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 ( , ). Its binding to scaffolding polyubiquitin plays a key role in IKK activation by multiple signaling receptor pathways (   ). Can recognize and bind both 'Lys-63'-linked and linear polyubiquitin upon cell stimulation, with a much higher affinity for linear polyubiquitin (  , ). Could be implicated in NF-kappa-B-mediated protection from cytokine toxicity. Essential for viral activation of IRF3 . Involved in TLR3- and IFIH1-mediated antiviral innate response; this function requires 'Lys-27'-linked polyubiquitination .
(Microbial infection) Also considered to be a mediator for HTLV-1 Tax oncoprotein activation of NF-kappa-B.
Subcellular locations: Cytoplasm, Nucleus
Sumoylated NEMO accumulates in the nucleus in response to genotoxic stress.
Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.