CAPS2

Model summary

A calcium-regulated adaptor that couples membrane lipids to the cytoskeleton. It uses a phosphoinositide-targeting module to dock at membrane-proximal cytoskeletal hubs and a paired calcium-sensing module to tune partner binding in response to intracellular calcium. This switchable scaffold assembles and modulates complexes that organize the mitotic spindle and drive cytokinesis, while also coordinating cytoskeletal remodeling that underlies neuronal progenitor and cortical cell migration. It concentrates at basal-body–associated structures and operates within the cytoplasm and cytoskeletal network.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture.

   The central region contains IPR057461 (Calcyphosin-2, PH domain, residues 290–386), followed by a calcium-sensing module: IPR011992 (EF-hand domain pair homologous superfamily, residues 410–538) and a more specific EF-hand call IPR002048 (EF-hand domain, residues 426–497). These calcium-binding motifs are encompassed by IPR051581 (Calcium-Binding Signalling family, residues 295–538), which frames the PH–EF-hand tandem as a calcium-regulated signaling scaffold. The ordered layout—an N-proximal PH domain that targets membranes and phosphoinositides, followed by a C-proximal EF-hand pair that binds Ca2+—creates a switchable adaptor. The PH domain anchors the protein to membrane-proximal cytoskeletal hubs, while Ca2+ occupancy of the EF-hands remodels affinity and partner selection. This architecture causes multivalent protein binding as the primary molecular function (GO:0005515), with calcium-tuned assembly of complexes rather than enzymatic catalysis.

2. 02

   From this molecular function, I infer roles in cell division and neurodevelopmental programs.

   Calcium-responsive scaffolds at membrane–cytoskeleton interfaces govern spindle assembly and cytokinesis by coordinating microtubule-organizing centers and cortical machinery. Such control maps directly onto mitotic spindle organization (GO:0007052) and mitotic cytokinesis (GO:0000281). In neural progenitors and migrating neurons, the same membrane-cytoskeleton coupling steers nucleokinesis and leading-process dynamics, aligning with cerebral cortex cell migration (GO:0021795). The EF-hand–PH tandem thus provides a mechanistic conduit from Ca2+ transients to cytoskeletal remodeling that underlies both mitosis and neuronal migration.

3. 03

   Cellular placement follows from the same logic.

   A PH domain biases localization to membrane-rich microtubule-organizing regions, and EF-hand–mediated interactions concentrate the scaffold at specialized cytoskeletal nodes. This explains accumulation at the ciliary basal body (GO:0036064), a cytoskeleton-associated organelle that seeds ciliogenesis and interfaces with signaling pathways. The broader subcellular distribution—cytoplasm and cytoskeleton—fits a soluble adaptor that transiently docks onto filament systems and membrane-associated hubs.

4. 04

   Mechanistically, I hypothesize that Ca2+ binding to the EF-hand pair triggers a conformational switch that exposes or masks PH-mediated lipid contacts and partner-binding surfaces.

   This switchable tether likely nucleates assemblies with microtubule- and membrane-associated proteins at basal bodies and division sites. Partners are expected to include tubulin and centrosomal scaffolds (e.g., γ-tubulin ring complex components), dynein–dynactin and kinesin motors for spindle mechanics, and phosphoinositide-binding adaptors that stabilize membrane–cytoskeleton junctions. Through these interactions, the protein coordinates calcium signals with spindle organization and cortical cell migration.