E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as ECSIT, IKBKG, IRAK1, AKT1 and AKT2 (  ). Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation . Leads to the activation of NF-kappa-B and JUN ( ). Seems to also play a role in dendritic cells (DCs) maturation and/or activation (By similarity). Represses c-Myb-mediated transactivation, in B-lymphocytes (, ). Adapter protein that seems to play a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor ( ). Regulates osteoclast differentiation by mediating the activation of adapter protein complex 1 (AP-1) and NF-kappa-B, in response to RANK-L stimulation (By similarity). Together with MAP3K8, mediates CD40 signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production (By similarity). Participates also in the TCR signaling by ubiquitinating LAT (, ).
Subcellular locations: Cytoplasm, Cytoplasm, Cell cortex, Nucleus, Lipid droplet
Found in the nuclei of some aggressive B-cell lymphoma cell lines as well as in the nuclei of both resting and activated T- and B-lymphocytes. Found in punctate nuclear body protein complexes. Ubiquitination may occur in the cytoplasm and sumoylation in the nucleus. RSAD2/viperin recruits it to the lipid droplet (By similarity).
Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.