id: P46857
gene_symbol: yrhB
locus_tag: b3446
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli K-12
status: COMPLETE
description: >-
  YrhB DeepECTF prediction review. The DeepECTF prediction of 6-carboxytetrahydropterin
  synthase (EC 4.1.2.50) is incorrect. This activity is already catalyzed by QueD/b2765
  in E. coli, and queD mutants lack this activity entirely, demonstrating no redundancy.
  YrhB adopts the Imm35 fold but is experimentally supported as an ATP-independent
  chaperone-like protein, a function unrelated to EC:4.1.2.50.
references:
  - id: PMID:37963869
    title: Functional annotation of enzyme-encoding genes using deep learning with transformer layers.
  - id: PMID:40703034
    title: Limitations of current machine learning models in predicting enzymatic functions for uncharacterized
      proteins.
  - id: PMID:22569261
    title: YrhB is a highly stable small protein with unique chaperone-like activity in Escherichia coli
      BL21(DE3).
  - id: file:ECOLI/yrhB/yrhB-hypotheses/fold-assignment-imm35/openscientist.md
    title: 'OpenScientist hypothesis run: YrhB Imm35 fold vs function'
    publication_type: DEEP_RESEARCH
    findings:
    - statement: OpenScientist confirmed the Imm35 fold but found that chaperone activity, not bacteriocin
        immunity or peptidase inhibition, is the supported YrhB function.
      supporting_text: The ISS-based immunity annotations should not be assigned; instead, **GO:0044183
        (protein folding chaperone)** is the best-supported molecular function term.
source_documents:
  - genes/ECOLI/yrhB/yrhB-hypotheses/fold-assignment-imm35/openscientist.md
  - publications/PMID_37963869.md
  - publications/PMID_40703034.md
  - publications/PMID_22569261.md
predictions:
  - source_method: DeepECTF
    source_version: "2023"
    source_reference_id: PMID:37963869
    predicted_term:
      id: EC:4.1.2.50
      label: 6-carboxytetrahydropterin synthase
    predicted_term_type: EC
    review:
      assessment: NPI
      confidence_score: 0
      summary: >-
        Nonparalog incorrect. The 6-carboxytetrahydropterin synthase (EC 4.1.2.50) activity
        in E. coli is catalyzed by QueD/b2765. A queD mutant completely lacks this activity,
        demonstrating that YrhB does not serve as a redundant enzyme for this function.
        YrhB has no sequence similarity to the QueD family. Instead, YrhB adopts the
        Imm35 fold and direct BL21(DE3) assays on a protein identical to K-12 YrhB support
        ATP-independent chaperone-like activity, which is an entirely different biological
        function.
      supported_by:
        - reference_id: PMID:40703034
          supporting_text: "YrhB/b3446 is predicted to be a 6-carboxytetrahydropterin synthase (EC 4.1.2.50), but E. coli already encodes this enzyme (QueD/b2765) and a queD mutant lacks this activity"
        - reference_id: file:ECOLI/yrhB/yrhB-hypotheses/fold-assignment-imm35/openscientist.md
          supporting_text: YrhB functions as a chaperone-like protein with aggregation-prevention, ATP-independent refolding, and thermal-protection activities
        - reference_id: PMID:22569261
          supporting_text: YrhB effectively prevented heat-induced aggregation of ribonucleotide synthetase (PurK).