{"uniprot":"Q9UKL2","gene":"OR52A1","name":"Olfactory receptor 52A1","organism":"Homo sapiens (Human)","status":"dark","length":312,"sequence":"MSISNITVYMPSVLTLVGIPGLESVQCWIGIPFCAIYLIAMIGNSLLLSIIKSERSLHEPLYIFLGMLGATDIALASSIMPKMLGIFWFNVPEIYFDSCLLQMWFIHTLQGIESGILVAMALDRYVAICYPLRHANIFTHQLVIQIGTMVVLRAAILVAPCLVLIKCRFQFYHTTVISHSYCEHMAIVKLAAANVQVNKIYGLFVAFTVAGFDLTFITLSYIQIFITVFRLPQKEARFKAFNTCIAHICVFLQFYLLAFFSFFTHRFGSHISPYIHILFSSIYLLVPPFLNPLVYGAKTTQIRIHVVKMFCS","function_summary":"A cell-surface, multi-pass receptor that detects volatile odorants and converts their binding into intracellular signaling. Its seven-helix bundle forms an extracellular binding pocket and an intracellular G-protein coupling interface, initiating cyclic-nucleotide pathways that underlie smell perception. By residing in the plasma membrane and engaging heterotrimeric G proteins, it drives odor-evoked signal transduction in olfactory sensory pathways.","plain_language":"OR52A1 has barely been studied. The model's best guess: A cell-surface, multi-pass receptor that detects volatile odorants and converts their binding into intracellular signaling. Its seven-helix bundle forms an extracellular binding pocket and an intracellular G-protein coupling interface, initiating cyclic-nucleotide pathways that underlie smell perception.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0004888","label":"transmembrane signaling receptor activity"}],"biological_process":[{"id":"GO:0007165","label":"signal transduction"},{"id":"GO:0007608","label":"sensory perception of smell"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR017452","name":"GPCR, rhodopsin-like, 7TM","type":"domain","start":43,"end":295},{"id":"IPR050402","name":"Olfactory receptor 51/52/56-like","type":"family","start":7,"end":311},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":28,"end":52},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":33,"end":311},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":61,"end":82},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":106,"end":128},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":277,"end":303}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 43–295), which encodes the canonical seven-helix bundle that transduces extracellular ligand binding into intracellular G-protein activation. This structural core is embedded within multiple olfactory/rhodopsin-like GPCR family signatures that collectively define both fold and physiological specialization: IPR050402 (Olfactory receptor 51/52/56-like family, residues 7–311) and IPR000725 (Olfactory receptor family, residues 33–311) specify an olfactory receptor subclass of class A GPCRs. Three independent rhodopsin-like family marks reinforce the GPCR identity and conserved motifs across the N- and C-terminal halves: IPR000276 (G protein-coupled receptor, rhodopsin-like family, residues 28–52), IPR000276 (residues 61–82), and IPR000276 (residues 106–128), with an additional conserved region IPR000276 (residues 277–303). The ordered layout—an N-terminal extracellular segment, seven transmembranes, and intracellular C-terminal signaling tail—creates a membrane-embedded receptor that couples to heterotrimeric G proteins.\n\nThis seven-helix architecture causes transmembrane signaling receptor activity, matching GO:0004888. The extracellular-facing pocket formed by the 7TM bundle binds small, volatile organic molecules; ligand engagement stabilizes active-state conformations that recruit and activate G proteins. That activation initiates second-messenger cascades, establishing signal transduction (GO:0007165). Because the receptor subclass is olfactory, its physiological role is sensory perception of smell (GO:0007608): odorant binding triggers G-protein signaling that converts a chemical cue into an electrical signal.\n\nThe membrane-embedded 7TM fold and the absence of soluble domains localize the protein to the plasma membrane (GO:0005886), consistent with a multi-pass cell-surface receptor. The provided subcellular description of a cell membrane, multi-pass membrane protein aligns with this architecture: the N-terminus and extracellular loops form the odorant-binding vestibule, while intracellular loops and the C-terminus couple to G proteins and regulatory machinery.\n\nMechanistically, the receptor likely binds a subset of hydrophobic odorants within the transmembrane pocket, then stabilizes a G-protein–coupled active state that preferentially engages the olfactory Gα subunit. This triggers GDP–GTP exchange on Gα, dissociation of Gβγ, and activation of cyclic nucleotide pathways that encode the neuronal response. From this, I hypothesize interactions with the olfactory heterotrimeric G protein complex (Gα_olf/Gαs family, Gβ, Gγ), membrane-associated odorant-binding proteins that shuttle hydrophobic ligands, and regulatory partners such as GPCR kinases and arrestins that tune signaling and desensitization. Together, these features define a cell-surface olfactory GPCR that detects odorants and transduces the signal through G-protein pathways to drive smell perception.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9UKL2.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9UKL2"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9UKL2/entry","atlas":"/p/Q9UKL2"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}