SUMO-specific proteases/isopeptidases: SENPs and beyond

Abstract

We summarize the evolutionary relationship, structure and subcellular distribution of SUMO proteases (or SUMO isopeptidases). We also discuss their functions and allude to their involvement in human disease.

Figure 1

Evolutionary relationship of Ulp/SENP family members. The phylogenetic tree displays the relationship between Saccharomyces cerevisiae (S.c.), Drosophila melanogaster (Dm) and human Ulp/SENP family members. Confidence numbers generated by the bootstrapping procedure are shown for each branch in the tree. The following sequences were used for input: SENP1 UniProtKB, Q9P0U3; SENP2 UniProtKB, Q9HC62; SENP3 UniProtKB, Q9H4L4; SENP5 UniProtKB, Q96HI0; SENP6 UniProtKB, Q9GZR1; SENP7 UniProtKB, Q9BQF6; Dm_ULP1, GenBank AAF48933.1; Dm_ULP2 (Velo; verloren), GenBank AAS65070.1; S.c._ULP1, UniProtKB/Swiss-Prot Q02724.1; S.c._ULP2, UniProtKB/Swiss-Prot P40537.

Figure 2

Structural organization of SUMO-specific-proteases/isopeptidases. The domain organizations of Ulp/SENPs and Desi family members are shown. Green ovals represent the catalytic domain. The sequence determinants that are responsible for subcellular targeting are represented by orange ovals. The length of the proteins as total number of amino acids is presented on the right side. For the catalytic domains of SENP family members, sequence identity shared with SENP1 is also shown.

Figure 3

Schematic representation of the subcellular distribution of mammalian SUMO-specific isopeptidases of the SENP and Desi families. The predominant subcellular distribution of the respective SENPs is indicated by the green color. Mit, mitochondria; NE, nuclear envelope; No, nucleolus; PML, promyelocytic leukemia nuclear bodies.

Figure 4

SUMO processing and SUMO deconjugation activities of human SENP family members. Schematic representation of SENP processing and deconjugation activities towards distinct SUMO paralogs. The left part summarizes the activities of SENPs in maturation/processing of human SUMO paralogs. The maturation process removes the amino acids carboxy-terminal to a di-glycine (GG) motif (sequences are given for the human SUMO variants). The middle part describes the specificity for deconjugating distinct SUMO forms from substrates (isopeptidase activity). The right part highlights the activity of SENP6 and SENP7 for editing lysine (K)-linked SUMO2/3 chains. These chains are predominantly formed by SUMO2 and SUMO3 and are preferentially linked via K11. The figure tries to integrate data from biochemical in vitro experiments and cell-based assays.