Protease that releases SUMO2 and SUMO3 monomers from sumoylated substrates, but has only weak activity against SUMO1 conjugates (PubMed:11029585). Deconjugates SUMO2 from MEF2D, which increases its transcriptional activation capability (By similarity). Deconjugates SUMO2 and SUMO3 from CDCA8 (By similarity). Redox sensor that, when redistributed into nucleoplasm, can act as an effector to enhance HIF1A transcriptional activity by desumoylating EP300 (By similarity). Required for rRNA processing through deconjugation of SUMO2 and SUMO3 from nucleophosmin, NPM1 (By similarity). Plays a role in the regulation of sumoylation status of ZNF148 (By similarity). 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 (By similarity). 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 (By similarity). Interacts with EP300, NPM1 and CDCA8 (By similarity). 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 (PubMed:22872859). Interacts with CCAR2 (By similarity). Redistributes between the nucleolus and the nucleoplasm in response to mild oxidative stress (By similarity). Mainly found in the nucleoplasm, with low levels detected in the cytoplasmic and chromatin fractions (PubMed:22872859). Belongs to the peptidase C48 family.