sptl-1 (C. elegans, P91079) - manual literature research

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PubMed searches ("sptl-1 elegans sphingolipid") and the UniProt record.

Identity and family

• sptl-1 = C23H3.4 (formerly spt-1), Swiss-Prot SPTC1_CAEEL, 458 aa, PE 3 (inferred from homology).
  PMID:15340492
• Class-II PLP-dependent aminotransferase fold (Pfam PF00155; PANTHER PTHR13693:SF2 SERINE PALMITOYLTRANSFERASE 1).
• Pairwise alignment (sptl-1-bioinformatics/RESULTS.md): 50.3% identity to human SPTLC1, 30.1% to SPTLC2;
  Asn297 sits at the SPTLC2 K379 PLP Schiff-base lysine position, so SPTL-1 is the non-catalytic LCB1-type subunit.
• UniProt (by similarity): "The catalytic core is composed of a heterodimer of sptl-1 and sptl-2 or sptl-1 and sptl-3".

Biochemical role in the worm

• SPTL-1 is "predicted to condense a fatty acid with serine to form the long-chain-base (LCB) sphinganine as
  the first committed step in de novo sphingolipid synthesis" PMID:21926990.
• C. elegans sphingoid bases are C17 iso-branched; sptl-1 is "required for d17iso-SPA biosynthesis" and
  d17iso-SPA suppresses sptl-1(RNAi) L1 arrest PMID:23705068.
• LC-MS/MS: "RNAi targeting the first key enzyme (SPT) in the de novo sphingolipid biosynthesis pathway caused a
  decrease of nearly all sphingolipids in Caenorhabditis elegans." PMID:38704027
• sptl-1 loss "alleviates sphingosine accumulation" in sphk-1 mutants [PMID:41191545, abstract].

Phenotypes

• Intestinal apicobasal polarity conversion with ectopic lateral lumens at L1 arrest; phenocopied by
  sptl-2;sptl-3 double RNAi, myriocin and fumonisin B; partially rescued by glycosphingolipids; ER and Golgi
  distended PMID:21926990.
• "sptl-1(−) disrupts all sphingolipid biosynthesis and its phenotype is ... highly pleiotropic" PMID:23705068.
• HSAN1 model: SPTL-1(C121W) (= SPTLC1 C133W) homozygotes show "the same larval lethality and epithelial polarity
  defect as observed in sptl-1(RNAi) animals"; heterozygotes show neuronal polarity defects; dominant-negative on
  overexpression, lowering glucosylceramide [PMID:31138658, abstract].

Localization

• No direct C. elegans data. Orthologs are ER membrane proteins; PMID:38704027 (note: the
  "catalytic subunit" wording is imprecise; SPTL-1 is the SPTLC1-type subunit).