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. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B . Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR . 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.
Cytoplasm . Nucleus . Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner. .
Widely expressed. Abundant in kidney, heart and fetal liver. Expressed differentially among B-cells at distinct developmental stages. Higher expression seen in primary immature B-cells as compared to the mature cells.