KIF3AB

KIF3AB refers to the heterodimeric kinesin-2 motor complex composed of the kinesin heavy chain subunits KIF3A and KIF3B. While KIF3A (chromosome 3q22.3) and KIF3B (chromosome 19p13.2) are encoded by distinct genes, the functional motor that carries out microtubule-based trafficking in many vertebrate cells contains both subunits. The two proteins associate through their coiled‑coil stalks to form a stable dimer that includes the motor domain at the N‑terminus, a γ‑tubulin‑binding domain, and a cargo‑binding tail region. The HSP90 cochaperone Tetherin facilitates dimerization and stabilization of KIF3AB in the cytosol.

KIF3AB is a processive plus‑end directed motor that moves along microtubules using ATP hydrolysis. It functions predominantly in intraflagellar transport, especially the anterograde movement of cargo into primary cilia, and is required for ciliogenesis in numerous cell types. In nonciliated cells, KIF3AB participates in vesicle trafficking, cell migration, and centrosomal organization. Loss‑of‑function studies in mice and zebrafish reveal developmental defects such as impaired left‑right axis specification and skeletal abnormalities, underscoring its importance in signaling pathways mediated by ciliary function.

Expression of KIF3A and KIF3B is widespread, with highest levels in neurons, kidney epithelium, and craniofacial tissues. Their mRNA transcripts show similar half‑lives, but post‑translational regulation of the dimer complex includes phosphorylation by 14‑3‑3 proteins that modulates cargo selection. Current literature describes a regulatory interplay between KIF3AB and other kinesin‑2 motors, such as KIF17, suggesting a coordinated network for organelle trafficking. Future studies are exploring how alterations in KIF3AB activity contribute to ciliopathies and cancer progression.