Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:
9751060, PubMed:
14695475, PubMed:
20724660). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (PubMed:
16547522, PubMed:
18287044, PubMed:
19033441, PubMed:
21606507, PubMed:
27777308, PubMed:
19185524, PubMed:
33567255). Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (PubMed:
16547522, PubMed:
18287044, PubMed:
27777308, PubMed:
19033441, PubMed:
21606507, PubMed:
19185524). Could be implicated in NF-kappa-B- mediated protection from cytokine toxicity. Essential for viral activation of IRF3 (PubMed:
19854139). Involved in TLR3- and IFIH1- mediated antiviral innate response; this function requires 'Lys-27'- linked polyubiquitination (PubMed:
20724660).
