ST8SIA1 (GD3 synthase; ST8Sia I; alpha-2,8-sialyltransferase 8A; SAT-II) is a Golgi-membrane sialyltransferase of the glycosyltransferase 29 (GT29/CAZy) family that initiates the b-series branch of ganglioside biosynthesis. It is a type II single-pass membrane protein that transfers a second sialic acid, in alpha-2,8 linkage, from CMP-N-acetylneuraminate onto the terminal sialic acid of ganglioside GM3 to form ganglioside GD3 (releasing CMP), and can add a further alpha-2,8 sialic acid to GD3 to make GT3 (the c-series precursor); it therefore acts as a b/c-series ganglioside (poly)sialyltransferase. In vitro it also sialylates other terminal Sia-alpha-2,3-Gal acceptors (GM1b, GD1a, GT1b) to GD1c, GT1a and GQ1b, and in cancer cells can behave as an oligosialyltransferase generating unusual GQ3/GP3 species. GD3 and downstream b-series gangliosides (GD2, GD1b, GT1b) are important in neurodevelopment and apoptosis regulation, and GD3/GD2 are tumor-associated antigens strongly expressed in melanoma and other neuroectodermal tumors. Expression is high in melanoma cell lines and in adult and fetal brain.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic (IBA) assertion of the core catalytic activity of ST8SIA1/GD3 synthase. This is well supported by direct experimental evidence for this gene and matches the UniProt-assigned function and EC 2.4.3.8. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3 |
| GO:0006491 N-glycan processing | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Over-annotation propagated across the ST8Sia phylogenetic family. ST8SIA1 acts on glycolipid (ganglioside) acceptors, not on N-linked glycans of glycoproteins; UniProt describes it exclusively as a GM3->GD3 ganglioside sialyltransferase. The N-glycan processing role belongs to other family members (e.g. polysialylation of NCAM by ST8SIA2/4), not to GD3 synthase. Marked as over-annotated rather than removed because it is an IBA family inference. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt gangliosides are a subfamily of complex glycosphingolipds that contain |
| GO:0009311 oligosaccharide metabolic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Over-broad phylogenetic annotation. The physiological substrates and products of ST8SIA1 are gangliosides (sialylated glycosphingolipids), so a glycolipid/ganglioside biosynthesis term is far more informative than the generic oligosaccharide metabolic process. Kept but marked as over-annotated. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3 |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Correct subcellular location. ST8SIA1 is a Golgi apparatus membrane, single-pass type II membrane protein, consistent with its role as a Golgi ganglioside sialyltransferase. Core location. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Automated (Rhea/EC) assignment of the core catalytic activity, consistent with EC 2.4.3.8 and the GM3->GD3 reaction. Redundant with the experimental annotations but correct. Core function. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt EC=2.4.3.8 |
| GO:0008373 sialyltransferase activity | IEA GO_REF:0000120 | MODIFY | Summary: Correct but too general: this is the parent of the specific and experimentally supported GO:0003828 (alpha-2,8-sialyltransferase activity). Modify to the more informative child term. Proposed replacements: alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt Catalyzes the addition of sialic acid in alpha 2,8-linkage to |
| GO:0009101 glycoprotein biosynthetic process | IEA GO_REF:0000002 | REMOVE | Summary: Incorrect InterPro-based electronic inference. ST8SIA1 sialylates glycosphingolipid (ganglioside) acceptors, not glycoproteins; its products are b/c-series gangliosides, not glycoproteins. This IEA mis-assigns a substrate class the enzyme does not act on and should be removed (glycoprotein biosynthesis is a role of other GT29 members, not GD3 synthase). Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Bare "protein binding" from a single high-throughput yeast two-hybrid/interactome screen (interaction with OPTN, Q96CV9) in a neurodegenerative-disease network study. Uninformative about ST8SIA1's molecular function and unrelated to its Golgi ganglioside sialyltransferase activity. Retained per policy (experimental IPI) but flagged as an over-annotation. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt Q92185; Q96CV9: OPTN; NbExp=3 |
| GO:0006665 sphingolipid metabolic process | IEA GO_REF:0000041 | KEEP AS NON CORE | Summary: True but general (via the UniPathway sphingolipid-metabolism mapping). Gangliosides are sialylated glycosphingolipids, so this is an ancestor of the specific ganglioside biosynthetic process. Correct; kept as non-core because a more specific term captures the function. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt Lipid metabolism; sphingolipid metabolism. |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | TAS Reactome:R-HSA-4084978 | ACCEPT | Summary: Reactome (TAS) assertion of the core alpha-2,8-sialyltransferase activity, matching the experimental evidence. Core function. |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | EXP PMID:7937974 Isolation of GD3 synthase gene by expression cloning of GM3 ... | ACCEPT | Summary: Direct experimental support: expression cloning of the GD3 synthase gene (via anti-GD2 mAb selection); transfection directs GD3 (and GD2) expression, establishing the GM3 alpha-2,8-sialyltransferase activity. Core function. Supporting Evidence: PMID:7937974 For the isolation of ganglioside GD3 synthase (EC 2.4.99.8) cDNA |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | EXP PMID:8058740 Expression cloning of a CMP-NeuAc:NeuAc alpha 2-3Gal beta 1-... | ACCEPT | Summary: Direct experimental support: expression cloning of the CMP-NeuAc:GM3 alpha-2,8- sialyltransferase (GD3 synthase); transfected cells display cell-surface GD3. Establishes the core catalytic activity and its role as a key ganglioside-pathway regulator. Core function. Supporting Evidence: PMID:8058740 we have isolated a cDNA encoding GD3 synthase PMID:8058740 which is a key regulatory enzyme determining the prominence of the ganglioside biosynthesis pathway |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | EXP PMID:8195250 Expression cloning of a GM3-specific alpha-2,8-sialyltransfe... | ACCEPT | Summary: Direct experimental support: expression cloning of a GM3-specific alpha-2,8- sialyltransferase that specifically converts GM3 to GD3, with reconstituted GD3 synthase activity from the purified catalytic domain. Core function. Supporting Evidence: PMID:8195250 alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3 |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | EXP PMID:8631981 Expression cloning of a human GT3 synthase. GD3 AND GT3 are ... | ACCEPT | Summary: Direct experimental support showing the same enzyme adds a second alpha-2,8 sialic acid to GD3 to form GT3, i.e. it is a b/c-series polysialyltransferase (GD3/GT3 synthase). Confirms and extends the core alpha-2,8-sialyltransferase activity. Core function. Supporting Evidence: PMID:8631981 cloning and characterization of GT3 synthase that adds the second |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | IDA PMID:18348864 Identification and analysis of novel functional sites in hum... | ACCEPT | Summary: Direct assay (IDA) of human GD3 synthase activity with structure-guided mutagenesis (Asn188, Pro189, Ser190, Arg272) defining residues that determine alpha-2,8-linkage specificity, with measured kinetics for GM3 and CMP-Neu5Ac. Strong support for the core catalytic activity. Core function. Supporting Evidence: PMID:18348864 in determining the alpha2,8-linkage specificity of GD3-synthase. |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | IDA PMID:22885356 Accumulation of unusual gangliosides G(Q3) and G(P3) in brea... | ACCEPT | Summary: Direct assay (IDA) in ST8Sia I-expressing MCF-7 breast cancer cells: expression drives b- and c-series gangliosides plus unusual tetra-/pentasialylated GQ3 and GP3, demonstrating alpha-2,8-sialyltransferase (and oligosialyltransferase) activity in a cellular context. Core function. Supporting Evidence: PMID:22885356 showing that this enzyme can act as an oligosialyltransferase. |
| GO:0003828 alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity | IDA PMID:8706663 Acceptor substrate specificity of a cloned GD3 synthase that... | ACCEPT | Summary: Direct assay (IDA) of acceptor-substrate specificity: the cloned GD3 synthase makes GD3 from GM3 and also GD1c/GT1a/GQ1b from GM1b/GD1a/GT1b, i.e. it has both SAT II and SAT V alpha-2,8-sialyltransferase activities. Supports the core catalytic activity and its acceptor range. Core function. Supporting Evidence: PMID:8706663 of not only GD3 but also GD1c, GT1a, and GQ1B in vitro. |
| GO:0000139 Golgi membrane | TAS Reactome:R-HSA-4084978 | ACCEPT | Summary: Reactome (TAS) placement in the Golgi membrane, consistent with the UniProt subcellular location and its function as a Golgi ganglioside sialyltransferase. Core location. Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
| GO:0005975 carbohydrate metabolic process | TAS PMID:8195250 Expression cloning of a GM3-specific alpha-2,8-sialyltransfe... | KEEP AS NON CORE | Summary: True but very general legacy (ProtInc) annotation. The specific process is ganglioside (glycosphingolipid) biosynthesis via alpha-2,8-sialylation. Correct at a high level; retained as non-core. Supporting Evidence: PMID:8195250 alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3 |
| GO:0006688 glycosphingolipid biosynthetic process | TAS PMID:8195250 Expression cloning of a GM3-specific alpha-2,8-sialyltransfe... | MODIFY | Summary: Correct process, but a more specific term is available and better supported: ST8SIA1 is the branch-point enzyme of ganglioside biosynthesis (GM3->GD3), so GO:0001574 (ganglioside biosynthetic process), a child of this term, is the more informative assignment. Proposed replacements: ganglioside biosynthetic process Supporting Evidence: PMID:8195250 alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3 |
| GO:0008373 sialyltransferase activity | TAS PMID:8195250 Expression cloning of a GM3-specific alpha-2,8-sialyltransfe... | MODIFY | Summary: Correct but too general: parent of the experimentally supported GO:0003828 (alpha-2,8-sialyltransferase activity). Modify to the specific child term. Proposed replacements: alpha-N-acetylneuraminate alpha-2,8-sialyltransferase activity Supporting Evidence: PMID:8195250 alpha-2,8-sialyltransferase, which specifically converts GM3 to GD3 |
| GO:0016020 membrane | TAS PMID:8195250 Expression cloning of a GM3-specific alpha-2,8-sialyltransfe... | MODIFY | Summary: Correct but uninformative: ST8SIA1 is a type II transmembrane protein of the Golgi membrane. Modify to the specific Golgi membrane location (GO:0000139). Proposed replacements: Golgi membrane Supporting Evidence: file:human/ST8SIA1/ST8SIA1-uniprot.txt SUBCELLULAR LOCATION: Golgi apparatus membrane |
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