ERG9

Summary: CGD no-data molecular-function placeholder.

Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the molecular function is inferred (from orthologs, family membership or sequence features) or comes from other species; none of it is literature on this gene product in this species. This was judged from the review's own content during the NO_DATA re-action pass, not from a new literature search. Earlier action: REMOVE. Re-checked 2026-10-31: the azole study cited in core_functions (PMID:39060235) does not assay squalene synthase activity. The gene's notes record a 2026-11-06 web/PubMed search that found no paper directly assaying C. albicans ERG9 enzymology.

Summary: EnsemblFungi transfer from S. cerevisiae supports an ER location.

Reason: The EnsemblFungi transfer from S. cerevisiae ERG9 correctly places the Candida enzyme in the endoplasmic reticulum. This organelle-level row should be retained rather than replaced with a subcompartment; ERG9's more precise endoplasmic-reticulum membrane location is already captured by separate accepted GO:0005789 rows.

Summary: CGD transfer to ER is directionally correct and retained beside the ER-membrane placement.

Reason: The cited C. albicans paper assayed ERG9 expression in sterol-drug responses, not ERG9 localization. The endoplasmic-reticulum claim is nevertheless biologically sound by orthology and PAINT; the more specific endoplasmic-reticulum membrane location is already captured by separate accepted GO:0005789 rows.

Summary: PANTHER IBA places ER membrane at a sound eukaryote-wide PTHR11626 node.

Reason: Accept the PTN000179294 IBA as a core localization. The PTHR11626 family review judges this ER-membrane node sound across the family, and Candida ERG9 is the canonical SF2 squalene synthase with a C-terminal transmembrane helix.

Summary: UniProt subcellular-location mapping to ER membrane agrees with PAINT.

Reason: The mapped UniProt subcellular-location call matches the ER-membrane placement accepted for PTHR11626 squalene synthases and is consistent with the Candida sequence's predicted C-terminal membrane anchor.

Summary: Plasma-membrane proteome hit for ERG9 is not verifiable from the cached abstract.

Reason: The abstract describes LC-MS/MS analysis of enriched C. albicans plasma-membrane fractions, but the cached paper is abstract-only and does not show the ERG9 peptides, enrichment level, or contaminating ER markers. Because canonical fungal squalene synthase is an ER-membrane enzyme, retain this row as undecided until the full proteomics table can be checked.

Summary: PAINT confines ergosterol biosynthesis to a fungal PTHR11626 node.

Reason: Accept the fungal PTN000907895 IBA. ERG9 catalyzes the squalene-forming step at the start of fungal sterol synthesis, and the PTHR11626 review scopes ergosterol biosynthetic process to fungal SF2 squalene synthases rather than to animal or plant paralogs.

Summary: EnsemblFungi transfer from S. cerevisiae supports fungal ergosterol biosynthesis.

Reason: The transferred process is correct: Candida ERG9 is the fungal SF2 squalene synthase ortholog and catalyzes the farnesyl-diphosphate to squalene step that feeds ergosterol biosynthesis.

Summary: C. albicans ERG9 expression in sterol-pathway drug responses is consistent with ergosterol biosynthesis.

Reason: This expression-only paper should not be read as direct catalytic evidence, but it is consistent with ERG9 acting in the later sterol/ergosterol program; the process assignment is independently supported by the fungal PAINT node and the conserved PTHR11626 squalene synthase function.

Summary: Lipid biosynthesis is true but less precise than ergosterol biosynthesis.

Reason: The InterPro squalene-synthase-like mapping is directionally correct but too broad for canonical fungal ERG9. The supported biological process is the more specific ergosterol biosynthetic process.

Proposed replacements: ergosterol biosynthetic process

Summary: Generic membrane transfer should be refined to ER membrane.

Reason: ERG9 is a membrane protein, but the accepted PAINT and UniProt-derived localization is specifically the endoplasmic reticulum membrane.

Proposed replacements: endoplasmic reticulum membrane

Summary: Generic alkyl/aryl transferase activity should be refined to squalene synthase activity.

Reason: The IPR019845 signature supports a type-I isoprenoid transferase fold, but Candida ERG9 is assigned to PTHR11626:SF2 and to squalene synthase-specific InterPro/PANTHER families, so the molecular function should be the specific squalene synthase [NAD(P)H] activity term.

Proposed replacements: squalene synthase [NAD(P)H] activity

Summary: The FPP-metabolism IBA follows the same node as squalene synthase activity.

Reason: ERG9 consumes farnesyl diphosphate, so farnesyl diphosphate metabolic process is a true inherited statement for active SF2 squalene synthases. It is kept as non-core because it describes the substrate pool rather than the sterol pathway output captured by ergosterol biosynthesis.

Summary: InterPro transfer of FPP metabolism is true but peripheral.

Reason: The trans-isoprenyl diphosphate synthase signature is consistent with ERG9 acting on farnesyl diphosphate, and the family review judges this process true for active SF2 members. The central curated process for Candida ERG9 remains ergosterol biosynthesis.

Summary: PANTHER IBA places squalene synthase activity on the active SF2 lineage.

Reason: Accept the PTN001700951 IBA. Candida ERG9 is in PTHR11626:SF2, and the family review scopes squalene synthase activity to active SF2 enzymes while excluding the inactive Arabidopsis SQS2 branch and partial Botryococcus SSL proteins.

Summary: Multiple UniProt automated signals converge on squalene synthase activity.

Reason: The combined EC, InterPro, S. cerevisiae ortholog, and PAINT/family evidence all support Candida ERG9 as an NAD(P)H-dependent squalene synthase.

Summary: Curated transfer from S. cerevisiae ERG9 supports the same squalene synthase activity.

Reason: Candida ERG9 and S. cerevisiae ERG9 are canonical fungal SF2 squalene synthases. The direct ortholog transfer is concordant with the accepted PAINT node and PANTHER family assessment.