RidA (formerly YjgF) is a cytosolic homotrimeric 2-iminobutanoate/2-iminopropanoate deaminase (EC 3.5.99.10) that accelerates ammonia release from reactive enamine/imine intermediates generated by pyridoxal-phosphate-dependent enzymes such as threonine dehydratase (IlvA), thereby protecting amino-acid metabolism. During hypochlorous-acid stress, reversible N-chlorination converts RidA into an ATP-independent holdase that binds unfolded cytosolic proteins and prevents their aggregation. This antiaggregation activity is modification-dependent: untreated RidA does not suppress IlvA aggregation.
Definition: Binding to an unfolded or misfolded protein to prevent its aggregation without actively catalyzing refolding. The holdase maintains the client protein in a soluble, folding-competent state.
Justification: N-chlorinated RidA directly prevents aggregation of chemically denatured citrate synthase and IlvA without ATP. Obsolete GO:0051082 records binding but not aggregation prevention, while GO:0140309 requires escort to a defined acceptor or location that is not demonstrated for RidA.
Parent term: molecular_function
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0019239 deaminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for deaminase activity, consistent with the primary enzymatic function of RidA as a 2-iminobutanoate/2-iminopropanoate deaminase (EC 3.5.99.10). This is the core molecular function. Reason: Deaminase activity is the well-established primary function of RidA, supported by phylogenetic inference and experimental evidence from multiple organisms. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000211014 · PANTHER:PTN000211014 SUPPORTS TRANSFER Current PTHR11803 PAINT retains GO:0019239 at this ancestral node. TAIR:locus:2092374 · TAIR:locus:2092374 SUPPORTS TRANSFER Listed as descendant evidence in the exact GOA WITH/FROM; current PAINT serializes its plant seed with an AGI locus identifier. UniProtKB:P0AF93 · UniProtKB:P0AF93 SUPPORTS TRANSFER RidA itself is descendant evidence for the node and has direct deaminase evidence. UniProtKB:P0AFQ5 · UniProtKB:P0AFQ5 SUPPORTS TRANSFER Listed descendant evidence in both the GOA trace and current node assertion. UniProtKB:P37552 · UniProtKB:P37552 SUPPORTS TRANSFER Listed descendant evidence in both the GOA trace and current node assertion. UniProtKB:Q7CP78 · UniProtKB:Q7CP78 SUPPORTS TRANSFER Listed descendant evidence in both the GOA trace and current node assertion. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA annotation for cytosol localization. Consistent with IDA evidence from proteomics studies (PMID:15911532, PMID:18304323) and UniProt annotation. Reason: Cytosolic localization is well-established for RidA. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000211014 · PANTHER:PTN000211014 SUPPORTS TRANSFER Current PTHR11803 PAINT retains GO:0005829 at this ancestral node. RGD:70940 · RGD:70940 SUPPORTS TRANSFER Listed descendant localization evidence in both the GOA trace and current PAINT. SGD:S000000859 · SGD:S000000859 SUPPORTS TRANSFER Listed descendant localization evidence in both the GOA trace and current PAINT. UniProtKB:P0AF93 · UniProtKB:P0AF93 SUPPORTS TRANSFER RidA itself supplies descendant localization evidence and is expected in the trace. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | MODIFY | Summary: IEA annotation for cytoplasm localization. Broader parent of cytosol. Consistent with UniProt subcellular location annotation. Reason: Cytoplasmic localization is correct but less informative than the directly supported cytosol localization. Replace this broad mapping with GO:0005829. Proposed replacements: cytosol |
| GO:0008652 amino acid biosynthetic process | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation for amino acid biosynthetic process. RidA detoxifies reactive enamine/imine intermediates from PLP-dependent enzymes in amino acid metabolism, supporting isoleucine biosynthesis. Reason: The annotation is biologically sound but too broad. RidA's established pathway context is branched-chain amino acid biosynthesis, represented by GO:0009082. That replacement is already present as a separate accepted GOA row, so this recommendation narrows the broad mapping rather than requesting a duplicate annotation. Proposed replacements: branched-chain amino acid biosynthetic process |
| GO:0009082 branched-chain amino acid biosynthetic process | IEA GO_REF:0000043 | ACCEPT | Summary: IEA annotation for branched-chain amino acid biosynthesis. RidA deaminates reactive intermediates from threonine dehydratase (IlvA), which is part of the isoleucine biosynthetic pathway. Reason: This is a more specific and appropriate annotation. RidA's primary biological role is in the isoleucine biosynthetic pathway via detoxification of IlvA intermediates. |
| GO:0009097 isoleucine biosynthetic process | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation to the obsolete isoleucine biosynthetic process term. RidA supports the IlvA branch of branched-chain amino acid biosynthesis. Reason: The source term is obsolete, but the pathway assertion is sound. Replace it with current GO:1901705, which preserves the supported L-isoleucine branch specificity rather than collapsing this row into the separately accepted broad branched-chain amino acid biosynthetic annotation. Proposed replacements: L-isoleucine biosynthetic process |
| GO:0009636 response to toxic substance | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: IEA annotation for response to toxic substance. RidA detoxifies reactive enamine/imine intermediates that are nucleophilic and potentially toxic. Reason: RidA's primary function is detoxification of reactive intermediates. This term is consistent with its stress-protection role, though it is contextual rather than RidA's core deaminase function. The IDA annotation from PMID:25517874 provides stronger experimental support. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000043 | MODIFY | Summary: IEA annotation for hydrolase activity. RidA is classified as EC 3.5.99.10, which is a hydrolase. This is a very broad parent of the more specific deaminase activity. Reason: Hydrolase activity is correct by EC classification but is too broad to convey RidA's chemistry. Replace it with the experimentally and reaction-mapping-supported dual imino deaminase term, which is already present as a separate accepted GOA row rather than needing a duplicate annotation. Proposed replacements: 2-iminobutanoate/2-iminopropanoate deaminase activity |
| GO:0120241 2-iminobutanoate/2-iminopropanoate deaminase activity | IEA GO_REF:0000003 | ACCEPT | Summary: IEA annotation from EC number mapping. This is the most specific and accurate molecular function term for RidA, matching its EC 3.5.99.10 classification. Reason: This is the most precise term for RidA's core enzymatic function. It accurately reflects the dual substrate specificity for both 2-iminobutanoate and 2-iminopropanoate. |
| GO:0120242 2-iminobutanoate deaminase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA annotation from Rhea mapping for the 2-iminobutanoate-specific deaminase activity. This is one of the two specific substrate activities of RidA. Reason: Consistent with the known catalytic activity. UniProt lists the reaction 2-iminobutanoate + H2O = 2-oxobutanoate + NH4(+). |
| GO:0120243 2-iminopropanoate deaminase activity | IEA GO_REF:0000116 | ACCEPT | Summary: IEA annotation from Rhea mapping for the 2-iminopropanoate-specific deaminase activity. This is the second specific substrate activity of RidA. Reason: Consistent with the known catalytic activity. UniProt lists the reaction 2-iminopropanoate + H2O = pyruvate + NH4(+). |
| GO:0120242 2-iminobutanoate deaminase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ISS annotation based on sequence similarity transfer. The 2-iminobutanoate deaminase activity was first characterized in Salmonella enterica RidA and transferred to E. coli by sequence similarity. Reason: Well-supported by sequence similarity to the experimentally characterized Salmonella enterica homolog. Consistent with the IEA annotations for the same and related terms. |
| GO:0042802 identical protein binding | IDA PMID:10595546 A test case for structure-based functional assignment -- the... | KEEP AS NON CORE | Summary: IDA annotation for identical protein binding based on the crystal structure showing RidA forms a homotrimer (PMID:10595546). Reason: The structure directly demonstrates self-association, so the annotation is valid. Identical protein binding is nevertheless an uninformative generic molecular-function term; the homotrimerization and complex annotations capture the structural biology more clearly. Supporting Evidence: PMID:10595546 The YjgF molecule is a homotrimer with exact threefold symmetry. |
| GO:0070207 protein homotrimerization | IDA PMID:10595546 A test case for structure-based functional assignment -- the... | ACCEPT | Summary: IDA annotation for protein homotrimerization based on crystal structure (PMID:10595546). RidA is a homotrimer, which is the functional form. Reason: Directly supported by the 1.2A crystal structure. UniProt confirms homotrimer subunit structure. |
| GO:0032991 protein-containing complex | IDA PMID:10595546 A test case for structure-based functional assignment -- the... | ACCEPT | Summary: IDA annotation for protein-containing complex. RidA forms a homotrimeric complex. Reason: The homotrimer is the functional complex. This is a broad CC term consistent with the structural evidence. |
| GO:0009636 response to toxic substance | IDA PMID:25517874 Activation of RidA chaperone function by N-chlorination. | KEEP AS NON CORE | Summary: IDA annotation for response to toxic substance from Mueller et al. (2014). ridA deletion mutants are sensitive to HOCl stress, showing prolonged lag phase at medium HOCl concentrations (1-2 mM). RidA plays a role in protecting E. coli against HOCl-mediated stress. Reason: The ridA mutant is sensitive to HOCl, demonstrating a secondary stress-response role rather than the constitutive core deaminase function. This is supported by growth assays in the presence of HOCl (PMID:25517874). Note that this response involves the HOCl-activated chaperone function, not the deaminase activity. Supporting Evidence: PMID:25517874 Deletion of ridA results in an HOCl-sensitive phenotype. |
| GO:0019239 deaminase activity | IDA PMID:23696645 Redox proteomics uncovers peroxynitrite-sensitive proteins t... | ACCEPT | Summary: IDA annotation for deaminase activity based on experimental evidence. Reason: Direct experimental evidence for deaminase activity. This is the core molecular function of RidA. The cached paper is abstract-only and identifies in-vitro activity without exposing the full assay details, so the curator's IDA judgment is retained without claiming more detail than the cache supports. Supporting Evidence: PMID:23696645 In in vitro studies, we could show that the activity of RidA, a recently discovered enamine/imine deaminase, is regulated in a specific manner by the modification of its single conserved cysteine. |
| GO:0051082 unfolded protein binding | IDA PMID:25517874 Activation of RidA chaperone function by N-chlorination. | MODIFY | Summary: PMID:25517874 directly demonstrates that N-chlorinated RidA binds unfolded clients and prevents their aggregation without ATP. The activity is a genuine, reversible stress-activated holdase function, but GO:0051082 is obsolete and does not express aggregation prevention. Reason: Retain the demonstrated biology but replace the obsolete binding term with the project's general holdase chaperone activity NTR. GO:0140309 does not fit because the experiment shows in-situ aggregation prevention without escort to a defined acceptor or destination. The evidence is explicitly conditional on HOCl- or chloramine-mediated N-chlorination; untreated RidA did not prevent IlvA aggregation. See go-ontology#30962 and file:projects/UNFOLDED_PROTEIN_BINDING.md. Proposed replacements: holdase chaperone activity (NTR needed; GO:0140309 does not fit -- carrier-specific) Supporting Evidence: PMID:25517874 The addition of ATP did not enhance chaperone activity, consistent with a holdase function of HOCl-treated RidA PMID:25517874 In contrast, incubation of IlvA with a 10-fold molar excess of untreated RidA had no effect on IlvA’s aggregation behaviour file:projects/UNFOLDED_PROTEIN_BINDING.md Because GO:0051082 is already obsolete |
| GO:0005829 cytosol | IDA PMID:15911532 Localization, annotation, and comparison of the Escherichia ... | ACCEPT | Summary: IDA annotation for cytosol localization from proteomics study by Corbin et al. (2003). Reason: Proteomics-based experimental evidence for cytosol localization. |
| GO:0005829 cytosol | IDA PMID:18304323 Protein abundance profiling of the Escherichia coli cytosol. | ACCEPT | Summary: IDA annotation for cytosol localization from proteomics study by Ishihama et al. (2008). Reason: Independent proteomics confirmation of cytosol localization. Supporting Evidence: PMID:18304323 we identified 1103 proteins from the cytosolic fraction of the Escherichia coli |
| GO:0019239 deaminase activity | ISO PMID:22094463 Conserved YjgF protein family deaminates reactive enamine/im... | ACCEPT | Summary: ISO annotation for deaminase activity based on ortholog evidence. Lambrecht et al. (2012) showed that conserved YjgF/RidA family proteins deaminate reactive enamine/imine intermediates of PLP-dependent enzymes. Reason: Consistent with the core function of RidA. The study demonstrates the conserved deaminase function across the RidA family. |
| GO:0016020 membrane | HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona... | MARK AS OVER ANNOTATED | Summary: Recovered in a membrane-fraction proteome without protein-specific evidence that it associates with membranes. Reason: UniProt: cytoplasm only; RidA is a small soluble enamine/imine deaminase with no reported membrane association. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: KEEP_AS_NON_CORE.) |
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