{"uniprot":"Q96P67","gene":"GPR82","name":"Probable G-protein coupled receptor 82","organism":"Homo sapiens (Human)","status":"dark","length":336,"sequence":"MNNNTTCIQPSMISSMALPIIYILLCIVGVFGNTLSQWIFLTKIGKKTSTHIYLSHLVTANLLVCSAMPFMSIYFLKGFQWEYQSAQCRVVNFLGTLSMHASMFVSLLILSWIAISRYATLMQKDSSQETTSCYEKIFYGHLLKKFRQPNFARKLCIYIWGVVLGIIIPVTVYYSVIEATEGEESLCYNRQMELGAMISQIAGLIGTTFIGFSFLVVLTSYYSFVSHLRKIRTCTSIMEKDLTYSSVKRHLLVIQILLIVCFLPYSIFKPIFYVLHQRDNCQQLNYLIETKNILTCLASARSSTDPIIFLLLDKTFKKTLYNLFTKSNSAHMQSYG","function_summary":"A human seven-pass cell-surface receptor that transduces extracellular cues into intracellular signals via a rhodopsin-like transmembrane core. It likely operates as an orphan receptor that engages heterotrimeric G proteins and arrestin pathways to modulate downstream second-messenger cascades and trafficking decisions at the plasma membrane. Its multi-pass architecture positions it as a membrane-embedded signaling hub whose conformational switching governs pathway selection and desensitization dynamics.","plain_language":"GPR82 has barely been studied. The model's best guess: A human seven-pass cell-surface receptor that transduces extracellular cues into intracellular signals via a rhodopsin-like transmembrane core. It likely operates as an orphan receptor that engages heterotrimeric G proteins and arrestin pathways to modulate downstream second-messenger cascades and trafficking decisions at the plasma membrane.","uniprot_summary":"Orphan receptor.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0007186","label":"G protein-coupled receptor signaling pathway"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR017452","name":"GPCR, rhodopsin-like, 7TM","type":"domain","start":32,"end":309},{"id":"IPR042804","name":"Probable G-protein coupled receptor 82","type":"family","start":1,"end":335},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":17,"end":317}],"reasoning":"I begin with the InterPro architecture. The sequence carries IPR017452 (GPCR, rhodopsin-like, 7TM domain) spanning residues 32–309, establishing a canonical seven–transmembrane helical bundle that forms the activation-competent core of class A G protein-coupled receptors. This transmembrane scaffold is embedded within two family-level signatures: IPR000276 (G protein-coupled receptor, rhodopsin-like family) from residues 17–317 and IPR042804 (Probable G-protein coupled receptor 82 family) covering essentially the full length (residues 1–335). The ordered layout—an N-terminal extracellular segment, seven membrane-spanning helices, and cytosolic loops—creates a signal-transducing module that couples extracellular ligand or force cues to intracellular G protein engagement. The rhodopsin-like fold dictates conformational switching between inactive and active states, which in turn recruits heterotrimeric G proteins and arrestins. This architecture causes a molecular function centered on multivalent protein binding, particularly to Gαβγ complexes and cytosolic adaptors, aligning with GO:0005515 protein binding.\n\nFrom this molecular function, the biological process follows directly. The seven-helix switch controls nucleotide exchange on Gα subunits and downstream effector pathways, defining participation in the GO:0007186 G protein-coupled receptor signaling pathway. The absence of a conclusively identified endogenous ligand and the prominence of the 7TM core suggest either orphan receptor behavior or mechano/chemo-coupling that triggers G protein and arrestin cascades.\n\nCellular localization is dictated by the transmembrane architecture and signaling role. A seven-pass bundle is inherently membrane-embedded and functions at the cell surface to sense extracellular cues, supporting residence at the GO:0005886 plasma membrane. The multi-pass nature and extracellular/cytosolic topology further reinforce a cell-membrane sentinel role.\n\nMechanistically, the receptor likely cycles between inactive basal and active states stabilized by conserved class A motifs within the 7TM core. Upon activation, intracellular loops and the C-terminus recruit G proteins to initiate second-messenger production and can subsequently bind arrestins to modulate receptor desensitization and trafficking. I hypothesize that this receptor forms transient complexes with heterotrimeric G proteins (Gi/o, Gs, or Gq families), GPCR kinases, and beta-arrestins. It may preferentially signal through pathways that regulate membrane-associated processes—such as cytoskeletal remodeling or vesicle dynamics—consistent with a currently uncharacterized ligand environment and a plasma-membrane operating niche.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q96P67.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q96P67"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q96P67/entry","atlas":"/p/Q96P67"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}