id: P0AFR4
gene_symbol: yciO
locus_tag: b1267
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli K-12
status: COMPLETE
description: >-
  YciO DeepECTF prediction review. The DeepECTF prediction of L-threonylcarbamoyladenylate
  synthase (EC 2.7.7.87) is incorrect - a classic paralog overannotation error. YciO is a
  paralog of TsaC but shows 10,000x weaker activity and does not complement tsaC mutants
  in vivo. Structural and genomic context evidence suggests a distinct role in rRNA metabolism.
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:19287007
    title: The universal YrdC/Sua5 family is required for the formation of threonylcarbamoyladenosine
      in tRNA.
predictions:
  - source_method: DeepECTF
    source_version: "2023"
    source_reference_id: PMID:37963869
    predicted_term:
      id: EC:2.7.7.87
      label: L-threonylcarbamoyladenylate synthase
    predicted_term_type: EC
    review:
      assessment: PLI
      confidence_score: 0
      error_type: PARALOG_OVERANNOTATION
      summary: >-
        Paralog incorrect. YciO is a member of the same Pfam family (PF01300) as TsaC/Sua5,
        and DeepECTF assigns the same EC number. However: (1) In vitro activity is 10,000x
        weaker than TsaC (0.14 nM/min vs 2.8 uM/min). (2) YciO does not complement tsaC
        deletion in vivo. (3) YciO has a conserved positively charged surface patch absent
        in TsaC, suggesting RNA-binding function. (4) yciO genes co-localize with rnm
        (RNase AM) genes, suggesting a role in rRNA metabolism rather than tRNA modification.
        The weak in vitro activity likely represents residual ancestral catalytic activity
        from TsaC, not the evolved biological function.
      supported_by:
        - reference_id: PMID:40703034
          supporting_text: "the activity reported (0.14 nM/min TC-AMP production rate) for E. coli YciO is more than 4 orders of magnitude weaker than that of E. coli TsaC (2.8 μM/min)"
        - reference_id: PMID:40703034
          supporting_text: "YciO does not perform the same function as TsaC/Susa5 in vivo experiments"
        - reference_id: PMID:40703034
          supporting_text: "the structure of YciO exhibits a large positively charged surface predicted to interact with RNA...This large positively charged surface is conserved in YciO proteins and is absent in TsaC proteins"