{"uniprot":"Q8NH76","gene":"OR56B4","name":"Olfactory receptor 56B4","organism":"Homo sapiens (Human)","status":"dark","length":319,"sequence":"MDTSTSVTYDSSLQISQFILMGLPGIHEWQHWLSLPLTLLYLLALGANLLIIITIQHETVLHEPMYHLLGILAVVDIGLATTIMPKILAIFWFDAKAISLPMCFAQIYAIHCFFCIESGIFLCMAVDRYIAICRPLQYPSIVTKAFVFKATGFIMLRNGLLTIPVPILAAQRHYCSRNEIEHCLCSNLGVISLACDDITVNKFYQLMLAWVLVGSDMALVFSSYAVILHSVLRLNSAEAMSKALSTCSSHLILILFHTGIIVLSVTHLAEKKIPLIPVFLNVLHNVIPPALNPLACALRMHKLRLGFQRLLGLGQDVSK","function_summary":"A human odorant-sensing seven-helix receptor that resides at the cell surface and initiates olfactory signal transduction. Upon binding volatile chemicals, it switches into an active GPCR conformation that engages olfactory G proteins, elevates cyclic nucleotide signaling, and drives neuronal depolarization underlying smell perception. Its multi-pass membrane architecture positions it as a primary chemosensory gatekeeper at the plasma membrane, where it captures extracellular odorants and converts them into intracellular second-messenger cascades.","plain_language":"OR56B4 has barely been studied. The model's best guess: A human odorant-sensing seven-helix receptor that resides at the cell surface and initiates olfactory signal transduction. Upon binding volatile chemicals, it switches into an active GPCR conformation that engages olfactory G proteins, elevates cyclic nucleotide signaling, and drives neuronal depolarization underlying smell perception.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0004984","label":"olfactory receptor activity"}],"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":47,"end":256},{"id":"IPR050402","name":"Olfactory receptor 51/52/56-like","type":"family","start":14,"end":307},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":38,"end":309}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain) spanning residues 47–256, which encodes the canonical seven-helix bundle that transduces extracellular ligand binding into intracellular G-protein activation. This rhodopsin-like scaffold is embedded within two olfactory-receptor–specific family signatures: IPR050402 (Olfactory receptor 51/52/56-like family, residues 14–307) and IPR000725 (Olfactory receptor family, residues 38–309). The ordered layout—an N-terminal olfactory-receptor family envelope (IPR050402 and IPR000725) embracing a central rhodopsin-like 7TM core (IPR017452)—defines a class A GPCR specialized for volatile-odorant recognition. The seven-helix bundle dictates a membrane-embedded receptor that signals through heterotrimeric G proteins; the olfactory-receptor families constrain ligand chemistry toward odorants and specify coupling to olfactory G proteins.\n\nThis architecture causes olfactory receptor activity (GO:0004984) by creating an extracellular binding cavity formed by the 7TM bundle and intracellular loops that catalyze nucleotide exchange on Gα. The immediate molecular function is therefore a ligand-activated GPCR tuned for odorants. From this function, the signaling cascade follows: activation of the olfactory G protein pathway (GO:0007186 G protein-coupled receptor signaling pathway) proceeds via Gαolf to stimulate cyclic nucleotide production and downstream ion channel opening. The physiological role of this cascade is sensory perception of smell (GO:0007608), because odorant-triggered GPCR signaling encodes peripheral chemosensory information in olfactory neurons.\n\nThe seven-pass topology and absence of soluble domains anchor the protein in the plasma membrane (GO:0005886). The rhodopsin-like 7TM domain intrinsically forms a multi-pass membrane core, and olfactory receptors operate at the cell surface to detect extracellular odorants; thus the cellular component is a cell-surface, multi-pass membrane protein.\n\nMechanistically, odorant binding within the 7TM cavity stabilizes an active-state conformation that exposes intracellular interfaces for Gαolf and Gβγ, initiating second-messenger signaling. I hypothesize that this receptor transiently assembles with olfactory transduction machinery: the G protein heterotrimer (Gαolf/GNAL with Gβγ), adenylate cyclase type 3 for cAMP production, and the cyclic nucleotide–gated channel complex that depolarizes olfactory neurons. Accessory trafficking and folding factors likely chaperone the receptor to the membrane, while arrestins and GRKs terminate signaling. Together, these interactions produce a rapid, reversible chemosensory response at the plasma membrane.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NH76.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NH76"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NH76/entry","atlas":"/p/Q8NH76"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}