gacA notes
Identity and sequence context
- The requested
gacA locus in Pseudomonas putida KT2440 maps to UniProt Q88FJ6; UniProt records the gene name as uvrY, the locus tag as PP_4099, and the protein name as "Response regulator GacA (Global activator)." The protein is 212 aa long. [file:PSEPK/gacA/gacA-uniprot.txt "GN Name=uvrY ... OrderedLocusNames=PP_4099 ... DE RecName: Full=Response regulator GacA ... AltName: Full=Global activator"]
- Domain architecture is consistent with a classic DNA-binding two-component response regulator: an N-terminal response-regulator receiver domain, a C-terminal LuxR-type helix-turn-helix DNA-binding domain, and a predicted phosphoacceptor Asp54. [file:PSEPK/gacA/gacA-uniprot.txt "FT DOMAIN 3..119 /note=\"Response regulatory\" ... FT DOMAIN 141..206 /note=\"HTH luxR-type\" ... FT MOD_RES 54 /note=\"4-aspartylphosphate\""]
KT2440-focused functional evidence
- The strongest direct KT2440 evidence places the Gac system upstream of adhesin expression and biofilm development. The lapA/lapF study states that "Both lapA and lapF are under the control of the two-component regulatory system GacS/GacA" and concludes that "The two-component system GacS/GacA appears as a master regulator of the process" of biofilm formation in P. putida. PMID:24488315 PMID:24488315
- A KT2442 mutant screen recovered a
gacS insertion as a moderate biofilm-defective mutant, reinforcing that the Gac system contributes to biofilm development in the KT2440/KT2442 lineage. PMID:27190143
- A KT2440 c-di-GMP regulatory-network study identified GacA among the global regulators needed for the high-c-di-GMP crinkly/biofilm phenotype. The discussion also states that in KT2440 the GacS/GacA system is essential for
rpoS expression, which provides a plausible route by which this regulator affects broad lifestyle programs. PMID:27489550 PMID:27489550
- A 2023 KT2440 study expanded the phenotype space beyond biofilm control and found that K1 type VI secretion system expression is positively regulated by GacS-GacA and opposed by RetS. PMID:36748579
Broader Gac/Rsm interpretation
- Reviews of the Gac/Rsm cascade describe GacA/UvrY-family proteins as phosphorelay-activated transcription regulators that induce small RNAs, antagonize Rsm/Csr proteins, and thereby reprogram social behavior and secondary metabolism. This is useful mechanistic context, but strain-specific outputs should not be transferred uncritically into KT2440 curation. PMID:18047567 PMID:11768529
- Other P. putida strains show the same regulator controlling diverse downstream programs: quorum-sensing gene expression in WCS358, putisolvin biosynthesis in PCL1445, WLIP biosynthesis in RW10S2, and PHA accumulation in CA-3. These support the view that GacA is a pleiotropic lifestyle regulator, but they are secondary to the KT2440-specific biofilm and T6SS evidence. PMID:15345437 PMID:16109938 PMID:22544260 PMID:23291549
Curation takeaways
- Current GOA terms for phosphorelay signal transduction and transcription-related DNA binding are directionally correct.
GO:0003677 DNA binding is too broad to be a useful core annotation for this protein; GO:0000156 phosphorelay response regulator activity and GO:0003700 DNA-binding transcription factor activity are more informative.
- The best supported KT2440-specific process term to add is
GO:1900192 positive regulation of single-species biofilm formation.
- K1-T6SS regulation is real and experimentally supported in KT2440, but I am treating it as secondary/non-core until direct GacA target promoters are mapped in this strain.
- I did not find direct KT2440 evidence in the examined sources showing purified GacA binding a specific promoter or explicitly identifying the cognate
rsmY/rsmZ-like promoters. Any direct promoter-binding language in the review should therefore stay conservative.