id: L7N6F8
gene_symbol: Derp23
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:6956
  label: Dermatophagoides pteronyssinus
description: >-
  Der p 23, a major house dust mite allergen associated with the peritrophic matrix
  of mite faecal pellets. It contains a peritrophin-A-type (ChtBD2) chitin-binding
  domain fold, but direct assays found no chitin binding in vitro, so its molecular
  function is unresolved. Despite its small size and minor abundance it is a major
  allergen, recognized by IgE in a large fraction of dust-mite-allergic patients.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Der p 23 is secreted/excreted with mite faecal pellets (peritrophic matrix); extracellular localization is correct.
    action: ACCEPT
    reason: Excreted allergen of the faecal-pellet peritrophic matrix.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: ER localization reflects the secretory route in mite gut cells.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/secretory-route compartment; not the functional site.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Vesicular localization reflects the secretory route.
    action: KEEP_AS_NON_CORE
    reason: Secretory-route compartment; not the functional site.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IDA
  original_reference_id: PMID:23460742
  qualifier: located_in
  review:
    summary: Der p 23 was experimentally localized to the peritrophic matrix of mite faecal pellets (excreted).
    action: ACCEPT
    reason: Experimental support for extracellular/excreted localization.
    supported_by:
    - reference_id: PMID:23460742
      supporting_text: peritrophic matrix of mite fecal pellets
- term:
    id: GO:0008061
    label: chitin binding
  evidence_type: IDA
  original_reference_id: PMID:26602749
  qualifier: enables
  negated: true
  review:
    summary: >-
      This is a NOT (negated) annotation: GOA records that Der p 23 does NOT bind
      chitin. Despite its peritrophin-A (ChtBD2) chitin-binding-domain fold, direct
      assays (PMID:26602749) found no chitin binding in vitro, as also stated in
      UniProt. The negation is correct and informative.
    action: ACCEPT
    reason: >-
      The negated annotation accurately captures the experimental finding that Der p 23
      lacks chitin-binding activity in vitro; it correctly prevents domain-based
      over-annotation of chitin binding.
    supported_by:
    - reference_id: file:DERPT/Derp23/Derp23-uniprot.txt
      supporting_text: Does not bind chitin in vitro.
- term:
    id: GO:0019863
    label: IgE binding
  evidence_type: IMP
  original_reference_id: PMID:24733847
  qualifier: enables
  review:
    summary: Der p 23 binds IgE (basis of its allergenicity and hypoallergen-vaccine design); this reflects allergenicity toward humans, not its endogenous mite function.
    action: KEEP_AS_NON_CORE
    reason: Allergen/IgE-reactivity property, not the protein's endogenous molecular function.
- term:
    id: GO:0031410
    label: cytoplasmic vesicle
  evidence_type: IDA
  original_reference_id: PMID:23460742
  qualifier: located_in
  review:
    summary: Experimental vesicular localization consistent with the secretory route.
    action: KEEP_AS_NON_CORE
    reason: Secretory-route compartment; not the functional site.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: PMID:23460742
  qualifier: located_in
  review:
    summary: Experimental ER localization consistent with the secretory route.
    action: KEEP_AS_NON_CORE
    reason: Biosynthetic/secretory-route compartment; not the functional site.
core_functions:
- description: >-
    Secreted (faecal-pellet peritrophic-matrix) major mite allergen with a
    peritrophin-A (ChtBD2) chitin-binding domain fold. Its molecular function is
    unresolved: despite the domain, direct assays found no chitin binding in vitro.
  locations:
  - id: GO:0005576
    label: extracellular region
  knowledge_gaps:
  - gap_statement: >-
      The molecular function of Der p 23 is undetermined: it has a peritrophin-A
      chitin-binding-domain fold but does not bind chitin in vitro, and no alternative
      ligand or activity has been established.
    boundary: >-
      Established: Der p 23 is a secreted peritrophin-like mite protein of the faecal
      peritrophic matrix. Unknown: its actual ligand/biochemical activity (chitin
      binding is contradicted by direct assay).
    gap_kind:
    - BIOLOGY
    provenance:
    - reference_id: file:DERPT/Derp23/Derp23-uniprot.txt
      supporting_text: Does not bind chitin in vitro.
proposed_new_terms: []
suggested_questions:
- question: If Der p 23 does not bind chitin, what is the endogenous ligand/function of its peritrophin-A domain in the mite peritrophic matrix?
  experts: []
suggested_experiments:
- hypothesis: Der p 23's peritrophin domain binds a peritrophic-matrix component other than chitin (e.g. a glycoprotein or glycan).
  description: Screen recombinant Der p 23 for binding to peritrophic-matrix glycans/glycoproteins by pull-down and glycan-array assays.
  experiment_type: ligand identification / binding assay
references:
- 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:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:23460742
  title: Identification of Der p 23, a peritrophin-like protein, as a new major Dermatophagoides pteronyssinus allergen associated with the peritrophic matrix of mite fecal pellets.
  findings:
  - statement: Der p 23 is a peritrophin-like mite allergen associated with the peritrophic matrix of faecal pellets.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Primary identification of Der p 23 and its peritrophic-matrix/faecal-pellet localization.
- id: PMID:26602749
  title: Serological, genomic and structural analyses of the major mite allergen Der p 23.
  findings:
  - statement: Structural analysis of Der p 23; the protein does not bind chitin in vitro despite its peritrophin-A domain fold.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Cited for the chitin-binding annotation but reports no chitin binding in vitro; basis for flagging that annotation UNDECIDED.
- id: PMID:24733847
  title: Conversion of Der p 23, a new major house dust mite allergen, into a hypoallergenic vaccine.
  findings:
  - statement: Der p 23 is IgE-reactive; engineered hypoallergenic variants reduce IgE binding for vaccine use.
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Supports IgE-binding (allergenicity) property of Der p 23.
- id: file:DERPT/Derp23/Derp23-uniprot.txt
  title: UniProt entry L7N6F8 (Major mite allergen Der p 23), Dermatophagoides pteronyssinus
  findings:
  - statement: Der p 23 is a secreted peritrophin-like major mite allergen that does not bind chitin in vitro.
    supporting_text: Does not bind chitin in vitro.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source for the "does not bind chitin in vitro" finding underlying the function knowledge gap.