far-1

id: Q93142
gene_symbol: far-1
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:6279
  label: Brugia malayi
description: >-
  FAR-1 (Bm-FAR-1, also known as Bm20) is a small (~20 kDa), helix-rich,
  secreted fatty-acid- and retinol-binding protein of the filarial nematode
  Brugia malayi, belonging to the nematode-specific fatty-acid and
  retinol-binding protein (FARBP/Gp-FAR-1) family. It is synthesized with an
  N-terminal signal peptide and released into the extracellular environment
  (excretory-secretory product). Biochemically it binds all-trans-retinol and
  long-chain fatty acids: in fluorescence-based assays it binds the fluorescent
  fatty-acid analogue DAUDA and produces a characteristic blue-shift in DAUDA
  emission, and bound DAUDA and retinol are competitively displaced by the
  long-chain fatty acid oleic acid. Unlike the orthologous proteins of some
  other filariae, Bm-FAR-1 is not glycosylated. As a secreted lipid carrier,
  FAR proteins are thought to scavenge and transport host-derived lipids
  (retinoids and fatty acids) that the parasite cannot synthesize de novo, and
  may sequester lipid signalling molecules at the host-parasite interface.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Localization to the extracellular region is well supported: the protein
      carries a cleaved N-terminal signal peptide and FAR proteins are released
      into culture medium by all filarial species and developmental stages
      tested. This IEA assignment (from the UniProt subcellular-location keyword
      mapping) agrees with the experimentally/ISS-supported "Secreted" location.
    action: ACCEPT
- term:
    id: GO:0008289
    label: lipid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Correct but general. This InterPro2GO mapping (from the Gp-FAR-1 domain,
      IPR008632) captures the lipid-binding activity of the family. It is
      subsumed by the more specific, experimentally supported fatty acid
      binding and retinol binding annotations, so it is accurate but not the
      most informative term for the core function.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005504
    label: fatty acid binding
  evidence_type: IDA
  original_reference_id: PMID:12106870
  qualifier: enables
  review:
    summary: >-
      Strongly supported experimental annotation. Recombinant Bm-FAR-1 was shown
      by fluorescence-based ligand-binding assays to bind the fatty-acid analogue
      DAUDA and the long-chain fatty acid oleic acid (by competition), producing
      a dramatic blue-shift in DAUDA emission. This is a core molecular function
      of the protein.
    action: ACCEPT
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: ISS
  original_reference_id: PMID:12106870
  qualifier: located_in
  review:
    summary: >-
      Accept. Consistent with the cleaved signal peptide and the demonstration
      that FAR proteins are released into the culture medium by all species and
      stages investigated; the ISS is propagated from the secreted ortholog
      Q25619.
    action: ACCEPT
- term:
    id: GO:0019841
    label: retinol binding
  evidence_type: IDA
  original_reference_id: PMID:12106870
  qualifier: enables
  review:
    summary: >-
      Strongly supported experimental annotation. Recombinant Bm-FAR-1 was shown
      to bind all-trans-retinol in fluorescence-based assays, with bound retinol
      competitively displaceable by oleic acid. Together with fatty acid binding,
      this defines the core lipid/retinoid-carrier function of the protein.
    action: ACCEPT
core_functions:
- description: >-
    Secreted retinol-binding activity; Bm-FAR-1 binds all-trans-retinol in a
    site shared with fatty-acid ligands (oleic acid competes off bound retinol).
  molecular_function:
    id: GO:0019841
    label: retinol binding
  supported_by:
  - reference_id: PMID:12106870
    supporting_text: >-
      Both were found to bind all-trans-retinol, (dansylamino)
      undecanoic acid (DAUDA), and oleic acid by competition.
- description: >-
    Secreted long-chain fatty-acid binding; binds the fluorescent fatty-acid
    analogue DAUDA (with a characteristic emission blue-shift) and oleic acid.
  molecular_function:
    id: GO:0005504
    label: fatty acid binding
  supported_by:
  - reference_id: PMID:12106870
    supporting_text: >-
      Both were found to bind all-trans-retinol, (dansylamino)
      undecanoic acid (DAUDA), and oleic acid by competition.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: PMID:12106870
  title: 'The FAR proteins of filarial nematodes: secretion, glycosylation and lipid
    binding characteristics.'
  findings:
  - statement: >-
      Recombinant Bm-FAR-1 from B. malayi binds all-trans-retinol, DAUDA, and
      oleic acid (by competition) in fluorescence-based assays, and produces a
      dramatic blue-shift in DAUDA fluorescence emission.
    supporting_text: >-
      Both were found to bind all-trans-retinol, (dansylamino) undecanoic acid
      (DAUDA), and oleic acid by competition.
  - statement: >-
      FAR proteins are released into the culture medium by all filarial species
      and developmental stages investigated, consistent with a secreted location.
    supporting_text: >-
      The proteins were released into
      culture medium by all the species and developmental stages investigated.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Primary reference establishing the retinol- and fatty-acid-binding
      activity and secretion of Bm-FAR-1. Abstract directly supports the IDA
      fatty acid binding and retinol binding annotations and the ISS secreted
      location.