id: P15494
gene_symbol: Betv1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:3505
  label: Betula pendula
description: >-
  Bet v 1 (isoform Bet v 1-A / Bet v 1.0101), the major birch pollen allergen and the
  prototype of the pathogenesis-related protein 10 (PR-10 / Bet v 1) family. It has
  the START-like Bet v 1 fold with a large hydrophobic cavity that promiscuously binds
  plant secondary metabolites (sterols, flavonoids, cytokinins, fatty acids), and is
  proposed to act as a general plant lipophilic-ligand/steroid carrier and a defence
  (PR) protein. It is the dominant sensitizer in birch pollinosis and the basis of the
  PR-10 birch–food cross-reactivity syndrome. Its precise in-planta ligand and
  physiological role remain unresolved.
existing_annotations:
- term:
    id: GO:0004864
    label: protein phosphatase inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      This activity is propagated from the structurally related PYR/PYL/RCAR abscisic
      acid receptors, which share the START/Bet v 1 fold and inhibit PP2C phosphatases.
      It is not established for Bet v 1, a PR-10 pollen protein, and reflects fold-based
      over-propagation.
    action: MARK_AS_OVER_ANNOTATED
    reason: Fold-based over-propagation from PYR/PYL ABA receptors; not demonstrated for Bet v 1.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: located_in
  review:
    summary: Nuclear localization is part of the ABA-receptor-like over-propagation; Bet v 1 is a cytoplasmic PR-10 protein.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-propagated with the ABA-receptor annotations; inconsistent with the cytoplasmic localization of Bet v 1.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Bet v 1 is a cytoplasmic (and pollen-cytosolic) PR-10 protein.
    action: ACCEPT
    reason: Consistent with the curated cytoplasmic localization.
    supported_by:
    - reference_id: file:BETPN/Betv1/Betv1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm.'
- term:
    id: GO:0006952
    label: defense response
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: As a pathogenesis-related (PR-10) protein, Bet v 1 is associated with plant defence responses.
    action: KEEP_AS_NON_CORE
    reason: Plausible PR-10 family role; electronic and not specifically demonstrated for this protein.
- term:
    id: GO:0009738
    label: abscisic acid-activated signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: involved_in
  review:
    summary: Propagated from PYR/PYL ABA receptors that share the Bet v 1 fold; not an established function of the PR-10 allergen.
    action: MARK_AS_OVER_ANNOTATED
    reason: Fold-based over-propagation from ABA receptors; not demonstrated for Bet v 1.
- term:
    id: GO:0010427
    label: abscisic acid binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      The Bet v 1 cavity binds many lipophilic ligands; specific abscisic-acid binding
      is propagated from PYR/PYL ABA receptors and is not established for Bet v 1.
    action: MARK_AS_OVER_ANNOTATED
    reason: Fold-based over-propagation; Bet v 1's documented binding is promiscuous (sterols/flavonoids/cytokinins), not specifically ABA as a receptor.
- term:
    id: GO:0038023
    label: signaling receptor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: Receptor activity is propagated from the PYR/PYL ABA receptors; Bet v 1 is a ligand-carrier/PR protein, not a signalling receptor.
    action: MARK_AS_OVER_ANNOTATED
    reason: Fold-based over-propagation from ABA receptors; not demonstrated for Bet v 1.
- term:
    id: GO:0005496
    label: steroid binding
  evidence_type: IEA
  original_reference_id: file:BETPN/Betv1/Betv1-uniprot.txt
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). UniProt notes Bet v 1 "may be a general steroid carrier
      protein"; its hydrophobic cavity binds sterols (and other plant lipophilic
      ligands). Steroid binding captures the best-supported molecular function and is
      not in GOA.
    action: NEW
    reason: Curated "general steroid carrier" function and the PR-10 ligand-binding cavity support a steroid/lipophilic-ligand binding molecular function.
    supported_by:
    - reference_id: file:BETPN/Betv1/Betv1-uniprot.txt
      supporting_text: May be a general steroid carrier protein.
core_functions:
- description: >-
    Cytoplasmic PR-10 (Bet v 1-fold) protein with a large hydrophobic cavity that
    promiscuously binds plant lipophilic ligands (sterols, flavonoids, cytokinins,
    fatty acids); proposed general steroid/lipophilic-ligand carrier and plant
    defence protein.
  molecular_function:
    id: GO:0005496
    label: steroid binding
  supported_by:
  - reference_id: file:BETPN/Betv1/Betv1-uniprot.txt
    supporting_text: May be a general steroid carrier protein.
  locations:
  - id: GO:0005737
    label: cytoplasm
  knowledge_gaps:
  - gap_statement: >-
      The specific physiological ligand and in-planta function of Bet v 1 are
      unresolved; it binds many lipophilic ligands in vitro but its endogenous cargo
      and role (defence vs. hormone/sterol transport) are not established.
    boundary: >-
      Established: PR-10 fold with a promiscuous hydrophobic-ligand-binding cavity,
      cytoplasmic. Unknown: the physiological ligand and biological process; the
      ABA-receptor annotations are fold-based over-propagation, not a demonstrated role.
    gap_kind:
    - BIOLOGY
    - CURATION
    provenance:
    - reference_id: file:BETPN/Betv1/Betv1-uniprot.txt
      supporting_text: May be a general steroid carrier protein.
proposed_new_terms: []
suggested_questions:
- question: What is the physiological ligand of Bet v 1 in birch pollen, and is its function defence, hormone/sterol transport, or both?
  experts: []
suggested_experiments:
- hypothesis: Bet v 1 functions as a plant lipophilic-ligand (sterol/flavonoid) carrier rather than an ABA receptor.
  description: Identify endogenous ligands co-purifying with Bet v 1 from birch pollen by LC-MS, and test PP2C inhibition / ABA binding directly to confirm or exclude ABA-receptor activity.
  experiment_type: ligand identification / biochemical assay
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000118
  title: TreeGrafter-generated GO annotations
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: file:BETPN/Betv1/Betv1-uniprot.txt
  title: UniProt entry P15494 (Major pollen allergen Bet v 1-A), Betula pendula
  findings:
  - statement: Bet v 1 is a cytoplasmic PR-10 (BetVI family) protein that may be a general steroid carrier; major birch pollen allergen.
    supporting_text: May be a general steroid carrier protein.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Curated UniProt record; source for the steroid/lipophilic-ligand carrier function
      and cytoplasmic localization. ABA-receptor annotations are fold-based
      over-propagation from PYR/PYL receptors.