anchored proteins, was a null mutant of PIG-Y.