SNO2 (YNL334C) is one of three near-identical Saccharomyces cerevisiae SNO paralogs (SNO1/2/3) and is a member of the glutaminase PdxT/SNO family (class-I glutamine amidotransferase fold). SNO proteins are the glutaminase subunit of the two-subunit pyridoxal 5'-phosphate (PLP, vitamin B6) synthase, working together with a SNZ (PdxS/PDX1) synthase subunit: the SNO subunit hydrolyses L-glutamine to L-glutamate plus ammonia and channels the ammonia to the SNZ subunit, which condenses it with ribose 5-phosphate and glyceraldehyde 3-phosphate to form PLP. SNO2 carries the canonical Cys-His-Glu catalytic triad of the class-I glutamine amidotransferase glutaminase and is curated in a physical PLP-synthase glutaminase complex with SNZ1. The three yeast SNZ-SNO gene pairs are functionally specialized: the SNO1-SNZ1 pair is dedicated to vitamin B6 biosynthesis under B6-limiting conditions, whereas the SNO2/SNO3 (copy 2/3) genes are induced by thiamine (vitamin B1) limitation and are linked to B1 biosynthesis in exponentially growing cells. Direct enzymatic characterization of the SNO2 protein itself has not been reported; its molecular function is assigned from family membership, an intact catalytic triad, and functional characterization of fungal SNO orthologs.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0042823 pyridoxal 5'-phosphate biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: Core biological process for the PdxT/SNO family. SNO2 is the glutaminase subunit of the PLP synthase and the SNO glutaminase subunit is required for pyridoxine/PLP biosynthesis in fungal orthologs (N. crassa pdx-2). IBA from the PANTHER PLP-synthase-subunit-SNO tree is well founded. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000774355 · PTN000774355 SUPPORTS TRANSFER Current PTHR31559 PAINT places pyridoxal 5'-phosphate biosynthesis on PTN000774355, and SNO2 is in the SNO/PdxT glutaminase family descending from that ancestral node. SGD:S000004701 · S. cerevisiae SNO1 SUPPORTS TRANSFER SNO1 is the budding-yeast SNO/PdxT paralog seed for this IBD; SNO2 is not self-seeded, but SNO2 retains the same catalytic triad and has no evidence of PLP-synthase glutaminase loss. UniProtKB:P9WII7 · M. tuberculosis PdxT SUPPORTS TRANSFER M. tuberculosis PdxT co-seeds the refreshed PLP-biosynthesis IBD, showing the inference is deep across bacterial and fungal PdxT/SNO glutaminase subunits rather than a yeast-only paralog transfer. Supporting Evidence: PMID:11238395 pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog |
| GO:0004359 glutaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: The molecular activity of the SNO/PdxT glutaminase subunit. SNO2 retains the intact class-I glutamine amidotransferase catalytic triad (Cys91 nucleophile, His197/Glu199 charge-relay; UniProt), so glutaminase activity is domain-defensible. The contributes_to qualifier is appropriate because the glutaminase is a subunit whose in-vivo activity is coupled to (and ammonia-channeled into) the SNZ synthase subunit within the PLP synthase. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000774355 · PTN000774355 SUPPORTS TRANSFER Current PTHR31559 PAINT places glutaminase activity on PTN000774355; transfer to SNO2 is supported by the conserved SNO/PdxT catalytic mechanism and retention of the Cys91/His197/Glu199 catalytic triad. SGD:S000004701 · S. cerevisiae SNO1 SUPPORTS TRANSFER SNO1 is the same-organism SNO paralog seed for this glutaminase-activity IBD; SNO2's intact class-I GATase triad argues against target-specific loss. Supporting Evidence: PMID:11238395 pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog |
| GO:0008614 pyridoxine metabolic process | IBA GO_REF:0000033 | MODIFY | Summary: Over-scoped legacy pyridoxine/vitamin-B6 process term. Fungal SNO/PdxT glutaminase subunits support de novo PLP and vitamin B6 biosynthesis, but GO:0008614 is a parallel pyridoxine-specific branch rather than a parent of PLP biosynthesis. Reason: PdxT/SNO proteins provide the glutaminase half-reaction of the de novo PLP synthase and do not perform pyridoxine-specific salvage chemistry. QuickGO confirms GO:0008614 is not an ancestor of GO:0042823; GO:0042819 vitamin B6 biosynthetic process is the true parent of PLP biosynthesis and captures the older pyridoxine-requiring-mutant literature without naming the wrong B6 vitamer. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000774355 · PTN000774355 SOURCE BAD Current PTHR31559 PAINT places pyridoxine metabolic process on PTN000774355. The underlying PLP-synthase biology is family-consistent for SNO/PdxT glutaminase subunits, but the IBD uses a pyridoxine-specific sibling of the correct PLP and vitamin B6 biosynthetic terms. SGD:S000004701 · S. cerevisiae SNO1 SOURCE BAD SNO1 is a paralog seed for this row; its evidence supports SNO-family vitamin B6 biosynthesis, but the pyridoxine-specific GO term over-scopes the de novo PLP-synthase reaction. SGD:S000001834 · S. cerevisiae SNO3 SOURCE BAD SNO3 is the second S. cerevisiae paralog seed for this row. It reinforces the legacy yeast SNO family placement, not pyridoxine handling by the SNO glutaminase subunits. Proposed replacements: vitamin B6 biosynthetic process Supporting Evidence: PMID:10438537 define this gene family as encoding an enzyme specifically required for pyridoxine biosynthesis |
| GO:1903600 glutaminase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Complex membership as the glutaminase subunit of the two-subunit PLP synthase. Directly corroborated for SNO2 by ComplexPortal CPX-1371 (SNO2-SNZ1 pyridoxal 5'-phosphate synthase complex). GO:1903600 (glutaminase complex; synonym Sno1p-Snz1p) is the generic term for a complex capable of glutaminase activity and is correctly applied here. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000774355 · PTN000774355 SUPPORTS TRANSFER Current PTHR31559 PAINT places glutaminase-complex membership on PTN000774355, and ComplexPortal independently curates SNO2 in a physical PLP-synthase glutaminase complex with SNZ1. SGD:S000004701 · S. cerevisiae SNO1 SUPPORTS TRANSFER SNO1 is the budding-yeast SNO seed for the glutaminase-complex IBD, and ComplexPortal independently places SNO2 in the same two-subunit PLP-synthase complex class with SNZ1. Supporting Evidence: ComplexPortal:CPX-1371 SNO2-SNZ1 pyridoxal 5'-phosphate synthase complex |
| GO:0004359 glutaminase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Same molecular activity as the IBA glutaminase-activity annotation above, here derived by automated EC/RHEA mapping (EC 3.5.1.2). The MF term is correct given the intact catalytic triad. The enables qualifier (vs the more accurate contributes_to used by the IBA pipeline for the subunit) is a pipeline artifact of EC-based IEA; the underlying activity assignment is sound, so the annotation is retained. Supporting Evidence: PMID:11238395 pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog |
| GO:0008614 pyridoxine metabolic process | IEA GO_REF:0000117 | MODIFY | Summary: Duplicate of the pyridoxine metabolic process annotation, from the ARBA machine-learning pipeline. It has the same legacy pyridoxine-specific scope problem as the IBA row; the correct family process is de novo PLP/vitamin B6 biosynthesis rather than pyridoxine metabolism. Proposed replacements: vitamin B6 biosynthetic process Supporting Evidence: PMID:10438537 define this gene family as encoding an enzyme specifically required for pyridoxine biosynthesis |
| GO:0036381 pyridoxal 5'-phosphate synthase (glutamine hydrolysing) activity | IEA GO_REF:0000120 | ACCEPT | Summary: The holoenzyme-level molecular function (EC 4.3.3.6) of the two-subunit PLP synthase. This activity is strictly a property of the assembled SNO+SNZ complex (the SNO subunit alone provides only the glutaminase half-reaction), so contributes_to would be more precise than enables. The term is a correct family assignment via EC/RHEA mapping and is retained. Supporting Evidence: PMID:10438537 define this gene family as encoding an enzyme specifically required for pyridoxine biosynthesis |
| GO:0042819 vitamin B6 biosynthetic process | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Vitamin B6 biosynthetic process, the parent process of PLP biosynthesis. Correct but more general than the PLP biosynthetic process (GO:0042823) annotation; retained as a valid non-core (broader) process term for the family. Supporting Evidence: PMID:10438537 define this gene family as encoding an enzyme specifically required for pyridoxine biosynthesis |
| GO:0042823 pyridoxal 5'-phosphate biosynthetic process | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate of the core PLP biosynthetic process annotation, from InterPro/UniPathway automated mapping. Same support as the IBA version; retained. Supporting Evidence: PMID:11238395 pyridoxine-requiring mutants of N. crassa were found to possess mutations that disrupt conserved regions in either the SNZ or SNO homolog |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular function ND annotation: when it was made, no molecular function had been curated for this gene product from literature. 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: KEEP_AS_NON_CORE. Re-checked 2026-10-31: the papers cited in core_functions are on N. crassa and A. nidulans orthologs (PMID:11238395, PMID:10438537). The gene's search record (SNO2-notes.md) finds no study directly demonstrating a molecular function of SNO2 itself. Supporting Evidence: file:yeast/SNO2/SNO2-notes.md No direct in-vitro demonstration** of SNO2 (P53823) glutaminase or PLP-synthase activity; |
| GO:0005575 cellular_component | ND GO_REF:0000015 | ACCEPT | Summary: Root cellular component ND annotation: when it was made, no cellular component had been curated for this gene product from literature. Reason: ACCEPT under the ND acceptance rule (projects/NO_DATA.md). The evidence this review cites for the cellular component 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: KEEP_AS_NON_CORE. |
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Download this section (compressed HTML)Q: Is the SNO2 protein a catalytically active glutaminase, and does it form a functional PLP synthase when reconstituted with SNZ1, SNZ2, or SNZ3?
Q: Under what physiological condition is SNO2 non-redundantly required, given that it is dispensable for vitamin B6-limited growth but induced by thiamine limitation?
Experiment: Express and purify recombinant SNO2 and SNZ1/2/3; assay glutaminase activity (L-glutamine to L-glutamate + ammonia) for SNO2 alone and coupled PLP synthesis (with ribose 5-phosphate and glyceraldehyde 3-phosphate) for SNO2+SNZ mixtures, using a Cys91 active-site mutant as a negative control.
Hypothesis: SNO2 is a catalytically competent glutaminase subunit that reconstitutes a functional PLP synthase with a SNZ synthase subunit.
Experiment: Phenotype sno2 single and sno1 sno2 sno3 combinatorial deletion strains under vitamin B6 and thiamine limitation; quantify intracellular PLP and thiamine and profile SNO2-SNZ physical associations by condition.
Hypothesis: SNO2 has a thiamine-limitation-linked and/or condition-specific role distinct from the B6-dedicated SNO1.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: The SNO2-specific in-vivo physiological role and its required condition are undetermined. SNO2 is dispensable for vitamin B6-limited growth, and it is unresolved whether its native function is in pyridoxal 5'-phosphate (B6) biosynthesis, in a thiamine (B1)-related process under which it is induced, or both, and which SNZ synthase subunit it partners in vivo.
OPEN BIOLOGY BP_DARK
What is known: SNO2 is a glutaminase PdxT/SNO family member with an intact catalytic triad, curated in a PLP-synthase glutaminase complex with SNZ1 (CPX-1371). The B6-dedicated pair is SNO1/SNZ1 (both required for B6-limited growth); SNO2/SNO3 (copies 2/3) are dispensable for B6-limited growth and are transcriptionally activated by thiamine limitation, appearing more related to B1 biosynthesis in exponential phase.
Significance: Resolving this would explain why yeast maintains three SNZ-SNO pairs and whether SNO2 represents a B1-linked or condition-specific branch of PLP-family metabolism rather than simple redundancy with SNO1. It is the crux of what distinguishes this understudied paralog from its well-characterized copy-1 counterpart.
What would resolve it: Condition-resolved phenotyping of sno2 single and sno1 sno2 sno3 combinatorial deletions under B6 and B1 limitation; measurement of intracellular PLP and thiamine; identification of the SNZ subunit(s) SNO2 associates with in each condition.
Provenance (the field's own admissions):
Gap: The degree and direction of functional redundancy among the three yeast SNO paralogs (SNO1/SNO2/SNO3) is unresolved: it is unknown whether SNO2 can substitute for SNO1 in B6 biosynthesis, whether SNO2 and SNO3 are interchangeable, and what unique contribution SNO2 makes despite their near-identical sequences.
OPEN BIOLOGY RESIDUAL_SUBGAP
What is known: Single-gene deletions of SNO2 (a copy-2/3 gene) do not impair B6-limited growth, and copies 2 and 3 are reported to have slightly different cellular functions despite extremely close sequence similarity; the B6 phenotype is carried by SNO1.
Significance: Distinguishing genuine paralog-specific function from redundancy is essential to attribute any SNO2-specific annotation correctly and to avoid over-propagating SNO1 evidence onto SNO2.
What would resolve it: Cross-complementation assays (express SNO2 in a sno1 background under B6 limitation and vice versa) and paralog-swap chimeras to map function-determining residues.
Provenance (the field's own admissions):
Protein of unknown function; nearly identical to Sno3p; expression is induced before the diauxic shift and also in the absence of thiamin
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