The Pellino proteins are a highly homologous family of E3 ubiquitin ligases that act as upstream mediators in Toll-like receptor (TLR) pathways that lead to activation of MAP kinases and transcription factors. Pellino 1 is required for interleukin-1-mediated signaling through its interaction with the IRAK4-IRAK-TRAF6 complex, ultimately resulting in the activation of NF-kB. Like other members of the Pellino family, Pellino 1 is an E3 ubiquitin ligase, able to catalyze the polyubiquitination of IRAK1. It is activated via phosphorylation by either IRAK1 and IRAK4 or the IKK-related kinases IKK-epsilon and TBK1. In addition to phosphorylation, Pellino 1 activity is also modulated via ubiquitination and sumoylation.Synonyms: PRISM, Pellino 1, Pellino-1, Pellino-related intracellular-signaling molecule, Protein pellino homolog 1