fur

Gene Description

Fur (ferric uptake regulation protein) is the master iron-responsive transcriptional regulator of Pseudomonas putida KT2440. It is a small (~134 aa) cytoplasmic homodimeric metalloprotein of the FUR family, built from an N-terminal winged-helix DNA-binding domain and a C-terminal dimerization domain. Each subunit binds a divalent metal ion (Fe(II), with Mn(II) often used as a surrogate in vitro) at a regulatory site; metal occupancy switches the protein to a DNA-binding-competent state. Holo-Fur binds conserved operator sequences (Fur boxes) in target promoters and chiefly acts as a transcriptional repressor of iron-acquisition genes (including siderophore/pyoverdine biosynthesis) when intracellular iron is replete, while iron limitation demetallates Fur and de-represses these genes. Fur thereby coordinates iron uptake, storage (e.g. bacterioferritins), and oxidative-stress homeostasis, balancing iron availability against Fenton-chemistry-driven reactive oxygen species damage. Fur can also affect gene expression positively, often indirectly via regulatory small RNAs or by acting on additional targets.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000976 transcription cis-regulatory region binding	IEA GO_REF:0000118	ACCEPT	Summary: Fur binds conserved operator sequences (Fur boxes) located in the cis-regulatory regions of iron-regulated promoters. This is a core, well-supported molecular function of the Fur family and is consistent with its winged-helix DNA-binding domain. Reason: Captures the specific DNA-binding mode of Fur (operator/Fur-box binding) and is supported by the canonical Fur mechanism and by purified Fur binding to Fur boxes in pseudomonads (e.g. P. aeruginosa Fur on pvdS/pchR promoters).
GO:0003677 DNA binding	IEA GO_REF:0000104	KEEP AS NON CORE	Summary: Fur binds DNA via its winged-helix domain. This is correct but is a parent/general term relative to the more informative cis-regulatory region binding annotation. Reason: True but generic; the more specific GO:0000976 (transcription cis-regulatory region binding) better captures the function. Retained as a non-core, broader supporting term rather than removed.
GO:0003700 DNA-binding transcription factor activity	IEA GO_REF:0000120	ACCEPT	Summary: Fur is a sequence-specific DNA-binding transcription factor that represses (and can indirectly activate) target genes. This is a core molecular function. Reason: Well-supported by the canonical Fur mechanism and the family/domain assignment; Fur acts as an iron-dependent transcriptional regulator binding operator DNA.
GO:0005737 cytoplasm	IEA GO_REF:0000044	ACCEPT	Summary: Fur is a soluble cytoplasmic protein, consistent with UniProt subcellular location and its role sensing intracellular iron and binding chromosomal operators. Reason: Correct localization for a cytoplasmic metal-sensing transcription factor.
GO:0005829 cytosol	IEA GO_REF:0000118	ACCEPT	Summary: More specific cytosolic localization annotation, consistent with Fur being a soluble intracellular regulator. Reason: Consistent with the cytoplasm annotation and the soluble nature of Fur; cytosol is the appropriate specific component for this regulator.
GO:0006355 regulation of DNA-templated transcription	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Fur regulates transcription of iron-homeostasis genes. This is the general parent process; the more specific negative regulation term is also annotated. Reason: Correct but general relative to GO:0045892 (negative regulation of DNA-templated transcription). Retained as a broader supporting process term.
GO:0008270 zinc ion binding	IEA GO_REF:0000118	MODIFY	Summary: This TreeGrafter annotation reflects that many Fur-family proteins contain a structural Zn(II) site and that the family includes zinc uptake regulators (Zur). However, for P. putida Fur the physiologically relevant, regulatory metal is ferrous iron; UniProt records Fe(II)/Mn(II) cofactor binding (1 ion per subunit) and Fe-binding residues, not a curated Zn site. The functionally salient metal-binding activity to annotate is ferrous iron binding. Reason: Fur is an iron sensor; its regulatory cofactor is Fe(II) (Mn(II) used as a surrogate in vitro), and UniProt annotates Fe cation binding sites (residues 86, 88, 107, 124). Ferrous iron binding more accurately reflects the iron-sensing function than the family-propagated zinc ion binding. If a structural Zn site is later confirmed for this protein, metal ion binding (GO:0046872) could be added. Proposed replacements: ferrous iron binding
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000118	ACCEPT	Summary: Holo-Fur predominantly acts as a transcriptional repressor of iron-acquisition genes when iron is replete. This negative-regulation role is the core biological process for Fur. Reason: Repression is the canonical and best-supported activity of Fur; UniProt also carries the Repressor keyword.
GO:1900376 regulation of secondary metabolite biosynthetic process	IEA GO_REF:0000118	KEEP AS NON CORE	Summary: Fur regulates siderophore (pyoverdine) biosynthesis; siderophores are secondary metabolites, so Fur participates in regulating secondary metabolite biosynthesis. This is broader than, and overlaps with, the more specific siderophore annotation. Reason: Plausible and consistent with Fur control of siderophore (a secondary metabolite) biosynthesis, but it is a general grouping term. The specific GO:1900705 captures the salient process; retained as non-core context rather than as a core function.
GO:1900705 negative regulation of siderophore biosynthetic process	IEA GO_REF:0000118	ACCEPT	Summary: When iron is replete, Fur represses siderophore (pyoverdine) biosynthesis genes, a defining iron-sparing function of Fur in pseudomonads. In P. aeruginosa Fur represses the siderophore regulators pvdS and pchR; KT2440 relies primarily on pyoverdine and Fur is its major iron-responsive regulator. Reason: Core, biologically specific process for Fur consistent with its repressor role and the pseudomonad iron-acquisition literature.

Core Functions

Iron(II)-dependent, sequence-specific DNA-binding transcriptional repressor that binds Fur-box operators in iron-regulated promoters to repress iron-acquisition genes when intracellular iron is replete.

Molecular Function:

DNA-binding transcription factor activity

Directly Involved In:

negative regulation of DNA-templated transcription

Cellular Locations:

cytosol

Supporting Evidence:

PMID:8522528
Purified Pseudomonas Fur binds Fur boxes in iron-regulated promoters (pvdS, pchR) and represses siderophore-pathway regulators, establishing Fur as an iron-dependent operator-binding repressor.

Ferrous-iron sensing via metal binding at a regulatory site, switching Fur to a DNA-binding-competent state that couples intracellular iron status to transcriptional output.

Molecular Function:

ferrous iron binding

Cellular Locations:

cytosol

Repression of siderophore (pyoverdine) biosynthesis as part of the iron-sparing response, coordinating iron acquisition, storage, and oxidative-stress homeostasis in P. putida.

Directly Involved In:

negative regulation of siderophore biosynthetic process

Cellular Locations:

cytosol

Supporting Evidence:

PMID:20562273
A P. putida KT2440 fur deletion mutant shows altered expression of iron-homeostasis (bacterioferritin) genes and increased hydrogen peroxide sensitivity, demonstrating Fur's role in iron storage and oxidative-stress homeostasis.

Gene Description

Existing Annotations Review

Core Functions

Iron(II)-dependent, sequence-specific DNA-binding transcriptional repressor that binds Fur-box operators in iron-regulated promoters to repress iron-acquisition genes when intracellular iron is replete.

Ferrous-iron sensing via metal binding at a regulatory site, switching Fur to a DNA-binding-competent state that couples intracellular iron status to transcriptional output.

Repression of siderophore (pyoverdine) biosynthesis as part of the iron-sparing response, coordinating iron acquisition, storage, and oxidative-stress homeostasis in P. putida.

References

Deep Research

Falcon

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