B4GALT6 (beta-1,4-galactosyltransferase 6) is a Golgi-resident, single-pass type II membrane glycosyltransferase of the glycosyltransferase 7 (GT7) family that functions as a lactosylceramide synthase (EC 2.4.1.274). It transfers galactose from UDP-galactose to glucosylceramide (GlcCer) on the lumenal face of the Golgi to produce lactosylceramide (LacCer, Gal-beta-1,4-Glc-ceramide) plus UDP. LacCer is the branch-point precursor from which the ganglio-, globo-, and (neo)lacto-series glycosphingolipids and gangliosides are built, so B4GALT6 catalyzes a committed step of glycosphingolipid biosynthesis. B4GALT6 shares this reaction with its close paralog B4GALT5 (68% identity); B4GALT5 is the major LacCer synthase in cells while B4GALT6 contributes to a lesser extent, with comparatively restricted, brain-enriched expression. The gene was originally cloned from brain as human lactosylceramide synthase, and the enzyme was biochemically purified and characterized (Mn2+/Mg2+-dependent) from human kidney. Through the gangliosides that derive from LacCer, the enzyme has been linked to central nervous system processes including neuronal maturation and axon and myelin formation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005794 Golgi apparatus | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (PAN-GO) inference that B4GALT6 acts in the Golgi apparatus. Consistent with UniProt subcellular location as a single-pass type II Golgi stack membrane protein. Correct but non-specific; the more precise Golgi membrane term (GO:0000139) is preferred as the core location. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0006688 glycosphingolipid biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that B4GALT6 is involved in glycosphingolipid biosynthesis. This is correct and core: by making lactosylceramide from glucosylceramide, B4GALT6 catalyzes the committed step generating the central glycosphingolipid precursor. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt starting point in the biosynthesis of all gangliosides (membrane-bound |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of the core lactosylceramide synthase activity (UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase). This is the defining molecular function of B4GALT6 and is independently supported by direct human experimental evidence (PMID:1551920, PMID:3099851, PMID:24498430). Accept as core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) |
| GO:0000139 Golgi membrane | IEA GO_REF:0000117 | ACCEPT | Summary: Electronic (ARBA) location in the Golgi membrane. Correct and the most appropriate core cellular-component term for this single-pass type II Golgi stack membrane protein. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0005975 carbohydrate metabolic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO electronic annotation of a generic carbohydrate metabolic process. Not wrong (a galactosyltransferase transfers a sugar) but far too general; the specific biology is lactosylceramide/glycosphingolipid biosynthesis. Keep as non-core high-level parent. |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic (combined IEA, via RHEA:31495 / EC 2.4.1.274 and ortholog transfer) assignment of the core lactosylceramide synthase activity. Correct and redundant with the experimentally supported annotations of the same term. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) |
| GO:0016757 glycosyltransferase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO electronic annotation to the broad glycosyltransferase-activity parent. Correct but uninformative; the specific activity (UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase, GO:0008489) is well established. Modify toward the specific term. Proposed replacements: UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Catalyzes the synthesis of lactosylceramide (LacCer) via the |
| GO:0032580 Golgi cisterna membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic mapping from the UniProt Subcellular Location (Golgi stack membrane / trans cisternae) to Golgi cisterna membrane. Consistent with the UniProt note that the protein resides in the trans cisternae of the Golgi stack. Correct; a specific Golgi sub-compartment term, kept as non-core relative to Golgi membrane. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:1901137 carbohydrate derivative biosynthetic process | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA electronic annotation to a very high-level biosynthetic parent. Glycosphingolipids are carbohydrate derivatives, so this is not wrong, but it is far too general relative to the specific lactosylceramide/ glycosphingolipid biosynthetic process. Keep as non-core parent. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare protein binding from a single high-throughput AP-MS interactome study (BioPlex 3.0), recording co-purification with MAN2A2 (P49641), a Golgi glycosylation enzyme. This is an uninformative term reflecting a Golgi-neighbor co-purification rather than a characterized functional complex, and it does not describe B4GALT6 activity. Per policy this IPI is not removed but flagged as over-annotated. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt MAN2A2; NbExp=2; IntAct=EBI-21514152, EBI-713521 |
| GO:0001574 ganglioside biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer (Ensembl Compara) from mouse B4galt6 (Q9WVK5) of a role in ganglioside biosynthesis. B4GALT6 does not itself make gangliosides; it makes lactosylceramide, the upstream precursor from which gangliosides are built. Thus the enzyme is contributory/upstream rather than directly catalyzing a ganglioside biosynthetic step. Keep as a non-core, downstream pathway role. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt starting point in the biosynthesis of all gangliosides (membrane-bound |
| GO:0006688 glycosphingolipid biosynthetic process | IEA GO_REF:0000107 | ACCEPT | Summary: Electronic transfer (Ensembl Compara) from a rodent ortholog of involvement in glycosphingolipid biosynthesis. Correct and core; redundant with the IBA annotation of the same term. Accept. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt starting point in the biosynthesis of all gangliosides (membrane-bound |
| GO:0021955 central nervous system neuron axonogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse B4galt6 (Q9WVK5) of a CNS neuron axonogenesis role. This is a downstream, By-similarity physiological consequence of the ganglioside pathway rather than a direct B4GALT6 function, and mouse B4galt6 knockout shows no strong CNS phenotype (its LacCer role is largely redundant with B4GALT5). Keep as a non-core, pleiotropic developmental process. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0022010 central nervous system myelination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse B4galt6 of a CNS myelination role. As with the other neural terms, this is a downstream, By-similarity consequence of ganglioside biosynthesis and is largely redundant with B4GALT5. Keep as non-core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0042551 neuron maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Electronic transfer from mouse B4galt6 of a neuron maturation role, reflecting the CNS roles of gangliosides derived from lactosylceramide. Downstream, By-similarity and pleiotropic; keep as non-core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | EXP PMID:1551920 Purification of uridine diphosphate-galactose:glucosyl ceram... | ACCEPT | Summary: Direct experimental evidence: purification (440-fold, to apparent homogeneity) from human kidney of the UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase (GalT-2), whose preferred substrate is glucosylceramide and whose major product is lactosylceramide. This is a core enabling function of B4GALT6 (UniProt attributes this activity / EC 2.4.1.274 to Q9UBX8). Accept. Supporting Evidence: PMID:1551920 A galactosyltransferase that transfers galactose from UDP-galactose to glucosylceramide was purified 440-fold to apparent homogeneity from normal human |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | EXP PMID:3099851 UDPgalactose:glucosylceramide beta 1----4-galactosyltransfer... | ACCEPT | Summary: Direct experimental characterization of the same activity in cultured human proximal-tubular cells: transfer of galactose from UDP-galactose to glucosylceramide, with the product comigrating with authentic lactosylceramide and Mn2+/Mg2+ dependence. UniProt uses this reference for EC 2.4.1.274, cofactor, and kinetics. Core enabling function; accept. Supporting Evidence: PMID:3099851 The purified 14C-labelled product comigrated with authentic lactosylceramide |
| GO:0001574 ganglioside biosynthetic process | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Sequence-similarity (ISS) transfer from mouse B4galt6 (Q9WVK5) of a ganglioside biosynthetic role. Same interpretation as the IEA version: B4GALT6 makes the upstream precursor (lactosylceramide) rather than catalyzing a ganglioside step. Keep as non-core, downstream role. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt starting point in the biosynthesis of all gangliosides (membrane-bound |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer from mouse B4galt6 of the core lactosylceramide synthase activity. Correct and redundant with the direct human experimental evidence for the same term. Accept. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt transfer of galactose from UDP-galactose to glucosylceramide (GlcCer) |
| GO:0008489 UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity | IMP PMID:24498430 Establishment of HeLa cell mutants deficient in sphingolipid... | ACCEPT | Summary: Direct human genetic/cell evidence: in a B4GalT5-null HeLa clone lacking LacCer, retroviral overexpression of B4GalT6 rescued lactosylceramide and its downstream metabolites, confirming that B4GalT6 also has (lesser) lactosylceramide synthase activity in cells. This is the strongest human support for the core enabling function; accept. Supporting Evidence: PMID:24498430 In this study, we confirmed that B4GalT6 also exhibits discernible activity of LacCer synthase in cells. |
| GO:0021955 central nervous system neuron axonogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from mouse B4galt6 of a CNS neuron axonogenesis role. Downstream, By-similarity consequence of the ganglioside pathway; redundant with B4GALT5 and lacking a direct human phenotype. Keep as non-core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0022010 central nervous system myelination | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from mouse B4galt6 of a CNS myelination role. Downstream, By-similarity, pleiotropic; keep as non-core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0042551 neuron maturation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from mouse B4galt6 of a neuron maturation role. Downstream, By-similarity consequence of ganglioside biosynthesis; keep as non-core. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt neuronal maturation and axonal and myelin formation (By similarity). |
| GO:0001572 lactosylceramide biosynthetic process | IDA PMID:10320813 cDNA cloning and expression of human lactosylceramide syntha... | ACCEPT | Summary: Direct assay: the gene was cloned from human brain as lactosylceramide synthase and shown on expression to transfer galactose from UDP-Gal to glucosylceramide, producing lactosylceramide. This is the most specific and accurate biological-process term for B4GALT6 and is a core function. Supporting Evidence: PMID:10320813 Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide |
| GO:0008378 galactosyltransferase activity | IDA PMID:10320813 cDNA cloning and expression of human lactosylceramide syntha... | MODIFY | Summary: Direct assay of galactosyltransferase activity for the cloned human lactosylceramide synthase (B4GALT6). Correct but at a broad level; the specific enabling function is UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity (GO:0008489). Modify toward the specific term. Proposed replacements: UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity Supporting Evidence: PMID:10320813 Lactosylceramide synthase is an enzyme that catalyzes the transfer of galactose from UDP-Gal to glucosylceramide |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2025723 | ACCEPT | Summary: Reactome-asserted Golgi membrane location, from a generic B4GALT reaction (transfer of Gal to the N-glycan precursor). The Golgi membrane location is correct for B4GALT6 (single-pass type II Golgi stack membrane protein) even though the specific N-glycan reaction is a family-level context rather than the established glycolipid role. The Golgi membrane location is accepted. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2046265 | ACCEPT | Summary: Reactome-asserted Golgi membrane location from a generic B4GALT keratan-chain reaction. Location correct for B4GALT6; the specific keratan reaction is a family-level assignment. Golgi membrane location accepted. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-2046298 | ACCEPT | Summary: Reactome-asserted Golgi membrane location from a generic B4GALT keratan-branch reaction. Location correct; specific reaction is family-level. Golgi membrane location accepted. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-975919 | ACCEPT | Summary: Reactome-asserted Golgi membrane location from a generic beta-4-galactosyl transfer reaction. Location correct for B4GALT6. Golgi membrane location accepted. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-9851347 | ACCEPT | Summary: Reactome-asserted Golgi membrane location from the reaction B4GALT5/6 transfer Gal to GlcCer, i.e. lactosylceramide synthesis, the established B4GALT6 function. This is the most relevant Reactome context: correct Golgi membrane location for the LacCer-synthase activity. Accept the location. Supporting Evidence: file:human/B4GALT6/B4GALT6-uniprot.txt Golgi apparatus, Golgi stack membrane |
| GO:0008378 galactosyltransferase activity | TAS PMID:9597550 The expanding beta 4-galactosyltransferase gene family: mess... | MODIFY | Summary: Traceable statement (gene-family review that identified beta-4GalT-VI / B4GALT6 among the six-member family) supporting broad galactosyltransferase activity. Correct but general; the specific activity is UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase (GO:0008489). Modify toward the specific term. Proposed replacements: UDP-galactose:glucosylceramide beta-1,4-galactosyltransferase activity Supporting Evidence: PMID:9597550 we have identified five additional gene family members denoted as beta 4GalT-II, -III, -IV, -V, and -VI. |
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