ureF

UniProt ID: A0A0H2LZ72
Organism: Variovorax paradoxus
Review Status: COMPLETE
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Gene Description

UreF (VPARA_50930) in Variovorax paradoxus is a 223-amino-acid cytoplasmic urease accessory protein (HAMAP rule MF_01385, InterPro IPR002639, PANTHER PTHR33620:SF1, Pfam PF01730) encoded immediately downstream of ureE (VPARA_50940). Within the cytoplasmic UreD-UreF-UreG activation complex bound to apo-urease, UreF docks the SIMIBI-class GTPase UreG and gates its GTP hydrolysis to ensure faithful installation of the dinickel metallocenter into the UreC active site.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005737 cytoplasm
IEA
GO_REF:0000120 		ACCEPT
Summary: UreF functions in the cytoplasmic UreD-UreF-UreG urease activation complex.
Reason: A0A0H2LZ72 (VPARA_50930) is a soluble 223-residue cytoplasmic protein (HAMAP rule MF_01385) that assembles with UreD and UreG on cytoplasmic apo-urease.
Supporting Evidence:
UniProtKB:A0A0H2LZ72
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_01385}.
GO:0016151 nickel cation binding
IEA
GO_REF:0000120 		REMOVE
Summary: UniRule over-propagates nickel cation binding to UreF; nickel binding and delivery are mediated by UreE and UreG rather than UreF.
Reason: Biochemical and structural analyses of the bacterial UreD-UreF-UreG system establish that UreE and UreG bind and transfer Ni(2+), whereas UreF serves as an allosteric scaffold and GTPase-gating factor that recruits UreG without directly binding nickel as a metallochaperone (PMID:22369361).
Supporting Evidence:
PMID:22369361
UreE functions as a metallochaperone that delivers Ni to a UreD-UreF-UreG complex bound to urease apoprotein, with UreG serving as a GTPase during enzyme activation.
GO:0018237 urease activator activity
ISS
PMID:22369361
Klebsiella aerogenes UreF: identification of the UreG bindin... 		NEW
Summary: UreF promotes nickel incorporation into the UreC active site as a component of the UreD-UreF-UreG pre-activation complex.
Reason: Inferred from sequence and structural similarity (ISS) to Klebsiella aerogenes UreF (PMID:22369361; PANTHER PTHR33620:SF1), which docks UreG onto the UreD-apourease complex to promote productive nickel incorporation into the urease active site (GO:0018237).
Supporting Evidence:
PMID:22369361
Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the noncognate metal Zn.
GO:0030695 GTPase regulator activity
ISS
PMID:22369361
Klebsiella aerogenes UreF: identification of the UreG bindin... 		NEW
Summary: UreF binds the SIMIBI GTPase UreG and gates its nucleotide hydrolysis during urease metallocenter assembly.
Reason: Inferred from sequence similarity (ISS) to Klebsiella aerogenes UreF (PMID:22369361), which directly binds UreG and gates its GTPase activity to couple GTP hydrolysis to faithful nickel insertion.
Supporting Evidence:
PMID:22369361
Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the noncognate metal Zn.
GO:0043419 urea catabolic process
ISS
PMID:22369361
Klebsiella aerogenes UreF: identification of the UreG bindin... 		NEW
Summary: UreF is required for maturation of the urease enzyme that catalyzes urea catabolism.
Reason: Inferred from sequence similarity (ISS) to Klebsiella aerogenes UreF (PMID:22369361), where UreF-mediated recruitment and gating of UreG are required for assembly of catalytically active urease in the urea catabolic pathway.
Supporting Evidence:
PMID:22369361
Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the noncognate metal Zn.

Core Functions

Cytoplasmic urease activator that docks UreG onto the UreD-apourease scaffold to promote nickel incorporation into the UreC active site.

Molecular Function:
urease activator activity
Directly Involved In:
urea catabolic process
Cellular Locations:
cytoplasm
Supporting Evidence:
  • UniProtKB:A0A0H2LZ72
    CC -!- FUNCTION: Required for maturation of urease via the functional CC incorporation of the urease nickel metallocenter. {ECO:0000256|HAMAP- CC Rule:MF_01385}.
  • PMID:22369361
    Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the noncognate metal Zn.

GTPase regulator that binds UreG and gates its GTP hydrolysis to ensure high-fidelity nickel insertion into apo-urease.

Molecular Function:
GTPase regulator activity
Directly Involved In:
urea catabolic process
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:22369361
    Further experiments with these complexes provided evidence that UreF gates the GTPase activity of UreG to enhance the fidelity of urease metallocenter assembly, especially in the presence of the noncognate metal Zn.

References

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Suggested Questions for Experts

Q: Does Variovorax paradoxus UreF (VPARA_50930) protect urease maturation against mis-metallation by excess cytoplasmic Zn(2+) in heavy-metal-rich rhizosphere soils?

Suggested Experiments

Experiment: Compare GTP hydrolysis rates and nickel vs. zinc occupancy of reconstituted Variovorax paradoxus UreDFG-apourease complexes containing wild-type VPARA_50930 versus a conserved gating-loop Ala variant.

Hypothesis: VPARA_50930 (UreF) gates the GTPase activity of UreG to prevent noncognate Zn(2+) incorporation into apo-UreABC during metal stress.

Type: In vitro reconstitution, GTPase assay, and ICP-MS metal occupancy analysis

📚 Additional Documentation

Notes

(ureF-notes.md)

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