E3 ubiquitin-protein ligase Itchy (Itch)

Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the shape of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:15358865, PubMed:16446428, PubMed:17592138, PubMed:18628966, PubMed:20392206, PubMed:25632008). It catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (By similarity).

Involved in the management of inflammatory signaling pathways (By similarity). Is an essential element of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (By similarity).