PDE1 (Candida albicans, Q5AGE4, orf19.11710 / C5_02290W_A) — curation notes

Identity

• Low-affinity class II cyclic nucleotide phosphodiesterase (Pfam PF02112 PDEase_II; PROSITE PS00607; PANTHER PTHR28283:SF1).
• Orthologs: S. cerevisiae PDE1 (SGD:S000003217), S. pombe cgs2/pde1 (SPCC285.09c), Dictyostelium PdsA.
• Paralog-in-function: PDE2 (high-affinity class I PDE, distinct family).

Biochemistry

• Cloned by complementation of a S. cerevisiae PDEase-deficient mutant PMID:8075796
• Hydrolyses cAMP and cGMP PMID:8075796; no divalent cation requirement, poorly inhibited by standard PDE inhibitors.

Physiology

• Pde1 (not Pde2) terminates glucose- and acidification-induced cAMP signalling PMID:20558315. Same division of labour as S. cerevisiae PMID:9880329
• Morphogenesis/stress phenotypes are mainly synthetic with GPA2 PMID:20558315.
• Virulence: secondary to PDE2; pde1 pde2 double mutant avirulent PMID:20558315.
• Not required for farnesol repression of hyphae PMID:18078440
• S. cerevisiae Pde1 PKA site (Ser252) conserved in C. albicans Pde1 PMID:9880329.

Review decisions

• MF: cAMP PDE (core), cGMP PDE (accept; physiological relevance unclear), general PDE terms accepted.
• BP: negative regulation of cAMP/PKA signalling and of glucose-activated GPCR pathway accepted (Pde1 directly destroys the second messenger); cAMP catabolism accepted. (superseded for GO:0110034; see the Gpa2 and OpenScientist sections below)
• Filamentous growth IMPs kept as non-core (indirect, largely synthetic with gpa2; full text not cached).
• CC: no localisation data; ND accepted.
• Full text of PMID:20558315 and PMID:8075796 not available in cache (abstract only).

Deep research status (2026-10-02)

• just deep-research-falcon CANAL PDE1 --fallback perplexity-lite: the wrapper reported failure (falcon timed out after 600 s; perplexity not configured), but the falcon job itself completed at 898 s and wrote PDE1-deep-research-falcon.md, which was then used.
• Literature was instead gathered manually via PubMed search ("Candida albicans PDE1 phosphodiesterase" returned 5 hits: PMID:30299574, 20558315, 18078440, 9880329, 8075796), plus PMID:14523128 (PDE2). All cached publications are abstract-only.

Interaction with Gpa2 (follow-up, 2026-10-02)

There is no evidence of a physical Pde1-Gpa2 interaction; the "regulatory module" of Wilson et al. 2010 is functional/genetic.
- Gpa2 drives acidification-induced cAMP PMID:20558315; Pde1 terminates both glucose- and acidification-induced spikes.
- Synthetic pde1 gpa2 defects (growth, morphogenesis, stress) are read by the authors as Gpa2 acting outside the cAMP pathway PMID:20558315. Consistent with Gpa2 having a MAPK-linked role PMID:12477787
- Is the Gpr1-Gpa2 module glucose-activated in C. albicans? Disputed:
- Yes: PMID:15302825
- No: PMID:15673611; ligands appear to be methionine/lactate PMID:30761119; Gpr1 mediates lactate-induced beta-glucan masking PMID:27941860.
- Consequence for review: IBA GO:0110034 (negative regulation of adenylate cyclase-activating glucose-activated GPCR signalling, donor S. pombe cgs2) changed ACCEPT -> MARK_AS_OVER_ANNOTATED (TERM_SCOPING_PROBLEM). Receptor-agnostic GO:0141162 retained as core. PMID:15302825 finding marked DISPUTED.
- Deep research also notes (citing Inglis & Sherlock 2013) that a pde1 single mutant filaments normally, consistent with keeping the filamentous growth IMPs as non-core.

Locus identifiers

Falcon flagged that some literature labels PDE1 as orf19.4235 whereas UniProt Q5AGE4 lists orf19.11710. CGD's own PDE1 locus (CAL0000177603) cross-references Q5AGE4 and is the source of the IDA/IMP annotations, so the gene-to-accession mapping is CGD's. (Assembly 19 assigned separate orf19 numbers to allelic ORFs, which likely explains the two numbers; not independently verified here.)

OpenScientist run on the glucose-activated component (2026-10-02)

• Hypothesis (free-text, function-assignment): the cAMP rise Pde1 terminates after glucose addition is generated through Gpr1/Gpa2. References given: PMID:20558315, 15302825, 15673611. The review's verdict was withheld. 3 iterations, 827 s. Report: PDE1-hypotheses/pde1-glucose-gpcr-pathway/openscientist.md.
• Verdict: "Partially supported but over-annotated". It agrees that Pde1 terminates glucose-induced cAMP, and that the glucose-activated GPCR source is contradicted by PMID:15673611 and the Gpr1 ligand is ambiguous PMID:15667329.
• It recommended the parent GO:1902660 (negative regulation of glucose mediated signaling pathway). Verified via OLS that GO:1902660 is a direct parent of GO:0110034, and that GO:0010255 glucose mediated signaling pathway does not require a GPCR. Adopted: GO:0110034 changed from MARK_AS_OVER_ANNOTATED to MODIFY -> GO:1902660.
• Errors in the report, not imported: it calls the S. cerevisiae paradigm the source of the IBA (the PAINT donor is S. pombe cgs2, where Git3 is a genuine glucose receptor), and it treats Miwa 2004 as superseded rather than disputed. Its QuickGO evidence-code counts were not re-checked.
• No local bioinformatics holdout existed for PDE1, so there was nothing to compare against.