PELI2

E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Specifically recognizes and binds proteins phosphorylated on threonine residues. 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. Acts as a negative regulator of cGAS-STING signaling: recognizes and binds phosphorylated STING1 and mediates 'Lys-63'-linked polyubiquitination of TBK1, inhibiting cGAS-STING signaling, while simultaneously enhancing the STING1-dependent NF-kappa-B axis. 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..

Function from UniProtKB (Q9HAT8), read 2026-09-23. CC BY 4.0.