EFCAB13

Model 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.

Predicted Gene Ontology terms

1. 01

   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.

2. 02

   From 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.

3. 03

   The 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.

4. 04

   Mechanistically, 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.

5. 05

   Given 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.