Importin-11, a nuclear import receptor for the ubiquitin-conjugating enzyme, UbcM2.
Importins are members of a family of transport receptors (karyopherins) that mediate the nucleocytoplasmic transport of protein and RNA cargoes. We identified importin-11 as a potential new human member of this family, on the basis of limited similarity to the Saccharomyces cerevisiae protein, Lph2p, and cloned the complete open reading frame. Importin-11 interacts with the Ran GTPase, and constitutively shuttles between the nuclear and cytoplasmic compartments. A yeast dihybrid screen identified UbcM2, an E2-type ubiquitin-conjugating enzyme, as a binding partner and potential transport cargo for importin-11. Importin-11 and UbcM2 interact directly, and the complex is disassembled by Ran:GTP but not by Ran:GDP. UbcM2 is constitutively nuclear and shuttles between the nuclear and cytoplasmic compartments. Nuclear import of UbcM2 requires Ran and importin-11, and is inhibited by wheatgerm agglutinin, energy depletion or dominant interfering mutants of Ran and importin-beta. These data establish importin-11 as a new member of the karyopherin family of transport receptors, and identify UbcM2 as a nuclear member of the E2 ubiquitin-conjugating enzyme family.
Plafker
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Center for Cell Signaling, Box 800577, HSC and Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA. smp5g@virginia.edu
Macara
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D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D028884:Karyopherins; D008025:Ligases / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014452:Ubiquitins / Q000378:metabolism*; D020931:ran GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D028884:Karyopherins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014452:Ubiquitins; D006160:Guanosine Triphosphate; D020931:ran GTP-Binding Protein; D008025:Ligases