Exportin-4 (XPO4)

Exportin-4 (XPO4) is a member of the karyopherin nuclear transport receptor family that allows bidirectional shuttling of proteins and specific circular RNAs across the nuclear envelope[1][2][3][4]. It binds cargoes such as eIF5A, Smad3, PKM2, and SOX transcription factors, recognizing distinctive protein features such as the hypusine modification of eIF5A. Its activity is RanGTP-dependent and involves interaction with nuclear pore complex proteins. Besides protein export, XPO4 plays a critical role in the export of exonic circular RNAs (ecircRNAs) in metazoans, with deficiency causing nuclear circRNA accumulation, R-loop formation, DNA damage, and tissue dysfunction[4]. XPO4 also acts as a chaperone-like molecule, suppressing off-target nuclear interactions and regulating transcriptional activity. Dysfunction is linked to cancer, male infertility, and DNA damage syndromes. Therapeutic modulation presents challenges due to its broad cargo spectrum and essential cell viability roles.

Other names

Exportin 4KIAA1721Exp4FLJ13046xpo4exportin-4XPO4

Drugs targeting exportins generally block nuclear export or modulate nuclear/cytoplasmic shuttling, leading to altered protein localization and function. (No direct XPO4-targeted drugs; mechanism extrapolated from related exportins.)