Family C97
Summary for family C97
| Family type peptidase | C97.001 - desumoylating isopeptidase 1 (Mus musculus), MEROPS Accession MER0187565 (peptidase unit: 1-168) |
| Content of family | Peptidase family C97 contains SUMO (small ubiquitin-like modifier) deconjugating enzymes. |
| History |
Identifier created: MEROPS 9.7 (1 August 2012)
SUMO proteins are a group of proteins similar to ubiquitin. However, unlike ubiquitinated proteins, sumoylated proteins do not tend to be degraded. Instead SUMOylation has been implicated in processes such as intracellular transport, transcription, DNA repair, replication and cell signalling. Peptidase family C97 is the second of three families of SUMO-specific peptidases to be described, the first being peptidase family C48 and the third C98 (Hickey et al., 2012). The members of C97 are isopeptidases that mediate the reversal of SUMOylation and are known collectively as deSUMOylases (Shin et al., 2012). |
| Catalytic type | Cysteine |
| Active site residues | H38 C108 |
| Active site | The active site residue Cys108 has been verified as the reaction nucleophile by site-directed mutagenesis (Shin et al., 2012). The active site residues His38 and Cys108 are absolutely conserved and form a catalytic dyad (Suh et al., 2012). |
| Activities and specificities | DeSI-1 (C97.001) and DeSI-2 (C97.002) can deconjugate SUMO proteins from their targets, however, they do not possess the SUMO-processing activity present in the mammalian SENPs of peptidase family C48. DeSI-1 is capable of desumoylating the transcriptional repressor, BZEL, but unable to desumoylate PML or Np63, two known substrates of SENP1 (C48.002)(Shin et al., 2012). |
| Molecular structure | The tertiary structure of DeSI-1 has been solved (Suh et al., 2012) and is the type structure for clan CP. DeSI-1 forms a homodimer. There is a prominent surface groove between the two monomers, with the active sites directed towards the groove. Surprisingly, the three families of deSUMOlatying peptidases are members of three different clans despite being the same catalytic type. |
| Clan | CP |
| Basis of clan assignment | Type family of clan CP. |
| Biological functions | Unlike SENPs, peptidase family C97 protein members have been found to localize in the cytoplasm. This suggests that they may be responsible for the deSUMOylation of cytoplasmic proteins that the nuclear-associated SENPs can not access (Shin et al., 2012). The repressor BZEL has been shown to be a substrate of DeSI-1. SUMOylated BZEL is a transcriptional repressor of the blimp-1 gene, which encodes a transcription factor important for the differentiation of many cell types including B cells of the immune system (John & Garrett-Sinha, 2009). The desumoylating activity of DeSI-1 on BZEL reduces its repressor activity, increasing downstream blimp-1 expression (Shin et al., 2012). |
| Reviews | Hickey et al., 2012 |
| Statistics for family C97 | Sequences: | 2368 |
| Identifiers: | 14 |
| Identifiers with PDB entries: | 1 |
| Downloadable files |
Sequence library (FastA format) |
| Sequence alignment (FastA format) |
| Phylogenetic tree (Newick format) |
| Peptidases and Homologues |
MEROPS ID |
Structure |
| desumoylating isopeptidase 1 | C97.001 | Yes |
| desumoylating isopeptidase 2 | C97.002 | - |
| DDB_0191673 protein (Dictyostelium discoideum) | C97.A01 | - |
| DDB_G0282041 protein (Dictyostelium discoideum) | C97.A02 | - |
| At5g47310 g.p. (Arabidopsis thaliana) | C97.A03 | - |
| F23A5.4 g.p. (Arabidopsis thaliana) | C97.A04 | - |
| At4g17486 g.p. (Arabidopsis thaliana) | C97.A05 | - |
| At5g25170 g.p. (Arabidopsis thaliana) | C97.A06 | - |
| At4g31980 g.p. (Arabidopsis thaliana) | C97.A07 | - |
| At2g25190 g.p. (Arabidopsis thaliana) | C97.A08 | - |
| At1g47740 g.p. (Arabidopsis thaliana) | C97.A09 | - |
| PF10_0069 g.p. (Plasmodium falciparum) | C97.A10 | - |
| PFL0865w g.p. (Plasmodium falciparum) | C97.A11 | - |
| PFI0940c g.p. (Plasmodium falciparum) | C97.A12 | - |
| Family C97 non-peptidase homologues | non-peptidase homologue | - |
| Family C97 unassigned peptidases | unassigned | - |
