{"uniprot":"Q8NH95","gene":"OR13C6P","name":"Putative olfactory receptor 13C6","organism":"Homo sapiens (Human)","status":"dark","length":151,"sequence":"MVSANQTASVTEFILLGLSAHPKLEKTFFVLILLMYLVILLGNGVLILMTVSNSHLHMPMYFFLGNLSFLDICYTTSSVPLILDSFLTPRKTISFSACAVQMFLSFAMGATECVLLSMMAFDRYVAICNPLRYPVVMSKAAYMPIRLPAPG","function_summary":"A human seven-helix chemosensory receptor that resides at the cell surface and detects volatile odorants. Ligand binding within its transmembrane pocket triggers heterotrimeric G-protein signaling that initiates the neuronal cascade underlying smell perception. Its multi-pass membrane architecture positions it at the plasma membrane, where accessory trafficking and regulatory proteins shape receptor maturation, surface expression, and signal termination.","plain_language":"OR13C6P has barely been studied. The model's best guess: A human seven-helix chemosensory receptor that resides at the cell surface and detects volatile odorants. Ligand binding within its transmembrane pocket triggers heterotrimeric G-protein signaling that initiates the neuronal cascade underlying smell perception.","uniprot_summary":"Odorant receptor.","go_terms":{"molecular_function":[{"id":"GO:0004984","label":"olfactory receptor activity"}],"biological_process":[{"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":42,"end":151},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":27,"end":51},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":34,"end":140},{"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}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is defined by IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 42–151), 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, residues 27–51), IPR000276 (rhodopsin-like family, residues 60–81), and IPR000276 (rhodopsin-like family, residues 105–127). These overlapping family calls collectively specify the Class A GPCR fold and its intracellular coupling logic. Superimposed on this scaffold is IPR000725 (Olfactory receptor family, residues 34–140), which narrows the receptor subclass to odorant-sensing GPCRs. The ordered layout—an N-terminal extracellular region feeding into a 7TM bundle and cytosolic loops—causes ligand recognition on the extracellular side and G-protein engagement on the intracellular side, the defining causal architecture of olfactory GPCRs.\n\nThis architecture dictates the molecular function. The seven-helix rhodopsin-like core and olfactory-receptor family signature together specify GO:0004984 olfactory receptor activity: binding volatile odorants and triggering heterotrimeric G-protein signaling. The cytosolic loops and conserved rhodopsin-like motifs (captured by the multiple IPR000276 entries) enable nucleotide exchange on Gα and thus initiate downstream second-messenger cascades.\n\nFrom this function, the biological process follows. Odorant-triggered GPCR signaling initiates neuronal responses that encode chemical cues; therefore the receptor drives GO:0007608 sensory perception of smell. The causal chain is direct: odorant binding to the extracellular pocket induces conformational changes in the 7TM bundle, which activate G proteins and propagate the olfactory signal.\n\nCellular location is implied by both topology and domain composition. The 7TM architecture and absence of soluble domains place the protein in the lipid bilayer as a multi-pass membrane receptor. This supports a membrane-resident assignment and specifically aligns with GO:0005886 plasma membrane, consistent with the stated cell membrane localization and multi-pass topology.\n\nMechanistically, the receptor likely binds odorants within a transmembrane pocket formed by IPR017452 helices, stabilizing an active state that recruits and activates an olfactory Gα (such as the olfactory transducin-like G protein). This activation would stimulate cyclic nucleotide pathways in olfactory neurons, with trafficking and maturation aided by accessory factors that chaperone and localize olfactory GPCRs. I therefore hypothesize interactions with Gα-olf (GNAL), Gβγ subunits, receptor-transporting proteins (RTP1/2), REEP family members, and arrestins that mediate desensitization and internalization. Together, these partners would tune surface expression, ligand detection, and signal termination in the plasma membrane of human olfactory sensory cells.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NH95.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NH95"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NH95/entry","atlas":"/p/Q8NH95"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}