id: P14290
gene_symbol: eryCI
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: >-
  EryC1 (EryCI) is a pyridoxal-5'-phosphate (PLP)-dependent sugar aminotransferase of the
  TDP-D-desosamine biosynthetic pathway in Saccharopolyspora erythraea, installing the C-3 amino
  group on the deoxysugar precursor that is ultimately attached to the macrolactone by the
  desosaminyltransferase EryCIII. It is the eponymous member of the DegT/DnrJ/EryC1 family of
  PLP-dependent sugar aminotransferases. NOTE: the UniProt entry P14290 carries a legacy
  misannotation as an "erythromycin biosynthesis sensory transduction protein" (two-component /
  DNA-binding / cell-membrane), which predates characterization of the deoxysugar pathway; the
  family assignment (DegT/DnrJ/EryC1) and the transaminase/PLP annotations are the accurate ones.
references:
- id: file:SACEN/eryCI/eryCI-uniprot.txt
  title: UniProtKB P14290 (eryCI) record
  findings:
  - statement: >-
      EryC1 belongs to the DegT/DnrJ/EryC1 family of PLP-dependent sugar aminotransferases and
      binds pyridoxal phosphate.
    supporting_text: >-
      Belongs to the DegT/DnrJ/EryC1 family.
  reference_review:
    relevance: HIGH
    correctness: DISPUTED
    review_notes: >-
      The record's FUNCTION ("sensor protein... signal of environmental..."), name ("sensory
      transduction protein"), and keywords (DNA-binding, Two-component regulatory system, Cell
      membrane) are a legacy misannotation contradicted by the protein's own DegT/DnrJ/EryC1
      family membership (sugar aminotransferases) and PLP keyword, and by the GOA transaminase
      annotation. Used here only for the (correct) family and cofactor evidence.
- id: file:SACEN/eryCI/eryCI-notes.md
  title: eryCI review notes (erythromycin pathway concept) - discrepancy analysis
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
- id: GO_REF:0000118
  title: Gene Ontology annotation based on InterPro to GO mapping (sequence features)
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple Source Sequence Analysis
existing_annotations:
- term:
    id: GO:0008483
    label: transaminase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Transaminase activity - the correct molecular function. EryC1 is the founding member of the
      DegT/DnrJ/EryC1 PLP-dependent sugar-aminotransferase family and aminates the desosamine
      precursor. This (correctly) contradicts the UniProt "sensory transduction protein" name.
    action: ACCEPT
    reason: >-
      Accurate molecular function consistent with the DegT/DnrJ/EryC1 family assignment and PLP
      cofactor; the defining activity of EryC1.
    supported_by:
    - reference_id: file:SACEN/eryCI/eryCI-uniprot.txt
      supporting_text: >-
        Belongs to the DegT/DnrJ/EryC1 family.
- term:
    id: GO:0030170
    label: pyridoxal phosphate binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      PLP binding - the cofactor of the sugar aminotransferase reaction (UniProt retains the
      Pyridoxal phosphate keyword).
    action: ACCEPT
    reason: Correct cofactor binding for a PLP-dependent aminotransferase.
    supported_by:
    - reference_id: file:SACEN/eryCI/eryCI-uniprot.txt
      supporting_text: >-
        Belongs to the DegT/DnrJ/EryC1 family.
- 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. EryC1 contributes to 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), the
      cluster-level process to which desosamine biosynthesis contributes.
    proposed_replacement_terms:
    - id: GO:1901115
      label: erythromycin biosynthetic process
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Incorrect localization derived from UniProt's "Cell membrane (peripheral)" annotation, itself
      part of the legacy sensory/two-component misannotation. DegT/DnrJ/EryC1 sugar
      aminotransferases are soluble cytoplasmic enzymes.
    action: REMOVE
    reason: >-
      Demonstrably inappropriate: this is a soluble cytoplasmic PLP aminotransferase; the membrane
      location is a knock-on of the erroneous "sensory transduction protein" annotation.
    supported_by:
    - reference_id: file:SACEN/eryCI/eryCI-uniprot.txt
      supporting_text: >-
        Belongs to the DegT/DnrJ/EryC1 family.
core_functions:
- description: >-
    PLP-dependent sugar aminotransferase (DegT/DnrJ/EryC1 family) that installs the C-3 amino
    group during TDP-D-desosamine biosynthesis, supplying the aminodeoxysugar that EryCIII
    transfers to the macrolactone in erythromycin biosynthesis.
  molecular_function:
    id: GO:0008483
    label: transaminase activity
  directly_involved_in:
    - id: GO:1901115
      label: erythromycin biosynthetic process
  locations:
    - id: GO:0005737
      label: cytoplasm
  supported_by:
  - reference_id: file:SACEN/eryCI/eryCI-uniprot.txt
    supporting_text: >-
      Belongs to the DegT/DnrJ/EryC1 family.
suggested_questions:
- question: >-
    The UniProt entry P14290 should be re-curated: its "sensory transduction protein /
    two-component / DNA-binding / cell membrane" annotation contradicts its DegT/DnrJ/EryC1 family
    membership and PLP-dependent sugar-aminotransferase function. Should this be reported upstream?
suggested_experiments:
- description: >-
    In vitro reconstitution of EryC1 with the TDP-4-keto desosamine precursor and an amino donor
    (e.g. glutamate) to confirm PLP-dependent sugar transaminase activity and replace the IEA
    annotations with experimental (IDA) evidence.