id: P08176
gene_symbol: Derp1
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:6956
  label: Dermatophagoides pteronyssinus
description: >-
  Der p 1, a major house dust mite allergen and a secreted papain-like cysteine
  protease (peptidase C1 family). Produced in the mite digestive tract and excreted
  in faecal pellets, its proteolytic activity is central to its allergenicity: it
  cleaves epithelial tight-junction and immune proteins and activates host receptors
  (e.g. MRGPRX1), promoting allergic sensitization. It is recognized by IgE in the
  large majority of dust-mite-allergic patients.
existing_annotations:
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Der p 1 is a secreted/excreted mite protease; extracellular localization is correct.
    action: ACCEPT
    reason: Secreted in mite faeces; acts in the extracellular space.
- term:
    id: GO:0006508
    label: proteolysis
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: Der p 1 is a proteolytic enzyme; proteolysis is its core biological process.
    action: ACCEPT
    reason: Direct consequence of its cysteine-protease activity.
    supported_by:
    - reference_id: file:DERPT/Derp1/Derp1-uniprot.txt
      supporting_text: Thiol protease, with a preference for substrates with a large
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: Electronic assignment of cysteine-protease activity, consistent with the peptidase C1 family.
    action: ACCEPT
    reason: Der p 1 is a papain-family thiol protease.
    supported_by:
    - reference_id: file:DERPT/Derp1/Derp1-uniprot.txt
      supporting_text: Belongs to the peptidase C1 family.
- term:
    id: GO:0005576
    label: extracellular region
  evidence_type: EXP
  original_reference_id: PMID:16148130
  qualifier: located_in
  review:
    summary: Experimentally localized to the extracellular (excreted) mite material.
    action: ACCEPT
    reason: Experimental support for extracellular localization.
- term:
    id: GO:0008234
    label: cysteine-type peptidase activity
  evidence_type: IDA
  original_reference_id: PMID:28768771
  qualifier: enables
  review:
    summary: >-
      Direct demonstration of thiol-protease activity (preference for large hydrophobic
      or basic P2 residues); Der p 1 cleaves and activates the host receptor MRGPRX1.
    action: ACCEPT
    reason: Experimentally demonstrated cysteine-protease activity; the core molecular function.
    supported_by:
    - reference_id: file:DERPT/Derp1/Derp1-uniprot.txt
      supporting_text: Thiol protease, with a preference for substrates with a large
core_functions:
- description: >-
    Secreted papain-like cysteine protease; its proteolysis of host epithelial and
    immune substrates (and receptor activation) underlies its potent allergenicity.
  molecular_function:
    id: GO:0008234
    label: cysteine-type peptidase activity
  directly_involved_in:
  - id: GO:0006508
    label: proteolysis
  supported_by:
  - reference_id: file:DERPT/Derp1/Derp1-uniprot.txt
    supporting_text: Thiol protease, with a preference for substrates with a large
  locations:
  - id: GO:0005576
    label: extracellular region
proposed_new_terms: []
suggested_questions:
- question: Which host substrates cleaved by Der p 1 are most important for breaching the epithelial barrier and skewing toward Th2?
  experts: []
suggested_experiments:
- hypothesis: Der p 1 protease activity is required for its adjuvant/sensitizing effect.
  description: Compare wild-type and catalytically-inactive (active-site Cys mutant) Der p 1 in epithelial tight-junction cleavage and murine sensitization assays.
  experiment_type: structure-function / in vivo 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:16148130
  title: The crystal structure of recombinant proDer p 1, a major house dust mite proteolytic allergen.
  findings: []
- id: PMID:28768771
  title: Activation of mas-related G-protein-coupled receptors by the house dust mite cysteine protease Der p1 provides a new mechanism linking allergy and inflammation.
  findings: []
- id: file:DERPT/Derp1/Derp1-uniprot.txt
  title: UniProt entry P08176 (Peptidase 1 / Der p 1), Dermatophagoides pteronyssinus
  findings:
  - statement: Der p 1 is a secreted papain-family thiol (cysteine) protease; major house dust mite allergen.
    supporting_text: Thiol protease, with a preference for substrates with a large
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Curated UniProt record; source for the core cysteine-protease activity and family assignment.