id: O18873
gene_symbol: Canf1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9615
  label: Canis lupus familiaris
description: >-
  Can f 1, the major dog allergen: a secreted lipocalin (calycin superfamily,
  lipocalin family) homologous to human tear lipocalin / von Ebner's gland protein
  (LCN1). Produced in tongue (von Ebner) and salivary/skin glands and deposited on
  hair, it is the dominant dog allergen, recognized by IgE in the majority of
  dog-allergic patients. Its beta-barrel calyx binds fatty acids (preferring
  palmitic and oleic acid), as shown by crystallography, fluorescence and NMR
  studies (PDB structures of Can f 1 with its cross-reactive homolog Fel d 7); the
  carried lipid may influence allergenicity. The native in-vivo ligand and
  physiological role of Can f 1 remain to be confirmed.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Can f 1 is a secreted lipocalin; extracellular localization is well supported.
    action: ACCEPT
    reason: Secretory lipocalin acting in the extracellular space.
    supported_by:
    - reference_id: file:CANLF/Canf1/Canf1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Secreted'
- 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 consistent with secretion.
    action: ACCEPT
    reason: Consistent with the secreted nature of the lipocalin.
    supported_by:
    - reference_id: file:CANLF/Canf1/Canf1-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 small-molecule-binding term. A specific ligand class is now
      experimentally established for Can f 1 (fatty acids; see the NEW annotation
      below), so the uninformative parent is superseded.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative broad parent; the specific fatty-acid binding activity is now demonstrated and annotated.
- term:
    id: GO:0005504
    label: fatty acid binding
  evidence_type: IDA
  original_reference_id: PMID:36960093
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). Crystallographic, fluorescence (ANS-displacement) and NMR
      analyses show Can f 1 (with its cross-reactive homolog Fel d 7) binds fatty
      acids in its calyx, preferring palmitic acid (16:0) and oleic acid (18:1).
    action: NEW
    reason: Direct experimental demonstration of fatty-acid binding (Min et al. 2023); the specific molecular function of this lipocalin's calyx.
    supported_by:
    - reference_id: PMID:36960093
      supporting_text: Can f 1 and Fel d 7 bind multiple ligands with
core_functions:
- description: >-
    Secreted lipocalin (von Ebner's gland protein / tear lipocalin homolog) that
    binds fatty acids (palmitic/oleic) in its beta-barrel calyx; a candidate
    lipid-transport/carrier function whose endogenous cargo and physiological role
    in the dog remain to be confirmed.
  molecular_function:
    id: GO:0005504
    label: fatty acid binding
  supported_by:
  - reference_id: PMID:36960093
    supporting_text: preferences for palmitic acid (16:0) among saturated fatty acids and oleic acid
  locations:
  - id: GO:0005576
    label: extracellular region
  knowledge_gaps:
  - gap_statement: >-
      The native (in-vivo) ligand and physiological role of Can f 1 remain
      unconfirmed: fatty acids are demonstrated as surrogate ligands in vitro, but
      the endogenous cargo carried in the dog and the biological function are not
      established.
    boundary: >-
      Established: Can f 1 is a secreted lipocalin (calyx fold) homologous to von
      Ebner's gland protein / tear lipocalin that binds fatty acids in vitro.
      Unknown: its endogenous hydrophobic ligand and the biological process it
      serves in the dog.
    gap_kind:
    - BIOLOGY
    provenance:
    - reference_id: PMID:36960093
      supporting_text: little is known about
proposed_new_terms: []
suggested_questions:
- question: >-
    What hydrophobic ligand does the major dog allergen Can f 1 transport, and does
    it share the broad ligand-binding / reported antimicrobial properties of its
    homolog tear lipocalin (LCN1)?
  experts: []
suggested_experiments:
- hypothesis: Can f 1 binds a specific small hydrophobic ligand like other von Ebner gland / tear lipocalins.
  description: >-
    Identify ligands co-purifying with native Can f 1 by LC-MS and test binding of
    candidate lipids/odorants to recombinant Can f 1 by fluorescent-probe displacement.
  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: PMID:36960093
  title: Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7.
  findings:
  - statement: >-
      Can f 1 (and its homolog Fel d 7) bind fatty acids in their calyx, preferring
      palmitic acid (16:0) and oleic acid (18:1); the carried lipid may influence
      allergenicity.
    supporting_text: Can f 1 and Fel d 7 bind multiple ligands with
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      PMC full text; primary structural/biophysical characterization of Can f 1
      (and Fel d 7) fatty-acid binding.
- id: file:CANLF/Canf1/Canf1-uniprot.txt
  title: UniProt entry O18873 (Major allergen Can f 1), Canis lupus familiaris
  findings:
  - statement: Can f 1 is a secreted lipocalin (calycin superfamily) major dog allergen; no specific curated molecular function.
    supporting_text: Belongs to the calycin superfamily. Lipocalin family.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; supports secreted lipocalin classification. Specific ligand/role recorded as a knowledge gap.