FBXL13

FBXL13 (F-box and leucine-rich repeat protein 13; also Dynein regulatory complex subunit 6, DRC6) is a multi-domain protein with an N-terminal region, an F-box domain, and an extensive C-terminal leucine-rich repeat (LRR) array. It has two distinct, tissue-dependent roles. As an SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase substrate-recognition subunit, FBXL13 docks onto SKP1/CUL1 through its F-box domain and uses its LRRs to recruit substrates; it localizes to the centrosome (diffusely cytoplasmic with clear centrosomal enrichment), where it binds centrosomal proteins (Centrin-2, Centrin-3 via its N-terminus, CEP152, and CEP192 via its C-terminal region) and specifically targets CEP192 (notably the CEP192 isoform 3) for SCF/F-box-dependent polyubiquitination and proteasomal degradation, binding the N-terminal region of CEP192; the bound Centrins are not detectably degraded. By fine-tuning CEP192 abundance it downregulates centrosomal gamma-tubulin recruitment, modulates microtubule nucleation/regrowth, restrains centrosome overduplication, and promotes cell migration. Independently, in motile cilia and flagella FBXL13/DRC6 is a structural component of the nexin-dynein regulatory complex (N-DRC), a regulator of axonemal dynein activity and ciliary/flagellar beating; within the N-DRC its lysine-rich C-terminus contributes to the electrostatic distal link between neighbouring doublet microtubules. The ciliary role is less firmly established functionally: in mice Fbxl13/Drc6 knockouts show normal spermatogenesis, sperm morphology and motility and normal tracheal multicilia, suggesting the N-DRC role is dispensable or redundant under tested conditions. It is expressed broadly with enrichment in testis and stomach and in ciliated tissues.