E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates 'Lys-63'-linked polyubiquitination of IRAK1. Can activate AP1/JUN and ELK1. Not required for NF-kappa-B activation. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with TRAF6, IRAK1, MAP3K14 and MAP3K7. Highly expressed in brain, heart and testis, and at lower level in kidney, liver, lung, placenta, small intestine, spleen and stomach. Isoform 1 is not expressed in lung. Phosphorylated by IRAK1 enhancing its E3 ligase activity. Belongs to the pellino family.