Nuclear pore complex protein Nup358 (NUP358 (also known as RANBP2))

Nuclear pore complex protein Nup358 (NUP358, also known as RAN binding protein 2 or RANBP2) is a large, multifunctional nucleoporin that forms part of the cytoplasmic filaments of the nuclear pore complex (NPC)[1][2][7]. It acts as a scaffold for the assembly of protein interactions essential for nucleocytoplasmic transport, particularly influencing shuttling of proteins, RNAs, and ribonucleoprotein complexes between the nucleus and cytoplasm[1][4]. Nup358 contains multiple distinct domains, including Ran-binding domains, an E3 SUMO-protein ligase domain that facilitates SUMOylation, and interfaces for karyopherins, importins, and exportins[3][7]. Its functions extend to regulation of mRNA export and translation, mitotic spindle formation, and the cellular stress response[1][2][4]. Clinically, NUP358 is linked to acute necrotizing encephalopathy 1 (ANE1/ADNE1), carcinogenesis, aneuploidy, and photoreceptor neuroprotection[1][2]. Mutations or dysfunction in Nup358 disrupt nucleocytoplasmic trafficking and cellular homeostasis, and it is targeted by some viral pathogens[4]. No approved drugs directly target NUP358, but it remains a research focus for therapies aimed at modulating nuclear transport and post-translational modification pathways.

Other names

RAN binding protein 2RANBP2NUP358E3 SUMO-protein ligase RanBP2358 kDa nucleoporinNucleoporin Nup358Acute necrotizing encephalopathy 1 (autosomal dominant) (ANE1)ADANEp270Transformation-related protein 2TRP1, TRP2IIAE3

For hypothetical drugs targeting NUP358/RANBP2: Inhibition of protein-protein interactions (blocking nuclear transport factors binding); Modulation of SUMOylation processes (affecting SUMO conjugation via E3 ligase domain); Interference with nucleocytoplasmic trafficking; Stabilization or disruption of nuclear pore complex architecture.