PIGX (phosphatidylinositol-glycan biosynthesis class X protein) is the non-catalytic stabilizing subunit of GPI mannosyltransferase I (GPI-MT-I), the endoplasmic reticulum complex that adds the first mannose during glycosylphosphatidylinositol (GPI) anchor biosynthesis. GPI-MT-I transfers this mannose in an alpha-1,4 linkage from dolichyl-phosphate-mannose (Dol-P-Man) onto the glucosaminyl-(acyl)phosphatidylinositol (GlcN-(acyl)PI) intermediate; PIGX itself has no catalytic activity and instead binds and stabilizes the catalytic mannosyltransferase PIGM, protecting it from degradation, so that PIGX is required for GPI-MT-I activity. PIGX is a single-pass type I endoplasmic reticulum membrane protein and functions as part of the GPI-MT-I complex on the lumenal side of the ER membrane. Loss of PIGX/GPI-MT-I function causes inherited GPI deficiency (GPI biosynthesis defect), a developmental and epileptic encephalopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (InterPro PIG-X/PBN1 signature plus UniProt Subcellular Location mapping) placing PIGX in the ER membrane. This is correct; PIGX is a single-pass type I ER membrane protein and GPI biosynthesis occurs on the ER membrane, so this is the core localization. Reason: Correct localization, consistent with the UniProt-annotated single-pass ER membrane topology and with the ComplexPortal, ISS, and Reactome ER-membrane annotations. Supporting Evidence: file:human/PIGX/PIGX-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum file:human/PIGX/PIGX-uniprot.txt Single-pass type I membrane protein |
| GO:0006506 GPI anchor biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic annotation (InterPro PIG-X signatures and UniPathway GPI-anchor biosynthesis) to the GPI anchor biosynthetic process. PIGX is a required subunit of GPI-MT-I, which performs the first-mannose-addition step of GPI biosynthesis, so this is the core biological process for the gene. Reason: Correct and central biological process; PIGX is essential for GPI-MT-I activity, which catalyzes step 6 (first mannose) of GPI-anchor biosynthesis. Supporting Evidence: PMID:32156170 PIGM functions in association with PIGX, which stabilizes PIGM file:human/PIGX/PIGX-uniprot.txt participates in |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:32156170 Biosynthesis and biology of mammalian GPI-anchored proteins. | ACCEPT | Summary: ComplexPortal (CPX-2697) traceable assertion that PIGX localizes to the ER membrane, where GPI is assembled. Consistent with the electronic, ISS, and Reactome ER-membrane annotations and with the UniProt single-pass ER topology. Reason: Correct localization; the GPI-MT-I complex acts on the lumenal side of the ER membrane and PIGX is an ER membrane protein. Supporting Evidence: PMID:32156170 The core GPI is assembled on the endoplasmic reticulum (ER) membrane file:human/PIGX/PIGX-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:1990529 glycosylphosphatidylinositol-mannosyltransferase I complex | NAS PMID:32156170 Biosynthesis and biology of mammalian GPI-anchored proteins. | ACCEPT | Summary: ComplexPortal (CPX-2697) assertion that PIGX is part of the GPI-mannosyltransferase I complex, which in mammals comprises the catalytic subunit PIGM and the stabilizing subunit PIGX. This is the defining, characteristic complex membership for PIGX and captures how the gene product acts. Reason: Well-established complex membership; PIGX is the stabilizing subunit of GPI-MT-I and binds/stabilizes catalytic PIGM. Supporting Evidence: PMID:32156170 PIGM functions in association with PIGX, which stabilizes PIGM file:human/PIGX/PIGX-uniprot.txt complex that is composed of PIGM and PIGX. Interacts with PIGM; PIGX |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer (from mouse Pigx, UniProtKB:Q60GF7) of ER membrane localization. Consistent with the human UniProt topology and with the electronic, ComplexPortal, and Reactome ER-membrane annotations. Reason: Correct localization, corroborated by orthology and by the human single-pass type I ER membrane topology. Supporting Evidence: file:human/PIGX/PIGX-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-162830 | ACCEPT | Summary: Reactome traceable assertion placing the PIG-M/PIG-X-catalyzed addition of the first mannose to glucosaminyl-acyl-PI at the lumenal surface of the ER membrane. Consistent with all other ER-membrane annotations for PIGX. Reason: Correct localization from an authoritative pathway resource; matches the UniProt ER topology and the complex's lumenal ER activity. Supporting Evidence: Reactome:R-HSA-162830 The reaction takes place at the lumenal surface of the endoplasmic reticulum membrane Reactome:R-HSA-162830 It is catalyzed by a complex of at least two components, PIG-M and PIG-X |
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Download this section (compressed HTML)Q: Does PIGX have any function beyond stabilizing PIGM (e.g. substrate presentation or lipid recognition within GPI-MT-I), or is protecting PIGM from degradation its sole role?
Experiment: Structural determination of the human PIGM-PIGX GPI-MT-I complex to define how PIGX binds and stabilizes PIGM and whether it contributes to Dol-P-Man or GlcN-(acyl)PI recognition.
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