PIGW (phosphatidylinositol-glycan biosynthesis class W protein; PIG-W) is the GPI inositol acyltransferase of glycosylphosphatidylinositol (GPI) anchor biosynthesis. It is a multi-pass endoplasmic reticulum membrane protein that catalyses the fourth step of GPI-anchor assembly: transfer of an acyl group (usually palmitate) from acyl-CoA to the 2-OH of the inositol ring of glucosaminyl-phosphatidylinositol (GlcN-PI), producing 2-acyl-GlcN-PI (GlcN-(acyl)PI). This inositol acyl group is required for downstream recognition of the GPI intermediate by the GPI transamidase complex and is normally removed by PGAP1 after the anchor is attached to protein. Through this activity PIGW is essential for the ER synthesis of GPI anchors and hence for the transport of GPI-anchored proteins to the cell surface. Biallelic loss-of-function variants cause an autosomal-recessive inherited GPI-deficiency disorder (glycosylphosphatidylinositol biosynthesis defect 11, GPIBD11) on the hyperphosphatasia-with-mental-retardation / epileptic-encephalopathy spectrum, characterised by developmental delay, intellectual disability, seizures (including West syndrome with hypsarrhythmia), dysmorphic features, and elevated serum alkaline phosphatase.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: PIGW acts in the endoplasmic reticulum, where GPI-anchor biosynthesis occurs. This phylogenetic (IBA) location is correct but general; the ER membrane (GO:0005789) is the precise compartment for this multi-pass membrane enzyme. Reason: Consistent with UniProt subcellular location and with GPI biosynthesis being an ER process. Kept as a correct-but-broad cellular component; the membrane-specific term is the core location. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process: PIGW catalyses the fourth step of GPI-anchor biosynthesis (inositol acylation of GlcN-PI). The IBA is well supported across orthologues (PomBase, SGD, CGD, RGD) and matches the human function. Reason: This is the central biological role of PIGW and is corroborated experimentally and by UniProt. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt participates in the fourth step of GPI-anchor biosynthesis |
| GO:0032216 glucosaminyl-phosphatidylinositol O-acyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function: PIGW is the GPI inositol acyltransferase, transferring an acyl group from acyl-CoA to the 2-OH of the inositol of GlcN-PI. This specific term is the correct MF and is supported by the UniProt catalytic activity (RHEA:60496/RHEA:83759) and by the IBA across orthologues. Reason: Specific, correct molecular function directly matching the characterised reaction. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Acyltransferase that catalyzes the acyl transfer from an |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: PIGW is a multi-pass ER membrane protein; the ER membrane is its precise location. This SubCell-mapping IEA is correct and represents the core cellular component. Reason: Matches UniProt subcellular location (ER membrane, multi-pass) and the topology features. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane file:human/PIGW/PIGW-uniprot.txt Multi-pass membrane protein |
| GO:0006505 GPI anchor metabolic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: GPI anchor metabolic process is the broad parent of GPI anchor biosynthetic process. PIGW is a biosynthetic enzyme, so the more specific biosynthetic term (GO:0006506) is the informative core annotation. This ARBA-generated IEA to the parent is redundant with that specific term. Reason: Not wrong, but a less-informative parent that is fully subsumed by the accepted biosynthetic process annotation. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt participates in the fourth step of GPI-anchor biosynthesis |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the core GPI anchor biosynthetic process annotation, here via combined-IEA (InterPro IPR009447 / UniPathway UPA00196). Correct and consistent with the IBA/ISS/TAS annotations to the same term. Reason: Correctly captures the core biosynthetic role; duplicates of a correct term are acceptable. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor |
| GO:0016020 membrane | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic "membrane" from an InterPro2GO mapping. PIGW is specifically an ER membrane protein, so this uninformative parent is superseded by GO:0005789 (ER membrane). Reason: Too general; the specific ER membrane location is annotated and preferred. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0016746 acyltransferase activity | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic acyltransferase activity from InterPro2GO. This is a broad parent of the specific, correct MF GO:0032216 (glucosaminyl-phosphatidylinositol O-acyltransferase activity). Reason: Not wrong but uninformative relative to the specific inositol-acyltransferase term. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Acyltransferase that catalyzes the acyl transfer from an |
| GO:0032216 glucosaminyl-phosphatidylinositol O-acyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: Rhea-mapped IEA (RHEA:60496/RHEA:83759) to the specific GPI inositol acyltransferase activity, matching the UniProt catalytic activity. Duplicate of the accepted core MF term. Reason: Correct specific molecular function derived from the curated Rhea reaction. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Acyltransferase that catalyzes the acyl transfer from an |
| GO:0006506 GPI anchor biosynthetic process | TAS Reactome:R-HSA-162710 | ACCEPT | Summary: Reactome-traceable annotation to the core biosynthetic process, from the human GPI synthesis pathway (R-HSA-162710), in which PIGW catalyses the inositol-acylation step. Reason: Correctly captures the core biosynthetic role, consistent with the IBA/IEA/ISS annotations. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt participates in the fourth step of GPI-anchor biosynthesis |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of ER membrane localisation from the mouse orthologue (UniProtKB:Q7TSN4), consistent with the multi-pass ER membrane topology. Core cellular component. Reason: Matches UniProt subcellular location for the human protein. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0032216 glucosaminyl-phosphatidylinositol O-acyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of the GPI inositol acyltransferase activity from the mouse orthologue (UniProtKB:Q7TSN4). Duplicate of the accepted specific core MF term. Reason: Correct specific molecular function, supported by orthology and the curated reaction. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Acyltransferase that catalyzes the acyl transfer from an |
| GO:0006506 GPI anchor biosynthetic process | ISS GO_REF:0000024 | ACCEPT | Summary: ISS transfer of the core GPI-anchor biosynthetic process from the mouse orthologue (UniProtKB:Q7TSN4). Duplicate of the accepted core BP term. Reason: Correct core biological process, supported by orthology. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt participates in the fourth step of GPI-anchor biosynthesis |
| GO:0016747 acyltransferase activity, transferring groups other than amino-acyl groups | TAS Reactome:R-HSA-162683 | MARK AS OVER ANNOTATED | Summary: Reactome-traceable annotation to a broad acyltransferase-class term for the inositol-acylation reaction (R-HSA-162683). This is a general parent of the specific MF GO:0032216. Reason: Not wrong but uninformative relative to the specific glucosaminyl-PI O-acyltransferase term. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt Acyltransferase that catalyzes the acyl transfer from an |
| GO:0006505 GPI anchor metabolic process | IC PMID:24367057 Glycosylphosphatidylinositol (GPI) anchor deficiency caused ... | MARK AS OVER ANNOTATED | Summary: Curator-inferred (IC, from the GO:0072659 IMP in the same paper) annotation to the broad GPI anchor metabolic process. PIGW is specifically biosynthetic, so the biosynthetic child (GO:0006506) is the informative core term; this broad parent is a redundant over-annotation relative to the accepted biosynthetic-process term. Reason: Correct in essence (PIGW is in GPI-anchor metabolism) but a broad parent superseded by the specific biosynthetic-process term; kept rather than removed, consistent with the other GO:0006505 annotation. Supporting Evidence: PMID:24367057 involved in the addition of the acyl-chain to inositol in an early step of GPI |
| GO:0072659 protein localization to plasma membrane | IMP PMID:24367057 Glycosylphosphatidylinositol (GPI) anchor deficiency caused ... | KEEP AS NON CORE | Summary: Experimental (IMP) annotation from patient/variant studies: PIGW loss reduces surface expression of GPI-anchored proteins, i.e. PIGW is required for transport of GPI-APs to the plasma membrane. This is a downstream consequence of the enzyme's role in GPI-anchor synthesis rather than the direct molecular function, so it is retained as non-core. Reason: Valid experimental phenotype (defer to curator; not removed). Represents a downstream cellular outcome of GPI-anchor biosynthesis, not PIGW's direct acyltransferase function. Supporting Evidence: PMID:24367057 decreased surface expression of GPI-APs on file:human/PIGW/PIGW-uniprot.txt Required for the transport of GPI-anchored proteins to the |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162683 | ACCEPT | Summary: Reactome-traceable ER membrane localisation for the inositol-acylation reaction, consistent with the multi-pass ER membrane topology. Duplicate of the accepted core CC term. Reason: Correct core location, consistent with UniProt and the ISS/IEA annotations. Supporting Evidence: file:human/PIGW/PIGW-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
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