LYPD1 (LY6/PLAUR domain-containing protein 1) is a GPI-anchored member of the Ly6/uPAR family with a snake-toxin-like three-finger fold, related to the prototypic nicotinic receptor modulator lynx1. It is attached to the extracellular leaflet of the plasma membrane by a GPI anchor. LYPD1 behaves as an endogenous modulator of neuronal nicotinic acetylcholine receptors. It interacts with CHRNA4 and alpha4-beta2- and alpha7-containing nAChRs, increases receptor desensitization, lowers their apparent affinity for acetylcholine, and may limit their surface expression. It is implicated in the control of anxiety behavior.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005576 extracellular region | TAS Reactome:R-HSA-8940388 | KEEP AS NON CORE | Summary: A soluble/shed form of LYPD1 can occur in the extracellular region. Reason: LYPD1 is primarily GPI-anchored at the cell surface; like other Ly6/uPAR proteins it can be released extracellularly (the Reactome event models GPI-anchor cleavage), a secondary form of a membrane protein. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt Cell membrane {ECO:0000305}; Lipid-anchor, GPI- |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: LYPD1 is a GPI-anchored protein of the plasma membrane. Reason: The mature protein carries a C-terminal GPI anchor and is displayed on the cell membrane, where its three-finger ectodomain can engage cell-surface nAChRs. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt Cell membrane {ECO:0000305}; Lipid-anchor, GPI- |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8940388 | ACCEPT | Summary: LYPD1 is a GPI-anchored protein of the plasma membrane. Reason: The mature protein carries a C-terminal GPI anchor and is displayed on the cell membrane, where its three-finger ectodomain can engage cell-surface nAChRs. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt Cell membrane {ECO:0000305}; Lipid-anchor, GPI- |
| GO:0030550 acetylcholine receptor inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: LYPD1 inhibits/modulates nicotinic acetylcholine receptor activity. Reason: As a lynx1-like three-finger protein, LYPD1 interacts with alpha4-beta2 and alpha7 nAChRs, increases their desensitization and decreases their affinity for acetylcholine; this receptor-modulating activity is its core molecular function. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt In vitro increases receptor desensitization and decreases affinity for ACh of alpha-4:beta-2-containing nAChRs. file:human/LYPD1/LYPD1-uniprot.txt Interacts with CHRNA4 and nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits. |
| GO:0045202 synapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Synapse localization inferred from the nAChR-modulating role. Reason: LYPD1 modulates neuronal nicotinic receptors, consistent with a synaptic membrane location, but the localization is inferred from the pathway (inter-ontology link) rather than directly shown. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt Interacts with CHRNA4 and nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits. |
| GO:0095500 acetylcholine receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: LYPD1 acts in the acetylcholine receptor signaling pathway as a negative modulator. Reason: By binding nAChRs and altering their desensitization, affinity and surface expression, LYPD1 participates in regulating acetylcholine receptor signaling. Supporting Evidence: file:human/LYPD1/LYPD1-uniprot.txt In vitro increases receptor desensitization and decreases affinity for ACh of alpha-4:beta-2-containing nAChRs. |
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Download this section (compressed HTML)Q: Does human LYPD1 regulate nAChR surface trafficking in neurons, and how does this relate to its proposed role in anxiety?
Experiment: Co-express human LYPD1 with alpha4-beta2 and alpha7 nAChRs and measure desensitization, ACh affinity and surface receptor levels, with and without GPI anchoring.
Type: electrophysiology and surface biotinylation
Deep research (falcon / perplexity-lite) failed; no PMIDs in GOA (all IBA/IEA/TAS/by-similarity). Notes from UniProt Q8N2G4.
Localization conclusion: GPI-anchored plasma membrane (ectodomain exposed on outer leaflet); synaptic membrane
plausible (inferred); shed/extracellular form possible. Genuinely cell-surface accessible.
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