{"uniprot":"Q8NGX1","gene":"OR2T34","name":"Olfactory receptor 2T34","organism":"Homo sapiens (Human)","status":"dark","length":318,"sequence":"MCSGNQTSQNQTASTDFTLTGLFAESKHAALLYTVTFLLFLMALTGNALLILLIHSEPRLHTPMYFFISQLALMDLMYLCVTVPKMLVGQVTGDDTISPSGCGIQMFFHLTLAGAEVFLLAAMAYDRYAAVCRPLHYPLLMNQRVCQLLVSACWVLGMVDGLLLTPITMSFPFCQSRKILSFFCETPALLKLSCSDVSLYKMLTYLCCILMLLTPIMVISSSYTLILHLIHRMNSAAGRRKALATCSSHMIIVLLLFGASFYTYMLRSSYHTAEQDMMVSAFYTIFTPVLNPLIYSLRNKDVTRALRSMMQSRMNQEK","function_summary":"A human seven-helix chemosensory receptor that resides at the cell surface and detects volatile odorant molecules. Ligand binding within its transmembrane bundle triggers coupling to heterotrimeric G proteins, elevating cAMP and initiating the canonical cascade that encodes smell perception. Its multi-pass topology anchors it in the plasma membrane, where it assembles transient signaling complexes that control activation, desensitization, and trafficking during olfactory transduction.","plain_language":"OR2T34 has barely been studied. The model's best guess: A human seven-helix chemosensory receptor that resides at the cell surface and detects volatile odorant molecules. Ligand binding within its transmembrane bundle triggers coupling to heterotrimeric G proteins, elevating cAMP and initiating the canonical cascade that encodes smell perception.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007186","label":"G protein-coupled receptor signaling pathway"},{"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":46,"end":295},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":31,"end":310},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":38,"end":311}],"reasoning":"I begin with the InterPro architecture. The core of the protein is IPR017452 (GPCR, rhodopsin-like, 7TM domain) spanning residues 46–295, which encodes the canonical seven-transmembrane helical bundle that transduces extracellular ligand binding into intracellular G protein activation. This transmembrane core sits within two broader family signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family, residues 31–310) and IPR000725 (Olfactory receptor family, residues 38–311). The ordered layout—an N-terminal extracellular region leading into a rhodopsin-like 7TM bundle and concluding with a cytosolic C-terminus—establishes a class A GPCR specialized for odorant recognition and G protein coupling.\n\nThis architecture dictates molecular function. The rhodopsin-like 7TM fold creates a ligand-binding pocket accessible from the extracellular side and an intracellular cavity that engages heterotrimeric G proteins. Such a configuration causes G protein-coupled receptor activity and, in the olfactory receptor family context, confers olfactory receptor activity. The extensive intracellular surfaces and flexible loops that recruit Gα/β/γ subunits and accessory factors also necessitate multivalent protein binding, aligning with GO:0005515 protein binding.\n\nFrom function to process, activation of a rhodopsin-like GPCR initiates the canonical G protein-coupled receptor signaling pathway (GO:0007186). In the olfactory receptor lineage, coupling typically proceeds through Golf to stimulate adenylyl cyclase and elevate cAMP, which in turn opens cyclic nucleotide-gated channels—an electrogenic cascade that encodes sensory perception of smell (GO:0007608). Thus, the seven-helix transmembrane engine drives second-messenger signaling that converts volatile chemical cues into neuronal responses.\n\nCellular location follows directly from the fold and topology. A seven-pass bundle embedded in lipid bilayers is an integral membrane protein and is typically trafficked to the cell surface where odorant access is possible. This places the receptor in the plasma membrane (GO:0005886), consistent with a multi-pass membrane localization and the need to survey the extracellular milieu.\n\nMechanistically, the receptor likely binds small hydrophobic odorants within its transmembrane pocket, stabilizing an active conformation that opens the intracellular G protein-binding cavity. This conformation recruits and activates an olfactory Gα (e.g., Golf), leading to cAMP production via adenylyl cyclase and downstream ion channel opening. Accessory interactions with β-arrestins and GPCR kinases would tune desensitization and trafficking. I therefore hypothesize transient complexes with Golf (GNAL), Gβγ subunits, adenylyl cyclase 3, β-arrestins, and GRKs that together shape signal amplitude and duration in olfactory neurons.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGX1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGX1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGX1/entry","atlas":"/p/Q8NGX1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}