arr / PA2818 (Q9I025) review notes

Summary of the literature

Arr (aminoglycoside response regulator) is a 525-aa protein. UniProt (Phobius)
predicts two TM helices (12-33 and 240-259) flanking a CSS-motif domain (Pfam
PF12792), followed by a C-terminal EAL domain (262-514). My scan of the UniProt
sequence finds an intact EAL motif ("GVEALVRW", E at 297) and DDFGTG loop (416). The
gene lies on a genomic island near tRNA genes and is absent from PA14 and most
strains tested (PMID:16477007).

Literature search (Europe PMC, 2026-11-05; PubMed web search for "aminoglycoside
response regulator arr" returned PMID:16121184 plus two unrelated hits; E-utilities
returned server errors that day).

  1. Hoffman et al. 2005 PMID:16121184, Nature, abstract only (not in PMC). The
    PseudoCAP source of all three experimental rows. The abstract states that arr is
    needed for aminoglycoside-induced biofilm PMID:16121184, that it is a predicted inner-membrane c-di-GMP PDE, and that
    PMID:16121184
  2. Kulasekara et al. 2006 PMID:16477007; full text read on PMC (PMC1413825).
    Verbatim excerpts:
  3. Table 1: "PA2771 GGEEF — PA2818 EAL — PA2870 GGEEF +(96)". So lysates of a
    PA14 strain overexpressing arr showed no detectable c-di-GMP hydrolysis. This is
    the one PDE-only protein with no activity: "c-di-GMP hydrolysis was detected in
    all but one strain expressing genes encoding PDE enzymes".
  4. The authors' own caveat: "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. Phylogeny: "Three of these putative PDE modules, in PA2200, PA2818, and PA3285,
    appear to be more closely related and are not linked to DGCs."
    The negative result does not refute the activity: the motif is intact, Hoffman
    measured loss of membrane PDE activity in the mutant, and the lysate assay may
    miss a membrane protein that is poorly expressed or inactive without its signal.
    It does mean no purified-enzyme or overexpression evidence of activity exists.
  6. Eilers et al. 2022 PMID:35935233: deletion of PA2818 disrupted mushroom
    structures PMID:35935233.

Bearing of the Kulasakara negative result on seeding

Arr is NOT a seed of PTN002105365 (GO:0071111): Q9I025 is absent from that IBD's
WITH/FROM in .cache/paint/IBD.gaf, because arr's own PDE row is GO:0004114, not
GO:0071111. The lysate result therefore bears only on arr's own MF rows, not on the
PDE IBD. Arr IS one of four seeds of PTN009140332 (GO:1900190), through its
biofilm row; that seeding rests on Hoffman's genetics, not on the lysate assay.

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?
PTN009140332 GO:1900190 regulation of single-species biofilm formation 4 84 (9 taxa) GO:1900190, IDA, PMID:16121184 (PseudoCAP) SOUND The abstract states that arr is essential for tobramycin-induced biofilm formation and that a catalytic-residue mutant is defective in this response, so Arr regulates biofilm formation through its own enzyme activity. The evidence described is genetic (IMP rather than IDA), but the term is right. Abstract only; full text not available. bifA (Q9HW35; SOUND, deletion + complementation + catalytic mutants), PA2133 (Q9I1Y2; INDIRECT-PHENOTYPE), E. coli PdeF (P77172) Yes. It stands on bifA as well (see bifA and PA2133 notes). No GO_CENTRAL defect.

Other PseudoCAP row: GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
(IDA, PMID:16121184) is not a seed but uses the wrong term. GO:0004114 is defined on
3',5'-cyclic nucleoside monophosphates and is not an ancestor of GO:0071111
(go-basic.obo: GO:0071111 is_a GO:0008081). The abstract names c-di-GMP as the
substrate. PSEUDOCAP WRONG_TERM defect, CONFIRMED (abstract states the substrate;
term relationship checked in the ontology file).

Annotation decisions