cyaA

UniProt ID: Q9HTS8
Organism: Pseudomonas aeruginosa PAO1
Review Status: COMPLETE
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Gene Description

cyaA (PA5272) encodes the class I adenylate cyclase of Pseudomonas aeruginosa, a 950-residue cytoplasmic protein with the four-part class I adenylate cyclase architecture (N-terminal catalytic domain plus second, third and fourth regulatory regions) shared with Escherichia coli CyaA. It is one of three adenylate cyclases in P. aeruginosa, alongside the membrane class III enzyme CyaB and the secreted class II toxin ExoY. CyaA converts ATP to cAMP, which binds the global regulator Vfr; CyaB provides the majority of intracellular cAMP, and CyaA makes a minor contribution whose physiological role is not yet known.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004016 adenylate cyclase activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN002215143 (class I adenylate cyclase clade, PTHR38760, 7 leaf IBAs in 7 taxa). Two seeds - E. coli CyaA (P00936, IDA) and this gene (PseudoCAP IMP to PMID:12586068).
Reason: Core enzymatic activity. The IBD stands on the E. coli CyaA seed alone, the prototype class I adenylate cyclase with an IDA activity annotation; PA CyaA carries the same class I catalytic domain (Pfam PF01295).
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN002215143 Β· PTN002215143 SUPPORTS TRANSFER
Class I adenylate cyclase clade; the node term suits every member.
UniProtKB:P00936 Β· E. coli CyaA SUPPORTS TRANSFER
IDA seed for GO:0004016 (EcoCyc, QuickGO 2026-11-05).
UniProtKB:Q9HTS8 Β· cyaA (self; PseudoCAP IMP PMID:12586068) SUPPORTS TRANSFER
Expected self-seed. The cached abstract does not separate cyaA from cyaB, so the gene-specific IMP could not be checked; the IBD does not depend on it.
Supporting Evidence:
file:PSEAE/cyaA/cyaA-uniprot.txt
Adenylate cyclase class-I N-terminal
PMID:22226839
The two other P. aeruginosa ACs, CyaA and CyaB, belong to Class I and III, respectively.
GO:0004016 adenylate cyclase activity
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO from the class I adenylate cyclase signature IPR000274.
Reason: Correct mapping; agrees with the IBA and the family placement.
Supporting Evidence:
file:PSEAE/cyaA/cyaA-uniprot.txt
Adenylate_cyclase_1
GO:0004016 adenylate cyclase activity
IMP
PMID:12586068
Coordinate regulation of bacterial virulence genes by a nove...
ACCEPT
Summary: PseudoCAP seed row for PTN002215143. The abstract describes mutants unable to synthesise cAMP; it does not say which adenylate cyclase genes were deleted, and the full text (Dev Cell 2003, not in PMC) could not be read. Topal et al. 2012 state that CyaB makes most intracellular cAMP and that the role of CyaA is unknown.
Reason: The function is clearly correct for the gene (class I catalytic domain, orthology to E. coli CyaA). The gene-specific genetic evidence the curator coded is likely the cyaA cyaB double mutant, which the cached abstract cannot confirm; deferred to the curator (seed verdict UNVERIFIABLE, no defect).
Supporting Evidence:
PMID:12586068
Transcriptome analysis of mutants lacking the ability to synthesize cAMP or the cAMP binding protein Vfr
GO:0006171 cAMP biosynthetic process
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO from IPR000274.
Reason: The enzyme catalyses the single step of cAMP synthesis from ATP.
Supporting Evidence:
file:PSEAE/cyaA/cyaA-uniprot.txt
Adenylate_cyclase_1
GO:0006171 cAMP biosynthetic process
IMP
PMID:12586068
Coordinate regulation of bacterial virulence genes by a nove...
ACCEPT
Summary: PseudoCAP seed row for the GO:0006171 IBD at PTN002215143 (IBD dated 2026-06-16; the matching leaf IBA is not yet in this gene's GOA file). Same paper and same limitation as the MF row.
Reason: Correct for the gene; seed verdict UNVERIFIABLE because the abstract does not name cyaA. The IBD also rests on E. coli CyaA (IMP, PMID:4310317).
Supporting Evidence:
PMID:12586068
Transcriptome analysis of mutants lacking the ability to synthesize cAMP or the cAMP binding protein Vfr
PMID:22226839
CyaB activity indeed accounts for the majority of intracellular cAMP

Core Functions

Cytoplasmic class I adenylate cyclase that converts ATP to cAMP, a minor contributor to the cellular cAMP pool that signals through Vfr.

Molecular Function:
adenylate cyclase activity
Directly Involved In:
Supporting Evidence:
  • file:PSEAE/cyaA/cyaA-uniprot.txt
    Adenylate cyclase class-I N-terminal
  • PMID:22226839
    The two other P. aeruginosa ACs, CyaA and CyaB, belong to Class I and III, respectively.

References

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Suggested Questions for Experts

Q: Under which growth conditions does CyaA, rather than CyaB, contribute to the cAMP pool, and is CyaA activity regulated by the PTS (EIIA-Glc) as in E. coli, given that P. aeruginosa lacks glucose PTS-mediated catabolite repression?

Suggested Experiments

Experiment: Purify PA CyaA and measure ATP-to-cAMP conversion kinetics; compare cAMP levels in cyaA, cyaB and cyaA cyaB mutants across carbon sources and oxygen levels.

πŸ“š Additional Documentation

Notes

(cyaA-notes.md)

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