title: Evolutionary specialization of the nuclear targeting apparatus.
abstract: 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.
authors.affiliation: Department of Biology, University of Rochester, Rochester, NY 14627, USA.
authors.forename: H S
authors.initials: HS
authors.lastname: Malik
authors.forename: T H
authors.initials: TH
authors.lastname: Eickbush
authors.forename: D S
authors.initials: DS
authors.lastname: Goldfarb
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D019143:Evolution, Molecular; D006801:Humans; D019476:Insect Proteins / Q000235:genetics; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D028901:alpha Karyopherins; D028961:beta Karyopherins
chemical_list: D051186:Armadillo Domain Proteins; D029721:Drosophila Proteins; D019476:Insect Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D028901:alpha Karyopherins; D028961:beta Karyopherins