XMog1, a nuclear Ran-binding protein in Xenopus, is a functional homologueof Schizosaccharomyces pombe Mog1p that co-operates with RanBP1 to controlgeneration of Ran-GTP

Ran is a multifunctional small GTPase of the Ras superfamily that plays rol es in nucleocytoplasmic transport, mitotic spindle assembly and nuclear env elope formation. By screening a Xenopus oocyte cDNA library for Ran-GTP-bin ding proteins using the two-hybrid system of co-expression in yeast, we ide ntified XMog1, a 20.4 kDa polypeptide related to Mog1p in Saccharomyces cer evisiae and similar gene products in Schizosaccharomyces pombe, Arabidopsis and mammals. We show that cDNAs encoding XMog1 and S. cerevisiae Mog1p res cue the growth defect of S. pombe cells lacking mog1, demonstrating conserv ation of their functions. In Xenopus somatic cells and transfected mammalia n cells, XMog1 is localised to the nucleus. XMog1 alone does not stimulate Ran GTPase activity or nucleotide exchange, but causes nucleotide release f rom Ran-GTP and forms a complex with nucleotide-free Ran. However, in combi nation with Ran-binding protein 1 (RanBP1), XMog1 promotes the release of G DP and the selective binding of GTP to Ran. XMog1 and RanBP1 also promote s elective GTP loading onto Ran catalysed by the nuclear guanine nucleotide e xchange factor, RCC1. We propose that Mog1-related proteins, together with RanBP1, facilitate the generation of Ran-GTP from Ran-GDP in the nucleus.