eryCIV

id: A4F7N3
gene_symbol: eryCIV
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:405948
  label: Saccharopolyspora erythraea (strain ATCC 11635 / DSM 40517 / JCM 4748 / NBRC
    13426 / NCIMB 8594 / NRRL 2338)
description: >-
  EryCIV is a pyridoxal-5'-phosphate (PLP)-dependent enzyme of the TDP-D-desosamine
  biosynthetic pathway in Saccharopolyspora erythraea, belonging to the DegT/DnrJ/EryC1 family.
  It is annotated (UniProt/EMBL, MIBiG) as an NDP-6-deoxyhexose 3,4-dehydratase acting in
  deoxysugar biosynthesis; the precise PLP-dependent reaction (dehydratase vs aminotransferase)
  has not been experimentally pinned down in the records available, and the existing GOA carries
  a family-default transaminase annotation that conflicts with the dehydratase name.
references:
- id: file:SACEN/eryCIV/eryCIV-uniprot.txt
  title: UniProtKB A4F7N3 (eryCIV) record - "NDP-6-deoxyhexose 3,4-dehydratase"; DegT/DnrJ/EryC1 family
  findings:
  - statement: >-
      EryCIV is a PLP-dependent DegT/DnrJ/EryC1-family enzyme named as an NDP-6-deoxyhexose
      3,4-dehydratase.
    supporting_text: >-
      EryCIV NDP-6-deoxyhexose 3,4-dehydratase
  reference_review:
    relevance: HIGH
    correctness: UNVERIFIED
    review_notes: >-
      TrEMBL entry; the dehydratase name (ECO:0000313|EMBL) and the GOA transaminase term are both
      electronic and conflict. PLP cofactor (keyword) is consistent across sources.
- id: GO_REF:0000118
  title: Gene Ontology annotation based on InterPro to GO mapping (sequence features)
existing_annotations:
- term:
    id: GO:0000271
    label: polysaccharide biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: involved_in
  review:
    summary: >-
      Incorrect biological process. EryCIV acts in biosynthesis of the aminodeoxysugar D-desosamine
      (a monosaccharide moiety of erythromycin), not a polysaccharide.
    action: MODIFY
    reason: >-
      Wrong process class; replace with GO:1901115 (erythromycin biosynthetic process), to which
      desosamine biosynthesis contributes.
    proposed_replacement_terms:
    - id: GO:1901115
      label: erythromycin biosynthetic process
- term:
    id: GO:0008483
    label: transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: enables
  review:
    summary: >-
      Family-default transaminase activity from the DegT/DnrJ/EryC1 fold. However EryCIV is named
      an NDP-6-deoxyhexose 3,4-dehydratase (UniProt/EMBL, MIBiG), and the dedicated desosamine
      aminotransferase of the cluster is EryCI. The two electronic assignments conflict and cannot
      be resolved from the available records.
    action: UNDECIDED
    reason: >-
      Genuine conflict between the dehydratase name and the family-default transaminase term, with
      no accessible experimental characterization to adjudicate. The PLP cofactor is not in doubt
      (see below); the precise reaction is.
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: enables
  review:
    summary: PLP binding; consistent across the family assignment and UniProt keyword.
    action: ACCEPT
    reason: Correct cofactor for this PLP-dependent DegT/DnrJ/EryC1-family enzyme.
    supported_by:
    - reference_id: file:SACEN/eryCIV/eryCIV-uniprot.txt
      supporting_text: >-
        EryCIV NDP-6-deoxyhexose 3,4-dehydratase
core_functions:
- description: >-
    PLP-dependent DegT/DnrJ/EryC1-family enzyme contributing to TDP-D-desosamine biosynthesis
    (named as an NDP-6-deoxyhexose 3,4-dehydratase), supplying the aminodeoxysugar used in
    erythromycin biosynthesis. The precise PLP reaction awaits experimental confirmation, so only
    the cofactor-binding MF is asserted here (see the EVIDENCE GAP in suggested_questions).
  molecular_function:
    id: GO:0030170
    label: pyridoxal phosphate binding
  directly_involved_in:
    - id: GO:1901115
      label: erythromycin biosynthetic process
  supported_by:
  - reference_id: file:SACEN/eryCIV/eryCIV-uniprot.txt
    supporting_text: >-
      EryCIV NDP-6-deoxyhexose 3,4-dehydratase
suggested_questions:
- question: >-
    EVIDENCE GAP: what is the actual PLP-dependent reaction of EryCIV? Its UniProt/EMBL name
    ("NDP-6-deoxyhexose 3,4-dehydratase") and the GOA term ("transaminase activity") are
    conflicting electronic (IEA) assignments, and no experimental annotation exists. The dedicated
    desosamine aminotransferase of the cluster is EryCI, so a second transaminase is unexpected.
    Tracked in projects/FUNCTION_KNOWLEDGE_GAPS.md.
suggested_experiments:
- description: >-
    Biochemically reconstitute EryCIV to determine whether it catalyzes a PLP-dependent 3,4-
    dehydration/isomerization or a transamination on the TDP-keto-deoxysugar precursor, resolving
    the conflicting electronic annotations.