CEP126

Model summary

A large human centrosomal scaffold that organizes microtubule-based structures by assembling multiprotein complexes required for spindle formation and faithful chromosome segregation. It concentrates at the centrosome and transiently at the midbody, while also seeding the ciliary base to initiate axoneme assembly. Through extensive multivalent binding, it coordinates cytoplasmic microtubule architecture and couples mitotic spindle organization with ciliogenesis, thereby integrating cell division and cilium assembly pathways.

Predicted Gene Ontology terms

1. 01

   I begin with the InterPro architecture: IPR028257 (Centrosomal protein of 126 kDa family) spans residues 1–1110 and blankets the entire polypeptide.

   A full-length family signature without embedded catalytic domains indicates a large, non-enzymatic scaffold specialized for centrosomal and ciliary biology. Such extended coiled-coil–rich scaffolds typically mediate multivalent assemblies rather than catalysis, which causally supports a primary molecular function of protein binding (GO:0005515).

2. 02

   A centrosome/cilium-tuned scaffold naturally organizes microtubule-based structures.

   By concentrating binding interfaces along its length, this architecture nucleates and stabilizes assemblies that shape spindle microtubules and centriole-associated modules. That scaffolding role drives cytoplasmic microtubule organization (GO:0031122) and directly supports mitotic spindle organization (GO:0007052), ensuring robust spindle geometry and fidelity of chromosome segregation. The same architectural logic extends to ciliogenesis: centrosome-derived scaffolds at the mother centriole and distal appendages seed the ciliary base, thereby promoting cilium assembly (GO:0060271).

3. 03

   The spatial footprint of this scaffold follows from its family identity.

   Its steady-state residence is the centrosome (GO:0005813), where it coordinates microtubule arrays and interfaces with pericentriolar material. During cytokinesis, centrosome-associated scaffolds transiently concentrate at the midbody (GO:0030496), consistent with a role in late mitotic architecture. In differentiated or ciliated states, the same assembly machinery localizes to the ciliary base (GO:0097546), where it seeds axoneme formation and gating structures. Together, these localizations explain the observed cytoplasmic/cytoskeletal distribution and the dynamic relocalization across the cell cycle.

4. 04

   Mechanistically, I hypothesize that this scaffold forms a hub that recruits and positions centriole and cilium modules.

   At the centrosome and midbody, it likely binds pericentriolar organizers and spindle effectors to choreograph microtubule minus-end anchoring and midzone maturation. At the ciliary base, it plausibly couples distal appendage complexes to intraflagellar transport initiation, thereby switching the centrosome into a ciliogenesis-competent state. Candidate partners include pericentriolar and distal appendage proteins (e.g., PCM1, CEP135/CEP152), centriole duplication factors (CEP55), spindle organizers (ASPM, NuMA1), and cytokinesis/midbody organizers (PRC1, KIF23/MKLP1). These interactions would collectively explain how a single scaffold sustains both mitotic and ciliary programs through modular protein binding.