PA0906 (alpR) encodes AlpR, an essential lambda CI/LexA-like transcriptional repressor with an N-terminal Cro/C1-type helix-turn-helix DNA-binding domain and a C-terminal peptidase S24 (LexA-like) domain carrying a Ser-Lys dyad. AlpR binds the alpR-alpA and alpA-alpB intergenic regions and directly represses its own gene and the divergent alpABCDE operon. DNA damage (ciprofloxacin, hydrogen peroxide) triggers Ser153-dependent cleavage of AlpR, which de-represses alpA; AlpA then activates the alpBCDE lysis cassette, causing lysis of a subset of cells in a programmed-cell-death pathway that enhances virulence in a mouse lung infection model. AlpR is essential because it keeps this lysis program off.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: Combined InterPro/UniRule IEA from the lambda repressor-like DNA-binding domain. Reason: Correct but general; ChIP-seq shows AlpR bound specifically to the two promoter-containing intergenic regions it represses, so GO:0000976 transcription cis-regulatory region binding is supported. Proposed replacements: transcription cis-regulatory region binding Supporting Evidence: PMID:26100878 ChIP-Seq with an epitope-tagged version of AlpR revealed that AlpR associates with only two regions of the PAO1 chromosome: the alpR-alpA and alpA-alpB intergenic regions |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: UniRule-based IEA. Reason: AlpR represses transcription; it is not part of the transcription machinery. Supporting Evidence: PMID:26100878 AlpR therefore exerts its effect on expression of these target genes directly. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from PTN002221379, whose sole seed is this gene's PseudoCAP IDA to negative regulation of transcription (PMID:26100878). The target appearing in its own WITH/FROM is expected. Reason: The IBD is sound and the generic term suits the node (CI/LexA-like repressors). For AlpR itself, the direct evidence is for repression, so the specific GO:0045892, which the gene carries by IDA, is the precise term. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002221379 · PTN002221379 SUPPORTS TRANSFER QuickGO (2026-10-28) lists 10 IBA leaves, all CI/LexA-like HTH-S24 repressors (PrtR Q06553, S. oneidensis prophage repressors, STM0898, HI_1476, NMB0910, NMB0556). UniProtKB:Q9I551 · PA0906 SUPPORTS TRANSFER The target's own experimental annotation is the IBD seed; expected, not circular. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:26100878 AlpR therefore exerts its effect on expression of these target genes directly. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000104 | MODIFY | Summary: UniRule-based IEA. Reason: Correct but general; AlpR is a direct repressor of alpR and alpA, so GO:0045892 is supported. Proposed replacements: negative regulation of DNA-templated transcription Supporting Evidence: PMID:26100878 These findings suggest that AlpR, either directly or indirectly, represses expression of the alpR and alpABCDE genes. |
| GO:0001896 autolysis | IMP PMID:26100878 A self-lysis pathway that enhances the virulence of a pathog... | MODIFY | Summary: PseudoCAP IMP; lysis follows AlpR depletion, ectopic AlpR-CTD expression, or DNA-damage-induced AlpR cleavage. Not a PAINT seed. Reason: AlpR does not carry out lysis; the alpBCDE products do, after AlpA activates them. AlpR is the repressor that keeps the lysis program off, and its cleavage releases it. The gene's role is therefore negative regulation of a programmed cell death process (autolysis is_a programmed cell death; GO has no regulation-of-autolysis term). Proposed replacements: negative regulation of programmed cell death Supporting Evidence: PMID:26100878 Cleavage of AlpR triggers a cell lysis program through de-repression of the alpA gene, which encodes a positive regulator that activates expression of the alpBCDE lysis cassette. PMID:26100878 suggesting that AlpR is essential because it represses expression of one or more of the alpABCDE genes |
| GO:0006974 DNA damage response | IDA PMID:26100878 A self-lysis pathway that enhances the virulence of a pathog... | ACCEPT | Summary: PseudoCAP IDA; AlpR is cleaved in cells exposed to ciprofloxacin or hydrogen peroxide, and the S153A mutant is not. Reason: AlpR's own Ser153-dependent cleavage in response to DNA damage is the step that transmits the damage signal to the alp genes, as for LexA in the SOS response. This is direct participation. Supporting Evidence: PMID:26100878 Exposure of P. aeruginosa cells to the antibiotic ciprofloxacin, which leads to DNA damage, resulted in cleavage of wild-type AlpR but not the AlpR mutant AlpR(S153A) |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:26100878 A self-lysis pathway that enhances the virulence of a pathog... | ACCEPT | Summary: PseudoCAP IDA from ChIP-seq, promoter-fusion repression and the non-cleavable S153A mutant. Sole seed of the GO:0006355 IBD at PTN002221379. Reason: AlpR binds the alpR-alpA and alpA-alpB intergenic promoter regions in vivo, ectopic AlpR represses those promoter fusions, and non-cleavable AlpR prevents their induction. This is direct evidence for transcriptional repression. Supporting Evidence: PMID:26100878 the expression of alpR promoter–, alpA promoter–, and alpB promoter– lacZ fusions was repressed by ectopic synthesis of AlpR PMID:26100878 AlpR therefore exerts its effect on expression of these target genes directly. |
| GO:0016540 protein autoprocessing | IMP PMID:26100878 A self-lysis pathway that enhances the virulence of a pathog... | NEW | Summary: Proposed. AlpR is cleaved after DNA damage, and replacing the Ser-Lys dyad serine (S153A) abolishes cleavage. Reason: AlpR carries the LexA/CI-type peptidase S24 domain and its cleavage depends on the dyad serine of that domain, so AlpR itself does the cleaving, the autoprocessing case named in CLAUDE.md. Cleavage was not reconstituted in vitro, so self-catalysis rests on the mutant plus family mechanism. Supporting Evidence: PMID:26100878 Like the related λCI and LexA proteins, AlpR contains a so-called Ser-Lys dyad that in LexA and in λCI mediates autocleavage PMID:26100878 These findings suggest that AlpR undergoes cleavage in response to DNA damage and establish that substitution S153A results in a mutant version of AlpR that cannot undergo autocleavage. |
| GO:0001217 DNA-binding transcription repressor activity | IDA PMID:26100878 A self-lysis pathway that enhances the virulence of a pathog... | NEW | Summary: Proposed. The GOA set has only DNA binding (IEA) as MF; AlpR's direct repressor activity is shown in the same paper that PseudoCAP cites. Reason: AlpR occupies the alpR-alpA and alpA-alpB promoter regions (ChIP-seq) and represses those promoters, so it enables DNA-binding transcription repressor activity. This is the core MF. Supporting Evidence: PMID:26100878 the expression of alpR promoter–, alpA promoter–, and alpB promoter– lacZ fusions was repressed by ectopic synthesis of AlpR PMID:26100878 AlpR therefore exerts its effect on expression of these target genes directly. |
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Download this section (compressed HTML)Q: Is AlpR cleavage RecA-dependent, and does it proceed by self-cleavage in vitro as for LexA?
Q: Should GO add a regulation-of-autolysis term so that bacterial lysis repressors need not use the generic programmed-cell-death regulation term?
Experiment: Reconstitute AlpR cleavage in vitro with purified AlpR, activated RecA filaments and alkaline pH, comparing wild type and S153A.
Type: in vitro autoproteolysis assay
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