UGCG

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006679 glucosylceramide biosynthetic process	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference that UGCG participates in glucosylceramide biosynthesis. This is the core biological process of the gene and is supported experimentally in the same gene (IDA, PMID:8643456). Accept. Supporting Evidence: PMID:8643456 The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis
GO:0008120 ceramide glucosyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (IBA) inference of the core molecular function, ceramide glucosyltransferase activity (EC 2.4.1.80). Directly supported experimentally in this gene (IDA, PMID:8643456) and matches the UniProt catalytic activity. Accept as a core function. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt EC=2.4.1.80
GO:0016020 membrane	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: IBA membrane localization. Correct but far less informative than the specific Golgi membrane annotation (GO:0000139) also present with IDA support. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0000139 Golgi membrane	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (IEA) assignment of Golgi membrane localization, consistent with the experimental IDA annotation (PMID:12873973) and UniProt. This is the correct core cellular location. Accept. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0008120 ceramide glucosyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic assignment of the core molecular function via multiple sources (ARBA, EC:2.4.1.80, RHEA:12088, mouse ortholog). Redundant with the experimental IDA (PMID:8643456) but correct. Accept. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt EC=2.4.1.80
GO:0016757 glycosyltransferase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO (IPR025993) parent-level molecular function. Correct as the general parent of the specific ceramide glucosyltransferase activity (GO:0008120), but too general to be a core function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt Belongs to the glycosyltransferase 2 family.
GO:0006679 glucosylceramide biosynthetic process	IEA GO_REF:0000107	ACCEPT	Summary: Ensembl Compara orthology transfer (from mouse O88693) of the core biological process. Redundant with the experimental IDA (PMID:8643456) but correct. Accept. Supporting Evidence: PMID:8643456 The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis
GO:0009966 regulation of signal transduction	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Orthology transfer (mouse O88693) of a very general process. The link is indirect: glycosphingolipids made by UGCG are components of membrane microdomains that influence signaling, but UGCG does not itself regulate signal transduction. This high-level term over-annotates the gene's function. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt essential components of membrane microdomains that mediate membrane
GO:0016020 membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of generic membrane localization. Correct but subsumed by the specific Golgi membrane annotation. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0030154 cell differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer of a broad differentiation term, the parent of the more specific keratinocyte differentiation. Downstream/pleiotropic consequence of glycosphingolipid production, not the core function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt including growth, differentiation, migration,
GO:0030216 keratinocyte differentiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of keratinocyte differentiation. Consistent with human data showing GCS up-regulation during keratinocyte differentiation (PMID:9545298) and with the enzyme's role in skin-barrier lipid synthesis. This is a genuine downstream role but not the core molecular function; keep as non-core. Supporting Evidence: PMID:9545298 GlcCer synthase (GCS) activity increases during keratinocyte differentiation
GO:0033210 leptin-mediated signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of a specific downstream signaling role, reflecting that glycosphingolipids regulate the leptin receptor LEPR. This is a distal, context-dependent consequence of UGCG activity, not its core function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt in the leptin-mediated signaling pathway
GO:0048666 neuron development	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of neuron development, reflecting the requirement of glycosphingolipids for proper development and function of the nervous system (neural Ugcg knockout is neurodegenerative/lethal in mouse). Genuine downstream role; not the core molecular function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt functioning of the nervous system
GO:0061436 establishment of skin barrier	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693). Supported by the role of GlcCer as the precursor of the ceramides forming the epidermal permeability barrier. A genuine downstream role but not the core function. Keep as non-core. Supporting Evidence: PMID:9545298 ceramide, a major component of the epidermal permeability barrier
GO:0098856 intestinal lipid absorption	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of a specific downstream physiological role; glycosphingolipid biosynthesis is required for intestinal endocytic uptake of nutritional lipids. Distal consequence of UGCG activity, not its core function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt required for the proper intestinal endocytic uptake of nutritional
GO:1903575 cornified envelope assembly	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Orthology transfer (mouse O88693) of a specific epidermal process; part of the same skin-barrier biology (GlcCer/ceramide supply for cornified envelope). Downstream role, not the core function. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt an important role in the establishment of the skin
GO:0006688 glycosphingolipid biosynthetic process	TAS Reactome:R-HSA-9840309	ACCEPT	Summary: TAS (Reactome) that UGCG is involved in glycosphingolipid biosynthesis. UGCG catalyzes the committed first step (GlcCer synthesis) of this pathway, so the broader biosynthetic-process annotation is a correct core process. Accept. Supporting Evidence: PMID:8643456 The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis
GO:0006665 sphingolipid metabolic process	IEA GO_REF:0000041	KEEP AS NON CORE	Summary: UniPathway-derived (UPA00222) sphingolipid metabolism. Correct as a broad parent process (UniProt PATHWAY line lists sphingolipid metabolism) but too general relative to the specific glucosylceramide/glycosphingolipid biosynthetic terms. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt PATHWAY: Lipid metabolism; sphingolipid metabolism.
GO:0008120 ceramide glucosyltransferase activity	TAS Reactome:R-HSA-1638104	ACCEPT	Summary: TAS (Reactome) of the core molecular function. Matches the experimental IDA (PMID:8643456), UniProt EC 2.4.1.80 and the Reactome reaction "UGCG transfers glucose to ceramide". Accept. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt EC=2.4.1.80
GO:0009966 regulation of signal transduction	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS from mouse O88693 of a very general regulatory process. As with the matching IEA, this is an indirect, high-level consequence of glycosphingolipid production rather than a direct function of UGCG. Over-annotated. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt essential components of membrane microdomains that mediate membrane
GO:0030154 cell differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693 of a broad differentiation term (parent of keratinocyte differentiation). Downstream/pleiotropic consequence; correct but general. Keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt including growth, differentiation, migration,
GO:0033210 leptin-mediated signaling pathway	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693. Same specific downstream signaling role as the matching IEA (glycosphingolipids regulating LEPR). Distal consequence of UGCG activity; keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt in the leptin-mediated signaling pathway
GO:0006497 protein lipidation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: ISS from mouse O88693. This annotation is biologically questionable: UGCG glucosylates the lipid ceramide to make the glycolipid glucosylceramide; it does not covalently attach a lipid to a protein, which is what protein lipidation denotes. There is no protein substrate. This appears to be an erroneous orthology transfer and over-annotates the gene. Retained (ISS, not experimental) but flagged. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt of glucose from UDP-glucose to ceramide to produce
GO:0030216 keratinocyte differentiation	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693 of keratinocyte differentiation. Consistent with human GCS up-regulation during keratinocyte differentiation (PMID:9545298). Genuine downstream role; keep as non-core. Supporting Evidence: PMID:9545298 GlcCer synthase (GCS) activity increases during keratinocyte differentiation
GO:0048666 neuron development	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693 of neuron development, reflecting the requirement of glycosphingolipids for nervous-system development. Genuine downstream role; keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt functioning of the nervous system
GO:0061436 establishment of skin barrier	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693. GlcCer is the precursor of the ceramides forming the epidermal permeability barrier. Downstream role; keep as non-core. Supporting Evidence: PMID:9545298 ceramide, a major component of the epidermal permeability barrier
GO:0098856 intestinal lipid absorption	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693 of a specific downstream physiological role (glycosphingolipid biosynthesis needed for intestinal lipid uptake). Distal consequence; keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt required for the proper intestinal endocytic uptake of nutritional
GO:1903575 cornified envelope assembly	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: ISS from mouse O88693 of cornified envelope assembly, part of the same skin-barrier biology. Downstream role; keep as non-core. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt an important role in the establishment of the skin
GO:0000139 Golgi membrane	IDA PMID:12873973 Glucosylceramide synthase and its functional interaction wit...	ACCEPT	Summary: Experimental (IDA) Golgi membrane localization from the RTN1-interaction study, which reports UGCG subcellular location at the Golgi/ER interface. Matches UniProt (Golgi apparatus membrane) and is the correct core cellular location. Accept. (Cache is abstract-only; the curator assessed full text.) Supporting Evidence: PMID:12873973 RTN-1C not only interacts with GCS at Golgi/ER interface
GO:0005515 protein binding	IPI PMID:12873973 Glucosylceramide synthase and its functional interaction wit...	MARK AS OVER ANNOTATED	Summary: IPI protein binding, with UniProtKB:Q16799 (RTN1). The interaction is real and functionally meaningful (RTN-1C modulates UGCG catalytic activity), but bare protein binding is uninformative about UGCG's own molecular function. Per policy the experimental IPI is retained, not removed; flagged as over-annotated. A more informative capture would be a regulatory partnership with RTN1 that modulates GCS activity. Supporting Evidence: PMID:12873973 we have identified a member of the reticulon (RTN) family (RTN-1C) as the major GCS-protein partner
GO:0006679 glucosylceramide biosynthetic process	IDA PMID:8643456 Expression cloning of a cDNA for human ceramide glucosyltran...	ACCEPT	Summary: Direct experimental (IDA) evidence that UGCG carries out glucosylceramide biosynthesis, from the expression-cloning study that isolated the human cDNA and demonstrated a catalytically active enzyme producing GlcCer. This is the core biological process. Accept. Supporting Evidence: PMID:8643456 The enzyme catalyzes the first glycosylation step of glycosphingolipid synthesis and the product, glucosylceramide, serves as the core of more than 300 glycosphingolipids.
GO:0008120 ceramide glucosyltransferase activity	IDA PMID:8643456 Expression cloning of a cDNA for human ceramide glucosyltran...	ACCEPT	Summary: Direct experimental (IDA) evidence for the core molecular function, ceramide glucosyltransferase (EC 2.4.1.80): a catalytically active enzyme was produced from the cloned cDNA in E. coli. This is the defining function of UGCG. Accept. Supporting Evidence: PMID:8643456 A catalytically active enzyme was produced from Escherichia coli transfected with the cDNA.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-1638104	ACCEPT	Summary: TAS (Reactome) Golgi membrane localization, consistent with the experimental IDA (PMID:12873973) and UniProt. Reactome notes UGCG acts on the cytosolic face of the cis-Golgi. Accept. Supporting Evidence: file:human/UGCG/UGCG-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane
GO:0008544 epidermis development	TAS PMID:9545298 Up-regulation of glucosylceramide synthase expression and ac...	KEEP AS NON CORE	Summary: TAS from the human keratinocyte-differentiation study showing GCS expression and activity rise ~5-fold during differentiation, supplying GlcCer/ceramide for the epidermal permeability barrier. A genuine downstream role in epidermis development, not the core molecular function. Keep as non-core. Supporting Evidence: PMID:9545298 GlcCer synthesis assayed in situ using a fluorescent ceramide analog increased approximately 5-fold during keratinocyte differentiation

Gene Description

Existing Annotations Review

Core Functions

Catalyzes the committed first step of glucosphingolipid biosynthesis: UDP-glucose:ceramide glucosyltransferase (glucosylceramide synthase, EC 2.4.1.80), transferring glucose from UDP-glucose to ceramide to produce glucosylceramide (GlcCer), acting on the cytosolic face of the Golgi membrane.

References

📚 Additional Documentation

Notes

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