{"uniprot":"Q8NGA1","gene":"OR1M1","name":"Olfactory receptor 1M1","organism":"Homo sapiens (Human)","status":"dark","length":313,"sequence":"MEPRNQTSASQFILLGLSEKPEQETLLFSLFFCMYLVMVVGNLLIILAISIDSHLHTPMYFFLANLSLVDFCLATNTIPKMLVSLQTGSKAISYPCCLIQMYFFHFFGIVDSVIIAMMAYDRFVAICHPLHYAKIMSLRLCRLLVGALWAFSCFISLTHILLMARLVFCGSHEVPHYFCDLTPILRLSCTDTSVNRIFILIVAGMVIATPFVCILASYARILVAIMKVPSAGGRKKAFSTCSSHLSVVALFYGTTIGVYLCPSSVLTTVKEKASAVMYTAVTPMLNPFIYSLRNRDLKGALRKLVNRKITSSS","function_summary":"A seven-helix chemosensory receptor at the cell surface that detects volatile odorants and converts their binding into intracellular signaling through heterotrimeric G proteins. By cycling between inactive and active conformations within the membrane, it recruits and activates G-protein complexes to drive second-messenger pathways that encode chemical cues into neuronal responses. Its multi-pass topology positions it in the plasma membrane where it undergoes regulated trafficking and desensitization to sustain odor-evoked signaling.","plain_language":"OR1M1 has barely been studied. The model's best guess: A seven-helix chemosensory receptor at the cell surface that detects volatile odorants and converts their binding into intracellular signaling through heterotrimeric G proteins. By cycling between inactive and active conformations within the membrane, it recruits and activates G-protein complexes to drive second-messenger pathways that encode chemical cues into neuronal responses.","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":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":307},{"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":140,"end":161},{"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 bracketed and reinforced by multiple olfactory/rhodopsin-like GPCR family signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family) appears in several internal windows—[26–50], [59–80], [104–126], [140–161], [199–222], and [272–298]—marking hallmark motifs across the bundle that stabilize the inactive and active states and create the intracellular G-protein coupling surface. Superimposed on this scaffold is IPR000725 (Olfactory receptor family, residues 32–307), which specifies the ligand class and physiological role: small, volatile odorants sensed by specialized chemosensory neurons. The ordered layout—olfactory receptor family signature spanning the full seven-helix region, with multiple rhodopsin-like family markers decorating the transmembrane core—causally defines a class A GPCR tuned for odorant detection.\n\nThis architecture dictates molecular function. The seven-helix rhodopsin-like fold (IPR017452 and IPR000276 windows) forms a ligand-binding pocket in the transmembrane bundle and an intracellular cavity that recruits heterotrimeric G proteins. The olfactory receptor family signature (IPR000725) narrows the chemistry to odorant recognition and G-protein signaling. Together, these features necessitate GPCR-mediated signal transduction and multivalent protein binding to Gα/βγ and accessory factors, aligning with GO:0005515 protein binding as a basal capability of this signaling module.\n\nFrom function to process, activation of a rhodopsin-like GPCR initiates second-messenger cascades that propagate information inward, which is the essence of GO:0007165 signal transduction. Because the receptor family is specialized for odorant detection, its activity directly instantiates GO:0007606 sensory perception of chemical stimulus: odorant binding triggers G-protein pathways that encode chemical cues into neuronal activity.\n\nCellular location follows directly from the fold and topology. The seven-pass bundle and absence of soluble domains anchor the protein in the lipid bilayer as a multi-pass membrane receptor. This necessitates residence at the cell surface, consistent with GO:0005886 plasma membrane and the experimentally supported designation as a cell membrane, multi-pass membrane protein.\n\nMechanistically, odorant entry into the transmembrane pocket stabilizes an active GPCR conformation that exposes a cytosolic cavity for Gα-olfactory subunit engagement and GDP-GTP exchange. This causes dissociation and downstream signaling through cyclic nucleotide pathways in olfactory neurons. I therefore hypothesize interactions with the olfactory G protein complex (GαO/GNAL with Gβ and Gγ), β-arrestins and GPCR kinases for desensitization, and accessory trafficking/chaperone systems that deliver receptors to the ciliary plasma membrane. These partners collectively tune sensitivity, sustain rapid response cycles, and ensure proper membrane targeting and turnover.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGA1.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGA1"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGA1/entry","atlas":"/p/Q8NGA1"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}