Fur-family zinc uptake transcriptional repressor Zur (VPARA_33720, A0A0H2LYR2) in Variovorax paradoxus strain TBEA6 is a 149-amino-acid cytosolic homodimeric metalloregulator (Pfam PF01475, CDD cd07153, InterPro IPR002481, PANTHER PTHR33202) encoded on genomic contig JZWI01000017 (EMBL KLN55348.1). Zur comprises an N-terminal winged-helix DNA-binding domain (Gene3D 1.10.10.10, InterPro IPR036388, SUPFAM SSF46785) and a C-terminal dimerization and metal-sensing domain (InterPro IPR043135) housing a four-cysteine structural Zn(2+)-binding site at Cys96, Cys99 (96-CGSC-99), Cys133, and Cys136 (133-CAAC-136; PIRSR PIRSR602481-1) together with a regulatory metal-sensing site containing His90 (within 87-HHHHYFH-93) and His125. Under zinc-replete conditions, Zn(2+)-bound holo-Zur binds cis-regulatory Zur-box operator sequences to repress transcription of high-affinity zinc acquisition genes and maintain cellular zinc ion homeostasis, whereas zinc limitation triggers derepression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000118 | ACCEPT | Summary: Core molecular function; holo-Zur binds palindromic Zur-box operator sequences in target promoter regions via its N-terminal winged-helix DNA-binding domain. Reason: Zur contains a conserved N-terminal winged-helix DNA-binding domain (Gene3D 1.10.10.10, InterPro IPR036388, SUPFAM SSF46785) and C-terminal homodimerization domain (InterPro IPR043135) that bind operator DNA in target promoters when metallated. Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR InterPro; IPR036388; WH-like_DNA-bd_sf. DR InterPro; IPR036390; WH_DNA-bd_sf. |
| GO:0003677 DNA binding | IEA GO_REF:0000104 | TOO GENERAL | Summary: True but uninformative parent molecular function already entailed by the accepted specific child term GO:0000976 (transcription cis-regulatory region binding). Reason: GO:0003677 (DNA binding) is a broad ancestor term already entailed by GO:0000976 (transcription cis-regulatory region binding) accepted in this review. Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR InterPro; IPR036390; WH_DNA-bd_sf. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: Correct but unsigned parent transcription factor term; refine to GO:0001217 (DNA-binding transcription repressor activity). Reason: GO:0003700 (DNA-binding transcription factor activity) is true of Zur but unsigned; refine to its specific child term GO:0001217 (DNA-binding transcription repressor activity), consistent with KW:Repressor in file:VARPD/zur/zur-uniprot.txt and matching VARPD/fur1. Proposed replacements: DNA-binding transcription repressor activity Supporting Evidence: file:VARPD/zur/zur-uniprot.txt KW Repressor {ECO:0000256|ARBA:ARBA00022491, ECO:0000256|RuleBase:RU364037}; |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | TOO GENERAL | Summary: True but uninformative parent cellular component already entailed by the specific child term GO:0005829 (cytosol). Reason: GO:0005737 (cytoplasm) is a general parent term already entailed by GO:0005829 (cytosol) added in this review (matching VARPD/fur1). Supporting Evidence: file:VARPD/zur/zur-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|RuleBase:RU364037}. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: True but uninformative unsigned parent process already entailed by the accepted specific child term GO:0045892 (negative regulation of DNA-templated transcription). Reason: GO:0006355 (regulation of DNA-templated transcription) is a general ancestor term already entailed by GO:0045892 (negative regulation of DNA-templated transcription) accepted in this review. Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR InterPro; IPR002481; FUR. |
| GO:0008270 zinc ion binding | IEA GO_REF:0000118 | ACCEPT | Summary: Core molecular function; Zur binds both a structural Zn(2+) ion at its four-cysteine site (Cys96, Cys99, Cys133, Cys136; PIRSR PIRSR602481-1) and a regulatory Zn(2+) ion at its metal-sensing site to trigger operator DNA binding. Reason: VPARA_33720 (zur, PANTHER PTHR33202 ZINC UPTAKE REGULATION PROTEIN) retains the four-cysteine structural Zn(2+)-binding motif (Cys96, Cys99 in 96-CGSC-99 and Cys133, Cys136 in 133-CAAC-136; PIRSR PIRSR602481-1) as well as the histidine-rich regulatory site (87-HHHHYFH-93 and His125) that senses intracellular Zn(2+). Supporting Evidence: file:VARPD/zur/zur-uniprot.txt CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000256|PIRSR:PIRSR602481-1}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000256|PIRSR:PIRSR602481-1}; |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000118 | ACCEPT | Summary: Core biological process; Zn(2+)-bound holo-Zur represses transcription of target zinc-uptake operons under zinc-replete conditions. Reason: Zur (PANTHER PTHR33202, Pfam PF01475, KW:Repressor) is a Zn(2+)-sensing transcriptional repressor that negatively regulates transcription of zinc-acquisition genes when intracellular zinc is sufficient. Supporting Evidence: file:VARPD/zur/zur-uniprot.txt KW Repressor {ECO:0000256|ARBA:ARBA00022491, ECO:0000256|RuleBase:RU364037}; |
| GO:1900376 regulation of secondary metabolite biosynthetic process | IEA GO_REF:0000118 | MARK AS OVER ANNOTATED | Summary: TreeGrafter over-annotation from Fur-family siderophore regulators; unlike Fur1 (VPARA_18200), Zur (VPARA_33720) is the zinc uptake transcriptional repressor, and a direct role in secondary metabolite biosynthesis in V. paradoxus TBEA6 has not been established. Reason: TreeGrafter propagated GO:1900376 from PANTHER PTHR33202 across the Fur/Zur family. While Variovorax paradoxus encodes a dedicated ferric uptake regulator Fur1 (VPARA_18200, A0A0H2M8T9) that represses siderophore biosynthesis (GO:1900705), VPARA_33720 is the zinc uptake regulator Zur (GN Name=zur), whose primary role is cellular zinc ion homeostasis (GO:0006882). Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR PANTHER; PTHR33202; ZINC UPTAKE REGULATION PROTEIN; 1. DR Pfam; PF01475; FUR; 1. |
| GO:0001217 DNA-binding transcription repressor activity | IC file:VARPD/zur/zur-uniprot.txt | NEW | Summary: Core molecular function; Zn(2+)-loaded Zur binds operator DNA to repress transcription of target genes. Reason: Inferred by curator (IC) from PANTHER PTHR33202 (ZINC UPTAKE REGULATION PROTEIN), Pfam PF01475 (FUR), and KW:Repressor in file:VARPD/zur/zur-uniprot.txt (matching VARPD/fur1). Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR PANTHER; PTHR33202; ZINC UPTAKE REGULATION PROTEIN; 1. DR Pfam; PF01475; FUR; 1. |
| GO:0005829 cytosol | IC file:VARPD/zur/zur-uniprot.txt | NEW | Summary: Core subcellular localization of the soluble 149-aa cytoplasmic Zur homodimer. Reason: Inferred by curator (IC) from CC:SUBCELLULAR LOCATION (Cytoplasm) and the 149-aa soluble transcription factor architecture in file:VARPD/zur/zur-uniprot.txt (matching VARPD/fur1). Supporting Evidence: file:VARPD/zur/zur-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|RuleBase:RU364037}. |
| GO:0006882 cellular zinc ion homeostasis | IC file:VARPD/zur/zur-uniprot.txt | NEW | Summary: Core biological process; Zur is the Zn(2+)-sensing transcriptional repressor that controls cellular zinc uptake and homeostasis. Reason: Inferred by curator (IC) from the gene symbol zur (EMBL KLN55348.1), PANTHER family PTHR33202 (ZINC UPTAKE REGULATION PROTEIN), and conserved Zn(2+)-binding motifs in file:VARPD/zur/zur-uniprot.txt. Supporting Evidence: file:VARPD/zur/zur-uniprot.txt DR PANTHER; PTHR33202; ZINC UPTAKE REGULATION PROTEIN; 1. DR Pfam; PF01475; FUR; 1. |
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Download this section (compressed HTML)Q: Does Variovorax paradoxus Zur (VPARA_33720) solely repress the high-affinity ZnuABC zinc uptake system and zinc-free ribosomal paralogs under zinc sufficiency, or does it also cross-regulate parts of the lanthanide / siderophore / heavy-metal homeostasis network?
Suggested experts: Helmann JD, Outten CE
Experiment: Purify recombinant Variovorax paradoxus Zur (A0A0H2LYR2) and perform electrophoretic mobility shift assays (EMSAs) and ChIP-seq in wild-type versus Ξzur strains grown under Zn(2+)-chelated (TPEN) and Zn(2+)-replete conditions.
Hypothesis: Zn(2+) binding at the His90/His125 regulatory site allosterically activates Zur binding to palindromic Zur-box operators upstream of high-affinity Zn(2+) importer genes to repress their transcription under zinc sufficiency.
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