Family S59

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

Summary for family S59

Family type peptidaseS59.001 - nucleoporin 145 (Homo sapiens), MEROPS Accession MER0020203 (peptidase unit: 710-937)
Content of familyFamily S59 contains an autolytic endopeptidase.
History Identifier created: MEROPS 6.4 (24 September 2003)
The nuclear pore is a complex of about fifty proteins that is important for the export of RNA molecules from the nucleus to the cytoplasm (Fontoura et al., 1999). One of the components of the nuclear pore is synthesized as a precursor which is autolytically processed. The precursor with endopeptidase activity (S59.001) is known as nucleoporin 145 in Saccharomyces cerevisiae.
Catalytic typeSerine
Active site residuesH879 S881 
Active siteA catalytic dyad was identified from the crystal structure (Hodel et al., 2002) and consists of a histidine and a serine within the motif HisPheSer (see the Alignment).
Activities and specificitiesThe only proteolysis performed is an autolytic reaction that cleaves the 186-kDa precursor into two components, known as Nup98 and Nup96 in human and mouse, or N-Nup145p and C-Nup145p in yeast (Fontoura et al., 1999). Cleavage occurs at the PheSer bond within the active site motif (Rosenblum & Blobel, 1999).
Molecular structureIn mammals, there are at least two alternatively spliced forms of the peptidase and both undergo autolytic cleavage. The cleaved products remain associated as either a Nup98-6kDa or a Nup98-Nup96 heterodimer (Fontoura et al., 2001). The tertiary structure of Nup98 is unlike that of any other protein (Hodel et al., 2002). Despite the fact that after cleavage the active site serine is at the new N-terminus, there is no structural relationship to N-terminal nucleophile hydrolases (clan PB). In the yeast Nup145 precursor, the peptidase unit is within the N-terminal half of the molecule, whereas in the mammalian Nup98 precursor it is the C-terminal domain. A second domain contains Gly-Leu-Phe-Gly repeats and is important for associating with the GLFG body in the nucleus (Fontoura et al., 1999).
ClanSP
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsAutolytic processing to generate Nup98 and Nup96 is essential for correct targeting of these components to the nucleoplasmic side of the nuclear pore complex and for correct formation of the nuclear pore. In NUP98 gene knockouts, cytoplasmically orientated nucleoporins were unable to assemble efficiently into nuclear pores, whereas nucleoplasmically orientated nucleoporins assembled normally (Wu et al., 2001). The cleavage product Nup98 is mobile and associates not only with the nuclear pore but also with the TPR (translocated promoter region) network that forms filaments between the nuclear pore and the nucleolus (Fontoura et al., 2001) and with the GLFG body within the nucleus (et al., 2002[20040510D611]>). Nup98 has also been shown to be essential for gastrulation in the mouse (Wu et al., 2001).
Statistics for family S59Sequences:1336
Identifiers:11
Identifiers with PDB entries:4
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
nucleoporin 145S59.001Yes
nuclear pore complex component Nup145 (Saccharomyces-type)S59.002Yes
nup 36 proteinS59.951Yes
At1g80680 (Arabidopsis thaliana)S59.A01-
At1g10390 (Arabidopsis thaliana)-type peptidaseS59.A02-
At1g59660 (Arabidopsis thaliana)S59.A03-
nucleoporin 98, isoform A (Drosophila melanogaster)S59.A04-
NPP-10 (Caenorhabditis elegans)S59.A06-
nup189 (Schizosaccharomyces pombe)S59.A07Yes
nup98 g.p. (Dictyostelium discoideum)S59.A08-
Nup100p (Saccharomyces cerevisiae)S59.A09-
family S59 non-peptidase homologuesnon-peptidase homologue-
family S59 unassigned peptidasesunassigned-