psrA

UniProt ID: Q9HZJ9
Organism: Pseudomonas aeruginosa PAO1
Review Status: COMPLETE
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Gene Description

PsrA (PA3006) is a TetR-family transcription factor with an N-terminal helix-turn-helix DNA-binding domain and a PsrA-type C-terminal ligand-binding domain. It binds a palindromic motif (G/CAAAC N2-4 GTTTG/C) in target promoters and acts as a global regulator. It represses its own gene and the fadBA5 beta-oxidation operon; long-chain fatty acids (oleate, palmitate, myristate) disrupt PsrA binding to the fadBA5 promoter and so induce fatty acid degradation genes. PsrA activates rpoS in stationary phase, and it is required for full transcription of the type III secretion regulatory operon exsCEBA, so it supports type III effector secretion. Other targets are regulated positively or negatively.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000976 transcription cis-regulatory region binding
IBA
GO_REF:0000033
MODIFY
Summary: IBA from the TetR-family node PTN004738546. PsrA binds specific promoter regions (fadBA5, its own promoter, PA0506, PA2952/PA2953, PA3571) through a defined palindromic motif.
Reason: Correct but general. Binding to a defined motif (G/CAAAC N2-4 GTTTG/C) in promoters supports the more specific child GO:0000987 cis-regulatory region sequence-specific DNA binding. The generic term remains right for the node.
Propagation Review
Root cause: NO FAILURE CORE
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN004738546 Β· PTN004738546 SUPPORTS TRANSFER
TetR-family node; 19 seeds, most of them experimentally characterised TetR regulators from E. coli, M. tuberculosis and P. aeruginosa. The node-level verdict is recorded on the nfxB/nalC/PA3678/atuR/nalD reviews.
Supporting Evidence:
PMID:15899403
Computer search was performed of the PsrA binding motif (G/CAAAC N(2-4) GTTTG/C) against the P. aeruginosa genome sequence. Four of 14 analysed promoters responded to and bound PsrA
PMID:18524913
Electrophoretic mobility shift assays indicate specific binding of PsrA to the fadBA5 promoter region
GO:0003677 DNA binding
IEA
GO_REF:0000120
MODIFY
Summary: Electronic mapping from the TetR HTH domain. True.
Reason: DNA binding is correct but general; the sequence-specific promoter binding shown for PsrA supports GO:0000987.
Supporting Evidence:
PMID:15899403
Computer search was performed of the PsrA binding motif (G/CAAAC N(2-4) GTTTG/C) against the P. aeruginosa genome sequence. Four of 14 analysed promoters responded to and bound PsrA
PMID:18524913
Electrophoretic mobility shift assays indicate specific binding of PsrA to the fadBA5 promoter region
GO:0003700 DNA-binding transcription factor activity
IBA
GO_REF:0000033
ACCEPT
Summary: IBA from PTN004738546. PsrA is a DNA-binding transcription factor that represses some targets (fadBA5, its own promoter, PA0506) and activates others (rpoS, PA2953, PA3571).
Reason: Because PsrA acts both as repressor and activator, the generic DNA-binding transcription factor activity is the right level for this gene.
Supporting Evidence:
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
PMID:18524913
Electrophoretic mobility shift assays indicate specific binding of PsrA to the fadBA5 promoter region
GO:0003700 DNA-binding transcription factor activity
IEA
GO_REF:0000002
ACCEPT
Summary: InterPro2GO from the TetR-like regulator family signature. Correct.
Reason: Same claim as the accepted IBA row.
Supporting Evidence:
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
GO:0006355 regulation of DNA-templated transcription
IBA
GO_REF:0000033
MODIFY
Summary: IBA from the PTN004738546 IBD (19 seeds). PsrA is one of the seeds through its own experimental rows, so its appearance in WITH/FROM is expected, not circular. The IBD stands on the other 18 seeds as well.
Reason: Correct and appropriate for the node, but PsrA has direct evidence for both signs of regulation. Both descendants, GO:0045892 and GO:0045893, are listed, matching the gene's own experimental rows.
Propagation Review
Root cause: NO FAILURE CORE
Failure modes: GRANULARITY MISMATCH
Sources checked:
PANTHER:PTN004738546 Β· PTN004738546 SUPPORTS TRANSFER
TetR-family node; 19 seeds, most of them experimentally characterised TetR regulators from E. coli, M. tuberculosis and P. aeruginosa. The node-level verdict is recorded on the nfxB/nalC/PA3678/atuR/nalD reviews.
UniProtKB:Q9HZJ9 Β· psrA (self; CollecTF EXP/IDA and PseudoCAP IMP) SUPPORTS TRANSFER
Expected self-seed reflecting the target's own experimental evidence.
Supporting Evidence:
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
GO:0006355 regulation of DNA-templated transcription
IEA
GO_REF:0000002
MODIFY
Summary: InterPro2GO from the TetR-like regulator family signature. Correct.
Reason: Same claim as the IBA row; the gene-level evidence supports both GO:0045892 and GO:0045893.
Supporting Evidence:
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
GO:0045892 negative regulation of DNA-templated transcription
EXP
PMID:18524913
The Pseudomonas aeruginosa PsrA responds to long-chain fatty...
ACCEPT
Summary: CollecTF row. PsrA binds the fadBA5 promoter and is needed to keep fadBA5 repressed until long-chain fatty acids disrupt its DNA binding.
Reason: Direct DNA binding plus genetic and ligand evidence for repression of fadBA5; a core function.
Supporting Evidence:
PMID:18524913
Electrophoretic mobility shift assays indicate specific binding of PsrA to the fadBA5 promoter region
PMID:18524913
This binding is disrupted by specific LCFAs
GO:0045892 negative regulation of DNA-templated transcription
IDA
PMID:15899403
Novel target genes of PsrA transcriptional regulator of Pseu...
ACCEPT
Summary: CollecTF row. PsrA binds and negatively regulates the PA0506 and PA2952-PA2951 promoters and its own promoter.
Reason: Abstract states direct binding and negative regulation of specific promoters; consistent with the EXP row.
Supporting Evidence:
PMID:15899403
Computer search was performed of the PsrA binding motif (G/CAAAC N(2-4) GTTTG/C) against the P. aeruginosa genome sequence. Four of 14 analysed promoters responded to and bound PsrA
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
GO:0045893 positive regulation of DNA-templated transcription
IMP
PMID:16428760
PsrA is a positive transcriptional regulator of the type III...
ACCEPT
Summary: PseudoCAP IMP and part of PsrA's seeding of the PTN004738546 IBD (a descendant of the node term). Full text read. Transcriptional fusions in an in-frame psrA deletion mutant, restored by complementation, show that PsrA is needed for full transcription of exsCEBA and exoS. rPsrA binds the exsCEBA promoter with low affinity. PsrA also activates rpoS, PA2953 and PA3571 (PMID:15899403).
Reason: The seed is sound. The mutant and complementation data directly show positive regulation of transcription. The authors leave open whether exsCEBA activation is direct, but the term does not require directness, and PsrA is an established DNA-binding activator of other promoters.
Supporting Evidence:
PMID:16428760
Using transcriptional fusions, we demonstrated that PsrA is required for the full activation of transcription of the TTSS regulatory operon exsCEBA and effector exoS
PMID:15899403
Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
GO:0050714 positive regulation of protein secretion
IMP
PMID:16428760
PsrA is a positive transcriptional regulator of the type III...
KEEP AS NON CORE
Summary: PseudoCAP IMP. Secretion of ExoS, ExoT and PopB falls in the psrA deletion mutant and is restored by complementation. This follows from PsrA's activation of exsCEBA transcription.
Reason: Correct as transcriptional regulation of genes that carry out type III protein secretion, which GO accepts for transcription factors, but peripheral to the core activity. GO has no regulation-of-type-III-secretion term, so this is as specific as available.
Supporting Evidence:
PMID:16428760
The psrA mutant showed a marked decrease in the secretion of the type III effectors
PMID:16428760
Using transcriptional fusions, we demonstrated that PsrA is required for the full activation of transcription of the TTSS regulatory operon exsCEBA and effector exoS

Core Functions

Sequence-specific DNA-binding transcription factor of the TetR family that represses fatty acid beta-oxidation genes (fadBA5) and its own gene, with repression relieved by long-chain fatty acids, and activates rpoS and the type III secretion regulatory operon exsCEBA.

Supporting Evidence:
  • PMID:18524913
    Electrophoretic mobility shift assays indicate specific binding of PsrA to the fadBA5 promoter region
  • PMID:15899403
    Promoters PA0506 and PA2952-PA2951 were regulated negatively whereas promoters of PA2953 and PA3571 were regulated positively by PsrA
  • PMID:16428760
    Using transcriptional fusions, we demonstrated that PsrA is required for the full activation of transcription of the TTSS regulatory operon exsCEBA and effector exoS

References

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Suggested Questions for Experts

Q: Does PsrA bind the exsCEBA promoter directly in vivo, or does it activate exsCEBA through another regulator?

Q: Which long-chain fatty acid or acyl species is the physiological PsrA ligand in the cell, and does ligand binding also modulate PsrA activation of rpoS and exsCEBA?

Suggested Experiments

Experiment: ChIP-seq of PsrA with and without oleate supplementation, combined with DNase I footprinting on the exsCEBA promoter, to separate direct from indirect targets.

Type: ChIP-seq and footprinting

πŸ“š Additional Documentation

Notes

(psrA-notes.md)

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