PA3825 (Q9HXH7) review notes

Summary of the literature

PA3825 is a 526-aa protein. UniProt (Phobius) predicts two TM helices (12-35 and
235-254) flanking a CSS-motif domain (Pfam PF12792), followed by a C-terminal EAL
domain (258-512). The EAL signature is the variant EVL (residues 293-295 in my scan
of the UniProt sequence, "GVEVLMRW"), and the catalytic DDFGTG loop is intact
(residue 414). UniProt FT BINDING rows (ECO:0007829, PDB 4Y9P, 5MF5, 5MFU, 4Y8E)
place c-di-GMP and Mg/Mn/Ca ions in the EAL active site.

Literature search (Europe PMC, query "PA3825 AND aeruginosa", 2026-11-05, 24 hits;
PubMed E-utilities returned server errors that day). Primary data on PA3825:

  1. Kulasekara et al. 2006 PMID:16477007 (PseudoCAP source of the IDA row). Cached
    copy is abstract-only; I read the full text on PMC (PMC1413825). Verbatim excerpts:
  2. Assay: "The ability of the PDE-containing proteins to hydrolyze c-di-GMP was
    tested by adding synthetic c-di-GMP to lysates of strains overexpressing these
    proteins and measuring the disappearance of the dinucleotide from the reaction
    mixture".
  3. Table 1: "PA3343 GGEEF +(22) PA3702 GGEEF +(445) PA3825 EVL +(27) PA3947 EVL
    +(100)" (PDE activity as percent of added c-di-GMP degraded).
  4. Footnote: "Given the limits of sensitivity of the HPLC assay (12 pmol/mg cell
    wet weight), we cannot conclude that any particular DGC or PDE domain does not
    have the corresponding enzymatic activity in vivo".
  5. Bellini et al. 2017 PMID:28186120, full text cached. The purified EAL domain is
    an active c-di-GMP PDE PMID:28186120. Crystal
    structures with substrate/product reveal a third metal site. The knockout had no
    motility phenotype PMID:28186120.
    The paper calls PA3825 "a two-domain cytoplasmic protein", which conflicts with the
    two predicted TM helices; the CSS domain is predicted to resemble periplasmic
    sensor domains, which fits a membrane topology.
  6. Eilers et al. 2022 PMID:35935233, PAO1 deletion library, full text cached.
    Deletion raised early attachment PMID:35935233 and flow-cell biomass PMID:35935233. So PA3825 restrains biofilm formation.
  7. Scherhag et al. 2023 (PMID:37441524; PMC10335732 Table 1, read on PMC, not cited
    in the YAML because the cached text omits the table) lists PA3825 as a
    cytoplasmic-membrane ("cm") protein found in their membrane proteome.

PseudoCAP IBA-seed assessment

PTN node node term n_seeds leaf IBAs seed annotation (term, evidence, PMID) verdict rationale other seeds IBD stands without this seed?
PTN002105365 GO:0071111 cyclic-guanylate-specific phosphodiesterase activity 18 162 (24 taxa) GO:0071111, IDA, PMID:16477007 (PseudoCAP) SOUND Lysates of the overexpressing strain degraded 27% of added c-di-GMP (full text read). Weak and crude, but later confirmed by purified-EAL-domain kinetics and substrate-bound crystal structures (PMID:28186120). E. coli PdeA/B/C/F/H/I/K/L/N, DosP; Mtb P9WM13; P. aeruginosa bifA, rocR, PA2133, PA2200, nbdA, PA2567 Yes. Many seeds have purified-enzyme evidence. Node-level defects (degenerate EAL leaves; PM term on soluble members) are recorded once in rocR-ai-review.yaml and not repeated here.

PA3825 is not a seed of PTN009140332 (GO:1900190), but inherits its IBA. The IBD
stands on bifA (see bifA, PA2133 and arr notes). PA3825 has its own supporting data:
the deletion increases attachment and biomass (PMID:35935233).

No PSEUDOCAP or GO_CENTRAL defects recorded for PA3825.

Annotation decisions