regA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference of cAMP phosphodiesterase activity is correct and represents the core catalytic function of RegA, which harbors a class I PDE domain that hydrolyzes intracellular cAMP. Reason: RegA/DdPDE2 is directly demonstrated to be a cAMP-specific phosphodiesterase that degrades intracellular cAMP. The IBA annotation matches the experimentally established core function. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity	IBA GO_REF:0000033	UNDECIDED	Summary: RegA is strongly cAMP-selective, but the evidence does not yet settle whether it retains a weak cGMP-hydrolyzing capability compatible with the ancestral PAINT annotation. Reason: PTHR11347-paint.tsv places the cGMP phosphodiesterase IBD at PTN001682918. The earlier review treated approximately 200-fold cAMP selectivity as proving absence of all cGMP activity. The primary kinetic summary (PMID:12429832) reports a lower bound on selectivity; the later recombinant-complex study (PMID:34063491) calls RegA dual-specific and directly shows cGMP competition, but the displacement assay does not independently establish cGMP hydrolysis. cAMP is the clearly established physiological substrate. Withdraw the categorical removal pending expert adjudication of the actual cGMP turnover data; do not infer catalysis from binding alone. The completed OpenScientist report correctly supports cAMP as the established physiological substrate, but its recommendation to remove or negate cGMP activity relies on IBA-only provenance, cAMP preference and alternative cGMP PDEs. It omits PMID:34063491, whose recombinant RegA-RD experiments explicitly discuss broader specificity and measure cGMP competition. Those experiments do not establish cGMP product formation, while the older kinetic table gives a selectivity bound. Neither selective physiology nor substrate binding resolves weak catalytic capacity. Retain UNDECIDED and seek expert inspection of substrate-turnover evidence; do not add a NOT annotation. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001682918 · PTN001682918 UNRESOLVED The cached PAINT IBD at this node was checked. RegA is strongly cAMP-selective, but the evidence does not yet settle whether it retains a weak cGMP-hydrolyzing capability compatible with the ancestral PAINT annotation. The prior categorical propagation-error assignment is withdrawn pending assessment of retention versus target-specific divergence. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP PMID:34063491 addition of cGMP (lilac plot) resulted in only a partial decrease in FP that remained stable over time. file:DICDI/regA/regA-hypotheses/function-hypothesis-go-0047555/openscientist.md no primary paper reports cGMP as a substrate
GO:0141162 negative regulation of cAMP/PKA signal transduction	IBA GO_REF:0000033	ACCEPT	Summary: By degrading intracellular cAMP, RegA lowers PKA activity, acting as a negative regulator of cAMP/PKA signaling. This is a well-supported core biological role. Reason: Genetic and biochemical evidence show that inhibition of the RegA phosphodiesterase increases PKA activity at a differentiation checkpoint, establishing RegA as a negative regulator of cAMP/PKA signal transduction. Supporting Evidence: PMID:9435289 inhibition of the phosphodiesterase results in an increase in the activity of PKA, which acts at a check point for terminal differentiation
GO:0030587 sorocarp development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: RegA is required for normal fruiting body (sorocarp) development; loss of RegA causes rapid, precocious development. This is a genuine developmental role but downstream of the core cAMP-degrading function. Reason: The developmental role in sorocarp formation is well established across multiple experimental studies, but it is a consequence of RegA's control over intracellular cAMP/PKA rather than a distinct core molecular activity. Supporting Evidence: PMID:9435289 inhibition of the phosphodiesterase results in an increase in the activity of PKA, which acts at a check point for terminal differentiation
GO:0000160 phosphorelay signal transduction system	IEA GO_REF:0000002	ACCEPT	Summary: RegA is the response-regulator component of the RdeA-RegA His-Asp phosphorelay, a core aspect of its regulation. Correct annotation. Reason: RegA contains a receiver domain that accepts phosphate from RdeA in a His-Asp phosphorelay, directly supported by biochemical and genetic evidence. Supporting Evidence: PMID:10488068 The response regulator, RegA, is composed of an N-terminal receiver domain linked to a C-terminal cAMP-phosphodiesterase domain
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity	IEA GO_REF:0000002	MODIFY	Summary: This is the general parent term for the phosphodiesterase family. It is correct but less informative than the specific cAMP phosphodiesterase activity that represents RegA's actual demonstrated specificity. Reason: The general cyclic-nucleotide PDE activity is technically correct (EC 3.1.4.53), but RegA is cAMP-specific, so the specific child term GO:0004115 better captures the core function. Proposed replacements: 3',5'-cyclic-AMP phosphodiesterase activity Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity	IEA GO_REF:0000120	ACCEPT	Summary: Correct core catalytic activity, consistent with direct experimental characterization of RegA as a cAMP-specific phosphodiesterase. Reason: This automated annotation agrees with the experimentally demonstrated cAMP phosphodiesterase activity of RegA. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: RegA is a cytosolic (internal) phosphodiesterase, consistent with its role in degrading intracellular cAMP. Correct localization. Reason: Subcellular location evidence and functional characterization place RegA in the cytosol where it degrades intracellular cAMP. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
GO:0007165 signal transduction	IEA GO_REF:0000002	ACCEPT	Summary: Signal transduction is a correct broad annotation for the phosphorelay-regulated cAMP phosphodiesterase RegA. Reason: RegA accepts phosphate through its receiver domain and changes cAMP turnover as the output of the RdeA-RegA signaling system. The term is broad, but breadth and coexistence with more specific terms do not make this an over-annotation. Supporting Evidence: PMID:10488068 The response regulator, RegA, is composed of an N-terminal receiver domain linked to a C-terminal cAMP-phosphodiesterase domain
GO:0008081 phosphoric diester hydrolase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: General grandparent hydrolase term. Correct but far less informative than the specific cAMP phosphodiesterase activity. Reason: RegA is a phosphoric diester hydrolase, but the specific cAMP phosphodiesterase activity (GO:0004115) captures the core function; this broad term is retained only as a non-core ancestor. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
GO:0120320 lateral pseudopodium retraction	IMP PMID:10930471 The internal phosphodiesterase RegA is essential for the sup...	KEEP AS NON CORE	Summary: RegA is essential for suppressing lateral pseudopod formation during chemotaxis. This is a genuine experimentally-supported role but is downstream of the core cAMP-degrading activity. Reason: Direct mutant phenotype analysis shows RegA is required to suppress lateral pseudopods during chemotaxis, a cell-motility role secondary to its control of internal cAMP levels. Supporting Evidence: PMID:10930471 RegA is essential for specifically suppressing lateral pseudopod formation during the response to an increasing temporal gradient of cAMP
GO:0000160 phosphorelay signal transduction system	IMP PMID:10488068 The RdeA-RegA system, a eukaryotic phospho-relay controlling...	ACCEPT	Summary: Experimental evidence for RegA as the response regulator in the RdeA-RegA His-Asp phosphorelay. Core regulatory mechanism. Reason: Biochemical phospho-transfer between RdeA (His65) and RegA (Asp212) demonstrates RegA participation in a eukaryotic His-Asp phosphorelay. Supporting Evidence: PMID:10488068 Phosphorylation of RegA by a heterologous phospho-donor protein activates RegA phosphodiesterase activity at least 20-fold
GO:0005515 protein binding	IPI PMID:31730032 Mitogen-activated protein kinase regulation of the phosphodi...	MODIFY	Summary: This IPI annotation records the physical association between RegA and the MAP kinase Erk2. The bare protein binding term is uninformative; the more specific protein kinase binding term better captures the interaction. Reason: Co-immunoprecipitation shows RegA associates with the atypical MAPK Erk2, which downregulates RegA. Replacing bare protein binding with protein kinase binding conveys the nature of the interactor. Proposed replacements: protein kinase binding Supporting Evidence: PMID:31730032 Co-immunoprecipitation analysis indicated that Erk2 associates with both RegA
GO:0010225 response to UV-C	IDA PMID:25858552 Response of Dictyostelium discoideum to UV-C and involvement...	KEEP AS NON CORE	Summary: In this study regA was one of several developmentally regulated genes whose transcript levels were monitored by RT-PCR following UV-C exposure. This reflects a transcriptional/developmental response rather than a dedicated molecular function of RegA in UV-C response. Reason: The evidence is an expression change of regA among many developmental genes after UV-C irradiation, not a direct functional role of RegA in the UV-C response; retained as non-core. Supporting Evidence: PMID:25858552 regA, ctnA, ctnB, gp24, hspD and dsn were analysed using semiquantitative RT-PCR
GO:0005829 cytosol	TAS PMID:17040207 Seven Dictyostelium discoideum phosphodiesterases degrade th...	ACCEPT	Summary: RegA/DdPDE2 is described as localized in the cytosol where it degrades intracellular cAMP. Correct core localization. Reason: The cytosolic localization is explicitly stated and is consistent with RegA's function in degrading intracellular cAMP. Supporting Evidence: PMID:17040207 DdPDE2 (RegA) encodes a cAMP-specific PDE localized in the cytosol of the cell where it degrades intracellular cAMP
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: DIF-2 enhances chemotaxis in shallow cAMP gradients via RegA as part of the DhkC-RdeA-RegA two-component system. A specialized signaling role downstream of the core cAMP-degrading function. Reason: Mutant analysis places RegA in the DhkC-RdeA-RegA pathway through which DIF-2 enhances chemotaxis, a specific regulatory role that is not the core molecular function. Supporting Evidence: PMID:26919666 DIF-2 enhances chemotaxis under the same conditions via a phosphodiesterase, response regulator A (RegA)
GO:1904776 regulation of protein localization to cell cortex	IMP PMID:10930471 The internal phosphodiesterase RegA is essential for the sup...	KEEP AS NON CORE	Summary: In regA-null cells myosin II fails to localize normally to the cortex during a temporal cAMP gradient, indicating RegA influences cortical protein localization. A downstream cytoskeletal consequence of altered cAMP levels. Reason: The mutant phenotype links RegA to cortical myosin II localization, but this is a downstream effect of cAMP/PKA dysregulation rather than a core molecular function. Supporting Evidence: PMID:10930471 myosin II does not localize in a normal manner to the cortex
GO:0005515 protein binding	IPI PMID:9435289 A cAMP-phosphodiesterase controls PKA-dependent differentiat...	MODIFY	Summary: RegA phosphodiesterase is stimulated by binding to the regulatory subunit (PKA-R) of cAMP-dependent protein kinase. The bare protein binding term is uninformative; a specific protein kinase A regulatory subunit binding term is more appropriate. Reason: The interaction partner is the PKA regulatory subunit (PKA-R), so the specific term protein kinase A regulatory subunit binding conveys the identity of the interactor better than bare protein binding. Proposed replacements: protein kinase A regulatory subunit binding Supporting Evidence: PMID:9435289 stimulated by binding to the regulatory subunit of cAMP-dependent protein kinase, PKA-R
GO:0031288 sorocarp morphogenesis	IMP PMID:9435289 A cAMP-phosphodiesterase controls PKA-dependent differentiat...	KEEP AS NON CORE	Summary: RegA loss alters fruiting body morphogenesis (precocious/aberrant development). A genuine developmental phenotype downstream of cAMP/PKA control. Reason: The morphogenesis phenotype reflects RegA's control of the PKA differentiation checkpoint rather than a distinct core molecular activity. Supporting Evidence: PMID:9435289 inhibition of the phosphodiesterase results in an increase in the activity of PKA, which acts at a check point for terminal differentiation
GO:0000156 phosphorelay response regulator activity	IMP PMID:10488068 The RdeA-RegA system, a eukaryotic phospho-relay controlling...	ACCEPT	Summary: RegA's N-terminal receiver domain functions as a phosphorelay response regulator, accepting phosphate at Asp212 which activates the phosphodiesterase. This is a core molecular function. Reason: Phospho-transfer experiments demonstrate RegA acts as a response regulator whose receiver-domain phosphorylation activates its enzymatic output, a core function of the protein. Supporting Evidence: PMID:10488068 Phosphorylation of RegA by a heterologous phospho-donor protein activates RegA phosphodiesterase activity at least 20-fold
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity	IDA PMID:9582277 An intersection of the cAMP/PKA and two-component signal tra...	MODIFY	Summary: Direct biochemical characterization measured a cAMP phosphodiesterase activity (Km ~5 uM for cAMP). Since RegA is cAMP-specific, the specific child term is more precise than this general parent. Reason: The IDA measured cAMP-specific phosphodiesterase activity; the specific term GO:0004115 better represents the demonstrated substrate specificity than the general cyclic-nucleotide PDE term. Proposed replacements: 3',5'-cyclic-AMP phosphodiesterase activity Supporting Evidence: PMID:9582277 One domain is a cAMP phosphodiesterase (Km approximately 5 microM); the other is homologous to response regulators
GO:0048837 sorocarp sorus development	IMP PMID:24511612 Loss of cAMP-specific phosphodiesterase rescues spore develo...	KEEP AS NON CORE	Summary: Loss of RegA accelerates spore/sorus development and can rescue sporulation defects of certain G-protein mutants. A developmental role downstream of cAMP/PKA control. Reason: The spore/sorus developmental phenotype results from elevated cAMP/PKA activity when RegA is absent, a downstream consequence rather than a core molecular function. Supporting Evidence: PMID:24511612 Loss of RegA also results in accelerated spore development
GO:0030587 sorocarp development	HMP PMID:17659086 High-throughput analysis of spatio-temporal dynamics in Dict...	KEEP AS NON CORE	Summary: This high-throughput spatio-temporal phenotype screen catalogs many mutant clones. The cached abstract does not contain a regA-specific statement that I can quote to verify the developmental phenotype for this gene, though RegA's sorocarp role is well supported elsewhere. Reason: RegA's role in sorocarp development is well established from multiple dedicated studies; this high-throughput resource is consistent with that role but the abstract lacks a regA-specific quotable statement, so it is retained as non-core corroboration. Supporting Evidence: PMID:9435289 inhibition of the phosphodiesterase results in an increase in the activity of PKA, which acts at a check point for terminal differentiation
GO:0030435 sporulation resulting in formation of a cellular spore	IMP PMID:12796307 Genetic interactions of the E3 ubiquitin ligase component Fb...	KEEP AS NON CORE	Summary: regA mutations were recovered as suppressors that restore sporulation in an fbxA background, consistent with RegA restraining sporulation by lowering cAMP/PKA. A developmental role downstream of the core function. Reason: RegA influences sporulation through its control of intracellular cAMP/PKA; the suppressor genetics support a role in sporulation that is downstream of the core cAMP-degrading activity. Supporting Evidence: PMID:12796307 both suppressors also rescued substantially the culmination deficiency of the fbxA strain
GO:0030587 sorocarp development	IMP PMID:12796307 Genetic interactions of the E3 ubiquitin ligase component Fb...	KEEP AS NON CORE	Summary: regA and dhkA suppressor mutations rescue the culmination/fruiting deficiency of fbxA cells, linking RegA to sorocarp development downstream of cAMP/PKA control. Reason: The genetic suppression of a fruiting-body defect places RegA in sorocarp development, but as a downstream regulatory consequence rather than a core molecular activity. Supporting Evidence: PMID:12796307 both suppressors also rescued substantially the culmination deficiency of the fbxA strain
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity	IDA PMID:9435289 A cAMP-phosphodiesterase controls PKA-dependent differentiat...	ACCEPT	Summary: RegA is directly characterized as a cAMP-specific phosphodiesterase stimulated by PKA-R binding. Core catalytic function. Reason: Direct experimental evidence establishes RegA as a cAMP-specific phosphodiesterase, its core molecular function. Supporting Evidence: PMID:9435289 stimulated by binding to the regulatory subunit of cAMP-dependent protein kinase, PKA-R
GO:0006970 response to osmotic stress	TAS PMID:14718564 Adenylyl cyclase G is activated by an intramolecular osmosen...	KEEP AS NON CORE	Summary: Osmotic up-shift converts the histidine kinase DokA into a phosphatase, which inactivates RegA and leads to cortex fortification. RegA is thus a node in the osmotic-stress cAMP response, downstream of histidine kinase signaling. Reason: RegA participates in the osmotic-stress response as a target of DokA-mediated regulation of its phosphorelay input, a specialized regulatory context rather than a core molecular function. Supporting Evidence: PMID:14718564 This results in inactivation of the cAMP phosphodiesterase RegA and ultimately in fortification of the cell cortex
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity	IMP PMID:15752425 cAMP controls cytosolic Ca2+ levels in Dictyostelium discoid...	ACCEPT	Summary: A regA-null mutant devoid of the main cAMP phosphodiesterase displays altered cAMP metabolism, confirming RegA as the principal internal cAMP phosphodiesterase. Supports the core activity. Reason: The mutant phenotype confirms RegA is the main cAMP phosphodiesterase controlling intracellular cAMP, consistent with its core catalytic function. Supporting Evidence: PMID:15752425 a mutant that is devoid of the main cAMP-phosphodiesterase (PDE) RegA and displays an altered cAMP metabolism
GO:0051281 positive regulation of release of sequestered calcium ion into cytosol	IMP PMID:15752425 cAMP controls cytosolic Ca2+ levels in Dictyostelium discoid...	KEEP AS NON CORE	Summary: In regA-null cells the elevated intracellular cAMP is associated with augmented release of Ca2+ from internal stores, linking RegA-controlled cAMP to calcium store dynamics. A downstream physiological consequence. Reason: The calcium-release phenotype is an indirect consequence of altered intracellular cAMP in the regA mutant, not a core molecular function of RegA. Supporting Evidence: PMID:15752425 an augmented release of Ca2+ from stores in the mutant
GO:0051279 regulation of release of sequestered calcium ion into cytosol	IMP PMID:15752425 cAMP controls cytosolic Ca2+ levels in Dictyostelium discoid...	KEEP AS NON CORE	Summary: The general regulation-of-calcium-release term parallels the positive regulation annotation from the same study; a downstream consequence of RegA's control of intracellular cAMP. Reason: As with the positive-regulation term, this reflects an indirect effect of altered cAMP levels in the regA mutant on calcium store release rather than a core function. Supporting Evidence: PMID:15752425 an augmented release of Ca2+ from stores in the mutant
GO:0120320 lateral pseudopodium retraction	IMP PMID:15752425 cAMP controls cytosolic Ca2+ levels in Dictyostelium discoid...	KEEP AS NON CORE	Summary: This study also examined chemotactic/pseudopod behavior of regA-null cells, consistent with the well-established role of RegA in suppressing lateral pseudopods. A motility role downstream of cAMP control. Reason: The pseudopod/chemotaxis phenotype is downstream of RegA's regulation of intracellular cAMP; retained as non-core and corroborated by the dedicated Wessels et al. study. Supporting Evidence: PMID:15752425 a mutant that is devoid of the main cAMP-phosphodiesterase (PDE) RegA and displays an altered cAMP metabolism

Gene Description

Existing Annotations Review

Core Functions

RegA is a cytosolic cAMP-specific 3',5'-cyclic-nucleotide phosphodiesterase that degrades intracellular cAMP, thereby limiting PKA activity and acting as a negative regulator of cAMP/PKA signaling that times terminal differentiation.

RegA's N-terminal receiver domain functions as a phosphorelay response regulator, accepting phosphate at Asp212 from the histidine phosphotransfer protein RdeA within a His-Asp two-component phosphorelay; phosphorylation of this domain activates the C-terminal phosphodiesterase.

References

Deep Research

OpenScientist

📚 Additional Documentation

Notes

📄 View Raw YAML