hutF (PA5106) encodes N-formimino-L-glutamate deiminase (formimidoylglutamate deiminase, FIGLU iminohydrolase, EC 3.5.3.13) of Pseudomonas aeruginosa, a cytoplasmic homodimeric member of the amidohydrolase superfamily with a distorted (beta/alpha)8-barrel catalytic domain and a single active-site zinc ion coordinated by His56, His58, His232 and Asp320. It hydrolyses the formimino group of N-formimino-L-glutamate (FIGLU) to give N-formyl-L-glutamate and ammonia, using a zinc-bound hydroxide activated by His269. This is the first of two steps of the deiminase branch of histidine utilization, after which HutG (PA5091) hydrolyses N-formyl-L-glutamate to formate and L-glutamate. P. aeruginosa also has a parallel route in which HutE (PA3175) cleaves FIGLU directly to formamide and glutamate. hutF lies in the hut gene cluster, and histidine catabolism lets the bacterium use histidine as a carbon and nitrogen source.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: IBA (is_active_in cytosol) from PTN000138454, seeded by mammalian guanine deaminase localizations. Reason: HutF is a soluble homodimer without signal peptide or transmembrane segment, purified from the soluble fraction, and acts on an intracellular pathway intermediate; cytosol is where the activity takes place. No direct localization assay exists for PA5106, so this rests on the inherited location plus these properties. Supporting Evidence: file:PSEAE/hutF/hutF-uniprot.txt SUBUNIT: Homodimer. |
| GO:0006548 L-histidine catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000138516 (8 leaf IBAs); the BP IBD has one seed, this gene's PseudoCAP IMP row to PMID:4290562. The target appearing in its own WITH/FROM is expected, not circular. Reason: HutF catalyses the first step of one FIGLU branch of histidine degradation, so the enzyme does part of the work of this process; it is a canonical HutF in the PAO1 hut cluster. The claim is accepted on the direct enzymology of PMID:16475788. The seed reference does not visibly tie the process to this gene (see the IMP row), so the IBD should be re-anchored, and three nematode leaves lacking HutF signatures may be over-propagated. Supporting Evidence: PMID:16475788 The protein Pa5106 was shown to catalyze the deimination of N-formimino-L-glutamate to ammonia and N-formyl-L-glutamate, while Pa5091 catalyzed the hydrolysis of N-formyl-L-glutamate to formate and L-glutamate. file:PSEAE/hutF/hutF-uniprot.txt Amino-acid degradation; L-histidine degradation into L- glutamate; L-glutamate from N-formimidoyl-L-glutamate (deiminase route): step 1/2. |
| GO:0006548 L-histidine catabolic process | IMP PMID:4290562 Formation and operation of the histidine-degrading pathway i... | ACCEPT | Summary: PseudoCAP IMP; sole seed of the PTN000138516 L-histidine catabolic process IBD (8 leaf IBAs). Lessie and Neidhardt (1967) studied induction and repression of histidine-degrading activities in P. aeruginosa with urocanase-deficient, auxotrophic and repression mutants. Reason: The claim is correct and accepted on independent evidence (PMID:16475788: PA5106 catalyses the first step of a FIGLU branch). The abstract of the cited paper does not visibly support it for this gene, though. It reports FIGLU-degrading capacity (step IV) as a pooled extract activity that two PAO1 enzymes provide (HutF and HutE), describes no hutF mutant, and as a 1967 study it cannot assign a mutation to PA5106. The full text (supplied by the user, read 2026-11-05) confirms that step IV is measured only as crude-extract activity and that there is no hutF mutant, so the reference does not support the row, as for the same paper on hutI. Supporting Evidence: PMID:4290562 Histidine ammonia lyase (histidase), urocanase, and the capacity to degrade formiminoglutamate, which are respectively involved in steps I, II, and IV in the catabolism of histidine PMID:16475788 The degradation of N-formimino-L-glutamate to L-glutamate can occur by three different pathways. |
| GO:0016787 hydrolase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO (IPR006680, amidohydrolase-related) mapping to hydrolase activity. Reason: Correct but too general; formimidoylglutamate deiminase activity (GO:0050416) is an is_a descendant already carried with experimental support. Proposed replacements: formimidoylglutamate deiminase activity Supporting Evidence: file:PSEAE/hutF/hutF-uniprot.txt Catalyzes the hydrolysis of N-formimino-L-glutamate to N- formyl-L-glutamate and ammonia. |
| GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds | IEA GO_REF:0000120 | MODIFY | Summary: Combined IEA (ARBA, IPR011059) hydrolase acting on C-N (non-peptide) bonds. Reason: Correct but general; replace with the is_a descendant GO:0050416, already on the gene. Proposed replacements: formimidoylglutamate deiminase activity Supporting Evidence: file:PSEAE/hutF/hutF-uniprot.txt Catalyzes the hydrolysis of N-formimino-L-glutamate to N- formyl-L-glutamate and ammonia. |
| GO:0019239 deaminase activity | IBA GO_REF:0000033 | MODIFY | Summary: IBA from PTN000138454, a broad amidohydrolase node seeded by guanine deaminases (human, mouse, rat, fly, yeast) and E. coli GuaD. Reason: The essence is right (hydrolytic release of ammonia from a nitrogenous substrate), but the inherited guanine-deaminase-level term does not describe HutF's reaction, and in GO formimidoylglutamate deiminase activity is not placed under deaminase activity. Replace with the specific, experimentally supported activity the gene already carries. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000138454 · PTN000138454 SUPPORTS SOURCE BUT NOT TARGET Broad amidohydrolase node seeded by guanine deaminases (human Q9Y2T3, mouse, rat, fly, yeast, E. coli P76641). The seeds' activity is guanine deamination; HutF is a FIGLU deiminase in a descendant subclade (PTN000138516), where the specific term is already inherited. Proposed replacements: formimidoylglutamate deiminase activity Supporting Evidence: PMID:16475788 The protein Pa5106 was shown to catalyze the deimination of N-formimino-L-glutamate to ammonia and N-formyl-L-glutamate |
| GO:0050416 formimidoylglutamate deiminase activity | EXP PMID:17128965 Mechanistic characterization of N-formimino-L-glutamate imin... | ACCEPT | Summary: UniProt EXP: mechanistic characterisation of purified HutF (zinc content, metal substitution, pH profiles, active-site mutants). Reason: Direct biochemical evidence for the core activity of this protein. Supporting Evidence: PMID:17128965 The metal was removed by dialysis against the metal chelator dipicolinate with the complete loss of catalytic activity. |
| GO:0050416 formimidoylglutamate deiminase activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PTN000138516 (8 leaf IBAs), whose MF IBD has one seed, this gene, supported by its PseudoCAP IDA and UniProt EXP rows. Reason: Soundly seeded: the activity was measured on purified PA5106 with kinetics, metal dependence, mutagenesis and structures. The term suits the bacterial HutF leaves; the nematode-leaf caveat is recorded on the BP IBA row. Supporting Evidence: PMID:16475788 The protein Pa5106 was shown to catalyze the deimination of N-formimino-L-glutamate to ammonia and N-formyl-L-glutamate |
| GO:0050416 formimidoylglutamate deiminase activity | IDA PMID:16475788 Annotating enzymes of unknown function: N-formimino-L-glutam... | ACCEPT | Summary: PseudoCAP IDA; supports the sole-seeded PTN000138516 MF IBD. Purified PA5106 was shown to deiminate FIGLU to N-formylglutamate and ammonia. Reason: Sound seed: a direct enzyme assay of the purified gene product, with kinetic constants and metal dependence. Supporting Evidence: PMID:16475788 The protein Pa5106 was shown to catalyze the deimination of N-formimino-L-glutamate to ammonia and N-formyl-L-glutamate |
| GO:0050416 formimidoylglutamate deiminase activity | IEA GO_REF:0000003 | ACCEPT | Summary: EC 3.5.3.13 mapping to formimidoylglutamate deiminase activity. Reason: Same correct core claim; the EC number rests on the experimental data. Supporting Evidence: PMID:17128965 N-Formimino-l-glutamate iminohydrolase (HutF) from Pseudomonas aeruginosa catalyzes the deimination of N-formimino-l-glutamate in the histidine degradation pathway. |
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Download this section (compressed HTML)Q: Does the full text of Lessie and Neidhardt 1967 (PMID:4290562) describe any mutant that maps to hutF? If not, the PseudoCAP IMP for L-histidine catabolic process on PA5106, sole seed of the PTN000138516 BP IBD, should be re-keyed to PMID:16475788.
Q: Do the nematode PTN000138516 leaves (C. elegans cpin-1 and relatives), which lack the HutF family signatures, have FIGLU deiminase activity?
Q: What are the relative contributions of the HutF/HutG and HutE branches to FIGLU degradation in P. aeruginosa under different growth conditions?
Experiment: Grow clean PAO1 hutF, hutE and hutF hutE deletion mutants on histidine as sole carbon or nitrogen source and measure FIGLU accumulation, to define whether either branch suffices; in parallel, assay recombinant C. elegans cpin-1 with FIGLU.
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