norR2 encodes a nitric oxide-responsive sigma-54-dependent transcriptional activator in Cupriavidus necator H16. It is the chromosomal paralog of the megaplasmid-encoded NorR1 and has the conserved NorR GAF, AAA+ ATPase, and Fis-family helix-turn-helix DNA-binding architecture.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005524 ATP binding | IEA GO_REF:0000002 | MODIFY | Summary: NorR2 contains the conserved sigma-54-interaction/AAA+ ATPase region of NorR-family bacterial enhancer-binding proteins. ATP binding is plausible, but ATP hydrolysis is the more informative molecular function. Reason: The InterPro evidence identifies the sigma-54 interaction ATP-binding region, while NorR-family biochemical work shows that NO binding stimulates ATPase activity to activate transcription by RNA polymerase. Proposed replacements: ATP hydrolysis activity Supporting Evidence: file:CUPNH/norR2/norR2-uniprot.txt InterPro; IPR002078; Sigma_54_int. PMID:16193057 Binding of NO stimulates the ATPase activity of NorR, enabling the activation of transcription by RNA polymerase. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | MODIFY | Summary: NorR2 positively activates NO-responsive transcription of nitric oxide reductase genes through the NorR/sigma-54 regulatory system. Reason: The existing term is correct but too broad. Ralstonia studies show NorR is required for transcriptional activation of the norA/norB nitric oxide reductase operon in response to NO. Proposed replacements: positive regulation of DNA-templated transcription Supporting Evidence: PMID:11069685 The regulator gene maps adjacent to norAB, is divergently transcribed and present in two copies on the megaplasmid pHG1 (norR1) and the chromosome (norR2). PMID:15667304 norB and the adjacent norA form an operon that is controlled by the sigma(54)-dependent transcriptional activator NorR in response to NO. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000002 | MODIFY | Summary: NorR2 has a Fis-family helix-turn-helix DNA-binding domain, but generic sequence-specific DNA binding misses its NO-responsive transcriptional activator function. Reason: NorR proteins bind upstream activator sequences and activate sigma-54-dependent transcription in response to NO. GO:0141097 captures this ligand-modulated activator activity more precisely than generic DNA binding. Proposed replacements: ligand-modulated transcription activator activity Supporting Evidence: PMID:15667304 A NorR derivative containing MalE in place of the N-terminal domain binds to a 73 bp region upstream of norA that includes three copies of the putative upstream activator sequence GGT-(N(7))-ACC. PMID:16193057 Here we show that the regulatory domain of NorR contains a mononuclear non-haem iron centre, which reversibly binds NO. |
| GO:0019333 denitrification pathway | IEA GO_REF:0000041 | MARK AS OVER ANNOTATED | Summary: NorR2 controls expression of NO reductase but is not itself a denitrification enzyme. The UniPathway row imports pathway context too directly for a regulator. Reason: Species-specific evidence supports NorR2 as the chromosomal copy of an NO-responsive regulator of nitric oxide reductase expression. UniProt records denitrification as regulatory context, and the Ralstonia NorR study states that other denitrification-chain steps are independent of NorR. Supporting Evidence: file:CUPNH/norR2/norR2-uniprot.txt PATHWAY: Nitrogen metabolism; nitrate reduction (denitrification) [regulation]. PMID:11069685 This reaction is not strictly co-ordinated on the regulatory level with the other nitrogen oxide-reducing steps of the denitrification chain that are independent of NorR. |
| GO:0141097 ligand-modulated transcription activator activity | ISS PMID:11069685 A novel NO-responding regulator controls the reduction of ni... | NEW | Summary: NorR2 is the chromosomal copy of the NO-responsive NorR transcriptional activator system in C. necator H16. Reason: The existing sequence-specific DNA-binding annotation is too narrow for NorR2. Direct mutant evidence in this organism was generated mainly for norR1, so this NEW term is treated as ISS for norR2 based on the chromosomal paralog relationship, conserved GAF/AAA+/Fis-domain NorR architecture, and NorR-family biochemical evidence for NO sensing and ATPase-stimulated sigma-54 activation. Supporting Evidence: PMID:11069685 The regulator gene maps adjacent to norAB, is divergently transcribed and present in two copies on the megaplasmid pHG1 (norR1) and the chromosome (norR2). PMID:15667304 The N-terminal domain of NorR contains a GAF module and is hypothesized to interact with a signal molecule. PMID:16193057 Binding of NO stimulates the ATPase activity of NorR, enabling the activation of transcription by RNA polymerase. file:CUPNH/norR2/norR2-deep-research-falcon.md Falcon synthesis treats NorR2 as the chromosomal NorR paralog in the norR2A2B2 locus, with conserved GAF, AAA+ ATPase, and DNA-binding architecture supporting NO-responsive sigma-54 transcriptional activation by homology and locus context. file:interpro/panther/PTHR32071/PTHR32071-deep-research-falcon.md PTHR32071 family research supports sigma-54 enhancer-binding proteins as conserved AAA+ transcriptional activators with pathway-specific sensory-domain inputs. |
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