E3 ubiquitin-protein ligase pellino homolog 3 (PELI3)

E3 ubiquitin-protein ligase pellino homolog 3 (PELI3) is an enzyme of the RING-type E3 ubiquitin ligase family involved in the transfer of ubiquitin chains to specific substrate proteins primarily in signal transduction pathways critical for innate immunity[1][2]. It mediates Lys63-linked ubiquitination of RIPK2 downstream of NOD1/2 receptors and regulates pathways downstream of Toll-like and interleukin-1 receptors, thereby modulating immune and inflammatory responses[2][1]. PELI3 localizes to autophagic membranes and interacts with ATG8 proteins (such as LC3 and GABARAP families) via an LC3-interacting region to control the ubiquitination and proteasomal degradation of ULK1, a key regulator of autophagy initiation[5]. Loss of PELI3 disrupts autophagy and promotes hepatic steatosis during nutrient deprivation[5]. PELI3 is also implicated in broader physiological and pathological pathways of immunity and metabolism, and may have context-dependent roles in diseases such as inflammatory disorders, infections, and metabolic liver conditions[1][5]. **Note:** - No drugs specifically targeting PELI3 are described in the literature or available databases; its mechanistic and disease roles are deduced from its molecular and cellular functions[2][5]. - Reduced PELI3 expression has potential as a biomarker for liver metabolic disease[5]. - Safety concerns for targeting PELI3 are hypothetical but may relate to immune dysregulation or impaired autophagy[5].

Other names

Pellino-3MGC35521RING-type E3 ubiquitin transferase pellino homolog 3pellino homolog 3protein pellino homolog 3PELI3

Catalyzes Lys63-linked and other (K48, K11) polyubiquitin chains on substrate proteins Modulates degradation and signaling functions via ubiquitination, especially of RIPK2 and ULK1[2][5]