Der p 2, a major house dust mite allergen of the NPC2 (ML-domain) family. It is a secreted lipid/sterol-binding protein structurally and functionally homologous to MD-2 (LY96), the LPS-binding component of the TLR4 signalling complex: Der p 2 reconstitutes LPS-driven TLR4 signalling in the absence of MD-2, giving it auto-adjuvant properties that drive allergic sensitization. It is recognized by IgE in most dust-mite-allergic patients, and is the archetype of the "lipid-binding protein as auto-adjuvant" allergen concept that also frames cat Fel d 1.
The preferred accession for this review is P49278. These relationships are manually assessed.
REFERENCE PROTEOME EQUIVALENT · Reviewed 2026-10-19
Reference proteome: UP000887458
Retain P49278 as the primary Swiss-Prot accession. The 146-residue reference sequence differs at three residues with full ungapped coverage (97.95% identity), and is strongly separated from other lipid-transfer-family matches. This supports a qualified sequence-based Der p 2 counterpart; its generic transfer-protein label does not independently establish allergenicity or identical immunological properties.
MMseqs2 searched 14,675 sequences across UP000887458 at E <= 1e-5 and sensitivity 7.5, returning 6 hits. Every returned sequence was globally aligned using BLOSUM62 with gap-open -10 and extension -0.5. Scores and sequences for all 6 returned candidates are retained, with 6 detailed alignment files. The heuristic search does not establish genomic absence or unique locus identity.
file:DERPT/Derp2/Derp2-record-evidence.yaml
target_sequence_count: 14675
file:DERPT/Derp2/Derp2-record-evidence.yaml
candidate_count: 6
A0ABQ8J715: 143 identities across 146 global-alignment columns (97.9452% identity including gaps), 3 substitutions and 0 gap columns. Query coverage is 100.0%; target coverage is 100.0%. Sequence similarity is interpreted in the manual rationale. Identity over paired residues is 97.9452% (143/146); gap columns are excluded from this denominator.
file:DERPT/Derp2/Derp2-record-evidence.yaml
query_length: 146 target_length: 146 alignment_columns: 146 identities: 143 mismatches: 3 gap_columns: 0 identity_percent: 97.9452 query_coverage_percent: 100.0 target_coverage_percent: 100.0
The primary accession is outside every searched exact-taxon reference proteome. Current UniProt records place A0ABQ8J715 in UP000887458 and give it the same taxon as the primary.
file:DERPT/Derp2/Derp2-record-evidence.yaml
primary_in_any_reference_proteome: false
file:DERPT/Derp2/Derp2-record-evidence.yaml
alternative_in_reference_proteome: true
file:DERPT/Derp2/Derp2-record-evidence.yaml
same_taxon: true
Sampled UniSave observations: 14-OCT-2015, entry version 77.: no Proteomes cross-reference; 07-OCT-2020, entry version 90.: no Proteomes cross-reference; 27-NOV-2024, entry version 102.: UP000515146. These dated observations do not establish uninterrupted membership/absence, the exact change date, or UniProt's motivation.
file:DERPT/Derp2/Derp2-record-evidence.yaml
entry_date: 14-OCT-2015, entry version 77. proteomes: []
file:DERPT/Derp2/Derp2-record-evidence.yaml
entry_date: 07-OCT-2020, entry version 90. proteomes: []
file:DERPT/Derp2/Derp2-record-evidence.yaml
entry_date: 27-NOV-2024, entry version 102. proteomes: - UP000515146
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | IEA GO_REF:0000044 | ACCEPT | Summary: Der p 2 is a secreted mite protein; extracellular localization is correct. Reason: Secreted/excreted mite allergen acting in the extracellular space. Supporting Evidence: file:DERPT/Derp2/Derp2-uniprot.txt Belongs to the NPC2 family. |
| GO:0015918 sterol transport | IEA GO_REF:0000120 | ACCEPT | Summary: NPC2/ML-domain proteins bind and transport sterols/lipids; consistent with Der p 2's family and hydrophobic cavity. Reason: Consistent with the NPC2 lipid/sterol-binding fold. Supporting Evidence: file:DERPT/Derp2/Derp2-uniprot.txt Belongs to the NPC2 family. |
| GO:0032934 sterol binding | IEA GO_REF:0000120 | ACCEPT | Summary: The NPC2/ML domain binds sterols/lipids in its hydrophobic cavity; the core molecular function of Der p 2. Reason: Core lipid/sterol-binding function of the NPC2 family. Supporting Evidence: file:DERPT/Derp2/Derp2-uniprot.txt Belongs to the NPC2 family. |
| GO:0005515 protein binding | IPI PMID:19060881 Allergenicity resulting from functional mimicry of a Toll-li... | KEEP AS NON CORE | Summary: Records the direct interaction of Der p 2 with the TLR4 receptor complex (MD-2 functional mimicry). The bare "protein binding" term is uninformative on its own; the meaningful activity is the TLR4-signalling enhancement captured as a NEW process annotation below. Reason: Uninformative parent term; the specific functional consequence (TLR4 signalling) is annotated separately. Supporting Evidence: PMID:19060881 facilitating signalling through direct interactions with the TLR4 complex, and |
| GO:0034145 positive regulation of toll-like receptor 4 signaling pathway | IDA PMID:19060881 Allergenicity resulting from functional mimicry of a Toll-li... | NEW | Summary: NEW (proposed). Der p 2 functionally mimics MD-2, reconstituting LPS-driven TLR4 signalling in the absence of MD-2 and thereby enhancing innate immune activation (auto-adjuvant). Directly parallels the LPS/TLR4 activity annotated for cat Fel d 1. Reason: Trompette et al. 2009 experimentally demonstrated Der p 2 reconstitutes/enhances TLR4 signalling via MD-2 mimicry. Supporting Evidence: PMID:19060881 reconstituting LPS-driven TLR4 signalling in the absence of MD-2. |
| GO:0001530 lipopolysaccharide binding | IDA PMID:19060881 Allergenicity resulting from functional mimicry of a Toll-li... | NEW | Summary: NEW (proposed). Der p 2 is a functional homolog of MD-2 (LY96), the LPS-binding component of the TLR4 complex, and reconstitutes LPS-driven TLR4 signalling in the absence of MD-2 — substituting for MD-2's LPS-presenting role, which implies LPS (lipid A) binding by its ML-domain cavity. This is the molecular basis of its auto-adjuvant activity and directly parallels the LPS binding annotated for cat Fel d 1. Reason: Der p 2 functionally substitutes for MD-2 (the LPS-binding TLR4 co-receptor), reconstituting LPS-driven TLR4 signalling; LPS/lipid-A binding by its ML domain is the mechanistic basis and a more specific MF than generic sterol binding for its immunomodulatory role. Supporting Evidence: PMID:19060881 reconstituting LPS-driven TLR4 signalling in the absence of MD-2. |
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Download this section (compressed HTML)Q: What endogenous lipid does Der p 2 carry, and is lipid cargo required for its TLR4 auto-adjuvant activity (as for MD-2)?
Experiment: Compare wild-type and cavity-mutant Der p 2 for LPS binding and TLR4 reporter activation in MD-2-deficient cells.
Hypothesis: Der p 2's lipid-binding cavity is required for its TLR4-reconstituting auto-adjuvant activity.
Type: structure-function / signalling assay
Der p 2, major mite allergen; NPC2/ML-domain sterol/lipid-binding protein. ACCEPT sterol binding+transport+extracellular. KEEP_AS_NON_CORE bare protein binding (= TLR4-complex interaction). NEW positive regulation of TLR4 signaling (GO:0034145): Der p 2 mimics MD-2 and reconstitutes LPS-driven TLR4 signaling [PMID:19060881 Trompette 2009] -> direct parallel to Fel d 1 LPS/TLR4 auto-adjuvant story.
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