id: Q5VFH6
gene_symbol: Feld4
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9685
  label: Felis catus
description: >-
  Fel d 4, a secreted lipocalin of the domestic cat (calycin superfamily,
  lipocalin family) and a minor but clinically relevant cat allergen. Like other
  mammalian secretory lipocalins it forms an eight-stranded antiparallel
  beta-barrel calyx that binds small hydrophobic ligands, and it functions as an
  odorant/pheromone carrier; the secreted protein acts as a kairomone detected by
  the vomeronasal organ of prey, inducing fear behavior. It is abundant in cat urine
  (and is also present in saliva/dander), and is recognized by IgE in a subset of
  cat-allergic patients; together with Fel d 1 and the other lipocalin Fel d 7 it is
  associated with co-sensitization and asthma risk.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Fel d 4 is a secreted lipocalin; extracellular localization is well supported.
    action: ACCEPT
    reason: Secretory lipocalin; the secreted protein acts in the extracellular space.
    supported_by:
    - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted.'
- term:
    id: GO:0005549
    label: odorant binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Lipocalins bind small hydrophobic odorant/pheromone molecules in their
      beta-barrel calyx. Fel d 4 is documented as a pheromone carrier/kairomone,
      consistent with odorant binding.
    action: ACCEPT
    reason: Phylogenetic inference matching the documented odorant/pheromone-carrier function of this lipocalin.
    supported_by:
    - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
      supporting_text: May be a pheromone carrier. Acts as a kairomone, detected by
- term:
    id: GO:0005549
    label: odorant binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: enables
  review:
    summary: TreeGrafter (IEA) duplicate of the odorant-binding inference; consistent with the lipocalin carrier function.
    action: ACCEPT
    reason: Electronic inference matching the documented pheromone/odorant-carrier role.
    supported_by:
    - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
      supporting_text: May be a pheromone carrier. Acts as a kairomone, detected by
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated subcellular-location annotation (UniProt "Secreted").
    action: ACCEPT
    reason: Consistent with the secreted nature of the lipocalin.
    supported_by:
    - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted.'
- term:
    id: GO:0036094
    label: small molecule binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      Generic InterPro-based "small molecule binding". This is the uninformative
      parent of the more specific odorant/pheromone binding already annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: Overly broad parent term; the specific ligand-binding activity (odorant/pheromone binding) is already captured.
- term:
    id: GO:0005550
    label: pheromone binding
  evidence_type: IEA
  original_reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). UniProt documents Fel d 4 as a pheromone carrier acting as a
      kairomone (PMID:20478258); pheromone binding is a more specific refinement of
      the existing odorant-binding annotation and is not currently in GOA.
    action: NEW
    reason: >-
      The curated function ("may be a pheromone carrier"; kairomone detected by the
      prey vomeronasal organ) supports the specific molecular function pheromone
      binding for this lipocalin.
    supported_by:
    - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
      supporting_text: May be a pheromone carrier. Acts as a kairomone, detected by
core_functions:
- description: >-
    Secreted lipocalin that binds and transports small hydrophobic ligands
    (odorants/pheromones) in its beta-barrel calyx; the secreted protein acts as a
    kairomone sensed by prey, inducing fear behavior.
  molecular_function:
    id: GO:0005550
    label: pheromone binding
  supported_by:
  - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
    supporting_text: May be a pheromone carrier. Acts as a kairomone, detected by
  - reference_id: file:FELCA/Feld4/Feld4-uniprot.txt
    supporting_text: the prey vomeronasal organ and inducing fear reactions in mice.
  locations:
  - id: GO:0005576
    label: extracellular region
proposed_new_terms: []
suggested_questions:
- question: >-
    What is the endogenous hydrophobic ligand transported by Fel d 4 in the cat,
    and does it correspond to a specific feline pheromone?
  experts: []
suggested_experiments:
- hypothesis: Fel d 4 binds a specific volatile pheromone that mediates its kairomone activity.
  description: >-
    Identify co-purifying ligands of native Fel d 4 by GC-MS and confirm binding of
    candidate volatiles to recombinant Fel d 4 by fluorescence displacement and
    co-crystallization.
  experiment_type: ligand identification / biophysical binding assay
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  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: GO_REF:0000118
  title: TreeGrafter-generated GO annotations
  findings: []
- id: file:FELCA/Feld4/Feld4-uniprot.txt
  title: UniProt entry Q5VFH6 (ALL4_FELCA), Allergen Fel d 4
  findings:
  - statement: Fel d 4 is a secreted lipocalin that may carry pheromones and acts as a kairomone detected by the prey vomeronasal organ.
    supporting_text: May be a pheromone carrier. Acts as a kairomone, detected by
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source for the secreted lipocalin odorant/pheromone-carrier function (FUNCTION cites PMID:20478258).