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 IL1B-induced IRAK1 'Lys-63'-linked polyubiquitination and possibly 'Lys-48'-linked ubiquitination. May be important for LPS- and IL1B-induced MAP3K7-dependent, but not MAP3K3-dependent, NF-kappa-B activation. Can activate the MAP (mitogen activated protein) kinase pathway leading to activation of ELK1. 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, IRAK4 and MAP3K7 (By similarity). Interacts with IRAK1. Interacts with BCL10; this interaction is impaired by SOCS3. Widely expressed both in embryos and adult. Weakly or not expressed in spleen and thymus. The atypical FHA domain contains a 'wing' insert and mediates binding to threonine-phosphorylated IRAK1. Phosphorylated by IRAK1 and IRAK4 enhancing its E3 ligase activity. Belongs to the pellino family.