pdsA

UniProt ID: P12019
Organism: Dictyostelium discoideum
Review Status: COMPLETE
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Gene Description

pdsA (PdsA, DdPDE1, PDE1) is the major extracellular and cell-surface cyclic nucleotide phosphodiesterase of Dictyostelium discoideum. It is a secreted glycoprotein of the class II cyclic nucleotide phosphodiesterase family that is synthesized with a cleaved signal peptide and can either be released into the medium or remain attached to the cell surface. The enzyme hydrolyzes extracellular 3',5'-cyclic AMP to 5'-AMP with a preference for cAMP over cGMP, but has dual specificity and also hydrolyzes 3',5'-cyclic GMP. By degrading the extracellular cAMP chemoattractant, PdsA sharpens the spatial cAMP gradient and terminates and resets the propagating cAMP waves that guide chemotaxis and streaming during starvation-induced aggregation; cells lacking PdsA fail to aggregate. Its activity is negatively modulated by a secreted heat-stable glycoprotein inhibitor (PdiA), and this inhibition is relieved by reducing agents such as dithiothreitol. PdsA expression is developmentally controlled through multiple promoters, including a prestalk-specific promoter whose activity is required for later morphogenesis (slug formation and culmination).

Existing Annotations Review

GO Term Evidence Action Reason
GO:0110034 negative regulation of adenylate cyclase-activating glucose-activated G protein-coupled receptor signaling pathway
IBA
GO_REF:0000033 		REMOVE
Summary: Phylogenetic (IBA) inference to a glucose-activated G-protein-coupled receptor signaling term. Dictyostelium PdsA modulates cAMP-receptor (cAR) GPCR signaling by degrading extracellular cAMP, not a glucose-sensing GPCR pathway. The glucose-activated context does not apply to this organism or gene.
Reason: This is an over-propagated phylogenetic inference to a glucose-sensing GPCR signaling branch that is not relevant to Dictyostelium. PdsA has no known role in glucose-activated receptor signaling; its genuine signaling role is the extracellular degradation of the cAMP chemoattractant that terminates cAR GPCR signaling. That role is better captured by the extracellular regulation of signal transduction annotation.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: CONTEXT OR TISSUE MISMATCH
Sources checked:
PANTHER:PTN002001416 · PANTHER node for cyclic-nucleotide phosphodiesterases SUPPORTS SOURCE BUT NOT TARGET
The negative-regulation term traces to a fungal glucose-sensing cAMP-GPCR pathway that does not correspond to PdsA's role in extracellular cAMP turnover
PomBase:SPCC285.09c · S. pombe glucose-sensing cAMP phosphodiesterase SUPPORTS SOURCE BUT NOT TARGET
Source enzyme acts in a yeast glucose and cAMP-sensing context absent in Dictyostelium
Supporting Evidence:
PMID:17040207
DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves
GO:0141162 negative regulation of cAMP/PKA signal transduction
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: IBA inference of negative regulation of cAMP/PKA signaling. PdsA acts on the extracellular cAMP pool that stimulates cell-surface cAMP receptors, not directly on the intracellular cAMP/PKA axis (which in Dictyostelium is controlled by the intracellular PDE RegA/DdPDE2). The effect on PKA signaling is therefore indirect.
Reason: PdsA degrades extracellular cAMP that activates cAR GPCRs; it does not degrade the intracellular cAMP that drives PKA. Attributing negative regulation of cAMP/PKA signal transduction to PdsA over-states its role by conflating the extracellular and intracellular cAMP pools, which are handled by distinct phosphodiesterases in this organism.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: ROLE CONFLATION
Sources checked:
PANTHER:PTN002001416 · PANTHER node for cyclic-nucleotide phosphodiesterases SUPPORTS SOURCE BUT NOT TARGET
PdsA degrades extracellular cAMP acting on cAR GPCRs; casting it as a negative regulator of cAMP/PKA signaling conflates an enzymatic effector with a pathway regulator
CGD:CAL0000177603 · Candida albicans phosphodiesterase ortholog SUPPORTS SOURCE BUT NOT TARGET
Source PDE participates in cAMP/PKA regulation in fungi; the indirect regulatory framing over-reaches for PdsA
Supporting Evidence:
PMID:17040207
The enzyme can be secreted in the medium, or exposed on the cell surface.
GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: PdsA is a dual-specificity phosphodiesterase that hydrolyzes both cAMP and cGMP, so cGMP phosphodiesterase activity is a genuine molecular function, although cAMP is the preferred substrate.
Reason: Direct biochemical characterization shows PdsA (DdPDE1) has dual cAMP/cGMP specificity, consistent with the assigned EC 3.1.4.35 (cGMP) activity. The IBA inference is corroborated by experimental evidence for this gene.
Supporting Evidence:
PMID:17040207
Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX.
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
IBA
GO_REF:0000033 		ACCEPT
Summary: cAMP phosphodiesterase activity is the core, well-established molecular function of PdsA and is strongly supported by direct biochemical evidence.
Reason: PdsA is the principal enzyme degrading extracellular cAMP in Dictyostelium; the IBA inference matches the experimentally determined activity.
Supporting Evidence:
PMID:17040207
Extracellular cAMP is degraded predominantly by the class II high-affinity enzyme DdPDE1
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of the core cAMP phosphodiesterase activity, consistent with direct experimental evidence.
Reason: This is the central catalytic activity of PdsA and is experimentally confirmed.
Supporting Evidence:
PMID:17040207
Extracellular cAMP is degraded predominantly by the class II high-affinity enzyme DdPDE1
GO:0005576 extracellular region
IEA
GO_REF:0000120 		ACCEPT
Summary: PdsA is a secreted enzyme released into the extracellular medium, so extracellular region localization is correct.
Reason: The protein carries a cleaved signal peptide and is secreted; extracellular localization is directly demonstrated by purification of active enzyme from culture supernatant.
Supporting Evidence:
PMID:17040207
both DdPDE1 and DdPDE7 are secreted into the medium and are attached to the cell surface
GO:0006198 cAMP catabolic process
IEA
GO_REF:0000002 		ACCEPT
Summary: Degradation of cAMP to AMP is the core biological process enabled by PdsA's phosphodiesterase activity.
Reason: PdsA is the main enzyme catabolizing extracellular cAMP in Dictyostelium, making this process annotation directly appropriate.
Supporting Evidence:
PMID:17040207
DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves
GO:0008081 phosphoric diester hydrolase activity
IEA
GO_REF:0000002 		MODIFY
Summary: This is a correct but overly general parent term for the specific cyclic-nucleotide phosphodiesterase activity of PdsA.
Reason: Phosphoric diester hydrolase activity is a high-level parent. The experimentally established activity is more precisely 3',5'-cyclic-nucleotide phosphodiesterase activity (dual cAMP/cGMP), so a more specific term is preferred.
Supporting Evidence:
PMID:17040207
Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX.
GO:0009986 cell surface
IEA
GO_REF:0000044 		ACCEPT
Summary: In addition to being secreted, PdsA is also exposed on the cell surface, so cell surface localization is correct.
Reason: Enzyme activity measurements show PdsA is attached to the cell surface as well as secreted into the medium.
Supporting Evidence:
PMID:17040207
both DdPDE1 and DdPDE7 are secreted into the medium and are attached to the cell surface
GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
IEA
GO_REF:0000120 		ACCEPT
Summary: Electronic annotation of cGMP phosphodiesterase activity, consistent with the enzyme's demonstrated dual specificity.
Reason: PdsA hydrolyzes cGMP in addition to cAMP, as shown biochemically.
Supporting Evidence:
PMID:17040207
Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX.
GO:0047555 3',5'-cyclic-GMP phosphodiesterase activity
IGI
PMID:17040207
Seven Dictyostelium discoideum phosphodiesterases degrade th... 		ACCEPT
Summary: Genetic interaction evidence supporting cGMP phosphodiesterase activity; the paper characterizes the contribution of PdsA (DdPDE1) to the degradation of cyclic nucleotide pools including cGMP.
Reason: The Bader et al. analysis confirms PdsA as a dual-specificity enzyme contributing to cGMP as well as cAMP degradation.
Supporting Evidence:
PMID:17040207
Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX.
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
IDA
PMID:6302095
Purification and characterization of the extracellular cycli... 		ACCEPT
Summary: Direct biochemical purification and characterization of the extracellular cyclic nucleotide phosphodiesterase demonstrates this activity for PdsA.
Reason: The enzyme was purified from aggregation-phase culture supernatant and characterized as a cyclic nucleotide phosphodiesterase, directly supporting this molecular function.
Supporting Evidence:
PMID:6302095
Extracellular phosphodiesterase for adenosine 3':5'-monophosphate [EC 3.1.4.17] was purified from the supernatant of aggregation phase culture of Dictyostelium discoideum
GO:0005576 extracellular region
IDA
PMID:6265455
The extracellular cyclic nucleotide phosphodiesterase of Dic... 		ACCEPT
Summary: The active extracellular phosphodiesterase was purified from culture medium, directly demonstrating that PdsA is active in the extracellular region.
Reason: Purification of the active secreted enzyme directly supports extracellular localization and activity.
Supporting Evidence:
PMID:6265455
Two forms of the extracellular cyclic nucleotide phosphodiesterase (EC 3.1.4.17) of Dictyostelium discoideum have been purified.
GO:0005783 endoplasmic reticulum
IDA
PMID:19477920
The group migration of Dictyostelium cells is regulated by e... 		ACCEPT
Summary: Endoplasmic reticulum localization from Garcia et al. 2009, whose cached full text directly reports that the intracellular pool of PdsA is in the ER, proposed as a storage/secretion compartment for this secreted phosphodiesterase. Verified against the cached publication.
Reason: The full text of PMID:19477920 is cached and explicitly localizes the intracellular pool of PdsA to the endoplasmic reticulum, consistent with ER transit of a signal-peptide-bearing secreted protein. This is a genuine (non-core) intracellular localization of an otherwise extracellular enzyme.
Supporting Evidence:
PMID:19477920
the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA
GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
IMP
PMID:17040207
Seven Dictyostelium discoideum phosphodiesterases degrade th... 		KEEP AS NON CORE
Summary: By removing the extracellular cAMP ligand of cAR receptors, PdsA modulates receptor-coupled adenylate cyclase signaling. This is a downstream signaling consequence of the enzyme's catalytic activity rather than its core molecular function.
Reason: The role of PdsA in cAR/adenylate-cyclase signaling arises indirectly from degrading the extracellular cAMP chemoattractant. It is a legitimate developmental/signaling context but not the core evolved molecular function, which is cyclic nucleotide hydrolysis.
Supporting Evidence:
PMID:17040207
DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves
GO:1900115 extracellular regulation of signal transduction
IMP
PMID:17040207
Seven Dictyostelium discoideum phosphodiesterases degrade th... 		ACCEPT
Summary: PdsA degrades extracellular cAMP, the diffusible chemotactic signal, thereby regulating signal transduction in the extracellular space. This term accurately captures the biological purpose of the enzyme.
Reason: Extracellular cAMP degradation by PdsA shapes and resets the cAMP waves that coordinate chemotaxis, which is precisely extracellular regulation of signal transduction.
Supporting Evidence:
PMID:17040207
DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves
GO:0005515 protein binding
IPI
PMID:230476
Binding of inhibitor alters kinetic and physical properties ... 		KEEP AS NON CORE
Summary: This IPI reflects the physical interaction between PdsA and its secreted heat-stable glycoprotein inhibitor (PdiA), which forms an enzyme-inhibitor complex. Bare protein binding is uninformative; the relevant, more informative relationship is binding by/to the PDE inhibitor.
Reason: The interaction is real and functionally important for regulating PdsA activity, but the generic protein binding term conveys little. It should be retained as non-core; a more specific descriptor of the inhibitor interaction would be preferable.
Supporting Evidence:
PMID:230476
The second form is the result of a complex formed with a heat-stable inhibitor and has a Km in the millimolar range.
GO:0031153 slug development involved in sorocarp development
IMP
PMID:7851634
The phosphodiesterase secreted by prestalk cells is necessar... 		KEEP AS NON CORE
Summary: Prestalk-specific PDE expression is required for morphogenesis; blocking PDE activity in prestalk cells (via targeted inhibitor overexpression) blocks slug formation and culmination. This supports a role of PdsA in slug/sorocarp development, downstream of its enzymatic function.
Reason: PdsA activity is required for the slug and later morphogenetic stages, but this is a developmental consequence of extracellular cAMP regulation rather than the core molecular function.
Supporting Evidence:
PMID:7851634
followed by a block in slug formation and an inability to culminate
GO:0072720 response to dithiothreitol
IDA
PMID:230476
Binding of inhibitor alters kinetic and physical properties ... 		KEEP AS NON CORE
Summary: Dithiothreitol strongly stimulates extracellular PDE activity by inactivating the heat-stable inhibitor bound to PdsA. This is an experimentally observed response but a peripheral property, not a core biological function.
Reason: The response to DTT reflects relief of inhibitor-mediated suppression of the enzyme rather than a physiological signaling role; keep as non-core.
Supporting Evidence:
PMID:230476
Treating the enzyme-inhibitor complex with dithiothreitol stimulated enzyme activity 20- to 100-fold
GO:0051591 response to cAMP
IDA
PMID:2162056
Conditions that alter intracellular cAMP levels affect expre... 		KEEP AS NON CORE
Summary: Expression of the PDE gene is regulated by intracellular cAMP levels, so PdsA responds to cAMP at the level of gene expression. This is a regulatory response rather than a core molecular function.
Reason: The response-to-cAMP annotation captures developmental/transcriptional regulation of the gene by cAMP, which is contextual rather than the enzyme's core evolved function.
Supporting Evidence:
PMID:2162056
the magnitude of PDE gene expression is negatively regulated by intracellular cAMP levels
GO:1903013 response to differentiation-inducing factor 1
IDA
PMID:2049870
Cyclic nucleotide phosphodiesterase of Dictyostelium discoid... 		KEEP AS NON CORE
Summary: The prestalk-specific (2.2 kb) PDE transcript is induced by differentiation-inducing factor (DIF), so PdsA expression responds to DIF-1. This is a transcriptional/developmental response.
Reason: DIF-1 induction of the prestalk PDE transcript is a developmental regulatory context, not the core molecular function of the enzyme.
Supporting Evidence:
PMID:2049870
is induced by differentiation-inducing factor
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
IDA
PMID:6265455
The extracellular cyclic nucleotide phosphodiesterase of Dic... 		ACCEPT
Summary: Direct purification and characterization of the extracellular cyclic nucleotide phosphodiesterase supports cAMP phosphodiesterase activity, the core molecular function of PdsA.
Reason: The purified secreted enzyme hydrolyzes cAMP, directly supporting this activity.
Supporting Evidence:
PMID:6265455
Two forms of the extracellular cyclic nucleotide phosphodiesterase (EC 3.1.4.17) of Dictyostelium discoideum have been purified.
GO:0030552 cAMP binding
IDA
PMID:2722797
The cyclic nucleotide specificity of eight cAMP-binding prot... 		KEEP AS NON CORE
Summary: The phosphodiesterase binds cAMP, as analyzed by cyclic nucleotide specificity studies. For PdsA this binding is substrate engagement that is part of catalysis rather than a distinct regulatory cAMP-binding function.
Reason: cAMP binding by PdsA reflects substrate recognition by the catalytic site and is largely subsumed by its phosphodiesterase activity; retain as non-core.
Supporting Evidence:
PMID:2722797
binding of cAMP to phosphodiesterase involves only O3' and exocyclic oxygen
GO:0005886 plasma membrane
IDA NOT
PMID:19477920
The group migration of Dictyostelium cells is regulated by e... 		UNDECIDED
Summary: A negated (NOT) plasma membrane annotation from Garcia et al. 2009. The cached full text localizes the intracellular pool of PdsA to the ER (consistent with a non-plasma-membrane intracellular form), but another IDA annotation (PMID:9168471) positively places the cell-surface PDE in plasma membrane microdomains. The two likely reflect distinct pools (secreted/ER versus surface-associated) rather than a clean negation.
Reason: With the Garcia et al. full text now verified, the negation reflects that the intracellular pool is ER rather than plasma membrane; however a positive plasma-membrane annotation (PMID:9168471) for the cell-surface form stands, so the blanket NOT-plasma-membrane call remains genuinely unresolved (distinct pools) rather than being accepted or removed outright.
GO:0031152 aggregation involved in sorocarp development
IMP
PMID:19477920
The group migration of Dictyostelium cells is regulated by e... 		ACCEPT
Summary: PdsA is required for starvation-induced aggregation; cells lacking PdsA fail to aggregate because extracellular cAMP waves cannot be properly shaped. This aggregation role is robustly documented for the gene.
Reason: Although the cited publication is not cached, the aggregation phenotype of pdsA-null cells is independently and directly established in the available literature, making this a well-supported developmental role.
Supporting Evidence:
PMID:17040207
UK7 cells fail to aggregate, but can be rescued by adding exogenous PDE activity
GO:0031152 aggregation involved in sorocarp development
IEP
PMID:25887420
Leaps and lulls in the developmental transcriptome of Dictyo... 		KEEP AS NON CORE
Summary: Developmental expression-pattern (IEP) evidence associating PdsA with the aggregation stage. Consistent with the enzyme's established role in aggregation, though expression correlation is weaker evidence than the loss-of-function phenotype.
Reason: The aggregation role of PdsA is genuine, but this IEP transcriptome annotation provides only correlative expression support and is not the core molecular function; retain as non-core.
Supporting Evidence:
PMID:17040207
UK7 cells fail to aggregate, but can be rescued by adding exogenous PDE activity
GO:0005886 plasma membrane
IDA
PMID:9168471
Identification of detergent-resistant plasma membrane microd... 		ACCEPT
Summary: The cell-surface phosphodiesterase was localized to detergent-resistant plasma membrane microdomains together with cAR1 and adenylate cyclase (ACA), supporting plasma membrane / cell-surface localization.
Reason: Immunoelectron microscopy and cell-surface biotinylation confirmed the plasma membrane origin of the fraction enriched in the cell-surface PDE, consistent with PdsA being membrane-attached at the cell surface.
Supporting Evidence:
PMID:9168471
The cell surface phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase (ACA), were specifically localized in these structures
PMID:9168471
both confirmed the plasma membrane origin of this preparation
GO:1902168 response to catechin
IDA
PMID:23516620
The green tea catechin epigallocatechin gallate (EGCG) block... 		KEEP AS NON CORE
Summary: The green tea catechin EGCG blocks Dictyostelium aggregation, streaming and cAMP-wave-dependent development. This is a peripheral pharmacological response context rather than a core function of PdsA.
Reason: The response-to-catechin annotation reflects a small-molecule perturbation of the cAMP-signaling/development program in which PdsA participates; it is contextual and non-core.
Supporting Evidence:
PMID:23516620
In the presence of EGCG aggregation is delayed, cells do not stream and development is typically stalled at the loose aggregate stage.
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
IMP
PMID:17040207
Seven Dictyostelium discoideum phosphodiesterases degrade th... 		ACCEPT
Summary: Loss-of-function (pdsA-null, strain UK7) evidence confirms that PdsA is the main cAMP phosphodiesterase degrading extracellular cAMP. This is the core molecular function.
Reason: The pdsA-null phenotype (loss of extracellular cAMP degradation, failure to aggregate) directly supports cAMP phosphodiesterase activity as the central function of the gene.
Supporting Evidence:
PMID:17040207
DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves

Core Functions

Secreted and cell-surface class II cyclic nucleotide phosphodiesterase that hydrolyzes extracellular 3',5'-cyclic AMP to 5'-AMP. By degrading the extracellular cAMP chemoattractant, PdsA shapes and resets the propagating cAMP waves that drive chemotactic streaming and aggregation during starvation-induced development.

Molecular Function:
3',5'-cyclic-AMP phosphodiesterase activity
Directly Involved In:
cAMP catabolic process extracellular regulation of signal transduction
Cellular Locations:
extracellular region cell surface
Supporting Evidence:
  • PMID:17040207
    DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves
  • PMID:17040207
    both DdPDE1 and DdPDE7 are secreted into the medium and are attached to the cell surface

Dual-specificity phosphodiesterase activity; in addition to its preferred cAMP substrate, PdsA also hydrolyzes 3',5'-cyclic GMP.

Molecular Function:
3',5'-cyclic-GMP phosphodiesterase activity
Directly Involved In:
cAMP catabolic process
Supporting Evidence:
  • PMID:17040207
    Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX.

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
GO_REF:0000120
Combined Automated Annotation using Multiple IEA Methods
PMID:17040207
Seven Dictyostelium discoideum phosphodiesterases degrade three pools of cAMP and cGMP.
  • DdPDE1 (PdsA) is a class II dual-specificity phosphodiesterase that degrades extracellular cAMP and cGMP and can be secreted or displayed on the cell surface.
    "DdPDE1 (PdsA) is a class II dual-specificity PDE that degrades extracellular cAMP and cGMP. The enzyme can be secreted in the medium, or exposed on the cell surface."
  • PdsA is the main enzyme degrading extracellular cAMP during aggregation and is essential for shaping cAMP waves; pdsA-null (UK7) cells fail to aggregate.
    "DdPDE1 is the main PDE that degrades extracellular cAMP during cell aggregation and is thereby essential for shaping cAMP waves"
  • PdsA and its homologue DdPDE7 have dual cAMP/cGMP specificity and are strongly inhibited by DTT and insensitive to IBMX.
    "Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity, and are strongly inhibited by DTT and insensitive to IBMX."
PMID:19477920
The group migration of Dictyostelium cells is regulated by extracellular chemoattractant degradation.
  • The intracellular pool of PdsA is localized to the endoplasmic reticulum, proposed as a storage/secretion compartment.
    "the intracellular pool of PdsA is localized to the endoplasmic reticulum, which may provide a compartment for storage and secretion of PdsA"
PMID:2049870
Cyclic nucleotide phosphodiesterase of Dictyostelium discoideum and its glycoprotein inhibitor: structure and expression of their genes.
  • The prestalk-specific 2.2 kb PDE transcript is induced by differentiation-inducing factor.
    "is induced by differentiation-inducing factor"
PMID:2162056
Conditions that alter intracellular cAMP levels affect expression of the cAMP phosphodiesterase gene in Dictyostelium.
  • PDE gene expression is negatively regulated by intracellular cAMP levels.
    "the magnitude of PDE gene expression is negatively regulated by intracellular cAMP levels"
PMID:230476
Binding of inhibitor alters kinetic and physical properties of extracellular cyclic AMP phosphodiesterase from Dictyostelium discoideum.
  • PdsA forms a complex with a heat-stable glycoprotein inhibitor that raises its Km; dithiothreitol relieves inhibition by inactivating the inhibitor.
    "Treating the enzyme-inhibitor complex with dithiothreitol stimulated enzyme activity 20- to 100-fold"
PMID:23516620
The green tea catechin epigallocatechin gallate (EGCG) blocks cell motility, chemotaxis and development in Dictyostelium discoideum.
  • EGCG delays aggregation and stalls development at the loose aggregate stage.
    "In the presence of EGCG aggregation is delayed, cells do not stream and development is typically stalled at the loose aggregate stage."
PMID:25887420
Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
PMID:2722797
The cyclic nucleotide specificity of eight cAMP-binding proteins in Dictyostelium discoideum is correlated into three groups.
  • cAMP binding to the phosphodiesterase involves only the O3' and exocyclic oxygen positions.
    "binding of cAMP to phosphodiesterase involves only O3' and exocyclic oxygen"
PMID:6265455
The extracellular cyclic nucleotide phosphodiesterase of Dictyostelium discoideum. Purification and characterization.
  • Two forms of the secreted extracellular cyclic nucleotide phosphodiesterase were purified from Dictyostelium.
    "Two forms of the extracellular cyclic nucleotide phosphodiesterase (EC 3.1.4.17) of Dictyostelium discoideum have been purified."
PMID:6302095
Purification and characterization of the extracellular cyclic AMP phosphodiesterase of Dictyostelium discoideum.
  • The extracellular cAMP phosphodiesterase was purified from aggregation-phase culture supernatant.
    "Extracellular phosphodiesterase for adenosine 3':5'-monophosphate [EC 3.1.4.17] was purified from the supernatant of aggregation phase culture of Dictyostelium discoideum"
PMID:7851634
The phosphodiesterase secreted by prestalk cells is necessary for Dictyostelium morphogenesis.
  • Blocking phosphodiesterase activity in prestalk cells blocks slug formation and culmination.
    "followed by a block in slug formation and an inability to culminate"
PMID:9168471
Identification of detergent-resistant plasma membrane microdomains in dictyostelium: enrichment of signal transduction proteins.
  • The cell-surface phosphodiesterase localizes to plasma membrane microdomains together with cAR1 and adenylate cyclase.
    "The cell surface phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase (ACA), were specifically localized in these structures"

📄 View Raw YAML

 
id: P12019
gene_symbol: pdsA
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:44689
  label: Dictyostelium discoideum
description: pdsA (PdsA, DdPDE1, PDE1) is the major extracellular and cell-surface
  cyclic nucleotide phosphodiesterase of Dictyostelium discoideum. It is a secreted
  glycoprotein of the class II cyclic nucleotide phosphodiesterase family that is
  synthesized with a cleaved signal peptide and can either be released into the medium
  or remain attached to the cell surface. The enzyme hydrolyzes extracellular 3',5'-cyclic
  AMP to 5'-AMP with a preference for cAMP over cGMP, but has dual specificity and
  also hydrolyzes 3',5'-cyclic GMP. By degrading the extracellular cAMP chemoattractant,
  PdsA sharpens the spatial cAMP gradient and terminates and resets the propagating
  cAMP waves that guide chemotaxis and streaming during starvation-induced aggregation;
  cells lacking PdsA fail to aggregate. Its activity is negatively modulated by a
  secreted heat-stable glycoprotein inhibitor (PdiA), and this inhibition is relieved
  by reducing agents such as dithiothreitol. PdsA expression is developmentally
  controlled through multiple promoters, including a prestalk-specific promoter whose
  activity is required for later morphogenesis (slug formation and culmination).
existing_annotations:
- term:
    id: GO:0110034
    label: negative regulation of adenylate cyclase-activating glucose-activated G
      protein-coupled receptor signaling pathway
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) inference to a glucose-activated G-protein-coupled
      receptor signaling term. Dictyostelium PdsA modulates cAMP-receptor (cAR) GPCR
      signaling by degrading extracellular cAMP, not a glucose-sensing GPCR pathway.
      The glucose-activated context does not apply to this organism or gene.
    action: REMOVE
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - CONTEXT_OR_TISSUE_MISMATCH
      source_entities:
      - source_id: PANTHER:PTN002001416
        source_label: "PANTHER node for cyclic-nucleotide phosphodiesterases"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "The negative-regulation term traces to a fungal glucose-sensing cAMP-GPCR pathway that does not correspond to PdsA's role in extracellular cAMP turnover"
      - source_id: PomBase:SPCC285.09c
        source_label: "S. pombe glucose-sensing cAMP phosphodiesterase"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Source enzyme acts in a yeast glucose and cAMP-sensing context absent in Dictyostelium"
    reason: This is an over-propagated phylogenetic inference to a glucose-sensing
      GPCR signaling branch that is not relevant to Dictyostelium. PdsA has no known
      role in glucose-activated receptor signaling; its genuine signaling role is
      the extracellular degradation of the cAMP chemoattractant that terminates cAR
      GPCR signaling. That role is better captured by the extracellular regulation
      of signal transduction annotation.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
        cell aggregation and is thereby essential for shaping cAMP waves
- term:
    id: GO:0141162
    label: negative regulation of cAMP/PKA signal transduction
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: IBA inference of negative regulation of cAMP/PKA signaling. PdsA acts
      on the extracellular cAMP pool that stimulates cell-surface cAMP receptors,
      not directly on the intracellular cAMP/PKA axis (which in Dictyostelium is
      controlled by the intracellular PDE RegA/DdPDE2). The effect on PKA signaling
      is therefore indirect.
    action: MARK_AS_OVER_ANNOTATED
    propagation_review:
      root_cause: PROPAGATION_BAD
      failure_modes:
      - ROLE_CONFLATION
      source_entities:
      - source_id: PANTHER:PTN002001416
        source_label: "PANTHER node for cyclic-nucleotide phosphodiesterases"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "PdsA degrades extracellular cAMP acting on cAR GPCRs; casting it as a negative regulator of cAMP/PKA signaling conflates an enzymatic effector with a pathway regulator"
      - source_id: CGD:CAL0000177603
        source_label: "Candida albicans phosphodiesterase ortholog"
        source_status: SUPPORTS_SOURCE_BUT_NOT_TARGET
        comment: "Source PDE participates in cAMP/PKA regulation in fungi; the indirect regulatory framing over-reaches for PdsA"
    reason: PdsA degrades extracellular cAMP that activates cAR GPCRs; it does not
      degrade the intracellular cAMP that drives PKA. Attributing negative regulation
      of cAMP/PKA signal transduction to PdsA over-states its role by conflating the
      extracellular and intracellular cAMP pools, which are handled by distinct
      phosphodiesterases in this organism.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: The enzyme can be secreted in the medium, or exposed on the
        cell surface.
- term:
    id: GO:0047555
    label: 3',5'-cyclic-GMP phosphodiesterase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: PdsA is a dual-specificity phosphodiesterase that hydrolyzes both cAMP
      and cGMP, so cGMP phosphodiesterase activity is a genuine molecular function,
      although cAMP is the preferred substrate.
    action: ACCEPT
    reason: Direct biochemical characterization shows PdsA (DdPDE1) has dual cAMP/cGMP
      specificity, consistent with the assigned EC 3.1.4.35 (cGMP) activity. The
      IBA inference is corroborated by experimental evidence for this gene.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
        and are strongly inhibited by DTT and insensitive to IBMX.
- term:
    id: GO:0004115
    label: 3',5'-cyclic-AMP phosphodiesterase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: cAMP phosphodiesterase activity is the core, well-established molecular
      function of PdsA and is strongly supported by direct biochemical evidence.
    action: ACCEPT
    reason: PdsA is the principal enzyme degrading extracellular cAMP in Dictyostelium;
      the IBA inference matches the experimentally determined activity.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Extracellular cAMP is degraded predominantly by the class II
        high-affinity enzyme DdPDE1
- term:
    id: GO:0004115
    label: 3',5'-cyclic-AMP phosphodiesterase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of the core cAMP phosphodiesterase activity,
      consistent with direct experimental evidence.
    action: ACCEPT
    reason: This is the central catalytic activity of PdsA and is experimentally
      confirmed.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Extracellular cAMP is degraded predominantly by the class II
        high-affinity enzyme DdPDE1
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: PdsA is a secreted enzyme released into the extracellular medium, so
      extracellular region localization is correct.
    action: ACCEPT
    reason: The protein carries a cleaved signal peptide and is secreted; extracellular
      localization is directly demonstrated by purification of active enzyme from
      culture supernatant.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: both DdPDE1 and DdPDE7 are secreted into the medium and are
        attached to the cell surface
- term:
    id: GO:0006198
    label: cAMP catabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Degradation of cAMP to AMP is the core biological process enabled by
      PdsA's phosphodiesterase activity.
    action: ACCEPT
    reason: PdsA is the main enzyme catabolizing extracellular cAMP in Dictyostelium,
      making this process annotation directly appropriate.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
        cell aggregation and is thereby essential for shaping cAMP waves
- term:
    id: GO:0008081
    label: phosphoric diester hydrolase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: This is a correct but overly general parent term for the specific
      cyclic-nucleotide phosphodiesterase activity of PdsA.
    action: MODIFY
    reason: Phosphoric diester hydrolase activity is a high-level parent. The
      experimentally established activity is more precisely 3',5'-cyclic-nucleotide
      phosphodiesterase activity (dual cAMP/cGMP), so a more specific term is
      preferred.
    proposed_replacement_terms:
    - id: GO:0004114
      label: 3',5'-cyclic-nucleotide phosphodiesterase activity
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
        and are strongly inhibited by DTT and insensitive to IBMX.
- term:
    id: GO:0009986
    label: cell surface
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: In addition to being secreted, PdsA is also exposed on the cell surface,
      so cell surface localization is correct.
    action: ACCEPT
    reason: Enzyme activity measurements show PdsA is attached to the cell surface
      as well as secreted into the medium.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: both DdPDE1 and DdPDE7 are secreted into the medium and are
        attached to the cell surface
- term:
    id: GO:0047555
    label: 3',5'-cyclic-GMP phosphodiesterase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Electronic annotation of cGMP phosphodiesterase activity, consistent
      with the enzyme's demonstrated dual specificity.
    action: ACCEPT
    reason: PdsA hydrolyzes cGMP in addition to cAMP, as shown biochemically.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
        and are strongly inhibited by DTT and insensitive to IBMX.
- term:
    id: GO:0047555
    label: 3',5'-cyclic-GMP phosphodiesterase activity
  evidence_type: IGI
  original_reference_id: PMID:17040207
  qualifier: enables
  review:
    summary: Genetic interaction evidence supporting cGMP phosphodiesterase activity;
      the paper characterizes the contribution of PdsA (DdPDE1) to the degradation
      of cyclic nucleotide pools including cGMP.
    action: ACCEPT
    reason: The Bader et al. analysis confirms PdsA as a dual-specificity enzyme
      contributing to cGMP as well as cAMP degradation.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
        and are strongly inhibited by DTT and insensitive to IBMX.
- term:
    id: GO:0004114
    label: 3',5'-cyclic-nucleotide phosphodiesterase activity
  evidence_type: IDA
  original_reference_id: PMID:6302095
  qualifier: enables
  review:
    summary: Direct biochemical purification and characterization of the extracellular
      cyclic nucleotide phosphodiesterase demonstrates this activity for PdsA.
    action: ACCEPT
    reason: The enzyme was purified from aggregation-phase culture supernatant and
      characterized as a cyclic nucleotide phosphodiesterase, directly supporting
      this molecular function.
    supported_by:
    - reference_id: PMID:6302095
      supporting_text: Extracellular phosphodiesterase for adenosine 3':5'-monophosphate
        [EC 3.1.4.17] was purified from the supernatant of aggregation phase culture
        of Dictyostelium discoideum
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IDA
  original_reference_id: PMID:6265455
  qualifier: is_active_in
  review:
    summary: The active extracellular phosphodiesterase was purified from culture
      medium, directly demonstrating that PdsA is active in the extracellular region.
    action: ACCEPT
    reason: Purification of the active secreted enzyme directly supports extracellular
      localization and activity.
    supported_by:
    - reference_id: PMID:6265455
      supporting_text: Two forms of the extracellular cyclic nucleotide phosphodiesterase
        (EC 3.1.4.17) of Dictyostelium discoideum have been purified.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:19477920
  qualifier: located_in
  review:
    summary: Endoplasmic reticulum localization from Garcia et al. 2009, whose
      cached full text directly reports that the intracellular pool of PdsA is in
      the ER, proposed as a storage/secretion compartment for this secreted
      phosphodiesterase. Verified against the cached publication.
    action: ACCEPT
    reason: The full text of PMID:19477920 is cached and explicitly localizes the
      intracellular pool of PdsA to the endoplasmic reticulum, consistent with ER
      transit of a signal-peptide-bearing secreted protein. This is a genuine
      (non-core) intracellular localization of an otherwise extracellular enzyme.
    supported_by:
    - reference_id: PMID:19477920
      supporting_text: the intracellular pool of PdsA is localized to the endoplasmic
        reticulum, which may provide a compartment for storage and secretion of PdsA
- term:
    id: GO:0007193
    label: adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:17040207
  qualifier: acts_upstream_of_or_within
  review:
    summary: By removing the extracellular cAMP ligand of cAR receptors, PdsA
      modulates receptor-coupled adenylate cyclase signaling. This is a downstream
      signaling consequence of the enzyme's catalytic activity rather than its core
      molecular function.
    action: KEEP_AS_NON_CORE
    reason: The role of PdsA in cAR/adenylate-cyclase signaling arises indirectly
      from degrading the extracellular cAMP chemoattractant. It is a legitimate
      developmental/signaling context but not the core evolved molecular function,
      which is cyclic nucleotide hydrolysis.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
        cell aggregation and is thereby essential for shaping cAMP waves
- term:
    id: GO:1900115
    label: extracellular regulation of signal transduction
  evidence_type: IMP
  original_reference_id: PMID:17040207
  qualifier: acts_upstream_of_or_within
  review:
    summary: PdsA degrades extracellular cAMP, the diffusible chemotactic signal,
      thereby regulating signal transduction in the extracellular space. This term
      accurately captures the biological purpose of the enzyme.
    action: ACCEPT
    reason: Extracellular cAMP degradation by PdsA shapes and resets the cAMP waves
      that coordinate chemotaxis, which is precisely extracellular regulation of
      signal transduction.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
        cell aggregation and is thereby essential for shaping cAMP waves
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:230476
  qualifier: enables
  review:
    summary: This IPI reflects the physical interaction between PdsA and its secreted
      heat-stable glycoprotein inhibitor (PdiA), which forms an enzyme-inhibitor
      complex. Bare protein binding is uninformative; the relevant, more informative
      relationship is binding by/to the PDE inhibitor.
    action: KEEP_AS_NON_CORE
    reason: The interaction is real and functionally important for regulating PdsA
      activity, but the generic protein binding term conveys little. It should be
      retained as non-core; a more specific descriptor of the inhibitor interaction
      would be preferable.
    supported_by:
    - reference_id: PMID:230476
      supporting_text: The second form is the result of a complex formed with a
        heat-stable inhibitor and has a Km in the millimolar range.
- term:
    id: GO:0031153
    label: slug development involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:7851634
  qualifier: acts_upstream_of_or_within
  review:
    summary: Prestalk-specific PDE expression is required for morphogenesis; blocking
      PDE activity in prestalk cells (via targeted inhibitor overexpression) blocks
      slug formation and culmination. This supports a role of PdsA in slug/sorocarp
      development, downstream of its enzymatic function.
    action: KEEP_AS_NON_CORE
    reason: PdsA activity is required for the slug and later morphogenetic stages,
      but this is a developmental consequence of extracellular cAMP regulation rather
      than the core molecular function.
    supported_by:
    - reference_id: PMID:7851634
      supporting_text: followed by a block in slug formation and an inability to
        culminate
- term:
    id: GO:0072720
    label: response to dithiothreitol
  evidence_type: IDA
  original_reference_id: PMID:230476
  qualifier: involved_in
  review:
    summary: Dithiothreitol strongly stimulates extracellular PDE activity by
      inactivating the heat-stable inhibitor bound to PdsA. This is an experimentally
      observed response but a peripheral property, not a core biological function.
    action: KEEP_AS_NON_CORE
    reason: The response to DTT reflects relief of inhibitor-mediated suppression
      of the enzyme rather than a physiological signaling role; keep as non-core.
    supported_by:
    - reference_id: PMID:230476
      supporting_text: Treating the enzyme-inhibitor complex with dithiothreitol
        stimulated enzyme activity 20- to 100-fold
- term:
    id: GO:0051591
    label: response to cAMP
  evidence_type: IDA
  original_reference_id: PMID:2162056
  qualifier: involved_in
  review:
    summary: Expression of the PDE gene is regulated by intracellular cAMP levels,
      so PdsA responds to cAMP at the level of gene expression. This is a regulatory
      response rather than a core molecular function.
    action: KEEP_AS_NON_CORE
    reason: The response-to-cAMP annotation captures developmental/transcriptional
      regulation of the gene by cAMP, which is contextual rather than the enzyme's
      core evolved function.
    supported_by:
    - reference_id: PMID:2162056
      supporting_text: the magnitude of PDE gene expression is negatively regulated
        by intracellular cAMP levels
- term:
    id: GO:1903013
    label: response to differentiation-inducing factor 1
  evidence_type: IDA
  original_reference_id: PMID:2049870
  qualifier: involved_in
  review:
    summary: The prestalk-specific (2.2 kb) PDE transcript is induced by
      differentiation-inducing factor (DIF), so PdsA expression responds to DIF-1.
      This is a transcriptional/developmental response.
    action: KEEP_AS_NON_CORE
    reason: DIF-1 induction of the prestalk PDE transcript is a developmental
      regulatory context, not the core molecular function of the enzyme.
    supported_by:
    - reference_id: PMID:2049870
      supporting_text: is induced by differentiation-inducing factor
- term:
    id: GO:0004115
    label: 3',5'-cyclic-AMP phosphodiesterase activity
  evidence_type: IDA
  original_reference_id: PMID:6265455
  qualifier: enables
  review:
    summary: Direct purification and characterization of the extracellular cyclic
      nucleotide phosphodiesterase supports cAMP phosphodiesterase activity, the
      core molecular function of PdsA.
    action: ACCEPT
    reason: The purified secreted enzyme hydrolyzes cAMP, directly supporting this
      activity.
    supported_by:
    - reference_id: PMID:6265455
      supporting_text: Two forms of the extracellular cyclic nucleotide phosphodiesterase
        (EC 3.1.4.17) of Dictyostelium discoideum have been purified.
- term:
    id: GO:0030552
    label: cAMP binding
  evidence_type: IDA
  original_reference_id: PMID:2722797
  qualifier: enables
  review:
    summary: The phosphodiesterase binds cAMP, as analyzed by cyclic nucleotide
      specificity studies. For PdsA this binding is substrate engagement that is
      part of catalysis rather than a distinct regulatory cAMP-binding function.
    action: KEEP_AS_NON_CORE
    reason: cAMP binding by PdsA reflects substrate recognition by the catalytic
      site and is largely subsumed by its phosphodiesterase activity; retain as
      non-core.
    supported_by:
    - reference_id: PMID:2722797
      supporting_text: binding of cAMP to phosphodiesterase involves only O3' and
        exocyclic oxygen
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:19477920
  qualifier: located_in
  negated: true
  review:
    summary: A negated (NOT) plasma membrane annotation from Garcia et al. 2009.
      The cached full text localizes the intracellular pool of PdsA to the ER
      (consistent with a non-plasma-membrane intracellular form), but another IDA
      annotation (PMID:9168471) positively places the cell-surface PDE in plasma
      membrane microdomains. The two likely reflect distinct pools (secreted/ER
      versus surface-associated) rather than a clean negation.
    action: UNDECIDED
    reason: With the Garcia et al. full text now verified, the negation reflects
      that the intracellular pool is ER rather than plasma membrane; however a
      positive plasma-membrane annotation (PMID:9168471) for the cell-surface form
      stands, so the blanket NOT-plasma-membrane call remains genuinely unresolved
      (distinct pools) rather than being accepted or removed outright.
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IMP
  original_reference_id: PMID:19477920
  qualifier: acts_upstream_of_or_within
  review:
    summary: PdsA is required for starvation-induced aggregation; cells lacking PdsA
      fail to aggregate because extracellular cAMP waves cannot be properly shaped.
      This aggregation role is robustly documented for the gene.
    action: ACCEPT
    reason: Although the cited publication is not cached, the aggregation phenotype
      of pdsA-null cells is independently and directly established in the available
      literature, making this a well-supported developmental role.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: UK7 cells fail to aggregate, but can be rescued by adding
        exogenous PDE activity
- term:
    id: GO:0031152
    label: aggregation involved in sorocarp development
  evidence_type: IEP
  original_reference_id: PMID:25887420
  qualifier: acts_upstream_of_or_within
  review:
    summary: Developmental expression-pattern (IEP) evidence associating PdsA with
      the aggregation stage. Consistent with the enzyme's established role in
      aggregation, though expression correlation is weaker evidence than the
      loss-of-function phenotype.
    action: KEEP_AS_NON_CORE
    reason: The aggregation role of PdsA is genuine, but this IEP transcriptome
      annotation provides only correlative expression support and is not the core
      molecular function; retain as non-core.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: UK7 cells fail to aggregate, but can be rescued by adding
        exogenous PDE activity
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:9168471
  qualifier: located_in
  review:
    summary: The cell-surface phosphodiesterase was localized to detergent-resistant
      plasma membrane microdomains together with cAR1 and adenylate cyclase (ACA),
      supporting plasma membrane / cell-surface localization.
    action: ACCEPT
    reason: Immunoelectron microscopy and cell-surface biotinylation confirmed the
      plasma membrane origin of the fraction enriched in the cell-surface PDE,
      consistent with PdsA being membrane-attached at the cell surface.
    supported_by:
    - reference_id: PMID:9168471
      supporting_text: The cell surface phosphodiesterase (PDE) and a downstream
        effector of cAR1, adenylate cyclase (ACA), were specifically localized in
        these structures
    - reference_id: PMID:9168471
      supporting_text: both confirmed the plasma membrane origin of this preparation
- term:
    id: GO:1902168
    label: response to catechin
  evidence_type: IDA
  original_reference_id: PMID:23516620
  qualifier: involved_in
  review:
    summary: The green tea catechin EGCG blocks Dictyostelium aggregation, streaming
      and cAMP-wave-dependent development. This is a peripheral pharmacological
      response context rather than a core function of PdsA.
    action: KEEP_AS_NON_CORE
    reason: The response-to-catechin annotation reflects a small-molecule perturbation
      of the cAMP-signaling/development program in which PdsA participates; it is
      contextual and non-core.
    supported_by:
    - reference_id: PMID:23516620
      supporting_text: In the presence of EGCG aggregation is delayed, cells do not
        stream and development is typically stalled at the loose aggregate stage.
- term:
    id: GO:0004115
    label: 3',5'-cyclic-AMP phosphodiesterase activity
  evidence_type: IMP
  original_reference_id: PMID:17040207
  qualifier: enables
  review:
    summary: Loss-of-function (pdsA-null, strain UK7) evidence confirms that PdsA
      is the main cAMP phosphodiesterase degrading extracellular cAMP. This is the
      core molecular function.
    action: ACCEPT
    reason: The pdsA-null phenotype (loss of extracellular cAMP degradation, failure
      to aggregate) directly supports cAMP phosphodiesterase activity as the central
      function of the gene.
    supported_by:
    - reference_id: PMID:17040207
      supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
        cell aggregation and is thereby essential for shaping cAMP waves
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:17040207
  title: Seven Dictyostelium discoideum phosphodiesterases degrade three pools of
    cAMP and cGMP.
  findings:
  - statement: DdPDE1 (PdsA) is a class II dual-specificity phosphodiesterase that
      degrades extracellular cAMP and cGMP and can be secreted or displayed on the
      cell surface.
    supporting_text: DdPDE1 (PdsA) is a class II dual-specificity PDE that degrades
      extracellular cAMP and cGMP. The enzyme can be secreted in the medium, or
      exposed on the cell surface.
  - statement: PdsA is the main enzyme degrading extracellular cAMP during aggregation
      and is essential for shaping cAMP waves; pdsA-null (UK7) cells fail to aggregate.
    supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
      cell aggregation and is thereby essential for shaping cAMP waves
  - statement: PdsA and its homologue DdPDE7 have dual cAMP/cGMP specificity and are
      strongly inhibited by DTT and insensitive to IBMX.
    supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
      and are strongly inhibited by DTT and insensitive to IBMX.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PMC full text available and read; directly characterizes PdsA
      (DdPDE1) function, localization, dual specificity, and the pdsA-null aggregation
      phenotype.
- id: PMID:19477920
  title: The group migration of Dictyostelium cells is regulated by extracellular
    chemoattractant degradation.
  findings:
  - statement: The intracellular pool of PdsA is localized to the endoplasmic reticulum,
      proposed as a storage/secretion compartment.
    supporting_text: the intracellular pool of PdsA is localized to the endoplasmic
      reticulum, which may provide a compartment for storage and secretion of PdsA
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Garcia et al. 2009 (Mol Biol Cell). Full text IS cached
      (content_type full_text_html) and directly localizes the intracellular pool
      of PdsA to the ER; the ER annotation is now ACCEPTed with a verbatim quote.
      The negated plasma-membrane call is kept UNDECIDED because a positive
      plasma-membrane annotation (PMID:9168471) for the cell-surface form
      coexists, i.e. distinct pools.
- id: PMID:2049870
  title: 'Cyclic nucleotide phosphodiesterase of Dictyostelium discoideum and its
    glycoprotein inhibitor: structure and expression of their genes.'
  findings:
  - statement: The prestalk-specific 2.2 kb PDE transcript is induced by
      differentiation-inducing factor.
    supporting_text: is induced by differentiation-inducing factor
- id: PMID:2162056
  title: Conditions that alter intracellular cAMP levels affect expression of the
    cAMP phosphodiesterase gene in Dictyostelium.
  findings:
  - statement: PDE gene expression is negatively regulated by intracellular cAMP levels.
    supporting_text: the magnitude of PDE gene expression is negatively regulated
      by intracellular cAMP levels
- id: PMID:230476
  title: Binding of inhibitor alters kinetic and physical properties of extracellular
    cyclic AMP phosphodiesterase from Dictyostelium discoideum.
  findings:
  - statement: PdsA forms a complex with a heat-stable glycoprotein inhibitor that
      raises its Km; dithiothreitol relieves inhibition by inactivating the inhibitor.
    supporting_text: Treating the enzyme-inhibitor complex with dithiothreitol
      stimulated enzyme activity 20- to 100-fold
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the PdsA-inhibitor (PdiA) interaction and DTT-mediated
      relief of inhibition; supports the protein-binding and response-to-DTT
      annotations.
- id: PMID:23516620
  title: The green tea catechin epigallocatechin gallate (EGCG) blocks cell motility,
    chemotaxis and development in Dictyostelium discoideum.
  findings:
  - statement: EGCG delays aggregation and stalls development at the loose aggregate
      stage.
    supporting_text: In the presence of EGCG aggregation is delayed, cells do not
      stream and development is typically stalled at the loose aggregate stage.
- id: PMID:25887420
  title: Leaps and lulls in the developmental transcriptome of Dictyostelium discoideum.
  findings: []
- id: PMID:2722797
  title: The cyclic nucleotide specificity of eight cAMP-binding proteins in Dictyostelium
    discoideum is correlated into three groups.
  findings:
  - statement: cAMP binding to the phosphodiesterase involves only the O3' and
      exocyclic oxygen positions.
    supporting_text: binding of cAMP to phosphodiesterase involves only O3' and
      exocyclic oxygen
- id: PMID:6265455
  title: The extracellular cyclic nucleotide phosphodiesterase of Dictyostelium discoideum.
    Purification and characterization.
  findings:
  - statement: Two forms of the secreted extracellular cyclic nucleotide
      phosphodiesterase were purified from Dictyostelium.
    supporting_text: Two forms of the extracellular cyclic nucleotide phosphodiesterase
      (EC 3.1.4.17) of Dictyostelium discoideum have been purified.
- id: PMID:6302095
  title: Purification and characterization of the extracellular cyclic AMP phosphodiesterase
    of Dictyostelium discoideum.
  findings:
  - statement: The extracellular cAMP phosphodiesterase was purified from
      aggregation-phase culture supernatant.
    supporting_text: Extracellular phosphodiesterase for adenosine 3':5'-monophosphate
      [EC 3.1.4.17] was purified from the supernatant of aggregation phase culture
      of Dictyostelium discoideum
- id: PMID:7851634
  title: The phosphodiesterase secreted by prestalk cells is necessary for Dictyostelium
    morphogenesis.
  findings:
  - statement: Blocking phosphodiesterase activity in prestalk cells blocks slug
      formation and culmination.
    supporting_text: followed by a block in slug formation and an inability to
      culminate
- id: PMID:9168471
  title: 'Identification of detergent-resistant plasma membrane microdomains in
    dictyostelium: enrichment of signal transduction proteins.'
  findings:
  - statement: The cell-surface phosphodiesterase localizes to plasma membrane
      microdomains together with cAR1 and adenylate cyclase.
    supporting_text: The cell surface phosphodiesterase (PDE) and a downstream
      effector of cAR1, adenylate cyclase (ACA), were specifically localized in
      these structures
core_functions:
- description: Secreted and cell-surface class II cyclic nucleotide phosphodiesterase
    that hydrolyzes extracellular 3',5'-cyclic AMP to 5'-AMP. By degrading the
    extracellular cAMP chemoattractant, PdsA shapes and resets the propagating cAMP
    waves that drive chemotactic streaming and aggregation during starvation-induced
    development.
  molecular_function:
    id: GO:0004115
    label: 3',5'-cyclic-AMP phosphodiesterase activity
  directly_involved_in:
  - id: GO:0006198
    label: cAMP catabolic process
  - id: GO:1900115
    label: extracellular regulation of signal transduction
  locations:
  - id: GO:0005576
    label: extracellular region
  - id: GO:0009986
    label: cell surface
  supported_by:
  - reference_id: PMID:17040207
    supporting_text: DdPDE1 is the main PDE that degrades extracellular cAMP during
      cell aggregation and is thereby essential for shaping cAMP waves
  - reference_id: PMID:17040207
    supporting_text: both DdPDE1 and DdPDE7 are secreted into the medium and are
      attached to the cell surface
- description: Dual-specificity phosphodiesterase activity; in addition to its
    preferred cAMP substrate, PdsA also hydrolyzes 3',5'-cyclic GMP.
  molecular_function:
    id: GO:0047555
    label: 3',5'-cyclic-GMP phosphodiesterase activity
  directly_involved_in:
  - id: GO:0006198
    label: cAMP catabolic process
  supported_by:
  - reference_id: PMID:17040207
    supporting_text: Both DdPDE1 and DdPDE7 are PDEs with dual cAMP/cGMP specificity,
      and are strongly inhibited by DTT and insensitive to IBMX.