id: P25816
gene_symbol: Betv2
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:3505
  label: Betula pendula
description: >-
  Bet v 2, birch profilin and a cross-reactive plant pan-allergen. Profilins are
  small actin-monomer-binding proteins that regulate cytoskeletal actin dynamics
  (sequestering G-actin and, depending on concentration, inhibiting or promoting
  polymerization) and bind poly-L-proline and phosphatidylinositol 4,5-bisphosphate
  (PIP2). Conserved across pollens, latex and plant foods, Bet v 2 underlies broad
  profilin cross-reactivity in pollen-allergic patients.
existing_annotations:
- term:
    id: GO:0003779
    label: actin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Profilins bind actin; actin binding is a core molecular function of Bet v 2.
    action: ACCEPT
    reason: Defining function of the profilin family.
    supported_by:
    - reference_id: file:BETPN/Betv2/Betv2-uniprot.txt
      supporting_text: Binds to actin and affects the structure of the cytoskeleton.
- term:
    id: GO:0003785
    label: actin monomer binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: enables
  review:
    summary: Profilin binds monomeric (G-)actin specifically; the precise core molecular function.
    action: ACCEPT
    reason: Profilins are G-actin (actin monomer) binding proteins.
    supported_by:
    - reference_id: file:BETPN/Betv2/Betv2-uniprot.txt
      supporting_text: Binds to actin and affects the structure of the cytoskeleton.
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Profilin acts on the actin cytoskeleton; cytoskeletal localization is appropriate.
    action: ACCEPT
    reason: Consistent with profilin's role in actin cytoskeleton regulation.
- term:
    id: GO:0005938
    label: cell cortex
  evidence_type: IEA
  original_reference_id: GO_REF:0000118
  qualifier: located_in
  review:
    summary: Profilin/actin regulation occurs at the cortical cytoskeleton.
    action: KEEP_AS_NON_CORE
    reason: Plausible cortical-actin localization; electronic, secondary to the cytoskeletal role.
- term:
    id: GO:0005546
    label: phosphatidylinositol-4,5-bisphosphate binding
  evidence_type: IEA
  original_reference_id: file:BETPN/Betv2/Betv2-uniprot.txt
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). Beyond actin binding, profilins bind phosphatidylinositol
      4,5-bisphosphate (PIP2); UniProt records that Bet v 2 binds PIP2 and thereby
      inhibits IP3/DG formation, linking it to phosphoinositide signalling. Not in GOA.
    action: NEW
    reason: Curated UniProt function documents PIP2 binding by Bet v 2 (a conserved profilin activity), a specific molecular function absent from the current annotations.
    supported_by:
    - reference_id: file:BETPN/Betv2/Betv2-uniprot.txt
      supporting_text: By binding to PIP2, it
- term:
    id: GO:0070064
    label: proline-rich region binding
  evidence_type: IDA
  original_reference_id: PMID:9271223
  qualifier: enables
  review:
    summary: >-
      NEW (proposed). Poly-L-proline (PLP) binding is a defining biochemical
      activity of profilins (the basis of the classic poly-L-proline affinity
      purification). NMR of birch profilin directly maps its PLP-binding site and
      measures binding to PLP peptides (KD ~0.2 mM for deca-L-proline), including the
      proline-rich VASP motif. Not currently in GOA.
    action: NEW
    reason: >-
      Direct NMR demonstration of poly-L-proline / proline-rich-motif binding by
      Bet v 2 (Domke et al. 1997); a defining profilin molecular function absent from
      the current annotations.
    supported_by:
    - reference_id: PMID:9271223
      supporting_text: poly-(L-proline) (PLP)-binding site.
core_functions:
- description: >-
    Actin-monomer (G-actin) binding protein (profilin) that regulates actin
    cytoskeleton dynamics; binds poly-L-proline and PIP2. A conserved plant
    pan-allergen.
  molecular_function:
    id: GO:0003785
    label: actin monomer binding
  supported_by:
  - reference_id: file:BETPN/Betv2/Betv2-uniprot.txt
    supporting_text: Binds to actin and affects the structure of the cytoskeleton.
  locations:
  - id: GO:0005856
    label: cytoskeleton
- description: >-
    Binds poly-L-proline / proline-rich motifs (e.g. the VASP motif) through its
    conserved profilin PLP-binding surface — the defining biochemical activity
    underlying classic poly-L-proline affinity purification of profilins and
    profilin's recruitment to proline-rich actin-regulatory ligands.
  molecular_function:
    id: GO:0070064
    label: proline-rich region binding
  supported_by:
  - reference_id: PMID:9271223
    supporting_text: poly-(L-proline) (PLP)-binding site.
  locations:
  - id: GO:0005856
    label: cytoskeleton
proposed_new_terms: []
suggested_questions:
- question: Do the conformational/sequence features that make Bet v 2 a cross-reactive pan-allergen differ from those required for its actin-regulatory function?
  experts: []
suggested_experiments:
- hypothesis: Bet v 2 IgE epitopes overlap conserved actin/PIP2-binding surfaces shared across plant profilins.
  description: Map Bet v 2 IgE epitopes and compare to actin- and PIP2-binding interfaces; test cross-reactivity against other plant profilins.
  experiment_type: epitope mapping / cross-reactivity 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: GO_REF:0000118
  title: TreeGrafter-generated GO annotations
  findings: []
- id: PMID:9271223
  title: 'Birch pollen profilin: structural organization and interaction with poly-(L-proline) peptides as revealed by NMR.'
  findings:
  - statement: >-
      NMR structure of birch profilin (Bet v 2) and mapping of its poly-(L-proline)
      (PLP)-binding site; binds PLP peptides (KD ~0.2 mM for deca-L-proline) and the
      proline-rich VASP motif.
    supporting_text: poly-(L-proline) (PLP)-binding site.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary NMR evidence for the poly-L-proline / proline-rich-motif binding activity of Bet v 2.
- id: file:BETPN/Betv2/Betv2-uniprot.txt
  title: UniProt entry P25816 (Profilin-1 / Bet v 2), Betula pendula
  findings:
  - statement: Bet v 2 is birch profilin; binds actin and affects cytoskeletal structure, and binds PIP2.
    supporting_text: Binds to actin and affects the structure of the cytoskeleton.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source for the profilin actin-binding core function.