Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B (PubMed:23334419). Negatively regulates mucosal immunity against infections (PubMed:23334419). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (PubMed:26903241). Mediates deubiquitination of EGFR (By similarity). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains. Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure. Hydrolyzes both linear and branched forms of polyubiquitin (By similarity). Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Deubiquitinase activity is inhibited following interaction with PARK7. Interacts with TRAF6. Interacts with PARK7, leading to inhibit deubiquitinase activity. Interacts with EGFR, ITCH and NEDD4 (By similarity). Interacts with TRAF3 (PubMed:23334419). Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241). Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner. The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate. Phosphorylated by EGFR. No visible phenotype in neonates (PubMed:26903241). Mice do not show obvious defects in survival, except a moderately reduced body weight (PubMed:23334419). They however display hyperactivation of non-canonical NF-kappa-B without affecting canonical NF-kappa-B activation. Mice show B-cell hyper-responsiveness to antigens, lymphoid follicular hyperplasia in the intestinal mucosa and elevated host-defense ability against an intestinal bacterial pathogen, Citrobacter rodentium (PubMed:23334419). At 12 months after birth, mutant mice display impaired T cell homeostasis with increased numbers of naive T cells and reduced numbers of Th1 memory-like T cells (PubMed:26903241). Young adults that have no overt change in T cell homeostasis still show impaired production of effector T cells in response to repeated stimulation with an antigen and an impaired defense against infection by L.monocytogenes (PubMed:26903241). Conversely, mutant mice are less susceptible to experimentally induced autoimmune encephalitis (PubMed:26903241). Belongs to the peptidase C64 family. Contaminating sequence. Potential poly-A sequence.