{"uniprot":"Q8NGQ5","gene":"OR9Q1","name":"Olfactory receptor 9Q1","organism":"Homo sapiens (Human)","status":"dark","length":310,"sequence":"MAEMNLTLVTEFLLIAFTEYPEWALPLFLLFLFMYLITVLGNLEMIILILMDHQLHAPMYFLLSHLAFMDVCYSSITVPQMLAVLLEHGAALSYTRCAAQFFLFTFFGSIDCYLLALMAYDRYLAVCQPLLYVTILTQQARLSLVAGAYVAGLISALVRTVSAFTLSFCGTSEIDFIFCDLPPLLKLTCGESYTQEVLIIMFAIFVIPASMVVILVSYLFIIVAIMGIPAGSQAKTFSTCTSHLTAVSLFFGTLIFMYLRGNSDQSSEKNRVVSVLYTEVIPMLNPLIYSLRNKEVKEALRKILNRAKLS","function_summary":"A seven-pass membrane chemosensor in human olfactory neurons that binds volatile odorants within a transmembrane pocket and activates heterotrimeric G proteins to initiate cyclic-nucleotide signaling. By coupling extracellular ligand recognition to intracellular effector engagement at the cell surface, it drives the neuronal programs that encode smell, with transient protein-binding interfaces coordinating signal initiation, amplification, and termination.","plain_language":"OR9Q1 has barely been studied. The model's best guess: A seven-pass membrane chemosensor in human olfactory neurons that binds volatile odorants within a transmembrane pocket and activates heterotrimeric G proteins to initiate cyclic-nucleotide signaling. By coupling extracellular ligand recognition to intracellular effector engagement at the cell surface, it drives the neuronal programs that encode smell, with transient protein-binding interfaces coordinating signal initiation, amplification, and termination.","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":289},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":26,"end":50},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":31,"end":305},{"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":271,"end":297}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 41–289), 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 [271–297]—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 31–305) 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 intracellular loops—creates a signal-transducing module that binds small hydrophobic ligands in the membrane and transmits the signal via heterotrimeric G proteins.\n\nThis architecture dictates molecular function. The rhodopsin-like 7TM fold and olfactory family signature cause G protein-coupled receptor activity that is specialized for odorant recognition and G-protein activation. The intracellular loops and C-terminal tail, shaped by the rhodopsin-like family motifs, provide multivalent interfaces for protein binding, consistent with GO:0005515 protein binding, particularly toward Gα/βγ subunits and arrestins. Thus, the primary molecular function is a GPCR that binds odorants and engages signaling proteins.\n\nFrom function to process, the receptor’s coupling to heterotrimeric G proteins places it squarely in GO:0007186 G protein-coupled receptor signaling pathway. In olfactory neurons, this signaling initiates cyclic nucleotide cascades that encode odor information, aligning with GO:0007608 sensory perception of smell. The causal chain is direct: odorant binding within the hydrophobic 7TM pocket triggers conformational changes that promote GDP-GTP exchange on Gα, releasing second-messenger pathways that open cation channels and produce neuronal firing.\n\nCellular location follows from the fold and topology. The seven-pass bundle and absence of soluble domains indicate a membrane-embedded receptor. The architecture and olfactory specialization point to the cell surface of sensory neurons, supporting GO:0005886 plasma membrane and the experimentally observed multi-pass membrane localization. The N-terminal extracellular exposure and intracellular loop arrangement are optimized for ligand capture and cytoplasmic G-protein engagement at the plasma membrane.\n\nMechanistically, I hypothesize that the receptor binds hydrophobic odorants within the transmembrane cavity, stabilizing an active state that recruits and activates the olfactory G protein (Golf). This activation elevates cAMP via adenylyl cyclase, leading to downstream ion channel opening and neuronal depolarization. Protein-binding interfaces on intracellular loops and the C-terminus likely mediate transient complexes with Gαolf, Gβγ, and arrestins, shaping signal amplitude and duration. In this framework, probable interaction partners include the olfactory G protein heterotrimers, adenylyl cyclase 3, and arrestin/scaffold proteins that tune receptor trafficking and desensitization.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGQ5.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGQ5"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGQ5/entry","atlas":"/p/Q8NGQ5"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}