{"uniprot":"Q8NGE9","gene":"OR9Q2","name":"Olfactory receptor 9Q2","organism":"Homo sapiens (Human)","status":"dark","length":314,"sequence":"MAERNYTVVTEFFLTAFTEHLQWRVPLFLIFLSFYLATMLGNTGMILLIRGDRRLHTPMYFFLSHLSLVDICYSSAIIPQMLAVLWEHGTTISQARCAAQFFLFTFFASIDCYLLAIMAYDRYTAVCQPLLYVTIITEKARWGLVTGAYVAGFFSAFVRTVTAFTLSFCGNNEINFIFCDLPPLLKLSCGDSYTQEVVIIVFALFVMPACILVILVSYLFIIVAILQIHSAGGRAKTFSTCASHLTAVALFFGTLIFMYLRDNTGQSSEGDRVVSVLYTVVTPMLNPLIYSLRNKEVKEATRKALSKSKPARRP","function_summary":"A multi-pass cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through a seven-helix transmembrane core. By engaging heterotrimeric G proteins at the plasma membrane, it elevates cyclic nucleotide signaling and triggers neuronal depolarization, thereby initiating the perception of smell. Its cytosolic interfaces mediate dynamic protein interactions that couple ligand recognition to second-messenger production and receptor desensitization.","plain_language":"OR9Q2 has barely been studied. The model's best guess: A multi-pass cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through a seven-helix transmembrane core. By engaging heterotrimeric G proteins at the plasma membrane, it elevates cyclic nucleotide signaling and triggers neuronal depolarization, thereby initiating the perception of smell.","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":41,"end":290},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":26,"end":50},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":33,"end":306},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":59,"end":80},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":104,"end":126},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":197,"end":220},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":272,"end":298}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 41–290), which encodes the canonical seven-helix bundle that transduces extracellular ligand binding into intracellular G-protein activation. This structural core is bracketed and reinforced by multiple olfactory/rhodopsin-like GPCR family signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family) appears in several internal windows—[26–50], [59–80], [104–126], [197–220], and [272–298]—marking hallmark motifs across the N-terminus and within the transmembrane region that stabilize the active and inactive states of the receptor. The presence of IPR000725 (Olfactory receptor family, residues 33–306) specifies the receptor subclass that binds volatile odorants and preferentially couples to the olfactory G protein. The ordered layout—an N-terminal extracellular segment feeding into a tightly conserved 7TM core and followed by cytosolic loops—creates a signal-transducing module that binds small hydrophobic ligands in the membrane and transmits the signal via conformational switching.\n\nThis architecture dictates molecular function. The rhodopsin-like 7TM fold and olfactory family identity cause G protein-coupled receptor activity that is specialized for odorant detection. The cytosolic loops and helical interfaces form docking surfaces for heterotrimeric G proteins and other signaling partners, which substantiates GO:0005515 protein binding as an intrinsic property of the receptor’s signaling cycle. Ligand binding within the transmembrane pocket triggers rearrangements that expose intracellular coupling surfaces, enabling high-affinity association with Gα and downstream effectors.\n\nFrom this molecular function, the biological process follows. Activation of heterotrimeric G proteins by this receptor initiates the canonical GO:0007186 G protein-coupled receptor signaling pathway. In olfactory neurons, this signaling cascade elevates cAMP and opens cyclic nucleotide-gated channels, producing neuronal depolarization; thus the receptor’s activity directly drives GO:0007608 sensory perception of smell. The causal chain runs from odorant capture in the hydrophobic cavity to G-protein activation, second-messenger production, and electrical response.\n\nCellular location is implied by both the 7TM topology and the olfactory receptor family. The multi-pass arrangement and absence of soluble domains place the protein in the plasma membrane, consistent with GO:0005886 plasma membrane and with the stated cell membrane localization. The N-terminal extracellular exposure and the intracellular C-terminal signaling surfaces are typical of plasma-membrane GPCRs that survey the extracellular milieu.\n\nMechanistically, I hypothesize that odorant binding within the membrane-embedded orthosteric pocket stabilizes an active-state ensemble that recruits olfactory G protein (Golf), promoting GDP-GTP exchange and stimulating adenylate cyclase. Elevated cAMP gates cyclic nucleotide–gated channels to amplify the signal. Receptor desensitization likely proceeds via phosphorylation by GPCR kinases and arrestin binding. Therefore, probable interaction partners include the olfactory heterotrimeric G protein complex, adenylate cyclase, cyclic nucleotide–gated channel subunits, GPCR kinases, and arrestins—partners that collectively implement and tune the odorant-induced signaling cascade.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGE9.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGE9"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGE9/entry","atlas":"/p/Q8NGE9"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}