Sentrin-specific protease 3 (SENP3, MEROPS identifier C48.003) is an isopeptidase that releases SUMO2 and SUMO3 monomers from sumoylated substrates by hydrolysing the isopeptide bond []. SENP3 is a cysteine peptidase with a fold similar to that of adenain, and has the catalytic triad His, Asp, Cys, the reverse of the order in papain. Among the proteins that are deconjugated by SENP3 are MEF2D [], CDCA8 [], EP300 [], and nucleophosmin []. SENP3 is a component of the 5FMC []and MLL1/MLL complexes [].
Sentrin/SUMO-specific proteases (SENPs) reversibly regulate the covalent modification of proteins by SUMO. SENP3 and 5 share considerable sequence homology and exhibit similar substrate specificity,as they are active against SUMO-2 and SUMO-3 but less so for SUMO-1. They are more closely related than to SENP1/2. This entry covers the N-terminal region of SENP3/5 containing a conserved domain directly preceding the catalytic domain. This domain is responsible for the subcellular localisation []. SENP3/5 co-localise in the nucleolus and their depletion causes defects in ribosome biogenesis [].
SENP5 peptidase (sentrin-specific peptidase 5, MEROPS identifier C48.008) is a deSUMOylating peptidase localized predominantly to the nucleolus. SENP5 releases the tag proteins SUMO-2 and -3 from conjugates, preferentially acting as an isopeptidase rather than an endopeptidase []. Simultaneous depletion of SENP3 and SENP5 results in enhanced SUMOylation of proteins such as RPL37A and GNL2, which are involved in the processing of pre-rRNA [], PELP1 and LAS1L, which are involved in the release of mature ribosomal particles [], and Nop58, which is a component of small nucleolar ribonucleoprotein (snoRNP) and SUMOlyation is required for binding of Nop58 to snoRNA to maintain nucleolar retention []. SENP5 depletion also affects mitotic progression, and cells arrest at the G2/M transition []. SENP5 is also involved in mitochondrial fusion and fission, because SUMOylated dynamin-1-like protein (Drp1), which is a mitochondrial fission factor, is a target for SENP5 []. DeSUMOylation of Drp1 is a contributory factor to cardiomyopathy []. During the G2/M transition stage of mitosis, SENP5 transiently locates to the mitochondrion []. SENP5 is also required for neutrophil differentiation, and the SNP5 gene is repressed in clinical acute myeloid leukemia [].
