{"uniprot":"Q8NGZ6","gene":"OR6F1","name":"Olfactory receptor 6F1","organism":"Homo sapiens (Human)","status":"dark","length":308,"sequence":"MDTGNKTLPQDFLLLGFPGSQTLQLSLFMLFLVMYILTVSGNVAILMLVSTSHQLHTPMYFFLSNLSFLEIWYTTAAVPKALAILLGRSQTISFTSCLLQMYFVFSLGCTEYFLLAAMAYDRCLAICYPLHYGAIMSSLLSAQLALGSWVCGFVAIAVPTALISGLSFCGPRAINHFFCDIAPWIALACTNTQAVELVAFVIAVVVILSSCLITFVSYVYIISTILRIPSASGRSKAFSTCSSHLTVVLIWYGSTVFLHVRTSIKDALDLIKAVHVLNTVVTPVLNPFIYTLRNKEVRETLLKKWKGK","function_summary":"A human seven-helix chemosensory receptor that detects extracellular odorant molecules and converts their binding into intracellular signaling through heterotrimeric G proteins. Embedded in the plasma membrane as a multi-pass protein, it uses a rhodopsin-like transmembrane core to stabilize active conformations that recruit and activate G proteins, triggering second-messenger pathways that drive neuronal responses underlying smell. Its mechanism centers on ligand-triggered conformational changes within the seven-helix bundle that enable efficient signal initiation and termination at the cell surface.","plain_language":"OR6F1 has barely been studied. The model's best guess: A human seven-helix chemosensory receptor that detects extracellular odorant molecules and converts their binding into intracellular signaling through heterotrimeric G proteins. Embedded in the plasma membrane as a multi-pass protein, it uses a rhodopsin-like transmembrane core to stabilize active conformations that recruit and activate G proteins, triggering second-messenger pathways that drive neuronal responses underlying smell.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007165","label":"signal transduction"},{"id":"GO:0007606","label":"sensory perception of chemical stimulus"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR017452","name":"GPCR, rhodopsin-like, 7TM","type":"domain","start":41,"end":290},{"id":"IPR047132","name":"Olfactory receptor subfamily 6C-like","type":"family","start":5,"end":305},{"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":303},{"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":199,"end":222},{"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 embedded within multiple rhodopsin-like GPCR family signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family) appears in several positions—[26–50], [59–80], [104–126], [199–222], and [272–298]—marking conserved motifs across the N-terminus and intracellular loops that coordinate G protein coupling and arrestin interactions. Two olfactory-focused family signatures, IPR000725 (Olfactory receptor family, residues 31–303) and IPR047132 (Olfactory receptor subfamily 6C-like, residues 5–305), specify that this rhodopsin-like scaffold is tuned for odorant recognition and olfactory signaling. The ordered layout—an N-terminal extracellular region feeding into a 7TM bundle and intracellular loop network—causes ligand-triggered conformational switching that recruits heterotrimeric G proteins.\n\nFrom this architecture, the molecular function resolves as a GPCR that binds protein partners to transmit signals. The rhodopsin-like 7TM fold and olfactory receptor family membership together enforce a mechanism in which extracellular odorant binding stabilizes an active state that binds and activates heterotrimeric G proteins; this supports GO:0005515 protein binding by necessitating direct coupling to Gα/βγ and regulatory adaptors.\n\nThis GPCR-driven activation propagates intracellular cascades, placing the protein squarely in GO:0007165 signal transduction. Because the receptor is an olfactory-type GPCR specialized for volatile ligand detection, its activity initiates the sensory pathway formalized as GO:0007606 sensory perception of chemical stimulus. The causal chain is: odorant binding in the extracellular pocket triggers helix rearrangements in the 7TM core, which in turn catalyze GDP-GTP exchange on Gα and launch second-messenger production.\n\nCellular location follows directly from the 7TM architecture and olfactory receptor identity. The multi-pass topology and signal initiation require residence in the plasma membrane, aligning with GO:0005886 plasma membrane and the experimentally grounded description as a cell-membrane, multi-pass protein. The absence of soluble domains and the presence of multiple membrane-spanning helices reinforce this membrane-embedded operational site.\n\nMechanistically, I hypothesize that the receptor resides in olfactory neuron membranes where it binds odorants via a hydrophobic pocket formed by the 7TM bundle. Ligand-induced rearrangements expose intracellular surfaces that capture olfactory-enriched G proteins (e.g., Gαolf), initiating cAMP signaling that opens cyclic nucleotide-gated channels and converts chemical cues into electrical signals. Likely interaction partners include Gαolf (GNAL), Gβ and Gγ subunits, receptor-transporting proteins that chaperone trafficking to the membrane, and arrestin/GRK modules that terminate signaling. Together, these interactions define a membrane-localized signal transducer that converts extracellular odorant occupancy into intracellular second-messenger waves and neuronal responses.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGZ6.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGZ6"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGZ6/entry","atlas":"/p/Q8NGZ6"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}