Family S59
Summary for family S59
Family type peptidase | S59.001 - nucleoporin 145 (Homo sapiens), MEROPS Accession MER0020203 (peptidase unit: 710-937) |
Content of family | Family 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 type | Serine |
Active site residues | H879 S881 |
Active site | A 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 specificities | The 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 structure | In 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). |
Clan | SP |
Biological functions | Autolytic 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 S59 | Sequences: | 1200 |
| Identifiers: | 11 |
| Identifiers with PDB entries: | 6 |
Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
Peptidases and Homologues |
MEROPS ID |
Structure |
nucleoporin 145 | S59.001 | Yes |
nuclear pore complex component Nup145 (Saccharomyces-type) | S59.002 | Yes |
nup 36 protein | S59.951 | Yes |
Nup100p (Saccharomyces cerevisiae) | S59.952 | Yes |
At1g80680 (Arabidopsis thaliana) | S59.A01 | - |
At1g10390 (Arabidopsis thaliana)-type peptidase | S59.A02 | - |
At1g59660 (Arabidopsis thaliana) | S59.A03 | - |
nucleoporin 98, isoform A (Drosophila melanogaster) | S59.A04 | - |
NPP-10 (Caenorhabditis elegans) | S59.A06 | - |
nup189 (Schizosaccharomyces pombe) | S59.A07 | Yes |
nup98 g.p. (Dictyostelium discoideum) | S59.A08 | - |
Family S59 non-peptidase homologues | non-peptidase homologue | - |
Family S59 unassigned peptidases | unassigned | Yes |