Existing Annotations Review

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.

Core Functions

Secreted NPC2/ML-domain lipid (sterol) binding protein that binds and transports sterols/lipids in its hydrophobic cavity.

Molecular Function:

sterol binding

Directly Involved In:

sterol transport

Cellular Locations:

extracellular region

Supporting Evidence:

file:DERPT/Derp2/Derp2-uniprot.txt
Belongs to the NPC2 family.

Immunomodulatory MD-2 mimic: Der p 2 binds LPS (lipid A) via its ML-domain cavity and engages the TLR4 complex, reconstituting/enhancing LPS-driven TLR4 signalling even without MD-2 and functioning as an auto-adjuvant that promotes allergic sensitization. (The same ML-domain hydrophobic cavity underlies its sterol/lipid binding above; LPS binding is the activity directly relevant to TLR4 engagement.)

Molecular Function:

lipopolysaccharide binding

Directly Involved In:

positive regulation of toll-like receptor 4 signaling pathway

Cellular Locations:

extracellular region

Supporting Evidence:

PMID:19060881
reconstituting LPS-driven TLR4 signalling in the absence of MD-2.

References

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Suggested Experiments

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

📚 Additional Documentation

Notes

(Derp2-notes.md)

Derp2 — curation notes (ALLERGENS backlog: mite/birch)

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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