Alternative titles; symbols
HGNC Approved Gene Symbol: SENP5
Cytogenetic location: 3q29 Genomic coordinates (GRCh38) : 3:196,867,920-196,934,714 (from NCBI)
The reversible posttranslational modification of proteins by the addition of small ubiquitin-like SUMO proteins (see SUMO1; 601912) is required for numerous biologic processes. SUMO-specific proteases, such as SENP5, are responsible for the initial processing of SUMO precursors to generate a C-terminal diglycine motif required for the conjugation reaction. They also have isopeptidase activity for the removal of SUMO from high molecular mass SUMO conjugates (Di Bacco et al., 2006).
By searching databases using SENP1 (612157) as query, followed by 5-prime RACE of a placenta cDNA library, Gong and Yeh (2006) cloned full-length SENP5. The deduced 755-amino acid protein contains a C-terminal catalytic domain. SENP5 shares highest similarity with SENP3 (612844), including 62% amino acid identity in the catalytic domain and 40% identity in the region preceding the catalytic domain. Gong and Yeh (2006) identified SENP5 orthologs in several mammalian species, but not in fish, worm, fly, or yeast. Western blot analysis detected SENP5 at an apparent molecular mass of 87 kD in human cell lines. Endogenous and epitope-tagged SENP5 localized primarily to the nucleolus, but also to the nucleus, in HeLa cells. Endogenous SENP5 colocalized with nucleophosmin (NPM1; 164040) in HeLa cell nucleoli.
Di Bacco et al. (2006) stated that the C-terminal catalytic domain of SENP5 includes the catalytic triad of his, asp, and cys.
Gong and Yeh (2006) found that recombinant SENP5 showed C-terminal hydrolase activity for the activation of SUMO3 (602231), but not SUMO1. SENP5 could remove SUMO from in vitro-translated RANGAP1 (602362), but its activity was much lower than that of SENP1. In vivo, SENP5 could cleave both SUMO2 (603042) and SUMO3 conjugates, and this isopeptidase activity required cys713 within the catalytic domain of SENP5. SENP5 could not process ubiquitin (see 191339) or NEDD8 (603171) conjugates. Truncation analysis revealed that an N-terminal sequence of SENP5 directed nucleolar localization. N-terminally truncated SENP5, but not full-length SENP5, colocalized with PML in HeLa cell nuclei. PML can be modified by SUMO1, SUMO2, and SUMO3 on lys65, lys160, and lys490. SENP5 removed SUMO2 and SUMO3 from all of 3 target lysines in PML, but it only removed SUMO1 when it was conjugated on lys65.
Di Bacco et al. (2006) showed that the recombinant C-terminal catalytic domain of human SENP5 displayed C-terminal hydrolase activity toward SUMO1, SUMO2, and SUMO3. SENP5 also showed isopeptidase activity and desumoylated SUMO-modified RANGAP1, with highest activity toward SUMO2 and SUMO3. In cotransfection assays, SENP5 preferentially reduced high molecular mass conjugates of SUMO2 compared with SUMO1. Deletion of the noncatalytic N-terminal domain of SENP5 led to loss of nucleolar localization and increased desumoylation activity. Knockdown of SENP5 in HeLa cells increased the number of multinucleated cells and the number of cells with aberrant nuclear structure, consistent with defects in mitosis and cytokinesis.
Yun et al. (2008) found that SENP3 and SENP5 colocalized with nucleophosmin, a protein involved in ribosome biogenesis, within the granular component of the nucleolus. Codepletion of SENP3 and SENP5 in HeLa cells via RNA interference (RNAi), but not depletion of either SENP alone, increased the nucleolar content of SUMO1, SUMO2, and SUMO3. Depletion of SENP3 alone inhibited production of 28S rRNA from the 32S precursor RNA, whereas depletion of SENP5 alone reduced 47S transcription. RNAi-mediated depletion of nucleophosmin reduced SENP3 and SENP5 levels, likely via increased degradation rather than decreased expression. Codepletion of SENP3 and SENP5 or depletion of nucleophosmin resulted in accumulation of sumoylated RPL37A and GNL2 (609365) proteins within nucleoli. Xenopus Senp5, which is highly similar to human SENP5, bound nucleophosmin in Xenopus oocyte extracts. Yun et al. (2008) concluded that sumoylation of nucleolar proteins by SENP3 and SENP5 is involved in the control of ribosome biogenesis.
Gong and Yeh (2006) determined that the SENP5 gene contains 9 exons and spans about 39 kb. Exon 1 is noncoding.
By genomic sequence analysis, Gong and Yeh (2006) mapped the SENP5 gene to chromosome 3.
Di Bacco, A., Ouyang, J., Lee, H.-Y., Catic, A., Ploegh, H., Gill, G. The SUMO-specific protease SENP5 is required for cell division. Molec. Cell. Biol. 26: 4489-4498, 2006. [PubMed: 16738315] [Full Text: https://doi.org/10.1128/MCB.02301-05]
Gong, L., Yeh, E. T. H. Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3. J. Biol. Chem. 281: 15869-15877, 2006. [PubMed: 16608850] [Full Text: https://doi.org/10.1074/jbc.M511658200]
Yun, C., Wang, Y., Mukhopadhyay, D., Backlund, P., Kolli, N., Yergey, A., Wilkinson, K. D., Dasso, M. Nucleolar protein B23/nucleophosmin regulates the vertebrate SUMO pathway through SENP3 and SENP5 proteases. J. Cell Biol. 183: 589-595, 2008. [PubMed: 19015314] [Full Text: https://doi.org/10.1083/jcb.200807185]