SPAC17A5.13

Summary: PAINT inference from characterised GCH1s (S. cerevisiae FOL2); sound.

Reason: No experimental data on the S. pombe enzyme; support is family membership (GTP cyclohydrolase I family; HAMAP MF_00223 FolE) and the PAINT node, whose donors include S. cerevisiae FOL2 and E. coli FolE.

Summary: EC/InterPro mapping; consistent.

Reason: EC/InterPro mapping consistent with GTP cyclohydrolase I family membership (TIGR00063 folE).

Summary: ORFeome YFP screen recorded nuclear signal for SPAC17A5.13. Soluble metabolic enzymes often show diffuse nucleocytoplasmic signal in this screen; no nuclear role is known.

Reason: Experimental HDA kept, but not part of the core function.

Summary: Phylogenetic inference of location; agrees with the localisation screen.

Summary: ORFeome YFP screen placed SPAC17A5.13 in the cytosol, consistent with a soluble metabolic enzyme.

Summary: PAINT inference of tetrahydrobiopterin biosynthesis from animal GCH1. Yeasts do not make tetrahydrobiopterin; in fungi GCH1 makes dihydroneopterin triphosphate for folate synthesis.

Reason: The PAINT node is seeded by animal and amoebozoan GCH1s (e.g. the Drosophila donor FB:FBgn0003162), which feed tetrahydrobiopterin synthesis. For this S. pombe protein UniProt's curated FUNCTION and PATHWAY lines place the product, 7,8-dihydroneopterin triphosphate, at the head of the folate pathway, and the gene carries folate/tetrahydrofolate biosynthesis rows. No S. pombe evidence links it to tetrahydrobiopterin; the quoted text argues for folate, not BH4, but nothing in the record or a cached publication directly states that fission yeast lacks BH4 synthesis, so that part rests on the reviewer's general knowledge of fungal pterin metabolism. The ACTIVITY REGULATION line (BH4 inhibition, ECO:0000250) is a by-similarity carry-over from animal GCH1 and is not evidence of a BH4 pathway in yeast. Family/by-similarity evidence only.

Summary: ARBA mapping to folic acid-containing compound biosynthesis; correct but less specific than the folate terms the gene already carries.

Reason: GTP cyclohydrolase I makes dihydroneopterin triphosphate, the first step of de novo folate synthesis (UniProt FUNCTION and PATHWAY; family-level, no S. pombe assay). The specific descendants GO:0046654 and GO:0046656 are already on this gene (ACCEPT).

Proposed replacements: tetrahydrofolate biosynthetic process folic acid biosynthetic process

Summary: InterPro mapping; consistent.

Reason: Family-level inference (HAMAP MF_00223 FolE): GTP cyclohydrolase I supplies the pterin for de novo folate synthesis, whose cellular product is tetrahydrofolate; no S. pombe-specific data.

Summary: Curator inference; GCH1 is the first step of de novo folate synthesis.

Reason: Curator inference from the GTP cyclohydrolase I activity; the UniProt FUNCTION and PATHWAY statements place the step at the head of folate synthesis (family-level, no S. pombe assay).