Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:16608850, PubMed:32832608). Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability (PubMed:15743823). Deconjugates SUMO2 and SUMO3 from CDCA8 (PubMed:18946085). Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300 (PubMed:19680224). Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1 (PubMed:19015314). Plays a role in the regulation of sumoylation status of ZNF148 (PubMed:18259216). Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Deconjugates SUMO2 from KAT5 (PubMed:32832608). On oxidative stress, SENP3 degradation is blocked by inhibition of its ubiquitination, which stabilizes it as it accumulates in the nucleoplasm. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10 (PubMed:15960975). Interacts with EP300, NPM1 and CDCA8 (PubMed:19015314, PubMed:18946085, PubMed:18259216, PubMed:19680224). Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148 (PubMed:22872859). Interacts with NOL9 (By similarity). Interacts with CCAR2 (PubMed:25406032). Redistributes between the nucleolus and the nucleoplasm in response to mild oxidative stress (PubMed:19680224). Mainly found in the nucleoplasm, with low levels detected in the cytoplasmic and chromatin fractions (By similarity). Belongs to the peptidase C48 family.