{"uniprot":"Q96RD0","gene":"OR8B2","name":"Olfactory receptor 8B2","organism":"Homo sapiens (Human)","status":"dark","length":313,"sequence":"MLARNNSLVTEFILAGLTDHPEFRQPLFFLFLVIYIVTMVGNLGLITLFGLNSHLHTPMYYFLFNLSFIDLCYSSVFTPKMLMNFVSKKNIISNVGCMTRLFFFLFFVISECYMLTSMAYDRYVAICNPLLYKVTMSHQVCSMLTFAAYIMGLAGATAHTGCMLRLTFCSANIINHYLCDILPLLQLSCTSTYVNEVVVLIVVGTNITVPSCTILISYVFIVTSILHIKSTQGRSKAFSTCSSHVIALSLFFGSAAFMYIKYSSGSMEQGKVSSVFYTNVVPMLNPLIYSLRNKDVKVALRKALIKIQRRNIF","function_summary":"A seven-pass cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through heterotrimeric G proteins. By residing in the plasma membrane and using a rhodopsin-like transmembrane core, it initiates cyclic-nucleotide signaling that underlies olfactory transduction and broader chemosensory pathways. Its intracellular loops and tail provide multivalent interfaces for assembling signaling complexes, enabling efficient activation and termination of pathways that encode the perception of smell.","plain_language":"OR8B2 has barely been studied. The model's best guess: A seven-pass cell-surface chemosensory receptor that detects volatile odorants and converts their binding into intracellular signals through heterotrimeric G proteins. By residing in the plasma membrane and using a rhodopsin-like transmembrane core, it initiates cyclic-nucleotide signaling that underlies olfactory transduction and broader chemosensory pathways.","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":289},{"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":199,"end":222},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":271,"end":297}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 41–289), 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], [199–222], and [271–297]—marking hallmark motifs across the N-terminus and within the transmembrane region that stabilize the active and inactive states of the receptor. The presence of IPR000725 (Olfactory receptor family, 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 segment feeding into a tightly conserved 7TM core and followed by intracellular loops—creates a signal-transducing module that binds small hydrophobic ligands in the membrane and transmits the signal via heterotrimeric G proteins.\n\nThis architecture dictates molecular function. The rhodopsin-like 7TM fold and olfactory family signature cause G protein-coupled receptor activity that is specialized for odorant recognition and G-protein activation. The intracellular loops and C-terminal tail, shaped by the rhodopsin-like family motifs, provide multivalent interfaces for protein binding, consistent with GO:0005515 protein binding, particularly toward Gα/βγ subunits and arrestins. Thus, the primary molecular function is a GPCR that binds odorants and engages signaling proteins.\n\nFrom function to process, the receptor’s GPCR chemistry drives the GO:0007186 G protein-coupled receptor signaling pathway. In the olfactory lineage, activation of the olfactory G protein triggers cyclic nucleotide signaling that encodes sensory input, aligning with GO:0007608 sensory perception of smell. The causal chain is direct: odorant occupancy in the hydrophobic binding pocket stabilizes an active 7TM conformation; this conformation catalyzes GDP-GTP exchange on Gα, initiating downstream second-messenger cascades that produce neuronal depolarization.\n\nCellular location follows from the fold and topology. The seven-pass bundle and absence of soluble domains place the protein in the plasma membrane, matching GO:0005886 plasma membrane and the experimentally supported designation as a multi-pass membrane protein. The extracellular N-terminus and intracellular C-terminus are arranged to face the lumen/extracellular space and cytosol, respectively, which is optimal for ligand capture and cytosolic G-protein engagement.\n\nMechanistically, I hypothesize that the receptor binds hydrophobic odorants within the transmembrane cavity formed by IPR017452, then shifts to an active state that recruits and activates the olfactory heterotrimeric G protein. This triggers adenylyl cyclase activity and downstream ion channel modulation to encode odor information. Likely interaction partners include the olfactory Gα subunit and its βγ partners, receptor-transporting proteins that chaperone trafficking to the membrane, and arrestin/GRK modules that terminate signaling. Together, these interactions ensure rapid, tunable odorant detection at the cell surface.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96RD0.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96RD0"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96RD0/entry","atlas":"/p/Q96RD0"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}