{"uniprot":"Q8N127","gene":"OR5AS1","name":"Olfactory receptor 5AS1","organism":"Homo sapiens (Human)","status":"dark","length":324,"sequence":"MLESNYTMPTEFLFVGFTDYLPLRVTLFLVFLLVYTLTMVGNILLIILVNINSSLQIPMYYFLSNLSFLDISCSTAITPKMLANFLASRKSISPYGCALQMFFFASFADAECLILAAMAYDRYAAICNPLLYTTLMSRRVCVCFIVLAYFSGSTTSLVHVCLTFRLSFCGSNIVNHFFCDIPPLLALSCTDTQINQLLLFALCSFIQTSTFVVIFISYFCILITVLSIKSSGGRSKTFSTCASHLIAVTLFYGALLFMYLQPTTSYSLDTDKVVAVFYTVVFPMFNPIIYSFRNKDVKNALKKLLERIGYSNEWYLNRLRIVNI","function_summary":"A seven-helix cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals by activating heterotrimeric G proteins. This multi-pass membrane protein resides at the plasma membrane, where ligand-induced conformational changes in its transmembrane bundle trigger second-messenger pathways that encode smell perception. Its activity depends on tight binding to signaling and regulatory proteins, enabling rapid activation and desensitization cycles characteristic of olfactory signal transduction.","plain_language":"OR5AS1 has barely been studied. The model's best guess: A seven-helix cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals by activating heterotrimeric G proteins. This multi-pass membrane protein resides at the plasma membrane, where ligand-induced conformational changes in its transmembrane bundle trigger second-messenger pathways that encode smell perception.","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":290},{"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":272,"end":298}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain) spanning 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 the N-terminal region at residues 26–50, again at residues 59–80, and again centrally at residues 104–126, and near the C-terminal end at residues 272–298. Together these overlapping family calls confirm a class A GPCR scaffold with the expected intracellular loop architecture for heterotrimeric G-protein coupling. The presence of IPR000725 (Olfactory receptor family) from 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 region feeding into a 7TM bundle and intracellular loops—causally establishes a signal-transducing receptor that binds small hydrophobic ligands and activates G proteins.\n\nFrom this architecture, the molecular function follows. The rhodopsin-like 7TM fold and olfactory receptor family membership define a receptor that binds odorant molecules and triggers G-protein signaling. This necessitates GO:0005515 protein binding because the receptor must bind intracellular transducers (Gα/β/γ) and regulatory partners. The same fold and coupling logic justify inferring olfactory receptor activity and GPCR activity: ligand-induced conformational changes in the 7TM core open an intracellular cavity that binds and activates heterotrimeric G proteins.\n\nThe biological process emerges directly from this chemistry. Activation of heterotrimeric G proteins situates the receptor in GO:0007186 G protein-coupled receptor signaling pathway. Because the receptor class is specialized for odorant detection, its signaling drives neuronal responses that constitute GO:0007608 sensory perception of smell. The causal chain is: odorant binding within the 7TM bundle shifts the receptor to an active state, promotes GDP-GTP exchange on Gα, and initiates second-messenger cascades that encode odor information.\n\nCellular location is dictated by the 7TM architecture and the need to sample extracellular odorants. The multi-pass topology and signal initiation at the cell surface place the protein at the GO:0005886 plasma membrane. The provided subcellular description of a cell membrane, multi-pass membrane protein is fully consistent with this conclusion.\n\nMechanistically, the receptor likely binds hydrophobic odorants within a transmembrane pocket formed by helices defined by IPR017452. Ligand engagement stabilizes an active conformation that exposes intracellular loops for high-affinity coupling to the olfactory G protein (Golf), leading to cAMP production via adenylyl cyclase 3 and subsequent opening of cyclic nucleotide-gated channels. I therefore hypothesize interactions with Gαolf (GNAL), Gβγ subunits, adenylyl cyclase 3, receptor-transporting proteins (RTP1/2) and REEP family chaperones that promote trafficking, as well as arrestins and GRKs that mediate desensitization. These partners collectively tune sensitivity, sustain rapid signaling cycles, and ensure robust odor detection at the plasma membrane.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8N127.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8N127"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8N127/entry","atlas":"/p/Q8N127"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}