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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IBA GO_REF:0000033 | ACCEPT | Summary: Fel d 4 is a secreted lipocalin; extracellular localization is well supported. Reason: Secretory lipocalin; the secreted protein acts in the extracellular space. Supporting Evidence: file:FELCA/Feld4/Feld4-uniprot.txt SUBCELLULAR LOCATION: Secreted. |
| GO:0005549 odorant binding | IBA GO_REF:0000033 | ACCEPT | 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. Reason: Phylogenetic inference matching the documented odorant/pheromone-carrier function of this lipocalin. Supporting Evidence: file:FELCA/Feld4/Feld4-uniprot.txt May be a pheromone carrier. Acts as a kairomone, detected by |
| GO:0005549 odorant binding | IEA GO_REF:0000118 | ACCEPT | Summary: TreeGrafter (IEA) duplicate of the odorant-binding inference; consistent with the lipocalin carrier function. Reason: Electronic inference matching the documented pheromone/odorant-carrier role. Supporting Evidence: file:FELCA/Feld4/Feld4-uniprot.txt May be a pheromone carrier. Acts as a kairomone, detected by |
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Automated subcellular-location annotation (UniProt "Secreted"). Reason: Consistent with the secreted nature of the lipocalin. Supporting Evidence: file:FELCA/Feld4/Feld4-uniprot.txt SUBCELLULAR LOCATION: Secreted. |
| GO:0036094 small molecule binding | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Generic InterPro-based "small molecule binding". This is the uninformative parent of the more specific odorant/pheromone binding already annotated. Reason: Overly broad parent term; the specific ligand-binding activity (odorant/pheromone binding) is already captured. |
| GO:0005550 pheromone binding | IEA file:FELCA/Feld4/Feld4-uniprot.txt | NEW | 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. 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. Supporting Evidence: file:FELCA/Feld4/Feld4-uniprot.txt May be a pheromone carrier. Acts as a kairomone, detected by |
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Download this section (compressed HTML)Q: What is the endogenous hydrophobic ligand transported by Fel d 4 in the cat, and does it correspond to a specific feline pheromone?
Experiment: 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.
Hypothesis: Fel d 4 binds a specific volatile pheromone that mediates its kairomone activity.
Type: ligand identification / biophysical binding assay
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