{"uniprot":"Q5JRS4","gene":"OR10J3","name":"Olfactory receptor 10J3","organism":"Homo sapiens (Human)","status":"dark","length":329,"sequence":"MPKLNSTFVTEFLFEGFSSFRRQHKLVFFVVFLTLYLLTLSGNVIIMTIIRLDHHLHTPMYFFLCMLSISETCYTVAIIPHMLSGLLNPHQPIATQSCATQLFFYLTFGINNCFLLTVMGYDRYVAICNPLRYSVIMGKRACIQLASGSLGIGLGMAIVQVTSVFGLPFCDAFVISHFFCDVRHLLKLACTDTTVNEIINFVVSVCVLVLPMGLVFISYVLIISTILKIASAEGQKKAFATCASHLTVVIIHYGCASIIYLKPKSQSSLGQDRLISVTYTHHSPTEPCCVQPEEQGGQRCSAQSRGAKNSVSLMKRGCEGFSFAFINMY","function_summary":"A seven-helix chemosensory receptor at the cell surface that detects small volatile molecules and converts their binding into intracellular signaling by coupling to heterotrimeric G proteins. This membrane-embedded switch initiates second-messenger cascades that encode chemical cues into neuronal activity central to smell perception. Its multi-pass architecture positions an extracellular ligand-binding pocket and a cytosolic signaling interface that together drive activation, coupling, and desensitization within olfactory membranes.","plain_language":"OR10J3 has barely been studied. The model's best guess: A seven-helix chemosensory receptor at the cell surface that detects small volatile molecules and converts their binding into intracellular signaling by coupling to heterotrimeric G proteins. This membrane-embedded switch initiates second-messenger cascades that encode chemical cues into neuronal activity central to smell perception.","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":42,"end":253},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":27,"end":51},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":33,"end":255},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":60,"end":81},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":105,"end":127},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":200,"end":223}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 42–253), 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, residues 27–51), IPR000276 family marks at residues 60–81, 105–127, and 200–223, and IPR000725 (Olfactory receptor family, residues 33–255). The ordered layout—N-terminal extracellular region feeding into a 7TM bundle and cytosolic loops—defines a class A GPCR specialized for odorant recognition and G-protein coupling. The olfactory receptor family signature (IPR000725) specifies the ligand class as volatile small molecules, while the rhodopsin-like family entries collectively indicate the conserved activation machinery (e.g., DRY and NPxxY motifs) that stabilizes active and inactive states.\n\nThis architecture causes a molecular function centered on signal initiation: the 7TM bundle binds odorants and rearranges intracellular loops to engage heterotrimeric G proteins. That mechanism substantiates a primary function of GPCR-mediated signal transduction and is consistent with GO:0005515 protein binding, because activation requires high-affinity binding to Gα/βγ and accessory proteins. The presence of multiple rhodopsin-like family entries and the olfactory receptor family signature together argue that the receptor’s binding pocket and cytosolic interface are tuned for odorant-induced G-protein activation rather than enzymatic catalysis.\n\nFrom this molecular function, the biological process follows. Odorant-triggered GPCR activation initiates second-messenger cascades (classically via Golf/Gαolf), which instantiate GO:0007165 signal transduction. In sensory neurons, this signaling underlies GO:0007606 sensory perception of chemical stimulus, because the receptor converts external chemical cues into intracellular signals that propagate to neuronal firing. The causal chain is direct: odorant binding in the extracellular vestibule shifts the 7TM core, which couples to G proteins, which liberate Gβγ and modulate downstream effectors to encode odor information.\n\nCellular location is dictated by the 7TM topology and the need to sample extracellular ligands. The multi-pass arrangement and extracellular N-terminus anchor the protein in the plasma membrane, aligning with GO:0005886 plasma membrane and the experimentally supported designation as a cell-membrane, multi-pass membrane protein. This placement ensures ligand access and efficient coupling to cytosolic G proteins.\n\nMechanistically, I hypothesize that the receptor resides in olfactory neuron membranes where it binds odorants via a hydrophobic pocket within the 7TM bundle. Ligand-induced rearrangement exposes cytosolic surfaces that recruit and activate Gαolf with Gβγ, stimulating adenylyl cyclase and downstream cAMP pathways. Accessory interactions likely include Golf (GNAL), Gβγ subunits, receptor kinases (GRKs), and arrestins that tune desensitization. Chaperones and trafficking factors probably assist folding and membrane delivery, but the dominant interaction sphere is the G-protein module that transduces the odorant signal into neuronal responses.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q5JRS4.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q5JRS4"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q5JRS4/entry","atlas":"/p/Q5JRS4"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}