In human, IkB (NFKBIA or NFKBIB) is an inhibitory protein that sequesters NF-kappa-B in the cytoplasm, by masking a nuclear localization signal, located just at the C-terminal end in each of the NF-kappa-B subunits.
A key event in NF-kappa-B activation involves phosphorylation of IkB by an IkB kinase (IKK). The phosphorylation and ubiquitination of IkB kinase complex is mediated by two distinct pathways, either the classical or alternative pathway. In the classical NF-kappa-B signaling pathway, the activated IKK (IkB kinase) complex, predominantly acting through IKK beta in an IKK gamma-dependent manner, catalyzes the phosphorylation of IkBs (at sites equivalent to Ser32 and Ser36 of human NFKBIA (IkB-alpha) or Ser19 and Ser22 of NFKBIB (IkB-beta)). Once phosphorylated, IkB undergoes ubiquitin-mediated degradation, releasing NF-kappa-B.