On the basis of both functional and structural considerations, members of the IkB family of proteins can be divided into four groups. The first of these groups, IkB-α, includes the avian protein pp40 and the mammalian MAD-3, both of which inhibit binding of p50-p65 NFkB complex or Rel protein to their cognate binding sites but do not inhibit the binding of p50 homodimer to kB sites, suggesting that the IkB-α family binds to the p65 subunit of p50-p65 heterocomplex through ankyrin repeats. The second member of the IkB family is represented by a protein designated IkB-β. The third group of IkB proteins is represented by IkB-ε, which is identical in sequence with the C-terminal domain of the p110 precursor of NFkB p50 and is expressed predominantly in lymphoid cells. An additional IkB family member, IkB-, has several phosphorylated forms and is primarily found complexed with Rel A and/or c-Rel.
