{"uniprot":"Q8NG95","gene":"OR7G3","name":"Olfactory receptor 7G3","organism":"Homo sapiens (Human)","status":"dark","length":312,"sequence":"MKAGNFSDTPEFFLLGLSGDPELQPILFMLFLSMYLATMLGNLLIILAVNSDSHLHTPMYFLLSILSLVDICFTSTTMPKMLVNIQAQAQSINYTGCLTQICFVLVFVGLENGILVMMAYDRFVAICHPLRYNVIMNPKLCGLLLLLSFIVSVLDALLHTLMVLQLTFCIDLEIPHFFCELAHILKLACSDVLINNILVYLVTSLLGVVPLSGIIFSYTRIVSSVMKIPSAGGKYKAFSICGSHLIVVSLFYGTGFGVYLSSGATHSSRKGAIASVMYTVVTPMLNPLIYSLRNKDMLKALRKLISRIPSFH","function_summary":"A multi-pass cell-surface chemosensory receptor that detects extracellular odorant molecules and transduces this information through a seven-helix signaling core to activate intracellular pathways. By engaging heterotrimeric G proteins at the plasma membrane, it initiates cyclic-nucleotide signaling that modulates neuronal activity and can drive downstream transcriptional programs. Its intracellular loops and C-terminal region provide binding sites for regulatory proteins that control activation, desensitization, and trafficking, thereby coupling acute odor recognition to longer-term gene-expression changes.","plain_language":"OR7G3 has barely been studied. The model's best guess: A multi-pass cell-surface chemosensory receptor that detects extracellular odorant molecules and transduces this information through a seven-helix signaling core to activate intracellular pathways. By engaging heterotrimeric G proteins at the plasma membrane, it initiates cyclic-nucleotide signaling that modulates neuronal activity and can drive downstream transcriptional programs.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0006355","label":"regulation of DNA-templated transcription"}],"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":32,"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":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 internal windows—[26–50], [59–80], [104–126], [199–222], and [272–298]—marking conserved motifs across the N-terminus and the helices that coordinate G protein coupling and arrestin recruitment. The presence of IPR000725 (Olfactory receptor family, residues 32–306) specifies the receptor subclass that senses volatile odorants. The ordered layout—an N-terminal extracellular region feeding into a 7TM bundle and followed by cytosolic loops—creates a signal-transducing platform that binds extracellular ligands and uses intracellular interfaces to engage heterotrimeric G proteins and other adaptors.\n\nThis architecture dictates molecular function. The rhodopsin-like 7TM fold and olfactory receptor family membership cause G protein-coupled receptor activity and odorant binding. The cytosolic loops and C-terminal tail, together with the intracellular faces of the helices, provide multivalent surfaces for protein binding, consistent with GO:0005515 protein binding. These surfaces mediate high-affinity coupling to Gα subunits and β-arrestins, and they enable assembly of downstream effectors.\n\nFrom this molecular function, the biological process follows. Odorant-triggered GPCR signaling initiates cyclic nucleotide cascades that modulate neuronal excitability and, in olfactory neurons, drive transcriptional programs via cAMP/PKA/CREB pathways. Thus, receptor activation can regulate gene expression, aligning with GO:0006355 regulation of DNA-templated transcription. In parallel, the primary sensory role places the receptor in the broader GPCR signaling and sensory perception pathways that tune odor-evoked responses.\n\nCellular location is determined by the 7TM architecture and the experimentally supported multi-pass topology. The hydrophobic bundle embeds the protein as an integral component of the plasma membrane, matching GO:0005886 plasma membrane and the stated cell membrane localization. The extracellular N-terminus and intracellular loops orient the receptor to sense extracellular odorants and signal internally.\n\nMechanistically, odorant binding within the transmembrane pocket stabilizes an active conformation that exposes cytosolic interfaces for G protein engagement. This triggers GDP-GTP exchange on Gα, liberating Gβγ and initiating second-messenger production. The receptor likely couples predominantly to Golf/Gs-like pathways in olfactory neurons, elevating cAMP and engaging PKA/CREB to regulate transcription. Arrestin binding then desensitizes and internalizes the receptor, while scaffolds and adaptors coordinate trafficking and resensitization.\n\nGiven this mechanism, I hypothesize interactions with heterotrimeric G proteins (e.g., Gαolf/Gαs and associated βγ subunits), β-arrestins, GPCR kinases, and membrane-associated scaffolds that organize signaling microdomains. These partners collectively tune signal amplitude and duration, linking acute odor detection to longer-term transcriptional responses.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NG95.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NG95"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NG95/entry","atlas":"/p/Q8NG95"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}