RdeA is the histidine-phosphotransfer (HPt / H2-module) intermediate of the two-component phosphorelay that controls the rate of Dictyostelium discoideum development. It is a small (~28 kDa), highly charged, hydrophilic, non-compartmentalised cytosolic protein that carries a conserved phosphoaccepting histidine at position 65. In the relay, sensor histidine kinases (such as DhkA, the SDF-2 receptor, and DhkC) transfer a phosphoryl group to His-65 of RdeA, which in turn exchanges phosphate with the response-regulator receiver aspartate (Asp-212) of the cAMP phosphodiesterase RegA; the transfer is bidirectional. Phospho-RegA is the active phosphodiesterase, so RdeA-mediated phosphotransfer tunes RegA activity, intracellular cAMP levels and hence PKA activity. Loss of RdeA (or replacement of His-65) lowers RegA activity and causes precocious, rapid development (aggregation and terminal spore/stalk differentiation within ~14 h instead of the normal ~24 h). RdeA is functionally interchangeable with the H2-module protein Ypd1 of budding yeast.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000160 phosphorelay signal transduction system | IBA GO_REF:0000033 | ACCEPT | Summary: RdeA is a core component of a multistep His-Asp phosphorelay; the phylogenetic inference is strongly corroborated by direct biochemical and genetic evidence in Dictyostelium. Reason: RdeA is the HPt intermediate of the DhkA/DhkC -> RdeA -> RegA phosphorelay; this is its defining process. Supporting Evidence: PMID:9582274 part of a multistep phosphorelay system that modulates the rate of development |
| GO:0005634 nucleus | IBA GO_REF:0000033 | REMOVE | Summary: Nuclear localization is a phylogenetic over-propagation from HPt family members in other lineages. Direct evidence shows Dictyostelium RdeA is not compartmentalised (cytosolic), with no support for a nuclear pool. Reason: RdeA is directly reported as not compartmentalised and cytosolic; the nuclear IBA is a compartment over-propagation from HPt orthologs. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: PANTHER:PTN002000688 · PANTHER HPt / H2-module phosphotransfer protein node SUPPORTS SOURCE BUT NOT TARGET The node's plant/fungal HPt members (Arabidopsis AHP, yeast Ypd1) can be nuclear, but Dictyostelium RdeA is directly shown to be non-compartmentalised, so the nuclear localization does not transfer. Supporting Evidence: PMID:9582274 RdeA is not compartmentalized |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic localization is consistent with direct evidence that RdeA is a soluble, non-compartmentalised protein. Reason: Matches the direct cytosol localization; RdeA acts as a soluble phosphotransfer intermediate. Supporting Evidence: PMID:9582274 RdeA is not compartmentalized |
| GO:0009927 histidine phosphotransfer kinase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Histidine phosphotransfer activity is the core molecular function of RdeA, strongly corroborated by direct biochemistry. Reason: RdeA transfers phosphate via His-65 between sensor kinases and RegA, the defining HPt-protein activity. Supporting Evidence: PMID:10488068 phospho-transfer between the two proteins in vitro |
| GO:0043424 protein histidine kinase binding | IBA GO_REF:0000033 | ACCEPT | Summary: As the HPt intermediate, RdeA physically communicates with the histidine-kinase/phosphodiesterase partners of the relay to shuttle phosphate. Reason: Binding to its two-component partners is intrinsic to the phosphotransfer mechanism. Supporting Evidence: PMID:10488068 phospho-transfer between the two proteins in vitro |
| GO:0000160 phosphorelay signal transduction system | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO annotation from the HPt domain, redundant with the experimentally supported phosphorelay annotations. Correct and core. Reason: Domain-based inference agrees with the direct evidence. Supporting Evidence: PMID:10488068 a phospho-transfer protein that supplies phosphates to RegA |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular-location mapping to cytoplasm, consistent with the direct cytosol evidence. Reason: Correct localization for this soluble phosphotransfer protein. Supporting Evidence: PMID:9582274 RdeA is not compartmentalized |
| GO:0009927 histidine phosphotransfer kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO annotation from the HPt/H2 module signature, redundant with the IDA evidence. Core molecular function. Reason: Domain-based inference agrees with the direct biochemical evidence. Supporting Evidence: PMID:9582274 members of the H2 module family of phosphotransferases that participate in multistep phosphoryl relays |
| GO:0043424 protein histidine kinase binding | IEA GO_REF:0000002 | ACCEPT | Summary: Domain-based inference of histidine-kinase binding, consistent with RdeA's role as the relay intermediate. Reason: Intrinsic to the phosphotransfer mechanism with its two-component partners. Supporting Evidence: PMID:10488068 phospho-transfer between the two proteins in vitro |
| GO:0005829 cytosol | IDA PMID:9582274 Evidence that the RdeA protein is a component of a multistep... | ACCEPT | Summary: Direct evidence (c-Myc/GFP tagging) shows RdeA is not compartmentalised, i.e. a soluble cytosolic protein. This is the core location. Reason: Directly demonstrated cytosolic distribution, where the soluble phosphorelay operates. Supporting Evidence: PMID:9582274 RdeA is not compartmentalized |
| GO:0009927 histidine phosphotransfer kinase activity | IDA PMID:10488068 The RdeA-RegA system, a eukaryotic phospho-relay controlling... | ACCEPT | Summary: Direct biochemical demonstration of bidirectional phosphotransfer between RdeA (His-65) and RegA (Asp-212). Core molecular function. Reason: In-vitro phosphotransfer dependent on His-65 establishes the HPt activity directly. Supporting Evidence: PMID:10488068 and aspartate 212 of RegA, and occurs in both directions |
| GO:0030435 sporulation resulting in formation of a cellular spore | IGI PMID:9582274 Evidence that the RdeA protein is a component of a multistep... | KEEP AS NON CORE | Summary: RdeA influences the timing of terminal spore differentiation via the RegA/PKA relay; a developmental output downstream of the core phosphotransfer function. Reason: Genuine but downstream developmental role, secondary to the molecular phosphotransfer activity. Supporting Evidence: PMID:9582274 aggregated rapidly and formed spores and stalk cells within 14 h of development instead of the normal 24 h |
| GO:0030587 sorocarp development | IMP PMID:9582274 Evidence that the RdeA protein is a component of a multistep... | KEEP AS NON CORE | Summary: rdeA loss accelerates the whole developmental program (rapid development). A pleiotropic developmental role downstream of the relay. Reason: Broad developmental-timing phenotype, secondary to the core phosphotransfer function. Supporting Evidence: PMID:9582274 aggregated rapidly and formed spores and stalk cells within 14 h of development instead of the normal 24 h |
| GO:0031288 sorocarp morphogenesis | IMP PMID:6298035 A new class of rapidly developing mutants in Dictyostelium d... | KEEP AS NON CORE | Summary: The classic rapid-developing (rde) mutants alter fruiting-body morphogenesis timing; a developmental output of the RdeA/RegA relay. Reason: Developmental morphogenesis phenotype, downstream of the core molecular function. Supporting Evidence: PMID:6298035 rapidly developing mutants |
| GO:0061128 positive regulation of chemotaxis to cAMP by DIF-2 | IMP PMID:26919666 Differentiation-inducing factor 2 modulates chemotaxis via t... | KEEP AS NON CORE | Summary: RdeA participates in a DIF-2/DhkC-dependent modulation of cAMP chemotaxis, a specific downstream signaling role of the phosphorelay. Reason: A specific, context-dependent downstream role via the DhkC branch of the relay; not the core phosphotransfer function. Supporting Evidence: PMID:26919666 histidine kinase DhkC |
| GO:0000160 phosphorelay signal transduction system | IMP PMID:9582274 Evidence that the RdeA protein is a component of a multistep... | ACCEPT | Summary: Genetic evidence that RdeA acts in a multistep phosphorelay controlling developmental rate. Core process. Reason: The rdeA mutant phenotype and His-65 requirement place RdeA in the phosphorelay. Supporting Evidence: PMID:9582274 part of a multistep phosphorelay system that modulates the rate of development |
| GO:0000160 phosphorelay signal transduction system | IDA PMID:10488068 The RdeA-RegA system, a eukaryotic phospho-relay controlling... | ACCEPT | Summary: Direct biochemical evidence of the RdeA-RegA phosphorelay. Core process. Reason: In-vitro reconstitution of RdeA-RegA phosphotransfer establishes the relay directly. Supporting Evidence: PMID:10488068 phospho-transfer between the two proteins in vitro |
| GO:0030587 sorocarp development | HMP PMID:17659086 High-throughput analysis of spatio-temporal dynamics in Dict... | KEEP AS NON CORE | Summary: High-throughput phenotyping places rdeA among genes affecting developmental progression; consistent with its rapid-development phenotype. Reason: Broad developmental-timing association, downstream of the core phosphotransfer function. Supporting Evidence: PMID:9582274 part of a multistep phosphorelay system that modulates the rate of development |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)