PIGB (GPI alpha-1,2-mannosyltransferase 3; also called GPI mannosyltransferase III, GPI-MT-III) is a multi-pass endoplasmic reticulum membrane protein that acts in glycosylphosphatidylinositol (GPI) anchor biosynthesis. It is a dolichyl-phosphate-mannose (Dol-P-Man)-dependent alpha-1,2-mannosyltransferase that transfers the third mannose, via an alpha-1,2 linkage, onto the growing GPI intermediate (Man2 to Man3) in the ER lumen. This third mannose is the residue that subsequently receives the bridging ethanolamine-phosphate (added by PIGO) to which the mature protein is ultimately attached, so PIGB activity is required for building a functional protein-anchoring GPI. The catalytic domain faces the ER lumen. Biallelic loss-of-function variants cause an inherited GPI-deficiency presenting as developmental and epileptic encephalopathy (DEE80), with refractory seizures, developmental delay/intellectual disability, and variable axonal neuropathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: PIGB is a multi-pass ER membrane protein and acts in the ER; the phylogenetic (IBA) is_active_in assertion of ER-membrane localization is correct and represents the core site of action. Reason: Consistent with experimental localization of human PIG-B to the ER membrane and with UniProt subcellular location. This is the compartment where GPI-anchor mannosylation occurs. Supporting Evidence: PMID:8861954 ER transmembrane protein with an amino-terminal portion of approximately 60 file:human/PIGB/PIGB-uniprot.txt Endoplasmic reticulum membrane |
| GO:0000026 alpha-1,2-mannosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: PIGB is a Dol-P-Man-dependent alpha-1,2-mannosyltransferase; this IBA term correctly captures the alpha-1,2-mannosyltransferase molecular function at a general level. A more specific term (GO:0120564) is also present for the exact reaction. Reason: The alpha-1,2-mannosyltransferase activity is well supported experimentally and by the enzyme's Rhea catalytic activity. It is a correct, if less specific, parent of the characterized reaction; retained as a correct MF. Supporting Evidence: file:human/PIGB/PIGB-uniprot.txt Alpha-1,2-mannosyltransferase that catalyzes the transfer of file:human/PIGB/PIGB-uniprot.txt the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate- |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: PIGB catalyzes an essential mannosylation step in GPI-anchor biosynthesis; the phylogenetic involved_in assertion for GPI anchor biosynthetic process is correct and represents the core biological process. Reason: Directly supported by experimental characterization (transfer of the third mannose of the GPI anchor) and by the UniProt pathway assignment to glycosylphosphatidylinositol-anchor biosynthesis. Supporting Evidence: PMID:8861954 is involved in transferring the third mannose of the GPI anchor file:human/PIGB/PIGB-uniprot.txt Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping from the UniProtKB/Swiss-Prot subcellular-location vocabulary to ER membrane; matches the experimentally determined location. Reason: The UniProt SubCell mapping to endoplasmic reticulum membrane is consistent with the experimental IDA localization and with the protein's multi-pass ER topology. Supporting Evidence: file:human/PIGB/PIGB-uniprot.txt Endoplasmic reticulum membrane file:human/PIGB/PIGB-uniprot.txt Multi-pass membrane protein |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-to-GO mapping (IPR005599, GPI mannosyltransferase) to the generic glycosyltransferase activity root term. Correct but uninformative relative to the specific mannosyltransferase terms already annotated. Reason: PIGB is a member of glycosyltransferase family 22 (GT22) and is a genuine glycosyltransferase, so the IEA mapping is not wrong; it is simply a broad parent of the more specific alpha-1,2-mannosyltransferase / GPI mannosyltransferase terms. Retained as a correct high-level MF (the specific terms carry the core function). Supporting Evidence: file:human/PIGB/PIGB-uniprot.txt Belongs to the glycosyltransferase 22 family. PIGB |
| GO:0006506 GPI anchor biosynthetic process | TAS Reactome:R-HSA-162710 | ACCEPT | Summary: Reactome-traceable assertion that PIGB participates in GPI (glycosylphosphatidylinositol) synthesis; correct core biological process. Reason: The Reactome pathway 'Synthesis of glycosylphosphatidylinositol (GPI)' places PIGB in the GPI-anchor biosynthetic process, in agreement with the experimental and phylogenetic BP annotations. Supporting Evidence: PMID:8861954 is involved in transferring the third mannose of the GPI anchor |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000041 | ACCEPT | Summary: UniPathway (UPA00196) vocabulary mapping to GPI-anchor biosynthetic process; consistent with the UniProt pathway annotation. Reason: The UniPathway mapping to glycosylphosphatidylinositol-anchor biosynthesis is correct and corroborates the core biological process from multiple independent evidence lines. Supporting Evidence: file:human/PIGB/PIGB-uniprot.txt Glycolipid biosynthesis; glycosylphosphatidylinositol-anchor |
| GO:0004376 GPI mannosyltransferase activity | TAS Reactome:R-HSA-162821 | ACCEPT | Summary: Reactome-traceable assertion (the reaction adding the third mannose of the GPI anchor) that PIGB has GPI mannosyltransferase activity; a correct family-level molecular-function term for this enzyme. Reason: The Reactome reaction catalyzed by PIG-B (addition of the third mannose) corresponds to GPI mannosyltransferase activity. This is a correct MF, more specific than the glycosyltransferase root and consistent with the specific IDA term GO:0120564. Supporting Evidence: PMID:8861954 is involved in transferring the third mannose of the GPI anchor |
| GO:0120564 dol-P-Man:Man(2)GlcN-acyl-PI alpha-1,2-mannosyltransferase activity | IDA PMID:8861954 PIG-B, a membrane protein of the endoplasmic reticulum with ... | ACCEPT | Summary: Experimentally supported (IDA) specific molecular function - the Dol-P-Man-dependent alpha-1,2-mannosyltransferase that adds the third mannose to the Man2 GPI intermediate. This is the most precise MF term for PIGB and its core catalytic activity. Reason: Directly matches the characterized reaction of human PIG-B (transfer of the third mannose, via an alpha-1,2 bond, from dolichol-phosphate-mannose to the GPI intermediate) and the corresponding UniProt catalytic activity (Rhea:RHEA:61004). This is the enzyme's defining function. Supporting Evidence: PMID:8861954 is involved in transferring the third mannose of the GPI anchor file:human/PIGB/PIGB-uniprot.txt the third mannose, via an alpha-1,2 bond, from a dolichol-phosphate- |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162821 | ACCEPT | Summary: Reactome-traceable assertion of ER-membrane localization; consistent with the experimentally determined location. Reason: GPI-anchor mannosylation occurs at the ER membrane; the Reactome location matches the IDA and IBA ER-membrane annotations and UniProt subcellular location. Supporting Evidence: file:human/PIGB/PIGB-uniprot.txt Endoplasmic reticulum membrane |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:8861954 PIG-B, a membrane protein of the endoplasmic reticulum with ... | ACCEPT | Summary: Experimentally determined (IDA) ER-membrane localization; PIG-B is an ER transmembrane protein with its catalytic (lumenal) domain in the ER lumen. This is the core cellular location. Reason: Takahashi et al. showed PIG-B is an ER transmembrane protein whose functional site resides on the lumenal side of the ER membrane, directly supporting ER membrane localization. Supporting Evidence: PMID:8861954 ER transmembrane protein with an amino-terminal portion of approximately 60 PMID:8861954 lumenal side of the ER membrane |
| GO:0006506 GPI anchor biosynthetic process | IDA PMID:8861954 PIG-B, a membrane protein of the endoplasmic reticulum with ... | ACCEPT | Summary: Experimentally supported (IDA) involvement in GPI-anchor biosynthesis - PIG-B was identified as the complementation-class-B gene required for transferring the third mannose of the GPI anchor. Core biological process. Reason: The defining experimental finding of Takahashi et al. 1996 is that PIG-B is required for GPI-anchor biosynthesis (transfer of the third mannose), directly supporting this BP annotation. Supporting Evidence: PMID:8861954 is involved in transferring the third mannose of the GPI anchor PMID:8861954 The GPI anchor precursor is synthesized in the endoplasmic |
| GO:0016020 membrane | NAS PMID:8861954 PIG-B, a membrane protein of the endoplasmic reticulum with ... | MARK AS OVER ANNOTATED | Summary: Generic 'membrane' localization asserted (NAS) from the 1996 paper. Not wrong, but it is an uninformative parent of the specific ER-membrane annotations already present. Reason: PIGB is a multi-pass ER membrane protein, so 'membrane' is technically correct but redundant and less informative than the endoplasmic reticulum membrane (GO:0005789) annotations supported by the same and other evidence. Marked as over-annotated rather than removed because the NAS assertion is not incorrect. Supporting Evidence: PMID:8861954 ER transmembrane protein with an amino-terminal portion of approximately 60 file:human/PIGB/PIGB-uniprot.txt Endoplasmic reticulum membrane |
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