InterPro domain: IPR037665

This entry represents nucleoporins, of which the precursors of some undergo autolytic processing. Some nucleoporins are synthesized as precursors, and each of these processes itself to release two large fragments that are both nucleoporins. Cleavage is dependent upon a His/Ser catalytic dyad, and cleavage occurs at the N-terminal side of the catalytic Ser. This means that the nucleoporin precursors are N-terminal nucleophile (NTN) hydrolases, but are structurally unrelated to other NTN hydrolases which are also peptidases, such as proteosome components. Autoprocessing nucleoporin precursors are members of peptidase family S59. The precursor Nup98-Nup96 (also known as nucleoporin 145 in Saccharomyces cerevisiae and Nup189 in Schizosaccharomyces pombe) processes itself to release Nup98 and Nup96 [ 1 , 2 , 3 ]. Nucleoporins Nup98 and Nup96 are components of the nuclear pore complex (NPC), which is the only means by which macromolecules enter and exit the nucleus. Other nucleoporins in family S59 are not synthesized as precursors and do not undergo autoprocessing, such as Nup100 (from Saccharomyces cerevisiae). Nup100 is also a component of the NPC and binds the karyopherin transport factor Kap95 at its repetitive tetrapeptide glycine-leucine-phenylalanine-glycine (GLFG) motifs [ 4 ].

1. The three-dimensional structure of the autoproteolytic, nuclear pore-targeting domain of the human nucleoporin Nup98. Mol. Cell 10, 347-58
2. NUP145 encodes a novel yeast glycine-leucine-phenylalanine-glycine (GLFG) nucleoporin required for nuclear envelope structure. J. Cell Biol. 125, 955-69
3. Uncleavable Nup98-Nup96 is functional in the fission yeast Schizosaccharomyces pombe. FEBS Open Bio 5, 508-14
4. The GLFG regions of Nup116p and Nup100p serve as binding sites for both Kap95p and Mex67p at the nuclear pore complex. J. Biol. Chem. 276, 6445-52