Vmn2r73

Gene Description

Vmn2r73 is a mouse vomeronasal type-2 receptor (V2R) gene in the class C G protein-coupled receptor family (PANTHER PTHR24061, subfamily SF413). Its canonical product (UniProt D3Z7M3, 851 residues) has the class C architecture of a signal peptide, an extracellular Venus-flytrap ligand-binding domain, a nine-cysteine domain and a seven-transmembrane domain. V2R receptors are expressed in basal vomeronasal sensory neurons and are thought to detect peptide and protein chemical cues; no ligand, expression pattern or function has been reported for Vmn2r73 itself, so it remains an orphan receptor. This entry, A0A3B2WCZ5 (496 residues), is the product of a non-canonical Ensembl transcript (ENSMUST00000232965). It shares residues 1-429 with the canonical product, skips canonical residues 430-505, retains the nine-cysteine domain and ends in a short divergent tail. It has no transmembrane segment, so if translated it would be an extracellular ligand-binding-domain-only protein rather than a membrane receptor. Whether this product is made in vivo, and whether it has any function, is unknown.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0004930 G protein-coupled receptor activity	IEA GO_REF:0000002	REMOVE	Summary: The InterPro family matches that drive this mapping (IPR000068, IPR000337, IPR011500) are satisfied by the extracellular Venus-flytrap and nine-cysteine regions that this product retains, but the activity they imply requires the seven-transmembrane domain, which this product lacks entirely (no UniProt TRANSMEM feature and no hydrophobic window outside the signal peptide in an independent scan). In class C receptors the 7TM domain is the G-protein-coupling module, distinct from the extracellular ligand-binding domain. The annotation is therefore wrong for this specific gene product. This is a product-level domain-architecture argument; the canonical Vmn2r73 product D3Z7M3 does have the full receptor architecture and is not affected. Reason: Electronic mapping applied to a product whose domain architecture does not support the mapped activity (DOMAIN_ARCHITECTURE_MISMATCH). Family membership is retained; GPCR activity is not. Supporting Evidence: file:mouse/Vmn2r73/Vmn2r73-bioinformatics/RESULTS-rereview.md UniProt records no TRANSMEM feature on A0A3B2WCZ5, against seven on D3Z7M3 PMID:30675062 Family C receptors are unusual in that, besides the GPCR-defining 7TM domain, they possess relatively large amino-terminal extracellular domains (ECDs) that form obligate dimers and contain the orthosteric ligand binding sites
GO:0005886 plasma membrane	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: This comes from the UniProt subcellular-location line "Cell membrane; Multi-pass membrane protein", which is an ARBA rule prediction transferred to every Vmn2r73 gene model. The multi-pass topology is false for this product, which has a signal peptide but no transmembrane segment. Such a product would enter the secretory pathway and, without a membrane anchor, would be secreted or retained rather than inserted into the plasma membrane. Association with the cell surface through dimerisation with a full-length V2R is conceivable for class C extracellular domains, but it is untested, so the annotation is not supported for this product. Reason: The source is an unvetted ARBA prediction whose multi-pass topology this product contradicts. Plasma-membrane location through a partner is not excluded, so the annotation is marked as over-annotated rather than removed. Supporting Evidence: file:mouse/Vmn2r73/Vmn2r73-bioinformatics/RESULTS-rereview.md the only hydrophobic windows in the target are residues 1-21 (signal peptide) file:mouse/Vmn2r73/Vmn2r73-uniprot.txt /evidence="ECO:0000256\|SAM:SignalP"
GO:0007186 G protein-coupled receptor signaling pathway	IEA GO_REF:0000002	REMOVE	Summary: This InterPro2GO mapping has the same basis as the GPCR activity row and assumes a complete class C receptor. Without its seven-transmembrane domain this product cannot couple to G proteins, so it cannot take part in GPCR signaling as a receptor. No evidence supports any other role, such as a soluble decoy or a modulating partner, and the product has not been shown to be expressed. The canonical product D3Z7M3 would be expected to take part in this pathway in vomeronasal neurons; this truncated product is not. Reason: DOMAIN_ARCHITECTURE_MISMATCH, kept consistent with the REMOVE of GO:0004930 on the same InterPro basis. Supporting Evidence: file:mouse/Vmn2r73/Vmn2r73-bioinformatics/RESULTS-rereview.md UniProt records no TRANSMEM feature on A0A3B2WCZ5, against seven on D3Z7M3 PMID:30675062 To understand how agonist binding at the VFT is relayed over 120Å to the intracellular G protein-coupling region of the 7TM domain
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: The InterPro2GO membrane mapping assumes the integral 7TM domain of a class C receptor. This product has none, so it has no intrinsic membrane anchor. As a signal-peptide protein it would be in the lumen of the secretory pathway, and it could only be membrane-associated through a partner, which has not been shown. Reason: Membrane location assumed by the family mapping is not supported by this product's topology; association through a partner is untested. Supporting Evidence: file:mouse/Vmn2r73/Vmn2r73-bioinformatics/RESULTS-rereview.md the only hydrophobic windows in the target are residues 1-21 (signal peptide)

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