PDE1

Summary: Pde1 was cloned by functional complementation of a S. cerevisiae cyclic-nucleotide phosphodiesterase-deficient mutant, and the recombinant enzyme hydrolyses both cAMP and cGMP.

Reason: Complementation of the yeast PDEase-deficient strain, together with direct biochemical assay of the recombinant enzyme, establishes cyclic-nucleotide phosphodiesterase activity. The term is the general parent of the more specific cAMP (GO:0004115) and cGMP (GO:0047555) phosphodiesterase activities that are also annotated; it is correct but less informative than those.

Summary: PAINT node PTN002001416 propagates 3',5'-cyclic-AMP phosphodiesterase activity across the fungal/amoebozoan class II (low-affinity) PDE family; C. albicans Pde1 has its own direct biochemical evidence for this activity.

Reason: Pde1 is a class II cyclic nucleotide phosphodiesterase (Pfam PF02112, PROSITE PS00607) orthologous to S. cerevisiae PDE1, S. pombe cgs2 and Dictyostelium PdsA. Cyclic-AMP hydrolysis is the ancestral activity of this clade and is directly demonstrated for the C. albicans enzyme; the appearance of CGD:CAL0000177603 among the IBA sources reflects that experimental grounding.

Summary: Recombinant C. albicans Pde1 produced in S. cerevisiae hydrolyses cAMP with a Km of 0.49 mM, characteristic of the low-affinity class II PDEs.

Reason: Direct enzyme assay of the recombinant protein. cAMP hydrolysis is the core physiological activity of Pde1, which in vivo is responsible for terminating agonist-induced (glucose, intracellular acidification) cAMP spikes.

Summary: UniRule/InterPro (IPR000396, class II PDE) based assignment of 3',5'-cyclic-AMP phosphodiesterase activity.

Reason: Consistent with the family membership and with direct biochemical evidence for cAMP hydrolysis by the recombinant enzyme.

Summary: No data root cellular component annotation.

Reason: No experimental localisation of C. albicans Pde1 has been reported in the cached literature. The ND placeholder correctly records that the subcellular location is unknown; it should be replaced when localisation data become available. The gene's deep-research record likewise finds no C. albicans study that localizes Pde1.

Summary: UniRule-based assignment of cAMP catabolic process.

Reason: Pde1 hydrolyses cAMP to AMP and is the phosphodiesterase responsible for removing the cAMP produced in response to glucose and intracellular acidification in C. albicans. The enzyme catalyses the catabolic step itself, so the process annotation is a direct consequence of its activity.

Summary: InterPro2GO mapping from the class II PDE signature (IPR024225) to phosphoric diester hydrolase activity.

Reason: Correct but very general parent of the cyclic-nucleotide phosphodiesterase activities that are directly demonstrated; acceptable as a broad IEA.

Summary: Filamentous growth phenotype attributed to PDE1 mutants in Wilson et al. 2010, chiefly seen as synthetic morphogenesis defects in combination with gpa2 (and pde2) mutations.

Reason: The abstract reports morphogenesis defects mainly as synthetic genetic interactions of PDE1 with GPA2, and the authors interpret these as Gpa2 acting through a cAMP-independent route. Pde1's contribution to hyphal growth is therefore indirect, via control of cAMP levels, and secondary to Pde2; a pde1 single mutant has been reported to filament normally (falcon deep research, citing a pathway review). Gpa2 itself controls filamentation at least partly outside the cAMP pathway: a gpa2 defect is not rescued by cAMP but is bypassed by the HST7 MAPK component (PMID:12477787). This row and the GO:0044182 row record the same IMP phenotype from the same paper at two granularities; GO:0044182 (filamentous growth of a population of unicellular organisms) is the more specific of the two and this general term is redundant with it. The full text (not cached) was read by the CGD curator, so the annotation is retained, as non-core.

Summary: As for GO:0030447; the CGD curator used the population-level filamentous growth term for the same mutant phenotypes.

Reason: Same IMP phenotype from PMID:20558315 as the GO:0030447 row, at the more specific population-level granularity. Pde1 modulates morphogenesis indirectly through cAMP turnover; the phenotype is mostly synthetic with gpa2, a pde1 single mutant has been reported to filament normally, and Gpa2 acts on filamentation partly through a cAMP-independent MAPK route (PMID:12477787). Retained, deferring to the CGD curator's full-text reading, as a non-core pleiotropic consequence of cAMP signalling.

Summary: PAINT propagation of 3',5'-cyclic-GMP phosphodiesterase activity in the class II PDE family; C. albicans Pde1 has direct biochemical evidence for cGMP hydrolysis.

Reason: Class II PDEs of fungi and Dictyostelium hydrolyse both cAMP and cGMP, and recombinant C. albicans Pde1 hydrolyses cGMP with a Km of 0.25 mM. The activity is real; its physiological relevance in C. albicans, where cGMP signalling is poorly defined, is uncertain, so cAMP hydrolysis remains the core activity.

Summary: Recombinant Pde1 hydrolyses cGMP (Km 0.25 mM).

Reason: Direct enzyme assay supports cGMP phosphodiesterase activity. The enzyme is a dual-specificity low-affinity PDE; cGMP hydrolysis is biochemically established even though its in vivo role is unclear.

Summary: PAINT propagation (node PTN002001416; donor S. pombe cgs2/pde1) of negative regulation of the adenylate cyclase-activating glucose-activated GPCR (Gpr1/Gpa2) signalling pathway. Pde1 does terminate the glucose-induced cAMP rise, but in C. albicans that rise is reported to come from Cdc25-Ras1 rather than a glucose-activated GPCR.

Reason: Pde1 hydrolyses the cAMP produced after glucose addition and is the phosphodiesterase that terminates that spike in C. albicans (and in the S. cerevisiae ortholog), so negative regulation of glucose signalling is well supported. The 'adenylate cyclase-activating glucose-activated G protein-coupled receptor' part of GO:0110034 does not transfer cleanly to C. albicans: Maidan et al. (2005) found glucose-induced cAMP intact in gpr1 and gpa2 deletions but abolished in cdc25 and ras1 deletions, and the CaGpr1 ligand appears to be methionine or lactate rather than sugar. Miwa et al. (2004) reported the opposite, so the receptor wiring is disputed rather than settled; Wilson et al. (2010) link Gpa2 to acidification-induced cAMP. The direct parent term GO:1902660 (negative regulation of glucose mediated signaling pathway) captures what Pde1 does on either reading, without committing to a GPCR input, and is therefore proposed as the replacement. The S. pombe placement is sound for fission yeast, where the Git3/Gpa2 receptor does sense glucose. An independent OpenScientist hypothesis run, given the competing references but not this review's verdict, reached the same conclusion and recommended GO:1902660.

Proposed replacements: negative regulation of glucose mediated signaling pathway

Summary: PAINT propagation of negative regulation of cAMP/PKA signal transduction across the class II PDE clade.

Reason: Pde1 hydrolyses cAMP and down-regulates agonist-induced cAMP signalling in C. albicans, as in S. cerevisiae; this is the principal physiological role of the enzyme.

Summary: pde1 mutants show defective down-regulation of glucose- and acidification-induced cAMP signalling.

Reason: Direct mutant evidence in C. albicans that Pde1 terminates agonist-induced cAMP signalling; core biological role.

Summary: CGD annotates positive regulation of filamentous growth based on reduced filamentation of PDE1-containing mutant combinations in Wilson et al. 2010.

Reason: The CGD curator annotated this from the full text of PMID:20558315, which is not cached; only the abstract is available here, so the action defers to the curator. No cached evidence supports the positive direction specifically. The abstract reports the morphogenesis defects as synthetic interactions with GPA2. Several observations make the direction hard to confirm without the full text. A cAMP-degrading enzyme would be expected to restrain hyphae, since elevated cAMP generally promotes them. A pde1 single mutant has been reported to filament normally (falcon deep research, citing a pathway review). Gpa2 acts on filamentation partly through a cAMP-independent MAPK route (PMID:12477787). By analogy, deletion of the paralog PDE2 also impairs hyphal development (PMID:14523128), so tuned cAMP turnover rather than low cAMP may be what is needed. Retained as an indirect, non-core consequence of cAMP homeostasis; the direction is raised as a suggested question.