{"uniprot":"Q8NGA8","gene":"OR4F17","name":"Olfactory receptor 4F17","organism":"Homo sapiens (Human)","status":"dark","length":305,"sequence":"MVTEFIFLGLSDSQGLQTFLFMLFFVFYGGIVFGNLLIVITVVSDSHLHSPMYFLLANLSLIDLSLSSVTAPKMITDFFSQRKVISFKGCLVQIFLLHFFGGSEMVILIAMGFDRYIAICKPLHYTTIMCGNACVGIMAVAWGIGFLHSVSQLAFAVHLPFCGPNEVDSFYCDLPRVIKLACTDTYRLDIMVIANSGVLTVCSFVLLIISYTIILMTIQHRPLDKSSKALSTLTAHITVVLLFFGPCVFIYAWPFPIKSLDKFLAVFYSVITPLLNPIIYTLRNKDMKTAIRQLRKWDAHSSVKF","function_summary":"A cell-surface, multi-pass chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through a seven-helix GPCR core. By engaging heterotrimeric G proteins at the plasma membrane, it initiates the canonical olfactory signaling cascade that underlies smell perception, with cytosolic coupling surfaces mediating activation and regulatory protein binding that tune signal amplitude and duration.","plain_language":"OR4F17 has barely been studied. The model's best guess: A cell-surface, multi-pass chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through a seven-helix GPCR core. By engaging heterotrimeric G proteins at the plasma membrane, it initiates the canonical olfactory signaling cascade that underlies smell perception, with cytosolic coupling surfaces mediating activation and regulatory protein binding that tune signal amplitude and duration.","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":34,"end":280},{"id":"IPR050427","name":"Human Olfactory Receptors","type":"family","start":2,"end":295},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":19,"end":43},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":27,"end":293},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":52,"end":73},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":97,"end":119},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":262,"end":288}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 34–280), 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 receptor and rhodopsin-like GPCR family signatures that span nearly the full length of the protein: IPR050427 (Human Olfactory Receptors family, residues 2–295) and IPR000725 (Olfactory receptor family, residues 27–293) define the receptor as a member of the vertebrate olfactory GPCR clade. Three additional rhodopsin-like family annotations—IPR000276 (G protein-coupled receptor, rhodopsin-like family, residues 19–43), IPR000276 (residues 52–73), and IPR000276 (residues 97–119)—plus a late-stage annotation IPR000276 (residues 262–288), collectively map the N-terminal extracellular region, the transmembrane bundle, and the cytosolic tail that couples to heterotrimeric G proteins and regulatory factors. The ordered layout—olfactory receptor family envelopes a rhodopsin-like 7TM core—causally specifies a ligand-activated GPCR tuned for odorant detection.\n\nThis architecture dictates molecular function. The seven-helix bundle and cytosolic coupling surfaces create a switch that binds and activates heterotrimeric G proteins; this is the essence of GPCR signaling and is captured by GO:0005515 protein binding through high-affinity interactions with Gα/β/γ subunits and arrestins. The olfactory receptor family signatures further constrain the ligand class to volatile small molecules, implying odorant-triggered conformational changes that recruit and activate G proteins.\n\nFrom this molecular function, the biological process follows. Activation of G proteins by this receptor initiates the canonical olfactory cascade—typically via Golf—leading to cAMP production and downstream ion channel opening. This places the protein squarely in GO:0007186 G protein-coupled receptor signaling pathway. Because the receptor’s specialization is chemosensation, its activity drives GO:0007608 sensory perception of smell, converting environmental chemical cues into neuronal signals.\n\nCellular location is dictated by the 7TM topology and the need to sample extracellular odorants. The multi-pass membrane core and extracellular N-terminus anchor the receptor in the plasma membrane, aligning with GO:0005886 plasma membrane and the experimentally supported designation as a cell-membrane, multi-pass membrane protein.\n\nMechanistically, odorant binding within the transmembrane bundle stabilizes an active state that exposes cytosolic interfaces for G protein engagement. This triggers GDP-GTP exchange on Gα and releases Gβγ, propagating second-messenger signaling. I therefore hypothesize interactions with the olfactory G protein heterotrimer (Golf/GNAL with Gβγ), β-arrestins for desensitization, and membrane-localized signaling partners that scaffold cAMP production and receptor trafficking. Together, these interactions enable rapid, tunable odorant detection at the cell surface and translate chemical stimuli into defined intracellular signaling outputs.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGA8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGA8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGA8/entry","atlas":"/p/Q8NGA8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}