The alpha- and beta-karyopherins (Kaps), also called importins, mediate the 
nuclear transport of proteins. All alpha-Kaps contain a central domain composed 
of eight approximately 40 amino acid, tandemly arranged, armadillo-like (Arm) 
repeats. The number and order of these repeats have not changed since the common 
origin of fungi, plants, and mammals. Phylogenetic analysis suggests that the 
various alpha-Kaps fall into two groups, alpha1 and alpha2. Whereas animals 
encode both types, the yeast genome encodes only an alpha1-Kap. The beta-Kaps 
are characterized by 14-15 tandemly arranged HEAT motifs. We show that the Arm 
repeats of alpha-Kaps and the HEAT motifs of beta-Kaps are similar, suggesting 
that the alpha-Kaps and beta-Kaps (and for that matter, all Arm and HEAT 
repeat-containing proteins) are members of the same protein superfamily. 
Phylogenetic analysis indicates that there are at least three major groups of 
beta-Kaps, consistent with their proposed cargo specificities. We present a 
model in which an alpha-independent beta-Kap progenitor gave rise to the 
alpha-dependent beta-Kaps and the alpha-Kaps.