B3GLCT is an endoplasmic-reticulum glycosyltransferase that extends O-linked fucose on folded thrombospondin type 1 repeat (TSR) domains. It transfers glucose from UDP-glucose in a beta-1,3 linkage to the fucose installed by POFUT2, forming the Glc-beta-1,3-Fuc disaccharide. Its adjoining GT-A domains form the acceptor-binding cleft: the C-terminal domain catalyzes transfer, while the inactive N-terminal domain contributes substrate recognition. Glucose addition stabilizes modified TSRs and can support secretion of selected TSR-containing proteins; the requirement varies among substrates. B3GLCT has a C-terminal ER retention signal. Biallelic pathogenic variants cause Peters plus syndrome, a congenital disorder with ocular, growth, and developmental abnormalities.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:16899492 Molecular cloning and characterization of a novel human beta... | ACCEPT | Summary: ER localization is directly supported, and the curated membrane assignment is retained. Reason: The cached primary abstract reports immunostaining of FLAG-tagged human B3GLCT and dependence on its C-terminal REEL retention signal. UniProt records a type II membrane topology. The abstract alone does not reproduce the complete topology experiments; retain the curator's IDA assignment rather than infer an error from incomplete Methods. PMID:17032646 describes soluble enzymes in its abstract, whereas UniProt curates type II topology with a predicted N-terminal anchor. Without the complete original topology and fractionation Methods, the endogenous membrane-association question remains unresolved; recombinant solubility alone does not overturn the curated IDA. Supporting Evidence: PMID:16899492 residing in the endoplasmic reticulum (ER) via retention signal |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic ER-membrane annotation agrees with the target-specific localization evidence. Reason: The mapping is corroborated by the human IDA and normal UniProt record. The orthology and subcellular-location mappings are not represented as additional human experiments. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5173005 | ACCEPT | Summary: The normal Reactome glucosylation reaction places B3GLCT at the ER membrane. Reason: The source explicitly identifies B3GALTL as the historical name of human B3GLCT and localizes the enzyme to the ER membrane. This supports the compartment of the wild-type catalyst. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-6785565 | ACCEPT | Summary: The disease-pathway source retains the normal enzyme's ER compartment. Reason: The Reactome record describes a defective B3GLCT variant, but its accompanying summary explicitly describes wild-type localization. The disease-event title does not negate the positive wild-type GOA location or establish that every pathogenic variant localizes normally. |
| GO:0008375 acetylglucosaminyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: Replace the inherited acetylglucosaminyltransferase assertion with the experimentally established glucosyltransferase activity. Reason: Human B3GLCT transfers glucose from UDP-glucose onto O-fucosylated TSRs. GO:0008375 instead specifies transfer of an N-acetylglucosaminyl group. Direct target chemistry supports the already present GO:0160265. The recorded PAINT node is PTN000087478; its ancestral placement has not been independently reconstructed. This challenge rests on target-specific substrate chemistry, not the number of donors, and does not assert the exact evolutionary node at which specificity changed. Proposed replacements: O-fucosylpeptide 3-beta-glucosyltransferase activity |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Refine the broad membrane annotation to the established ER membrane location. Reason: The domain-based membrane assignment is compatible with the protein, but target-specific IDA, UniProt topology and Reactome localization support the existing GO:0005789. The broad term is accurate rather than an unsupported over-annotation. Proposed replacements: endoplasmic reticulum membrane |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: Refine generic glycosyltransferase activity to O-fucosylpeptide 3-beta-glucosyltransferase activity. Reason: The automated sources do not distinguish the transferred sugar and acceptor as precisely as the human biochemical evidence. The established glucose-to-O-fucosyl-TSR reaction supports the existing GO:0160265; family membership alone would not establish that specificity. Proposed replacements: O-fucosylpeptide 3-beta-glucosyltransferase activity |
| GO:0016757 glycosyltransferase activity | TAS Reactome:R-HSA-5173005 | MODIFY | Summary: Refine the general activity to the specific reaction described by Reactome. Reason: The normal reaction states that B3GLCT transfers glucose to O-fucosylated proteins. Together with the direct biochemical IDA, this supports GO:0160265, which is already present. The catalyst performs the glycosylation step itself. Proposed replacements: O-fucosylpeptide 3-beta-glucosyltransferase activity |
| GO:0016757 glycosyltransferase activity | TAS Reactome:R-HSA-6785565 | MODIFY | Summary: Refine the general wild-type activity while preserving the disease-event provenance. Reason: This Reactome event describes loss of the wild-type glucose-transfer reaction in defective B3GLCT. Its title is not a NOT annotation of the wild-type protein. The accompanying normal-function summary and independent human biochemical evidence support the existing specific GO:0160265; no activity is attributed to the defective variant. Proposed replacements: O-fucosylpeptide 3-beta-glucosyltransferase activity |
| GO:0036066 protein O-linked glycosylation via fucose | IDA PMID:16899492 Molecular cloning and characterization of a novel human beta... | ACCEPT | Summary: B3GLCT directly catalyzes extension of the O-linked fucose glycan on TSR domains. Reason: POFUT2 first attaches fucose to the protein. B3GLCT then performs the glucose-addition step of that same O-fucose glycosylation pathway, as shown by the recombinant-enzyme assay. It is a catalyst of the process, not merely a substrate or a downstream requirement. |
| GO:0036066 protein O-linked glycosylation via fucose | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic process annotation agrees with direct target experiments. Reason: The experimentally established glucose-transfer step extends protein O-fucosylation. The annotation does not mean that B3GLCT itself transfers the initial fucose or acts on every O-fucosylated protein. |
| GO:0036066 protein O-linked glycosylation via fucose | TAS Reactome:R-HSA-5173214 | ACCEPT | Summary: The Reactome TSR glycosylation pathway correctly assigns B3GLCT the elongation step. Reason: The source distinguishes POFUT2-mediated O-fucose addition from B3GLCT-mediated glucose addition. Its list includes putative substrates inferred from similarity, so pathway membership is not treated as direct experimental confirmation of every listed substrate or as evidence for a B3GLCT Notch-signaling annotation. |
| GO:0160265 O-fucosylpeptide 3-beta-glucosyltransferase activity | IDA PMID:16899492 Molecular cloning and characterization of a novel human beta... | ACCEPT | Summary: Direct biochemical evidence establishes glucose transfer onto O-fucosylated TSR domains. Reason: The source describes recombinant human B3GLCT, glucose-containing product characterization, and use of a TSR first fucosylated by POFUT2. The specific term matches the transferred sugar, acceptor, and beta-1,3 linkage. |
| GO:0160265 O-fucosylpeptide 3-beta-glucosyltransferase activity | IEA GO_REF:0000116 | ACCEPT | Summary: The Rhea mapping captures the experimentally supported serine- and threonine-linked O-fucose acceptor reactions. Reason: RHEA:70543 and RHEA:70547, recorded in GOA and the normal UniProt entry, use UDP-glucose to extend O-fucose on protein serine or threonine. They map to the same specific glucosyltransferase activity as the direct IDA. |
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Download this section (compressed HTML)Q: Which TSR sequence or structural features make secretion dependent on B3GLCT-mediated glucose addition, and how do these requirements vary with the expressing cell type?
Q: Which client-specific glycosylation defects explain the ocular and skeletal features of Peters plus syndrome independently of the initial POFUT2-catalyzed fucosylation step?
Q: Does endogenous B3GLCT retain its predicted N-terminal membrane anchor, or undergo processing that yields a soluble ER-resident enzyme? Direct topology and N-terminus measurements could resolve the differing source descriptions.
Experiment: Compare TSR glycosylation occupancy and secretion of defined clients in matched B3GLCT-null cells rescued with wild-type or catalytically impaired B3GLCT, controlling expression, folding and ER localization.
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