Disease relevance of Kpna2

• To determine the structural basis of the recognition of diverse bipartite NLSs by mammalian importin-alpha, we co-crystallized a non-autoinhibited mouse receptor protein with peptides corresponding to the NLSs from human retinoblastoma protein and Xenopus laevis phosphoprotein N1N2, containing diverse sequences and lengths of the linker [1].

High impact information on Kpna2

• IGFBP-3 and -5 have carboxyl-terminal basic motifs incorporating heparin-binding and additional basic residues that interact with the cell surface and matrix, the nuclear transporter importin-beta, and other proteins [2].
• RAG1 appears to have a binary structure, each half containing multiple regions that can act as NLSs, binding sites for the SRP1/Rch1 family, and RNA binding domains [3].
• Thus, importin-alpha subtype switching has a major impact on cell differentiation through the regulated nuclear import of a specific set of transcription factors [4].
• In hippocampal neurons, NMDA receptor activation but not depolarization induced importin nuclear translocation [5].
• These data suggest a model whereby lesion-induced upregulation of axonal importin beta may enable retrograde transport of signals that modulate the regeneration of injured neurons [6].

Biological context of Kpna2

• Importin alpha/beta mediates nuclear transport of a mammalian circadian clock component, mCRY2, together with mPER2, through a bipartite nuclear localization signal [7].
• In this study, we used a fluorescence resonance energy transfer probe to measure RanGTP-regulated release of importin beta [8].
• Importin-alpha contains the NLS binding site, whereas importin-beta mediates the translocation through the nuclear pore [9].
• Importin alpha1 was mapped to a middle region of mouse chromosome 16 by fluorescence in situ hybridization analysis [10].
• Here we report on the organization of the importin alpha1 locus in the mouse genome [10].

Anatomical context of Kpna2

• Chronological quantitative analysis of importin beta-immunostained sections from the transgenic mice revealed a statistically significant progressive decrease in the proportion of the anterior horn cells exhibiting a more intense reactivity for these proteins in the nucleus than in the cytoplasm [11].
• These results provide in vivo evidence that m-importin is involved in nuclear protein import through association with a NLS in the cytoplasm before nuclear pore binding [12].
• We suggest that Srp1p interacts with multiple components of the cell nucleus that are required for mitosis and discuss its functional similarities to, and differences from Drosophila pendulin [13].
• This paper describes genes from yeast and mouse with significant sequence similarities to a Drosophila gene that encodes the blood cell tumor suppressor pendulin [13].
• An in vitro nuclear import assay using permeabilized HeLa cells revealed that rice importin alpha1, in conjunction with other vertebrate transport factors, mediates the nuclear envelope docking of NLS proteins and their subsequent translocation into the nucleus [14].

Associations of Kpna2 with chemical compounds

• Importin binding and nuclear localization of RXR were modestly enhanced by its ligand, 9-cis-retinoic acid [15].
• Glutathione S-transferase pulldown experiments showed that the nuclear receptor importin-alpha/beta mediates Mybbp1a nuclear import [16].
• Crystals of recombinant importin alpha, the nuclear-import receptor, have been obtained at two different pH conditions by vapour diffusion using sodium citrate as precipitant and dithiothreitol as an additive [17].

Physical interactions of Kpna2

• The mutation of a conserved Lys residue in the NLS abolishes nuclear localization of caspase-2 and binding to the importin alpha/beta heterodimer [18].
• Importin alpha transports CaMKIV to the nucleus without utilizing importin beta [19].
• Promotion of importin alpha-mediated nuclear import by the phosphorylation-dependent binding of cargo protein to 14-3-3 [20].
• These in vitro results suggest that the first step in nuclear import occurs through the targeting-complex formation of a karyophile with PTAC58 bound to PTAC97 [21].
• The crystal structure of the importin-alpha:Nup50 complex shows that Nup50 binds at two sites on importin-alpha [22].

Regulatory relationships of Kpna2

• The cytoplasmic microinjection of importin alpha-DeltaIBB enhanced the rate of nuclear translocation of CaMKIV in vivo [19].

Other interactions of Kpna2

• Role of prodomain in importin-mediated nuclear localization and activation of caspase-2 [18].
• We report here that importin alpha is able to carry CaMKIV into the nucleus without the need for importin beta or any other soluble proteins in digitonin-permeabilized cells [19].
• Importin beta1 (Impbeta)/karyopherin beta1 (Kpnb1) mediates the nuclear import of a large variety of substrates [23].
• In this study, we found that the 54 kDa component of PTAC is the mouse homologue of Xenopus importin (m-importin) [12].
• The Cse1p:Kap60p:RanGTP complex structure suggests how Nup50 is then displaced on formation of the importin-alpha export complex [22].

Analytical, diagnostic and therapeutic context of Kpna2

• Importin-alpha is shown to exist in a monomeric autoinhibited state (association with NLSs undetectable by biosensor) [9].
• Moreover, it was found by reverse transcriptase polymerase chain reaction analysis that importin alpha1 is widely expressed in various tissues in adult mice and at various stages during embyogenesis [10].
• Results from this study showed that fertilized porcine embryos injected with double stranded RNA (dsRNA) corresponding to the importin alpha homologue karyopherin alpha3 had significantly fewer nuclei following four days of culture than did embryos injected with dsRNA for another importin alpha homologue, karyopherin alpha2, or two control groups [24].
• We show that this sequence functions as an NLS in vivo but is not recognized by these two importin-alpha subtypes in a yeast two-hybrid assay and only weakly recognized in an in vitro binding assay [25].
• Sequence analysis of p97 identified it as the nuclear import factor p97 (importin-beta), which is an essential component of the nuclear import machinery [26].

References