PIGP (phosphatidylinositol N-acetylglucosaminyltransferase subunit P; PIG-P) is a small (158 aa) multi-pass endoplasmic reticulum membrane protein that is a required, non-catalytic accessory subunit of the GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex. GPI-GnT catalyzes the first, committed step of glycosylphosphatidylinositol (GPI) anchor biosynthesis: the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine onto phosphatidylinositol to give GlcNAc-phosphatidylinositol. The catalytic subunit of the complex is PIGA; PIGP is one of several accessory components (with PIGC, PIGH, PIGQ/GPI1, PIGY and the regulatory protein DPM2) that are together required for enzyme activity, and it interacts directly with PIGA and PIGQ. PIGP is broadly (ubiquitously) expressed. Biallelic loss-of-function variants in PIGP cause an autosomal-recessive inherited GPI-deficiency disorder, developmental and epileptic encephalopathy 55 (DEE55), characterized by early-onset refractory seizures, hypotonia and profound developmental delay, reflecting reduced surface expression of GPI-anchored proteins.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that PIGP is active in the endoplasmic reticulum. This is correct: the GPI-GnT complex is an ER-membrane enzyme and PIGP is one of its subunits. The more specific ER membrane term (GO:0005789) is also present with direct evidence and is the preferred location. Reason: Consistent with the established ER localization of the GPI-GnT complex. PIGP is a subunit of this ER-membrane complex (UniProt SUBUNIT; ComplexPortal IDA). Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt acetylglucosaminyltransferase (GPI-GnT) complex composed at least by |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) inference that PIGP is involved in GPI anchor biosynthetic process. This is the core biological process of PIGP: as a GPI-GnT subunit it participates in the first committed step of GPI-anchor biosynthesis. Reason: Well supported by experimental evidence in human and by the conserved role of PIGP orthologs (yeast GPI19, etc.); represents the core function of the gene. Supporting Evidence: PMID:28334793 PIGP encodes a subunit of the enzyme that catalyzes PMID:10944123 PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (IEA, multi-method / InterPro + UniPathway) inference of involvement in GPI anchor biosynthetic process. Redundant with the IBA/IDA/IMP annotations to the same term but biologically correct. Reason: Correct core biological process, consistent with all experimental evidence and the UniProt PATHWAY assignment (GPI-anchor biosynthesis). Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt Interacts directly with PIGA and PIGQ (PubMed:10944123). |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic (IEA) annotation to the generic term "membrane", derived from the UniProt Subcellular Location keyword (Membrane; Multi-pass membrane protein). Correct but uninformative: the specific location is the ER membrane (GO:0005789), which is annotated with direct evidence. Reason: Not wrong (PIGP is a multi-pass membrane protein) but far too general and subsumed by the more precise ER membrane annotation. Retain as a non-core, generic location rather than as a core statement. Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt SUBCELLULAR LOCATION: Membrane |
| GO:0017176 phosphatidylinositol N-acetylglucosaminyltransferase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Electronic (InterPro2GO, ECO:0000256) inference that PIGP "enables" phosphatidylinositol N-acetylglucosaminyltransferase activity. This is the complex-level catalytic activity of GPI-GnT, whose catalytic subunit is PIGA. PIGP is a required but non-catalytic accessory subunit and does not independently have this transferase activity; assigning it via the "enables" qualifier over-attributes the whole-complex activity to a single non-catalytic subunit. Reason: The catalytic activity resides in the complex (catalytic subunit PIGA); PIGP contributes to but does not independently enable it. The InterPro family (IPR016542, PIG-P_GPI19) propagates the pathway-level MF to all members. The correct representation of PIGP's relationship to this activity is the parallel IDA annotation with the "contributes_to" qualifier, which is accepted. Per policy, an IEA that mis-attributes a complex activity to a non-catalytic subunit is marked as over-annotated rather than removed. Supporting Evidence: PMID:10944123 associates with PIG-A and GPI1. |
| GO:0005515 protein binding | IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | MARK AS OVER ANNOTATED | Summary: IPI annotation (IntAct) recording physical interaction of PIGP with PIGA (UniProtKB:P37287). This is the functionally meaningful interaction that assembles PIGP into the GPI-GnT complex, but the bare "protein binding" term is uninformative on its own. Reason: The interaction is real and experimentally supported (PIG-P associates directly with the catalytic subunit PIG-A), but "protein binding" (GO:0005515) conveys no specific molecular function. The biology is captured by the GPI-GnT complex membership (GO:0000506, part_of) and the contributes_to GO:0017176 annotation. Not removed (experimental IPI); flagged as a non-informative over-annotation. Supporting Evidence: PMID:10944123 associates with PIG-A and GPI1. |
| GO:0005515 protein binding | IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | MARK AS OVER ANNOTATED | Summary: IPI annotation (IntAct) recording physical interaction of PIGP with PIGA (UniProtKB:P37287) in the study defining the seven-component GPI-GnT complex. As above, the interaction is meaningful but the bare "protein binding" term is uninformative. Reason: Real complex-assembly interaction, but "protein binding" is not an informative molecular function. The relationship is properly represented by GPI-GnT complex membership (GO:0000506) and contributes_to GO:0017176. Not removed (experimental IPI). Supporting Evidence: PMID:16162815 complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" IPIs from a proteome-scale binary (yeast two-hybrid) interactome map (HuRI). The many recorded partners (e.g. ITGAM, KLF11, PLP1, PLP2, PTPN1, FIS1, and other membrane proteins) are high-throughput hits with no established functional relationship to PIGP's role in GPI-GnT. Reason: High-throughput binary-interactome hits captured as generic "protein binding". They add no informative molecular function and largely reflect promiscuous or screen-specific membrane-protein interactions. Retained (experimental IPI) but flagged as over-annotation. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" IPIs from a neurodegenerative-disease interactome map (partners include DNALI1, KLF11, ARL6IP-like membrane proteins). Generic, uninformative interaction annotation from a large-scale screen. Reason: High-throughput screen interactions recorded as "protein binding"; no specific molecular function is conveyed and no functional link to PIGP's GPI-GnT role is established. Retained (experimental IPI) but flagged as over-annotation. Supporting Evidence: PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" IPI from a proteome-scale AP-MS interactome (BioPlex 3.0), recording interaction with PIGA (UniProtKB:P37287). Consistent with GPI-GnT complex membership but conveyed only as generic "protein binding". Reason: The PIGA interaction is consistent with the known complex, but "protein binding" is uninformative. The functional content is captured by GO:0000506 (part_of) and contributes_to GO:0017176. Retained (experimental IPI) but flagged as over-annotation. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162730 | ACCEPT | Summary: Traceable-author (Reactome) statement placing PIGP at the endoplasmic reticulum membrane, in the reaction "phosphatidylinositol + UDP-N-acetyl-D-glucosamine -> N-acetylglucosaminyl-PI + UDP". This is the correct, specific location of the GPI-GnT complex. Reason: Correct and specific subcellular location; the first step of GPI biosynthesis occurs on the cytoplasmic face of the ER membrane. Concordant with the IDA annotation to the same term. Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt Multi-pass membrane |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: PIGP is part of the GPI-GnT complex (GO:0000506). Curated by ComplexPortal from the study establishing the seven-component complex (PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, DPM2). This is a core structural/functional annotation. Reason: Directly supported experimental complex-membership annotation and central to PIGP's function as a required accessory subunit of GPI-GnT. Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PMID:16162815 GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct-assay (ComplexPortal IDA) localization of PIGP to the ER membrane. This is the correct, specific location of the GPI-GnT complex and PIGP within it. Reason: Specific, experimentally supported location; preferred over the generic "membrane" IEA. Consistent with the Reactome TAS and IBA(ER) annotations. Supporting Evidence: file:human/PIGP/PIGP-uniprot.txt Multi-pass membrane |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct-assay complex-membership annotation (UniProt) that PIGP is part of the GPI-GnT complex. Core annotation, duplicate of the ComplexPortal IPI to the same term. Reason: Experimentally supported and central to PIGP function; PIGP is one of the required components of the GPI-GnT complex. Supporting Evidence: PMID:16162815 GPI-anchored proteins, was a null mutant of PIG-Y. A complex of six components |
| GO:0006506 GPI anchor biosynthetic process | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct-assay annotation that PIGP is involved in GPI anchor biosynthetic process, from the study characterizing the GPI-GnT complex. Core biological process. Reason: Experimentally supported involvement in the first step of GPI-anchor biosynthesis; the core function of the gene. Supporting Evidence: PMID:16162815 complex GPI-N-acetylglucosaminyltransferase (GPI-GnT) consisting of at least six |
| GO:0006506 GPI anchor biosynthetic process | IMP PMID:28334793 Compound heterozygous mutations in the gene PIGP are associa... | ACCEPT | Summary: Mutant-phenotype (IMP) evidence that PIGP is involved in GPI anchor biosynthetic process: biallelic PIGP variants in patients reduce PIGP mRNA and GPI-anchored cell-surface proteins, rescued by wild-type PIGP. Core biological process. Reason: Strong loss-of-function genetic evidence in human that PIGP is required for GPI anchor biosynthesis; directly links the gene to its core process and to DEE55. Supporting Evidence: PMID:28334793 cells showed reduced PIGP mRNA levels, and an associated reduction of PMID:28334793 PIGP encodes a subunit of the enzyme that catalyzes |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | ACCEPT | Summary: Direct-assay (MGI) complex-membership annotation that PIGP is part of the GPI-GnT complex, from the study that identified PIG-P as an essential component and showed it associates with PIG-A and GPI1/PIGQ. Core annotation. Reason: Experimentally supported complex membership; PIG-P associates with the catalytic subunit PIG-A and GPI1 and is essential for the complex's activity. Supporting Evidence: PMID:10944123 associates with PIG-A and GPI1. |
| GO:0017176 phosphatidylinositol N-acetylglucosaminyltransferase activity | IDA PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | ACCEPT | Summary: Direct-assay annotation (MGI) with the "contributes_to" qualifier: PIGP contributes to the phosphatidylinositol N-acetylglucosaminyltransferase activity of the GPI-GnT complex. This is the correct way to record a required, non-catalytic subunit's participation in the complex's catalytic activity. Reason: The "contributes_to" qualifier appropriately captures that PIGP is essential for the complex-level transferase activity without itself being the catalytic subunit (PIGA is catalytic). PIG-P-null cells are GPI-anchor negative, demonstrating its necessity for the activity. Preferred over the IEA "enables" annotation to the same term. Supporting Evidence: PMID:10944123 PIG-P is essential for GPI-GnT since a cell lacking PIG-P is GPI-anchor |
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