id: E5D2Z5
gene_symbol: Feld7
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:9685
  label: Felis catus
description: >-
  Fel d 7, a secreted lipocalin of the domestic cat (calycin superfamily,
  lipocalin family) and a minor cat allergen, abundant in cat urine. It is closely
  related (~63% identity) and cross-reactive to the dog allergen Can f 1. Its
  beta-barrel calyx is open and positively charged and binds fatty acids (with
  preference for palmitic and oleic acid; ~2:1 fatty acid:protein), as shown by the
  crystal structure (PDB:8EPV), fluorescence and NMR studies; the carried lipid may
  influence allergenicity. The crystal structure also contains coordinated Zn(2+),
  although the zinc derives from the zinc-acetate crystallization buffer so its
  physiological relevance is uncertain. The native in-vivo ligand and biological
  role remain to be confirmed.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Fel d 7 is a secreted lipocalin (abundant in cat urine); extracellular localization is appropriate.
    action: ACCEPT
    reason: Secretory lipocalin acting in the extracellular space.
    supported_by:
    - reference_id: file:FELCA/Feld7/Feld7-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 (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      uninformative parent is superseded.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 Fel d 7 binds fatty acids in its calyx, preferring palmitic acid
      (16:0) and oleic acid (18:1), with ~2:1 fatty acid:protein stoichiometry.
    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
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IDA
  original_reference_id: PMID:36960093
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). The Fel d 7 crystal structure (PDB:8EPV) contains coordinated
      Zn(2+) at five residues (113, 137, 142, 143, 146), and UniProt records the
      protein as zinc/metal-binding (GO:0046872). Caveat: the zinc derives from the
      zinc-acetate crystallization buffer, so this captures a demonstrated structural
      metal-coordination capacity whose physiological relevance is not established.
    action: NEW
    reason: >-
      Structurally demonstrated zinc coordination (five Zn-binding residues in
      PDB:8EPV); the specific term zinc ion binding is preferred over the generic
      metal ion binding (GO:0046872) keyword annotation. Physiological relevance
      flagged as uncertain (crystallization-derived).
    supported_by:
    - reference_id: file:FELCA/Feld7/Feld7-uniprot.txt
      supporting_text: IN COMPLEX WITH ZN(2+)
core_functions:
- description: >-
    Secreted lipocalin that binds fatty acids (palmitic/oleic) in its beta-barrel
    calyx; a candidate lipid-transport/carrier function whose physiological cargo and
    role in the cat remain to be confirmed. The crystal structure also coordinates
    zinc, though likely as a crystallization artifact.
  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 Fel d 7 remain unconfirmed:
      fatty acids are demonstrated as surrogate ligands in vitro, but the endogenous
      cargo carried in the cat and the biological function are not established.
    boundary: >-
      Established: Fel d 7 is a secreted lipocalin that binds fatty acids in vitro and
      coordinates zinc in its crystal structure. Unknown: the physiological ligand and
      the biological process it serves; the crystallographic zinc may be a
      crystallization artifact.
    gap_kind:
    - BIOLOGY
    provenance:
    - reference_id: PMID:36960093
      supporting_text: little is known about
proposed_new_terms: []
suggested_questions:
- question: >-
    What endogenous fatty acid (or other lipid) does Fel d 7 carry in vivo, and does
    the carried ligand modulate its allergenicity (as proposed for lipocalin allergens)?
  experts: []
suggested_experiments:
- hypothesis: Fel d 7 carries a specific endogenous fatty-acid ligand in cat secretions that influences sensitization.
  description: >-
    Identify lipids co-purifying with native Fel d 7 from cat urine by LC-MS and
    test whether ligand-loaded vs delipidated Fel d 7 differ in dendritic-cell
    activation / sensitization assays.
  experiment_type: ligand identification / immunological assay
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:36960093
  title: Structural and ligand binding analysis of the pet allergens Can f 1 and Fel d 7.
  findings:
  - statement: >-
      Fel d 7 (and Can f 1) bind fatty acids in their calyx (preferring palmitic and
      oleic acid, ~2:1 stoichiometry); the Fel d 7 crystal structure (PDB:8EPV)
      coordinates zinc from the crystallization buffer.
    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 Fel d 7
      (and Can f 1) fatty-acid binding and the PDB:8EPV zinc complex.
- id: file:FELCA/Feld7/Feld7-uniprot.txt
  title: UniProt entry E5D2Z5 (Fel d 7 allergen), Felis catus
  findings:
  - statement: Fel d 7 is a secreted lipocalin (calycin superfamily) cat allergen; crystal structure PDB:8EPV in complex with Zn(2+); abundant in urine.
    supporting_text: IN COMPLEX WITH ZN(2+)
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record; documents the lipocalin classification, the PDB:8EPV
      Zn(2+) complex with five zinc-binding residues, and urine abundance.