lcb2

Summary: Serine palmitoyltransferase activity (PAINT/EC/similarity); the Lcb1-Lcb2 heterodimer is the catalytic SPT (contributes). Support is the curated UniProt FUNCTION comment, which describes lcb2 as the catalytic SPT subunit by similarity (ECO:0000250; no S. pombe enzyme assay), and membership of the class-II PLP-dependent aminotransferase (AON synthase) family to which SPT LCB2 subunits belong.

Summary: Serine palmitoyltransferase activity (PAINT/EC/similarity); the Lcb1-Lcb2 heterodimer is the catalytic SPT (contributes). Support is the curated UniProt FUNCTION comment, which describes lcb2 as the catalytic SPT subunit by similarity (ECO:0000250; no S. pombe enzyme assay), and membership of the class-II PLP-dependent aminotransferase (AON synthase) family to which SPT LCB2 subunits belong.

Summary: Cytoplasm is correct but general; SPT is an ER membrane complex, and the ER row in this review entails cytoplasm.

Reason: Changed from KEEP_AS_NON_CORE: the term is true (the ER is part of the cytoplasm, and UniProt records cytoplasm by similarity), but GO:0005783 endoplasmic reticulum, asserted in this review from the S. pombe localisation screen (PubMed:16823372), is part_of cytoplasm and entails it. A correct-but-general term with a more specific location asserted elsewhere is TOO_GENERAL, not non-core.

Summary: ORFeome screen: ER.

Summary: UniProt SubCell mapping of the curated ER location, which UniProt bases on the S. pombe ORFeome localization study (ECO:0000269, PubMed:16823372); consistent with SPT acting in the ER membrane.

Summary: Broad parent; Lcb2 catalyses the committed step of sphingoid base and ceramide synthesis, captured by the more specific rows.

Reason: By similarity to characterised SPT catalytic subunits (UniProt ECO:0000250) and class-II PLP aminotransferase family membership, Lcb2 makes 3-ketosphinganine, the committed step of sphingolipid synthesis. GO:0046513 ceramide biosynthetic process, asserted in this review, is a descendant of this term, so the row is correct but uninformative.

Summary: Generic membrane; Lcb2 has a single predicted transmembrane segment and localises to the ER, so the specific location is the ER membrane.

Reason: Changed from KEEP_AS_NON_CORE: membrane is correct but less specific than the evidence supports. Two independent lines agree on the ER membrane: a predicted single-pass transmembrane segment (FT TRANSMEM 90..107; UniProt single-pass membrane protein) and ER localisation of the S. pombe protein in the genome-wide GFP screen (PubMed:16823372, curated in UniProt). The replacement GO:0005789 is a part_of descendant of membrane.

Proposed replacements: endoplasmic reticulum membrane

Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.

Reason: Transferase activity is correct but too general. By similarity to characterised SPT catalytic subunits (ECO:0000250) and class-II PLP-dependent aminotransferase family membership (InterPro IPR001917, Pfam Aminotran_1_2), Lcb2 is the catalytic subunit of serine palmitoyltransferase; the specific activity GO:0004758 is already asserted in this review.

Proposed replacements: serine C-palmitoyltransferase activity

Summary: Subunit of the SPT complex (with the small subunit Tsc3-like SPAC23A1.05). The curated UniProt SUBUNIT comment (by similarity, ECO:0000250) states that lcb1 and lcb2 form the heterodimeric enzyme; the small-subunit association is inferred from the PAINT node, not shown in S. pombe.

Summary: PLP cofactor; Lcb2 carries the catalytic PLP-binding lysine (UniProt MOD_RES Lys398, N6-(pyridoxal phosphate)lysine, by similarity), Lcb1 is the non-catalytic partner. Consistent with the Aminotran_1_2 (PF00155) domain and class-II PLP-dependent aminotransferase family membership.

Summary: PAINT inference of sphingosine biosynthesis; SPT makes 3-ketosphinganine, the start of the sphingoid base pathway.

Reason: Family-membership inference: the PAINT node places Lcb2 among SPT catalytic subunits, and no S. pombe evidence argues for loss or divergence. SPT forms 3-ketosphinganine, the first intermediate of sphingoid long-chain base synthesis, so the gene participates in the first step of sphingoid base biosynthesis. Kept non-core because the core claim is the SPT activity and ceramide/sphingolipid synthesis; sphingosine itself is a downstream product of several further enzymes.

Summary: PAINT inference: first step of de novo ceramide (sphingolipid) synthesis. The curated UniProt FUNCTION comment (by similarity, ECO:0000250) has lcb2 catalysing the committed condensation step of sphingolipid synthesis, producing the long-chain base 3-ketosphinganine that is the precursor of ceramide.