OCA6 (YDR067C) is a small (224-residue) cytoplasmic protein of the budding yeast Saccharomyces cerevisiae that adopts a protein-tyrosine-phosphatase (PTP) superfamily fold and belongs to the fungal OCA family of PFA-DSP (Plant-and-Fungi Atypical Dual-Specificity Phosphatase)-related proteins, together with Oca1, Oca2, Siw14/Oca3, Oca4 and Oca5. Although classified within the PTP/DSP structural family (Pfam Y_phosphatase2 / Siw14-like; CDD PFA-DSP_Oca6) and carrying a predicted phosphocysteine active-site residue, its canonical CX5R catalytic loop is degenerate — the invariant phosphate-binding arginine is not present — so OCA6 is likely a catalytically impaired or pseudophosphatase member of the family rather than a bona fide protein-tyrosine phosphatase. The biochemically active prototype of the family, Siw14/Oca3, is an inositol-pyrophosphate (5-InsP7) phosphatase, not a phosphotyrosine phosphatase. OCA6 is genetically linked to the other OCA-family members and is implicated in cellular responses to caffeine, rapamycin and oxidative stress, and its deletion reduces replication of Brome mosaic virus in yeast. Its own catalytic status, physiological substrate, and precise role within the OCA family remain undetermined.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016791 phosphatase activity | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: General phosphatase activity inferred phylogenetically from membership in the PTP/PFA-DSP fold family. The fold is genuinely present, but OCA6's canonical CX5R catalytic loop is degenerate (missing the invariant P-loop arginine), so any catalytic activity is uncertain. Retained as a cautious, general, non-core molecular function that reflects the family fold without over-committing to a specific catalytic role. Reason: IBA reflects the ancestral phosphatase fold of the PFA-DSP/PTP family, of which OCA6 is a member (PMID:21409566). "phosphatase activity" (GO:0016791) is general enough to be defensible at the family level and is not contradicted outright by the fold. However, direct catalytic activity of OCA6 has never been demonstrated and its CX5R P-loop arginine is absent (reviewer sequence analysis in OCA6-notes.md; corroborated by a fungal pseudophosphatome analysis reporting catalytic-motif substitutions in Oca1/Oca2/Oca6), so this is kept as non-core and not promoted to any specific catalytic term. Supporting Evidence: PMID:21409566 Bioinformatic analysis revealed the existence of novel PFA-DSP-related proteins in fungi (Oca1, Oca2, Oca4 and Oca6 in Saccharomyces cerevisiae) and protozoa |
| GO:0004725 protein tyrosine phosphatase activity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: Specific protein-tyrosine-phosphatase catalytic activity, assigned electronically from the "Putative" EC 3.1.3.48 in UniProt. This is an over-annotation: it asserts a specific catalysis (phosphotyrosine hydrolysis) that is (i) not supported by OCA6's degenerate CX5R catalytic loop, and (ii) biochemically inconsistent with the family — the active family prototype Siw14/Oca3 is an inositol-pyrophosphate (5-InsP7) phosphatase, not a protein-tyrosine phosphatase. The EC number is explicitly marked "Putative" in UniProt. Reason: Electronic mapping from the UniProt "Putative" EC 3.1.3.48. There is no experimental evidence that OCA6 hydrolyzes phosphotyrosine, its P-loop arginine of the CX5R catalytic motif is absent (reviewer sequence analysis in OCA6-notes.md), and the characterized activity in this atypical DSP family is inositol-pyrophosphate phosphatase (Siw14/Oca3), not phosphotyrosine phosphatase. Asserting a specific PTP activity over-annotates a likely pseudophosphatase; the general fold-level phosphatase term (GO:0016791) already captures what the family membership supports. Supporting Evidence: PMID:21409566 Siw14/Oca3 was an active phosphatase in vitro, whereas no phosphatase activity could be detected for Oca1. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization asserted electronically from the UniProt subcellular-location vocabulary. Consistent with the experimental HDA localization and with the protein carrying no signal peptide or transmembrane segment. Reason: Correct localization; this IEA (SubCell mapping) is concordant with the experimentally supported HDA cytoplasm annotation from PMID:14562095. Cytoplasm is the core cellular component of OCA6. |
| GO:0005737 cytoplasm | HDA PMID:14562095 Global analysis of protein localization in budding yeast. | ACCEPT | Summary: Cytoplasmic localization from the genome-wide GFP-fusion localization study. This is the single highest-confidence attribute of OCA6 and is consistent with a soluble cytoplasmic protein lacking signal/transmembrane features. Reason: Direct high-throughput experimental localization evidence (GFP-tagged full-length protein). Cytoplasm is well supported and is the core cellular-component assignment for OCA6. Supporting Evidence: PMID:14562095 we describe the construction and analysis of a collection of yeast strains expressing full-length, chromosomally tagged green fluorescent protein fusion proteins. |
| GO:0003674 molecular_function | ND GO_REF:0000015 | ACCEPT | Summary: Root molecular_function with the ND (No biological Data) evidence code — the honest curator placeholder recording that no molecular function has been experimentally established for OCA6. This is accurate: OCA6's catalytic status and substrate are undetermined. Reason: ND correctly reflects the absence of experimentally demonstrated molecular function for OCA6. Retained as-is; the associated knowledge gap is captured in core_functions.knowledge_gaps. |
| GO:0008150 biological_process | ND GO_REF:0000015 | ACCEPT | Summary: Root biological_process with the ND evidence code — placeholder recording that no specific biological process has been experimentally established for OCA6 at annotation-grade evidence. Family-level genetic links to caffeine/rapamycin/oxidative-stress responses and a BMV-screen phenotype exist but are not curated here as specific BP annotations. Reason: ND appropriately reflects the lack of an annotation-grade, OCA6-specific biological process. The genome-wide BMV-replication phenotype (PMID:14671320) and family-level caffeine/rapamycin genetic linkage (PMID:21409566) are documented in the notes and knowledge gaps rather than asserted as specific process annotations, given their low specificity for OCA6 alone. |
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Download this section (compressed HTML)Q: Is OCA6 a catalytically active phosphatase, and if so what is its physiological substrate — a phosphoprotein or an inositol pyrophosphate such as 5-InsP7?
Suggested experts: Protein/inositol-pyrophosphate phosphatase biochemists, PTP/dual-specificity-phosphatase structural biologists
Q: What is the composition of the OCA complex, and does OCA6 function within it as a catalytic subunit, a regulatory subunit, or a redundant paralog?
Suggested experts: Yeast signaling / stress-response biologists
Experiment: Express and purify recombinant OCA6 and assay phosphatase activity against generic phosphatase substrates, phosphotyrosine peptides, and an inositol-pyrophosphate panel (including 5-InsP7), comparing wild type with active-site and P-loop-arginine-restored mutants to test whether the degenerate CX5R loop can be catalytically rescued.
Type: In-vitro enzymology
Experiment: Affinity-purify tagged OCA6 from yeast and identify interacting OCA-family members and other partners to define the OCA complex and place OCA6 within it.
Type: Affinity purification / mass spectrometry
Experiment: Characterize oca6 deletion phenotypes under oxidative stress, caffeine, and rapamycin, and in the BMV-replication assay, with epistasis against SIW14/OCA3 and the other OCA genes to determine OCA6's specific and redundant contributions.
Type: Phenotypic / genetic analysis
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