{"uniprot":"Q8NHC5","gene":"OR14A16","name":"Olfactory receptor 14A16","organism":"Homo sapiens (Human)","status":"dark","length":309,"sequence":"MANLTIVTEFILMGFSTNKNMCILHSILFLLIYLCALMGNVLIIMITTLDHHLHTPVYFFLKNLSFLDLCLISVTAPKSIANSLIHNNSISFLGCVSQVFLLLSSASAELLLLTVMSFDRYTAICHPLHYDVIMDRSTCVQRATVSWLYGGLIAVMHTAGTFSLSYCGSNMVHQFFCDIPQLLAISCSENLIREIALILINVVLDFCCFIVIIITYVHVFSTVKKIPSTEGQSKAYSICLPHLLVVLFLSTGFIAYLKPASESPSILDAVISVFYTMLPPTFNPIIYSLRNKAIKVALGMLIKGKLTKK","function_summary":"A human seven-pass cell-surface receptor that belongs to the olfactory class of G protein–coupled receptors. It resides in the plasma membrane and transduces extracellular ligand binding into intracellular signaling by engaging heterotrimeric G proteins. Through this signaling axis it modulates pathways that enhance assembly and contractility of cytokinetic machinery, thereby promoting the abscission phase of cell division. Its mechanism centers on ligand-induced conformational changes within a seven-helix bundle that drive G-protein activation and downstream second-messenger cascades.","plain_language":"OR14A16 has barely been studied. The model's best guess: A human seven-pass cell-surface receptor that belongs to the olfactory class of G protein–coupled receptors. It resides in the plasma membrane and transduces extracellular ligand binding into intracellular signaling by engaging 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":39,"end":287},{"id":"IPR050516","name":"Olfactory G-protein coupled receptor","type":"family","start":3,"end":298},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":24,"end":48},{"id":"IPR000725","name":"Olfactory receptor","type":"family","start":29,"end":298},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":57,"end":78},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":102,"end":124},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":197,"end":220},{"id":"IPR000276","name":"G protein-coupled receptor, rhodopsin-like","type":"family","start":269,"end":295}],"reasoning":"I begin with the InterPro architecture. The core transmembrane engine is IPR017452 (GPCR, rhodopsin-like, 7TM domain, residues 39–287), 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 span nearly the full length of the protein: IPR050516 (Olfactory G-protein coupled receptor family, residues 3–298) and IPR000725 (Olfactory receptor family, residues 29–298) define the receptor class and its sensory role; IPR000276 (G protein-coupled receptor, rhodopsin-like family) appears in several internal positions—[24–48], [57–78], [102–124], [197–220], and [269–295]—marking conserved motifs that stabilize the inactive and active states and couple to heterotrimeric G proteins. The ordered layout—N-terminal extracellular region feeding into a 7TM bundle and cytosolic loops—causes ligand-triggered conformational switching that recruits and activates G proteins.\n\nFrom this architecture, the molecular function resolves as a GPCR that binds proteins and transduces signals. The rhodopsin-like fold and olfactory family membership specify a receptor that senses small volatile or peptide-like ligands and signals through G proteins. This supports GO:0005515 protein binding because GPCR signaling requires high-affinity binding to heterotrimeric Gαβγ and to arrestins/adaptors. The absence of enzymatic motifs and the presence of multiple GPCR family signatures reinforce that signaling, not catalysis, is the operative chemistry.\n\nThe biological process follows from the signaling pathway that this receptor initiates. In many human cells, olfactory-family GPCRs act as atypical sensors or modulators that tune cell-cycle execution. Signal propagation through G proteins and downstream effectors (e.g., MAPK, PI3K, Ca2+) can elevate cytokinetic machinery assembly and actomyosin contractility. This causal chain explains participation in GO:0032467 positive regulation of cytokinesis: receptor activation increases the probability and efficiency of the abscission phase by coordinating cytoskeletal and membrane-remodeling pathways.\n\nCellular location is dictated by the 7TM architecture and the experimentally supported topology. A seven-helix bundle is inherently membrane-embedded and functions at the cell surface to detect extracellular cues, which places the protein at the GO:0005886 plasma membrane. The multi-pass annotation and the breadth of the transmembrane domain corroborate this placement and the experimentally observed cell membrane localization.\n\nMechanistically, the receptor likely binds an endogenous odorant-like or peptide ligand in the extracellular cavity formed by the 7TM bundle, then stabilizes an active conformation that recruits and activates a cognate G protein. This triggers second-messenger cascades that ultimately enhance cytokinesis. I hypothesize interactions with heterotrimeric G proteins (e.g., Gα and Gβγ subunits), GPCR kinases and arrestins for signal termination, and scaffolds that couple to cytoskeletal regulators. Such assemblies at the plasma membrane would coordinate signal-dependent control of cell division machinery.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8NHC5.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8NHC5"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8NHC5/entry","atlas":"/p/Q8NHC5"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}