cysB (PA1754) encodes CysB, a LysR-type transcriptional regulator with an N-terminal helix-turn-helix DNA-binding domain and a CysB-type co-inducer-binding domain, about 63% identical to CysB of Escherichia coli and Salmonella. CysB is the master regulator of sulfur metabolism, and a cysB insertion mutant is a cysteine auxotroph, as expected when the genes of sulfate assimilation and cysteine synthesis are not activated. CysB also binds the 3' region of the alginate algD promoter and can activate algD expression, and it binds the promoter of the iron-starvation sigma factor gene pvdS and activates pvdS expression, so that cysB mutants show reduced PvdS-dependent virulence phenotypes. CysB thus links the sulfur and iron regulons.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN001248394, seeded by other LysR regulators (P39376, P72131), not by CysB. Reason: P. aeruginosa CysB binds specific sites in the algD and pvdS promoter regions, which is binding to transcription cis-regulatory regions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001248394 · PTN001248394 SUPPORTS TRANSFER LysR-family node; promoter binding is conserved and shown for CysB itself. Supporting Evidence: PMID:20370820 The CysB protein directly binds to the pvdS promoter in vitro and acts as a positive regulator of PvdS expression in vivo. PMID:9218775 both p36 and S. typhimurium CysB bind the same site of palgD |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from PTN001248394 (7 seeds, including this gene's PseudoCAP IDA to positive regulation, PMID:20370820). The target appearing in its own WITH/FROM is expected. Reason: CysB is a DNA-binding transcriptional regulator. The generic regulation term is kept as the gene-level summary because CysB's sign of action is target-dependent across the sulfur regulon (it is shown here only as an activator, at algD and pvdS, which the separate GO:0045893 IDA row captures). Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001248394 · PTN001248394 SUPPORTS TRANSFER Worklist gives 202 leaf IBAs in 30 taxa, a LysR clade; seven seeds. UniProtKB:G3XCU6 · cysB SUPPORTS TRANSFER The target's own experimental annotation is one of the IBD seeds; expected, not circular. Supporting Evidence: PMID:20370820 This led to the identification and functional characterization of the LysR-like transcription factor CysB as a novel regulator of pvdS transcription. |
| GO:0019344 L-cysteine biosynthetic process | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: PAINT IBA from PTN002824317, whose sole seed is this gene's PseudoCAP IMP (PMID:9218775), the cysteine auxotrophy of a cysB mutant. Reason: CysB is the transcriptional activator of cysteine-synthesis genes, not a participant; it catalyses no step of L-cysteine biosynthesis (the enzymes are serine acetyltransferase and O-acetylserine sulfhydrylase). Auxotrophy of the mutant establishes necessity only. Every leaf of the node carries the LysR regulator architecture (Pfam PF00126 plus PF03466) and no biosynthetic-enzyme domain, and the only leaves with experimental data, E. coli CysB (IDA DNA binding) and the Cbl paralog (IDA positive regulation of sulfur utilization), are annotated as regulators; E. coli CysB has no experimental GO:0019344 of its own, so the IBD rests only on a phenotype-as-process seed. Propagation Review Root cause: SOURCE BAD Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002824317 · PTN002824317 SOURCE BAD QuickGO (2026-10-28) lists 10 GO:0019344 IBA leaves (CysB of P. aeruginosa, S. typhimurium, E. coli, H. influenzae, Y. pestis, S. oneidensis, X. campestris, N. meningitidis, V. cholerae, and E. coli Cbl), plus about 1,200 TreeGrafter IEAs from the same node. UniProtKB:G3XCU6 · cysB SOURCE BAD The seed is a mutant auxotrophy phenotype annotated as participation in the process. Supporting Evidence: PMID:9218775 A CysB-deficient mutant of CHA, constructed by insertional inactivation of cysB, was a cysteine auxotroph PMID:20370820 Given the role of CysB as master regulator of sulfur metabolism |
| GO:0003677 DNA binding | IEA GO_REF:0000104 | MODIFY | Summary: UniRule-based IEA for LysR-family HTH proteins. Reason: Correct but general; CysB binds specific promoter regions (algD, pvdS), so GO:0000976 transcription cis-regulatory region binding, which the gene already carries, is supported. Proposed replacements: transcription cis-regulatory region binding Supporting Evidence: PMID:20370820 The CysB protein directly binds to the pvdS promoter in vitro |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from the LysR HTH domain. Reason: CysB binds promoters and activates transcription of target genes; this is its core molecular function. Supporting Evidence: PMID:20370820 The CysB protein directly binds to the pvdS promoter in vitro and acts as a positive regulator of PvdS expression in vivo. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: UniRule-based IEA for LysR-family regulators. Reason: CysB regulates transcription; it is not part of the transcription machinery. Its process is captured by the regulation-of-transcription rows. Supporting Evidence: PMID:9218775 Thus, P. aeruginosa CysB can act as an activator of algD expression. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: Combined InterPro/UniRule IEA. Reason: Consistent with the IBA row and with direct evidence that CysB regulates transcription of pvdS and algD. Supporting Evidence: PMID:20370820 This led to the identification and functional characterization of the LysR-like transcription factor CysB as a novel regulator of pvdS transcription. |
| GO:0019344 L-cysteine biosynthetic process | IMP PMID:9218775 Cloning, sequence and mutagenesis of the structural gene of ... | MARK AS OVER ANNOTATED | Summary: PseudoCAP IMP from the cysteine auxotrophy of a cysB insertion mutant (strain CHA). Sole seed of the GO:0019344 IBD at PTN002824317. Reason: The abstract states the basis is a mutant phenotype (auxotrophy) and identifies CysB as a LysR-family transcription factor; the full text was not available here (no PMC copy, rechecked 2026-10-29). A regulator required for expression of the cysteine-synthesis genes is not a participant in cysteine biosynthesis; the enzymes of the pathway perform its steps. The regulatory role is already covered by the transcription-regulation rows. Supporting Evidence: PMID:9218775 A CysB-deficient mutant of CHA, constructed by insertional inactivation of cysB, was a cysteine auxotroph PMID:9218775 a transcriptional factor of the LysR superfamily |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:20370820 Transcriptional control of the pvdS iron starvation sigma fa... | ACCEPT | Summary: PseudoCAP IDA from DNA-affinity capture of CysB on the pvdS promoter, in vitro binding, and positive regulation of pvdS in vivo. Supporting annotation for the GO:0006355 IBD at PTN001248394. Reason: Direct binding of CysB to the pvdS promoter plus decreased PvdS expression in its absence supports CysB acting as a transcriptional activator. Supporting Evidence: PMID:20370820 The CysB protein directly binds to the pvdS promoter in vitro and acts as a positive regulator of PvdS expression in vivo. |
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Download this section (compressed HTML)Q: Which P. aeruginosa sulfate-assimilation and cysteine-synthesis promoters does CysB bind directly, and does it use N-acetylserine as co-inducer as in enterobacteria?
Q: Where a regulator's mutant is auxotrophic, should PAINT carry a regulatory term (e.g. GO:1900059 positive regulation of sulfate assimilation) rather than the biosynthetic process?
Q: GO has no term for regulation of cysteine biosynthesis, so CysB's role falls back to generic transcription regulation (GO:0045893, GO:0006355), which loses the cys-regulon content that the cysB auxotrophy reflects. Should GO add positive regulation of cysteine biosynthetic process, or should CysB carry GO:1900059 positive regulation of sulfate assimilation with an extension naming its target genes?
Experiment: ChIP-seq of CysB in PAO1 under sulfate-limited and sulfate-replete growth, with and without N-acetylserine, to define the direct regulon.
Type: ChIP-seq
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