{"uniprot":"Q8NGC8","gene":"OR11H7","name":"Olfactory receptor 11H7","organism":"Homo sapiens (Human)","status":"dark","length":314,"sequence":"MNNSQISTVTQFVLLGFPGPWKIQIIFFSMILLVYIFTLTGNMAIICAVRWDHRLHTPMYVLLANFSFLEIWYVTCTVPNMLVNFFSKTKTISFSGCFTQFHFFFSLGTTECFFLCVMAYDRYLAICHPLHYPSIMTGQLCGILVSLCWLIGFLGHSISIFFIFQLPFCGPNIIDHFLCDVDPLMALSSAPTHIIGHVFHSVSSLFINLTMVYILGSYTLVLRTVLQVPSSAGWQKAISTCGSHLVVVSLFYGAIMLMYVSPTPGNSVAMHKLITLIYSVVTPVLNPLIYSLRNKDMKYALHHVFCGMRIIQRS","function_summary":"A human seven-helix membrane receptor that belongs to the olfactory class of G protein–coupled receptors. It resides at the cell surface as a multi-pass protein and initiates signaling by binding a small, likely hydrophobic ligand within the membrane, thereby activating heterotrimeric G proteins. The ensuing second-messenger cascades that modulate cAMP and Ca2+ provide a route to enhance the terminal steps of cell division, aligning with a role in promoting cytokinesis. Its signaling depends on dynamic protein–protein interactions that couple extracellular cue detection to intracellular effector pathways at the plasma membrane.","plain_language":"OR11H7 has barely been studied. The model's best guess: A human seven-helix membrane receptor that belongs to the olfactory class of G protein–coupled receptors. It resides at the cell surface as a multi-pass protein and initiates signaling by binding a small, likely hydrophobic ligand within the membrane, thereby activating heterotrimeric G proteins.","uniprot_summary":"Orphan receptor.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0032467","label":"positive regulation of cytokinesis"}],"cellular_component":[{"id":"GO:0005886","label":"plasma membrane"}]},"interpro":[{"id":"IPR017452","name":"GPCR, rhodopsin-like, 7TM","type":"domain","start":41,"end":290},{"id":"IPR050939","name":"Olfactory G-protein coupled receptor 1","type":"family","start":2,"end":303},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":26,"end":50},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":33,"end":306},{"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":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 embedded within multiple olfactory/rhodopsin-like GPCR family signatures that collectively define both fold and lineage: IPR050939 (Olfactory G-protein coupled receptor 1 family, residues 2–303) and IPR000725 (Olfactory receptor family, residues 33–306) specify an olfactory-class GPCR scaffold; IPR000276 (G protein-coupled receptor, rhodopsin-like family, residues 26–50) and IPR000276 (rhodopsin-like family, residues 104–126) plus IPR000276 (rhodopsin-like family, residues 272–298) mark conserved substructures that stabilize the inactive and active states and couple to heterotrimeric G proteins. The ordered layout—N-terminal extracellular region, seven transmembranes, and intracellular C-terminal loops—creates a receptor that binds small hydrophobic ligands in the membrane plane and signals through G proteins.\n\nThis architecture causes a molecular function centered on receptor-mediated signal initiation. The rhodopsin-like 7TM fold and olfactory-family signatures together define a G protein-coupled receptor that binds intracellular partners and extracellular cues; thus protein binding (GO:0005515) is intrinsic, encompassing ligand capture and Gα/βγ engagement. The absence of catalytic motifs and the presence of multiple GPCR family signatures reinforce that signaling occurs via conformational switching and effector recruitment rather than enzymatic chemistry.\n\nFrom this molecular function, I infer the biological process. GPCR signaling can modulate cell-cycle machinery by controlling second messengers (cAMP, Ca2+) and kinase cascades that feed into cytokinesis checkpoints. An olfactory-class GPCR situated at the cell surface can elevate cAMP/PKA or Ca2+-dependent pathways that enhance contractile ring dynamics and abscission efficiency; this provides a mechanistic route to positive regulation of cytokinesis (GO:0032467). In this model, receptor activation biases cytoskeletal and membrane-trafficking modules that drive the terminal steps of cell division.\n\nThe cellular component follows directly from the seven-helix transmembrane core and the olfactory-family identity: the protein is an integral, multi-pass membrane receptor embedded in the plasma membrane (GO:0005886). The N-terminal extracellular region and the intracellular C-terminal tail position the receptor to sense the extracellular milieu and couple to cytosolic G proteins at the membrane interface.\n\nMechanistically, I hypothesize that the receptor binds a small, likely hydrophobic odorant or endogenous pheromone-like cue within the membrane, stabilizing an active state that recruits and activates a heterotrimeric G protein. The ensuing Gα exchange and Gβγ release modulate adenylyl cyclase and phosphodiesterase pathways, tuning cAMP and Ca2+ signals that secondarily enhance cytokinesis efficiency. Consistent with this, the receptor likely forms transient complexes with Gα subunits (e.g., Golf/Gs), Gβγ dimers, GPCR kinases, and arrestins, and may interface with membrane-associated scaffolds that coordinate actomyosin and membrane remodeling during cell division.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NGC8.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NGC8"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NGC8/entry","atlas":"/p/Q8NGC8"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}