{"uniprot":"Q8IY85","gene":"EFCAB13","name":"EF-hand calcium-binding domain-containing protein 13","organism":"Homo sapiens (Human)","status":"dark","length":973,"sequence":"METKVHLFCQAEENIDLLDDGSNSFATDLSSGTINHKKYIKFSKTIEKEISPEIRSLSPEYKKIFETSIIFCGEEKSSDFSGEKKVGRKSLQVQQHSKRTEIIPPFLKLSKEKVTRKENSLCKLPNQYSVHKTSSPLCTSSAITREKEMLSNLYMTLYDEVTHGYLHSKELSALHKACKIFSKIRSGKIYVNDLPVILCILRISISDLEMRQALKTVDIDAFQDALKIFCRIKGGRVSTDDVFAVLDSMGIPINREILEEVTKHTYIDSNHMVDIGDIIFTLNELQEQYEDVSITEGSPLNEITSDRKLSSVAGCYLKYKKKNSLSSKLPEPSISKKLNKKSNQYYSKIMENDDLESKRPKNTWQIRKFLGGVGSSNVGVQEPYSKNGINFKKHSEKGEIHDSKSKPQSLKSSTSLSKSLDKSDISSIPKLQKPAVRKHSSLQKQVSSTEKTAISTLENFCEAISKLQENYIAAEELQSILPSTGINLLDEEFQKIVTDTSRNENGMVELDDFVNALAKERSFPECNALPGVIKAIDKIKDKNVDYEDLNTCLQNFGIYLSKPEFKKITELTEAGETKKVNFKEFIDTMMSNTECFSEKLVLPDAIETLDDLRKETMSVSDLWNTLSSLNSNLKKDEFLAALELVTVDEGDKVQFEEFAKVVRNMRDAARLEELQEVVLAADLLEGDMIAGKNLEDFLRNVGIKSPKEEVEKILQSDFVSEDNMVNIKDCMRALRDTQKFSNYIDFRKEASNLKLPKVNEIKEAANILSHVDNGKIGIPDLEHALKCLNVNLTEEDFNEALNCCNVSDNMEVDLKDFLMKMKESPHFQKSKATQILLATTQILQNDLVDVSDLKTLLMDKDLHTANAILTVMLRHVPEHESGKVSIQEFMTKLSDILTIPKAAGKFYLICTYCPDLERQAVVYMLKTIQDSIVKAQVSKKQYNMNIKQHKISLHNFCLNSKANIAKLNPNSKF","function_summary":"A calcium-regulated cytoplasmic scaffold that associates with the intermediate filament network and coordinates cytoskeletal assemblies tied to cell-cycle transitions and cilium biogenesis. Multiple EF-hand modules tune protein–protein interactions in response to calcium, enabling the assembly and remodeling of complexes that operate at the G1/S and G2/M stages and interface with centrosome- and cilium-related pathways. Its filament-associated positioning provides a spatial hub that concentrates signaling and assembly factors during these transitions.","plain_language":"EFCAB13 has barely been studied. The model's best guess: A calcium-regulated cytoplasmic scaffold that associates with the intermediate filament network and coordinates cytoskeletal assemblies tied to cell-cycle transitions and cilium biogenesis. Multiple EF-hand modules tune protein–protein interactions in response to calcium, enabling the assembly and remodeling of complexes that operate at the G1/S and G2/M stages and interface with centrosome- and cilium-related pathways.","uniprot_summary":"May function in the G1/S and G2/M transitions of the mitotic cycle.","go_terms":{"molecular_function":[{"id":"GO:0005515","label":"protein binding"}],"biological_process":[{"id":"GO:0060271","label":"cilium assembly"}],"cellular_component":[{"id":"GO:0045111","label":"intermediate filament cytoskeleton"}]},"interpro":[{"id":"IPR011992","name":"EF-hand domain pair","type":"homologous_superfamily","start":165,"end":283},{"id":"IPR011992","name":"EF-hand domain pair","type":"homologous_superfamily","start":430,"end":599},{"id":"IPR011992","name":"EF-hand domain pair","type":"homologous_superfamily","start":600,"end":899}],"reasoning":"I begin with the InterPro architecture. Three EF-hand domain-pair signatures are present and spaced modularly along the polypeptide: IPR011992 (EF-hand domain pair, homologous_superfamily) occurs at residues 165–283, then again at 430–599, and once more at 600–899. EF-hand pairs form helix–loop–helix calcium-binding modules that undergo Ca2+-triggered conformational changes. The presence of multiple EF-hand pairs in tandem creates a calcium-regulated scaffold: Ca2+ binding stabilizes or exposes hydrophobic surfaces that mediate multivalent protein–protein interactions. This architecture causally supports a molecular function centered on protein binding (GO:0005515), with binding affinity and specificity tuned by calcium occupancy.\n\nFrom this calcium-responsive scaffold, I infer how the protein operates in cell-cycle–linked cytoskeletal control. Calcium-modulated scaffolds often coordinate microtubule- and filament-associated assemblies that time spindle formation and centrosome function. The stated role in the G1/S and G2/M transitions of mitosis aligns with a scaffold that organizes factors for cilium assembly (GO:0060271 cilium assembly) and coordinates with centrosome-derived structures. The cilium and centrosome share evolutionary and functional ties with the microtubule network; thus, a calcium-tuned binding platform can couple cilium biogenesis to cell-cycle checkpoints.\n\nThe cellular context is clarified by the localization terms. The protein is a component of the intermediate filament cytoskeleton (GO:0045111), which provides a structural and signaling hub that interfaces with microtubules and membrane-associated assemblies. A cytoplasm–cytoskeleton distribution is expected for a calcium-regulated scaffold that coordinates both filament systems and spindle-associated processes. Therefore, I place the protein in the cytoplasm and along intermediate filament arrays that anchor and communicate with centrosomal and ciliary machinery.\n\nMechanistically, I propose that Ca2+ binding at the EF-hand pairs (165–283, 430–599, 600–899) induces conformational states that switch the scaffold between low- and high-affinity complexes. During G1/S, this switching promotes assembly of ciliogenesis modules; during G2/M, it retunes interactions to support centrosome- and spindle-associated networks. The intermediate filament association provides a spatial framework that concentrates signaling and assembly factors.\n\nGiven this model, I hypothesize interaction partners that match the inferred functions and locales. Intermediate filament constituents (such as vimentin and neurofilaments) likely bind directly to the filament-associated state. At the ciliary interface, intraflagellar transport components and transition-zone adaptors are plausible partners. During mitosis and centrosome coupling, microtubule-associated proteins and cell-cycle regulators could transiently dock via the calcium-tuned EF-hand surfaces. Together, these interactions would allow the scaffold to choreograph cilium assembly and cell-cycle transitions from a filament-rich cytoplasmic platform.","category":"dark","control_evaluation":null,"validation_plan":null,"structure":{"source":"AlphaFold DB","pdb":"/structures/AF-Q8IY85.pdb","alphafold":"https://alphafold.ebi.ac.uk/entry/Q8IY85"},"links":{"uniprot":"https://www.uniprot.org/uniprotkb/Q8IY85/entry","atlas":"/p/Q8IY85"},"provenance":{"model":"BioReason-Pro (ESM3 esm3-sm-open-v1)","source_list":"Pharos Tdark","note":"AI prediction, not experimentally verified"}}