B3GNT5 encodes lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase (EC 2.4.1.206), also known as lactotriaosylceramide synthase or Lc3 synthase (beta-1,3-N-acetylglucosaminyltransferase 5). It is a Golgi-resident, single-pass type II membrane glycosyltransferase of the GT31 (glycosyltransferase 31) family that initiates the (neo)lacto-series branch of glycosphingolipid biosynthesis. The enzyme transfers N-acetylglucosamine from UDP-GlcNAc onto lactosylceramide (LacCer), producing lactotriaosylceramide (Lc3Cer, GlcNAcbeta1-3Galbeta1-4Glc-ceramide) plus UDP. Lc3Cer is the committed precursor of the lacto- and neolacto-series glycosphingolipids, which carry Lewis (Lewis X) and HNK-1 carbohydrate antigens; the enzyme also extends neolactotetraosylceramide (nLc4Cer, paragloboside) to neolactopentaosylceramide (nLc5Cer). Expression is widespread with enrichment in lung, colon, placenta, testis, pituitary and cerebellum, and is developmentally regulated, being elevated in the developing central nervous system during embryogenesis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000139 Golgi membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetically inferred Golgi-membrane localization. Consistent with the UniProt subcellular location (Golgi apparatus membrane, single-pass type II membrane protein) and with the enzyme acting in the Golgi glycosphingolipid assembly line. Accepted as a core localization. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0016757 glycosyltransferase activity | IBA GO_REF:0000033 | MODIFY | Summary: Correct but non-specific parent term. B3GNT5 is a glycosyltransferase, but its specific, experimentally defined activity is lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity (GO:0047256). Modify to the specific term. Proposed replacements: lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt EC=2.4.1.206 |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic annotation from the UniProt Subcellular Location mapping, consistent with the curated UniProt location and the IBA Golgi-membrane annotation. Accepted. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Over-annotation for this enzyme. This InterPro2GO IEA reflects a GT31 family-level default (and the UniProt "protein glycosylation" pathway line), but B3GNT5 glycosylates a glycolipid acceptor (lactosylceramide / ceramide), not a protein. Its product is a glycosphingolipid, not a glycoprotein. Not removed (retained as flagged) but marked as over-annotated; the correct biosynthetic process is glycolipid/glycosphingolipid biosynthesis. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt role in the synthesis of lacto- or neolacto-series carbohydrate chains |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Uninformative parent term. B3GNT5 is specifically a Golgi apparatus membrane protein; modify to the specific Golgi membrane term (GO:0000139). Proposed replacements: Golgi membrane Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0016758 hexosyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: Correct but non-specific parent (an N-acetylglucosaminyltransfer is a hexosyltransfer). The specific experimentally supported activity is GO:0047256. Modify to the specific term. Proposed replacements: lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt EC=2.4.1.206 |
| GO:0030148 sphingolipid biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Correct but general ARBA-derived annotation. Glycosphingolipids are sphingolipids, so this parent is accurate; the more informative process is glycosphingolipid biosynthetic process (GO:0006688). Kept as a valid non-core parent. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt role in the synthesis of lacto- or neolacto-series carbohydrate chains |
| GO:0047256 lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Precise molecular function, electronically assigned from the RHEA:13905 / EC 2.4.1.206 mapping. This exactly matches the UniProt catalytic activity (LacCer + UDP-GlcNAc -> Lc3Cer + UDP) and the experimental evidence. Core function; accepted. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt EC=2.4.1.206 |
| GO:1901135 carbohydrate derivative metabolic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Very high-level ARBA grouping term (UDP-GlcNAc and glycosphingolipids are carbohydrate derivatives). Technically true but uninformative; retained as a non-core parent rather than removed. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a single high-throughput binary interactome screen (HuRI); the partner is DCDC2 (Q9UHG0), matching the UniProt INTERACTION line. This is uninformative about molecular function and is not a curated adapter/complex role. Per policy on bare protein binding IPI, marked as over-annotated rather than removed. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt Q9BYG0; Q9UHG0: DCDC2 |
| GO:0006688 glycosphingolipid biosynthetic process | TAS Reactome:R-HSA-9840309 | ACCEPT | Summary: Accurate core biological process. B3GNT5 initiates the (neo)lacto-series branch of glycosphingolipid biosynthesis by making Lc3Cer. Supported by Reactome and consistent with UniProt. Accepted as the core process (no more specific lacto-series term exists in GO). Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt role in the synthesis of lacto- or neolacto-series carbohydrate chains |
| GO:0047256 lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity | TAS Reactome:R-HSA-9846501 | ACCEPT | Summary: Precise core molecular function, curated by Reactome from the reaction "B3GNT5 transfers GlcNAc to LacCer". Matches the experimental EC 2.4.1.206 activity. Accepted. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt EC=2.4.1.206 |
| GO:0047256 lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity | EXP PMID:11283017 Molecular cloning and characterization of UDP-GlcNAc:lactosy... | ACCEPT | Summary: Experimental (EXP) demonstration of the core activity from the enzyme's cloning/characterization paper. beta3Gn-T5 was shown to transfer GlcNAc to lactosylceramide to synthesize Lc3Cer. This is the defining core molecular function; accepted. Supporting Evidence: PMID:11283017 beta3Gn-T5 exhibited strong activity to transfer GlcNAc to glycolipid substrates, such as lactosylceramide (LacCer) and neolactotetraosylceramide (nLc(4)Cer; paragloboside), resulting in the synthesis of Lc(3)Cer and neolactopentaosylceramide (nLc(5)Cer), respectively |
| GO:0047256 lactosylceramide 1,3-N-acetyl-beta-D-glucosaminyltransferase activity | IDA PMID:11384981 Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase ... | ACCEPT | Summary: Direct experimental (IDA) support for the core Lc3 synthase activity from the mouse cloning paper; the enzyme efficiently uses the lactosylceramide acceptor. The human ortholog carries the same activity (EC 2.4.1.206). Accepted as core function. Supporting Evidence: PMID:11384981 The Lc3 synthase enzyme efficiently utilized the lactosyl ceramide glycolipid acceptor |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9846501 | ACCEPT | Summary: Golgi-membrane localization curated by Reactome, consistent with the UniProt location and the IBA/IEA Golgi annotations. Accepted as core localization. Supporting Evidence: file:human/B3GNT5/B3GNT5-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0007417 central nervous system development | IDA PMID:11384981 Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase ... | KEEP AS NON CORE | Summary: From the mouse Lc3 synthase paper, which reports developmentally regulated expression with elevation in the developing CNS (in situ hybridization) and postnatal expression in cerebellar Purkinje cells colocalizing with HNK-1 reactivity. This is a developmental expression/context annotation rather than a demonstrated core developmental function of the enzyme. Retained as non-core (pleiotropic/developmental context). Per policy, an experimental annotation is not removed. Supporting Evidence: PMID:11384981 the Lc3 synthase was expressed in most tissues at embryonic day 11 with elevated expression in the developing central nervous system |
| GO:0009101 glycoprotein biosynthetic process | TAS PMID:11384981 Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase ... | MARK AS OVER ANNOTATED | Summary: Over-annotation. The cited paper characterizes Lc3 synthase acting on the lactosylceramide glycolipid acceptor (a glycosphingolipid product), not on protein. B3GNT5 does not make glycoproteins; the correct process is glycolipid/glycosphingolipid biosynthesis (see GO:0009247, GO:0006688). Marked as over-annotated (not removed). Supporting Evidence: PMID:11384981 The Lc3 synthase enzyme efficiently utilized the lactosyl ceramide glycolipid acceptor |
| GO:0009247 glycolipid biosynthetic process | TAS PMID:11384981 Cloning of a mouse beta 1,3 N-acetylglucosaminyltransferase ... | KEEP AS NON CORE | Summary: Correct process, at a more general level than glycosphingolipid biosynthesis (GO:0006688). B3GNT5 synthesizes the glycolipid Lc3Cer from lactosylceramide. Accurate; kept as a valid non-core parent. Supporting Evidence: PMID:11384981 The Lc3 synthase enzyme efficiently utilized the lactosyl ceramide glycolipid acceptor |
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