FBXO47

FBXO47 (F-box only protein 47) is a 452-residue F-box-domain-containing protein (F-box at residues 41-91, plus an FBXO47-specific armadillo-like region) belonging to the FBXO ("F-box only") subfamily of F-box proteins, which canonically act as substrate-recognition receptors that, together with SKP1, CUL1 and RBX1, assemble SCF (SKP1-cullin-F-box) E3 ubiquitin ligase complexes. FBXO47 is strongly enriched in testis (HPA testis-enriched; expressed in male germline cells) and was originally cloned from a testis library. Functional studies in mouse have established FBXO47 as a germ-cell protein essential for meiotic prophase I in spermatocytes: Fbxo47-null males are infertile with spermatocytes arresting around late zygotene/pachytene, showing incomplete homologous synapsis, persistent autosomal gamma-H2AX, and failure to form XY bodies. Mechanistically, FBXO47 acts at meiotic chromosome subcompartments through SKP1-associated regulation: it localizes to the nuclear periphery and co-localizes with the shelterin component TRF2, where it promotes telomere-inner nuclear membrane attachment by stabilizing TRF2 (impairing TRF2 ubiquitination) during the bouquet stage; FBXO47 also interacts with SKP1 and the axis protein HORMAD1, contributing to HORMAD1 turnover and meiotic double-strand-break/ recombination homeostasis, and has been proposed to act in a centromeric SCF module that preserves centromeric SKP1 to support centromere pairing. Notably, several of its documented activities involve preventing rather than promoting substrate degradation (TRF2, SKP1), so its in vivo role may diverge from a classical SCF substrate receptor that drives degradation. A curated SCF E3 ligase complex variant containing FBXO47 has been recorded (ComplexPortal CPX-8006). FBXO47 maps to 17q12; human genetics associates the locus with azoospermia, and a missense variant has been reported as a candidate in autosomal recessive intellectual disability.