PIGC (phosphatidylinositol N-acetylglucosaminyltransferase subunit C; also known as GPI2) is a multi-pass endoplasmic reticulum membrane protein that is a required, non-catalytic subunit of the glycosylphosphatidylinositol N-acetylglucosaminyltransferase (GPI-GnT) complex. This complex catalyzes the first committed step of GPI-anchor biosynthesis: transfer of N-acetylglucosamine from UDP-N-acetylglucosamine onto phosphatidylinositol to form GlcNAc-PI. Within the complex the catalytic subunit is PIGA; PIGC is one of the accessory/structural subunits, alongside PIGH, PIGP, PIGQ (GPI1), PIGY and the regulatory factor DPM2. PIGC is the human homologue of Saccharomyces cerevisiae Gpi2. Loss-of-function variants in PIGC cause an autosomal recessive inherited GPI-deficiency disorder (glycosylphosphatidylinositol biosynthesis defect 16, GPIBD16) presenting as a developmental and epileptic encephalopathy with global developmental delay, intellectual disability and seizures, reflecting reduced cell-surface expression of GPI-anchored proteins.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: GPI anchor biosynthetic process is the core biological process of PIGC as a subunit of the GPI-GnT complex that performs the first step of GPI-anchor biosynthesis. The IBA (phylogenetic) call is consistent with the experimental literature and with the well-conserved role of the yeast orthologue GPI2. Reason: Directly supported by the demonstrated role of PIG-C in the first, committed step of GPI biosynthesis and conserved across the PIGC/GPI2 family. This is the core function of the gene. Supporting Evidence: PMID:8806613 mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IBA GO_REF:0000033 | ACCEPT | Summary: PIGC is a component of the GPI-GnT complex. The IBA assignment of complex membership is well supported by direct experimental evidence in human cells and by conservation of the complex across eukaryotes. Reason: Complex membership is directly demonstrated experimentally (see PMID:9463366, PMID:10944123, PMID:16162815) and the phylogenetic inference is consistent with this. This is a core aspect of PIGC's biology. Supporting Evidence: PMID:9463366 four mammalian gene products form a protein complex in the endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: PIGC localizes to the endoplasmic reticulum membrane, where the GPI-GnT complex operates. This IEA call (from the UniProt subcellular-location mapping) agrees with direct experimental evidence. Reason: The ER-membrane localization is experimentally established (PMID:8806613, PMID:16162815) and matches the UniProt subcellular location; the mapping is correct and specific. Supporting Evidence: file:human/PIGC/PIGC-uniprot.txt Endoplasmic reticulum membrane |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment (InterPro IPR009450 / UniPathway UPA00196) of the core GPI-anchor biosynthetic process. Consistent with the experimental and IBA evidence; correct and appropriately specific. Reason: The InterPro/UniPathway-driven mapping correctly reflects PIGC's role in the first step of GPI biosynthesis. This is a duplicate of the core BP call from other evidence sources. Supporting Evidence: PMID:8806613 mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic "membrane" localization from the InterPro-to-GO mapping. Not wrong (PIGC is a multi-pass membrane protein) but far less informative than the specific and experimentally supported endoplasmic reticulum membrane term. Reason: Subsumed by the more specific and better-supported GO:0005789 (endoplasmic reticulum membrane). The bare "membrane" term adds no specificity beyond what the ER-membrane annotation already conveys. Supporting Evidence: file:human/PIGC/PIGC-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005515 protein binding | IPI PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | MARK AS OVER ANNOTATED | Summary: IntAct IPI annotation recording a physical interaction between PIGC and DPM2 (UniProtKB:O94777). This reflects PIGC's participation in the GPI-GnT complex, where DPM2 associates through interactions with PIG-A, PIG-C and GPI1, but the bare "protein binding" term is uninformative about molecular function. Reason: Per curation guidelines, GO:0005515 "protein binding" is too generic to convey function. The biologically meaningful content of this interaction (membership of the GPI-GnT complex) is already captured by GO:0000506. Retained but marked as over-annotated rather than removed, as the IntAct interaction itself is valid. Supporting Evidence: PMID:10944123 associates with GPI-GnT through interactions with PIG-A, PIG-C and |
| GO:0005515 protein binding | IPI PMID:9463366 The first step of glycosylphosphatidylinositol biosynthesis ... | MARK AS OVER ANNOTATED | Summary: IntAct IPI annotation recording a physical interaction between PIGC and PIGQ (GPI1; UniProtKB:Q9BRB3). Consistent with PIGC and GPI1 co-assembling in the GPI-GnT complex, but the bare "protein binding" term is uninformative. Reason: Generic "protein binding" is discouraged as uninformative. The functional significance (PIGC's assembly into the GPI-GnT complex with PIGA, PIGH, PIGC and GPI1) is already represented by the GPI-GnT complex annotation (GO:0000506). Supporting Evidence: PMID:9463366 four mammalian gene products form a protein complex in the endoplasmic reticulum membrane |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IPI PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: ComplexPortal assignment of PIGC to the GPI-GnT complex based on the seven-component complex characterized in this study. Core, well-supported cellular-component annotation. Reason: PMID:16162815 defines the GPI-GnT complex composition (PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY, DPM2) with PIG-A as the catalytic subunit; PIGC is a bona fide component. Core function. Supporting Evidence: PMID:16162815 the catalytic subunit PIG-A |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct experimental evidence places PIGC (with the GPI-GnT complex) in the endoplasmic reticulum membrane. Core, well-supported localization. Reason: The GPI-GnT complex containing PIGC is an ER-membrane complex; ER-membrane localization is directly demonstrated and is the site of PIGC function. Supporting Evidence: PMID:9463366 four mammalian gene products form a protein complex in the endoplasmic reticulum membrane |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct experimental evidence (co-precipitation / reconstitution) that PIGC is part of the GPI-GnT complex. Duplicate of the ComplexPortal and IBA complex calls; core cellular-component annotation. Reason: Experimentally demonstrated membership of the seven-component GPI-GnT complex. This is a core aspect of PIGC's biology. Supporting Evidence: PMID:16162815 the catalytic subunit PIG-A |
| GO:0006506 GPI anchor biosynthetic process | IDA PMID:16162815 The initial enzyme for glycosylphosphatidylinositol biosynth... | ACCEPT | Summary: Direct experimental evidence for PIGC's involvement in GPI-anchor biosynthesis via the GPI-GnT complex that performs the first step of the pathway. Core BP. Reason: PIGC is required for the initial GPI-GnT reaction; loss of complex components abolishes surface GPI-anchored protein expression. Core function of the gene. Supporting Evidence: PMID:9463366 The protein complex had GPI-GlcNAc transferase (GPI-GnT) activity in vitro |
| GO:0006506 GPI anchor biosynthetic process | IMP PMID:27694521 Mutations in the phosphatidylinositol glycan C (PIGC) gene a... | ACCEPT | Summary: Patient-derived and engineered PIGC variants (L189W; L212P/R21X) reduce surface expression of GPI-anchored proteins, providing mutational (IMP) evidence that PIGC is required for GPI-anchor biosynthesis. Core BP. Reason: Loss-of-function PIGC variants cause a GPI-deficiency disorder (GPIBD16) with reduced surface GPI-anchored protein expression, directly supporting PIGC's requirement for the GPI-anchor biosynthetic process. Supporting Evidence: PMID:27694521 PIGC joins the list of genes in which mutations result in defective PMID:27694521 reduction of surface expression of GPI-anchored proteins |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162730 | ACCEPT | Summary: Reactome traceable-author statement placing the first-step GPI reaction (and its multimeric enzyme, including PIGC) in the endoplasmic reticulum membrane. Consistent with the direct experimental localization. Reason: Duplicate of the experimentally supported ER-membrane localization; correct and specific. Core localization. Supporting Evidence: PMID:9463366 four mammalian gene products form a protein complex in the endoplasmic reticulum membrane |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:10944123 Initial enzyme for glycosylphosphatidylinositol biosynthesis... | ACCEPT | Summary: Direct experimental evidence that PIGC is part of the GPI-GnT complex, here characterized as consisting of at least PIG-A, PIG-H, PIG-C and GPI1 (plus PIG-P and the regulator DPM2). Core cellular-component annotation. Reason: PMID:10944123 experimentally defines the GPI-GnT complex including PIG-C. Consistent with all other complex-membership annotations; core function. Supporting Evidence: PMID:10944123 PIG-A, PIG-H, PIG-C and GPI1 |
| GO:0003824 catalytic activity | TAS PMID:8806613 PIG-C, one of the three human genes involved in the first st... | MARK AS OVER ANNOTATED | Summary: Legacy TAS (ProtInc, 2003) annotation of the very general term "catalytic activity". The catalytic activity of the GPI-GnT complex resides in the PIG-A subunit; PIGC is a required accessory/structural subunit and is not itself the catalytic component. The broad "catalytic activity" term is therefore an over-annotation for this subunit and is uninformative even as a complex-level statement. Reason: PIGC is a non-catalytic subunit: PMID:16162815 explicitly identifies PIG-A as "the catalytic subunit". Assigning the root-level "catalytic activity" molecular function to PIGC overstates and mis-locates the enzymatic activity, which belongs to PIGA / the complex as a whole. The GOA carries no PIGC-specific glycosyltransferase MF, so no replacement molecular-function term is proposed for this subunit. Supporting Evidence: PMID:16162815 the catalytic subunit PIG-A |
| GO:0005789 endoplasmic reticulum membrane | TAS PMID:8806613 PIG-C, one of the three human genes involved in the first st... | ACCEPT | Summary: Traceable-author statement (original cloning paper) that PIG-C is an ER membrane protein. Consistent with the direct experimental and IEA localization. Core. Reason: The original characterization describes PIG-C as a 297-residue membrane protein in the endoplasmic reticulum, matching all other localization evidence. Core localization. Supporting Evidence: PMID:8806613 mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) |
| GO:0006506 GPI anchor biosynthetic process | TAS PMID:8806613 PIG-C, one of the three human genes involved in the first st... | ACCEPT | Summary: Traceable-author statement that PIG-C is one of the genes involved in the first step of GPI-anchor biosynthesis. Core BP; duplicate of the other GPI-anchor biosynthesis annotations. Reason: The cloning study assigns PIG-C to the first step of GPI biosynthesis, matching the IBA, IEA, IDA and IMP evidence. This is the core function of the gene. Supporting Evidence: PMID:8806613 mediated by at least three genes in mammalian cells (PIG-A, PIG-H and PIG-C) |
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