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. alternative_records: - id: A0ABQ8JGY3 relationship: REFERENCE_PROTEOME_CANDIDATE reference_proteome: UP000887458 reviewed_on: '2026-10-19' reason: 'Retain P08176 as the primary Swiss-Prot accession. The full 320-residue query is represented within a much longer 837-residue reference model: 300 identities over 320 paired residues, but only 35.84% identity when all global-alignment columns are counted. The target is labeled MCM2_2/MCM DNA helicase despite peptidase-C1 family evidence. This is a possible fused or otherwise problematic gene model, not an established intact equivalent; retain a candidate for genomic/model review.' evidence: - type: PROTEOME_SEARCH description: MMseqs2 searched 14,675 sequences across UP000887458 at E <= 1e-5 and sensitivity 7.5, returning 22 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 22 returned candidates are retained, with 10 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity. supported_by: - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'target_sequence_count: 14675' - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'candidate_count: 22' - type: SEQUENCE_COMPARISON description: 'A0ABQ8JGY3: 300 identities across 837 global-alignment columns (35.8423% identity including gaps), 20 substitutions and 517 gap columns. Query coverage is 100.0%; target coverage is 38.2318%. Sequence similarity is interpreted in the manual rationale. Identity over paired residues is 93.7500% (300/320); gap columns are excluded from this denominator.' supported_by: - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: |- query_length: 320 target_length: 837 alignment_columns: 837 identities: 300 mismatches: 20 gap_columns: 517 identity_percent: 35.8423 query_coverage_percent: 100.0 target_coverage_percent: 38.2318 - type: PROTEOME_MEMBERSHIP description: The primary accession is outside every searched exact-taxon reference proteome. Current UniProt records place A0ABQ8JGY3 in UP000887458 and give it the same taxon as the primary. supported_by: - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'primary_in_any_reference_proteome: false' - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'alternative_in_reference_proteome: true' - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'same_taxon: true' - type: RECORD_HISTORY description: 'Sampled UniSave observations: 14-OCT-2015, entry version 114.: no Proteomes cross-reference; 07-OCT-2020, entry version 131.: no Proteomes cross-reference; 29-MAY-2024, entry version 142.: UP000515146. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt''s motivation.' supported_by: - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: |- entry_date: 14-OCT-2015, entry version 114. proteomes: [] - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: |- entry_date: 07-OCT-2020, entry version 131. proteomes: [] - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: |- entry_date: 29-MAY-2024, entry version 142. proteomes: - UP000515146 - type: CURATION_CONTEXT description: The reference model is named MCM2_2 but also carries peptidase-C1 family membership; the very long model and strong embedded query match require inspection rather than trusting its name. supported_by: - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml supporting_text: 'value: MCM2_2' - reference_id: file:DERPT/Derp1/Derp1-record-evidence.yaml record_section: ["CC:SIMILARITY"] supporting_text: Belongs to the peptidase C1 family 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 record_section: ["CC:FUNCTION"] 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 record_section: ["CC:SIMILARITY"] 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 record_section: ["CC:FUNCTION"] 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 record_section: ["CC:FUNCTION"] 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: file:DERPT/Derp1/Derp1-record-evidence.yaml title: Compact archived record and sequence evidence for P08176 - 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. record_section: ["CC:FUNCTION"] 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.