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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Der p 1 is a secreted/excreted mite protease; extracellular localization is correct. Reason: Secreted in mite faeces; acts in the extracellular space. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: Der p 1 is a proteolytic enzyme; proteolysis is its core biological process. Reason: Direct consequence of its cysteine-protease activity. Supporting Evidence: file:DERPT/Derp1/Derp1-uniprot.txt Thiol protease, with a preference for substrates with a large |
| GO:0008234 cysteine-type peptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Electronic assignment of cysteine-protease activity, consistent with the peptidase C1 family. Reason: Der p 1 is a papain-family thiol protease. Supporting Evidence: file:DERPT/Derp1/Derp1-uniprot.txt Belongs to the peptidase C1 family. |
| GO:0005576 extracellular region | EXP PMID:16148130 The crystal structure of recombinant proDer p 1, a major hou... | ACCEPT | Summary: Experimentally localized to the extracellular (excreted) mite material. Reason: Experimental support for extracellular localization. |
| GO:0008234 cysteine-type peptidase activity | IDA PMID:28768771 Activation of mas-related G-protein-coupled receptors by the... | ACCEPT | 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. Reason: Experimentally demonstrated cysteine-protease activity; the core molecular function. Supporting Evidence: file:DERPT/Derp1/Derp1-uniprot.txt Thiol protease, with a preference for substrates with a large |
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Download this section (compressed HTML)Q: Which host substrates cleaved by Der p 1 are most important for breaching the epithelial barrier and skewing toward Th2?
Experiment: Compare wild-type and catalytically-inactive (active-site Cys mutant) Der p 1 in epithelial tight-junction cleavage and murine sensitization assays.
Hypothesis: Der p 1 protease activity is required for its adjuvant/sensitizing effect.
Type: structure-function / in vivo assay
Der p 1, major house dust mite allergen; secreted papain-like cysteine protease (peptidase C1). ACCEPT cysteine-type peptidase activity (IDA) + proteolysis + extracellular. Protease activity (cleaves tight junctions, activates MRGPRX1) underlies allergenicity. Characterized.
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