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. 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. 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 | KEEP AS NON CORE | Summary: Pyridoxine (vitamin B6) metabolic process. Consistent with the family role in PLP/B6 biosynthesis and with SGD's ISS annotation of the same term (supported by the Aspergillus pyroA and Neurospora pdx-1/pdx-2 orthologs). Slightly more general/parallel to the PLP biosynthetic process term; retained as a valid family process annotation. 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. 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 | KEEP AS NON CORE | Summary: Duplicate of the pyridoxine metabolic process annotation, from the ARBA machine-learning pipeline. Same domain/orthology support; retained as a valid but non-core family process term. 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 | KEEP AS NON CORE | Summary: Root molecular_function placeholder with ND (no biological data) evidence, an SGD no-data stub predating the electronic/phylogenetic MF assignments. Uninformative; kept as-is per convention for ND root annotations (superseded by the specific MF terms above). |
| GO:0005575 cellular_component | ND GO_REF:0000015 | KEEP AS NON CORE | Summary: Root cellular_component placeholder with ND evidence, an SGD no-data stub. Uninformative; kept as-is per convention (superseded by the glutaminase-complex and cytosol IBA annotations for the family). |
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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):
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