{"uniprot":"Q9BU20","gene":"CPLANE2","name":"Ciliogenesis and planar polarity effector 2","organism":"Homo sapiens (Human)","status":"dark","length":258,"sequence":"MARPPVPGSVVVPNWHESAEGKEYLACILRKNRRRVFGLLERPVLLPPVSIDTASYKIFVSGKSGVGKTALVAKLAGLEVPVVHHETTGIQTTVVFWPAKLQASSRVVMFRFEFWDCGESALKKFDHMLLACMENTDAFLFLFSFTDRASFEDLPGQLARIAGEAPGVVRMVIGSKFDQYMHTDVPERDLTAFRQAWELPLLRVKSVPGRRLADGRTLDGRAGLADVAHILNGLAEQLWHQDQVAAGLLPNPPESAPE","function_summary":"A centrosome- and centriole-anchored small GTPase that orchestrates ciliogenesis and planar polarity by switching between GTP- and GDP-bound states to assemble trafficking and gating complexes at the ciliary base and transition zone. By coupling vesicle supply from the Golgi and endosomes to axoneme–membrane coupling, it promotes cilium assembly while restricting inappropriate cargo entry into the cilium. Through this trafficking checkpoint, it indirectly tunes cell–matrix adhesion and broader surface delivery pathways via regulated protein–protein interactions.","plain_language":"CPLANE2 has barely been studied. The model's best guess: A centrosome- and centriole-anchored small GTPase that orchestrates ciliogenesis and planar polarity by switching between GTP- and GDP-bound states to assemble trafficking and gating complexes at the ciliary base and transition zone. By coupling vesicle supply from the Golgi and endosomes to axoneme–membrane coupling, it promotes cilium assembly while restricting inappropriate cargo entry into the cilium.","uniprot_summary":"Involved in ciliogenesis.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"},{"id":"GO:0005525","label":"GTP binding"},{"id":"GO:0003924","label":"GTPase activity"}],"biological_process":[{"id":"GO:1903828","label":"negative regulation of protein localization"},{"id":"GO:0007160","label":"cell-matrix adhesion"},{"id":"GO:0043001","label":"Golgi to plasma membrane protein transport"},{"id":"GO:0060271","label":"cilium assembly"}],"cellular_component":[{"id":"GO:0097546","label":"ciliary base"},{"id":"GO:0035869","label":"ciliary transition zone"},{"id":"GO:0005814","label":"centriole"}]},"interpro":[{"id":"IPR027417","name":"P-loop containing nucleoside triphosphate hydrolase","type":"homologous_superfamily","start":51,"end":215},{"id":"IPR039677","name":"Ciliogenesis and planar polarity effector 2","type":"family","start":1,"end":254},{"id":"IPR001806","name":"Small GTPase","type":"family","start":57,"end":200}],"reasoning":"I begin with the InterPro architecture. The sequence is encompassed by IPR039677 (Ciliogenesis and planar polarity effector 2 family, residues 1–254), which frames the entire polypeptide as a member of a ciliogenesis/planar polarity module. Nested within this scaffold, IPR027417 (P-loop containing nucleoside triphosphate hydrolase homologous superfamily, residues 51–215) and IPR001806 (Small GTPase family, residues 57–200) define a canonical small GTPase core. The ordered layout—an N-terminal family-defining envelope that houses a central P-loop NTPase engine and a small GTPase fold—causes nucleotide-dependent switching behavior. This architecture dictates high-affinity GTP binding and regulated hydrolysis, which in turn drives assembly of transient effector complexes. Consequently, the molecular functions deduced are GTP binding (GO:0005525), GTPase activity (GO:0003924), and multivalent protein binding (GO:0005515) mediated by switch-region-dependent interactions.\n\nA small GTPase switch localized to the ciliogenesis pathway will control membrane–cytoskeleton interfaces that build and gate the cilium. The family assignment to a ciliogenesis/planar polarity effector positions the protein upstream of axoneme extension and membrane docking, aligning with cilium assembly (GO:0060271). The GTPase-driven assembly of trafficking modules at the Golgi–endosome interface explains Golgi to plasma membrane protein transport (GO:0043001): by coupling GTP-dependent effector binding to vesicle formation and targeting, the protein promotes forward trafficking toward the cell surface and ciliary membrane sources. Its role in restricting entry of membrane proteins into the cilium follows directly from a switch that organizes the ciliary base and transition zone, thereby exerting negative regulation of protein localization to cilium (GO:1903828). Because ciliary membrane composition feeds back on integrin and ECM signaling, this trafficking checkpoint propagates to cell-matrix adhesion (GO:0007160), where altered receptor delivery modulates adhesion dynamics.\n\nCellular placement is dictated by the need to coordinate membrane delivery with axonemal gating. The ciliogenesis effector family signature and the small GTPase core together target the microtubule-organizing center and its satellite structures. This predicts residence at the centriole (GO:0005814), the foundation of the basal body, and at the ciliary base (GO:0097546) and ciliary transition zone (GO:0035869), where membrane–axoneme coupling is established and regulated. The experimentally observed centrosomal and centriolar localization are a direct consequence of this assembly logic.\n\nMechanistically, the protein operates as a nucleotide-gated organizer. In its GTP-bound state, it recruits effectors that steer vesicle supply and cargo selection at the Golgi–endosome–cilium axis; GTP hydrolysis then triggers complex disassembly, enforcing a selective barrier at the transition zone. This switch likely interfaces with intraflagellar transport adaptors and membrane-tethering modules to both supply and gate ciliary components. I therefore hypothesize interactions with transition zone scaffolds (e.g., CEP290 and MKS/NPHP modules), basal body organizers (CEP135/CEP164), and Golgi/endosomal trafficking hubs (Rab8/Rab11 pathways and exocyst). Together, these contacts would couple vesicle delivery to the centriole/basal body with the initiation and quality control of cilium assembly and with broader adhesion signaling.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q9BU20.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q9BU20"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q9BU20/entry","atlas":"/p/Q9BU20"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}