Importin

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Function

Importins (IPO) mediate the import of cellular proteins into the nucleus by binding to the Nuclear Localization Signal (NLS). IPO has 2 subunits: α and β. IPO-α is an adaptor protein which binds the NLS[1]. IPOs can contain one or two NLS motifs.

  • IPO-α contains several armadillo repeats with two NLS-binding sites and an IPO-β binding (IBB) site.
  • IPO-β contains 19 HEAT (solenoid domain) repeats. Many nuclear proteins contain Phe-Gly sequences which can bind to HEAT repeats and thus be transported.
  • IPO-4 binds histones H3 and H4 and histone chaperone ASF1 for nuclear import[2].
  • IPO-7 drives the nuclear import of the regulator of mechanotransduction pathway YAP[3].
  • IPO-9 binds histones H2A and H2B for nuclear import[4].
  • IPO-13 has a role in oxidative stress-dependent nuclear export[5].

See also Protein Transport Membrane Protein.

Disease

IPO-α isoform expression is altered in many kinds of cancer.

Relevance

Specific IPO-α isoforms are critical in nerve regenerative response after injury. Loss of IPO-α expression in aging myocardial cells could make recovery after heart disease in elderly patients more difficult[6].

Structural highlights

3D structures of importin

Importin 3D structures


Structure of yeast importin α NLS-binding domain (grey) complex with nucleoplasmin peptide (green) (PDB code 1ee5).

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Mattaj IW, Englmeier L. Nucleocytoplasmic transport: the soluble phase. Annu Rev Biochem. 1998;67:265-306. PMID:9759490 doi:http://dx.doi.org/10.1146/annurev.biochem.67.1.265
  2. ↑ Bernardes NE, Fung HYJ, Li Y, Chen Z, Chook YM. Structure of IMPORTIN-4 bound to the H3-H4-ASF1 histone-histone chaperone complex. Proc Natl Acad Sci U S A. 2022 Sep 20;119(38):e2207177119. PMID:36103578 doi:10.1073/pnas.2207177119
  3. ↑ García-García M, Sánchez-Perales S, Jarabo P, Calvo E, Huyton T, Fu L, Ng SC, Sotodosos-Alonso L, Vázquez J, Casas-Tintó S, Görlich D, Echarri A, Del Pozo MA. Mechanical control of nuclear import by Importin-7 is regulated by its dominant cargo YAP. Nat Commun. 2022 Mar 4;13(1):1174. PMID:35246520 doi:10.1038/s41467-022-28693-y
  4. ↑ Padavannil A, Sarkar P, Kim SJ, Cagatay T, Jiou J, Brautigam CA, Tomchick DR, Sali A, D'Arcy S, Chook YM. Importin-9 wraps around the H2A-H2B core to act as nuclear importer and histone chaperone. Elife. 2019 Mar 11;8. pii: 43630. doi: 10.7554/eLife.43630. PMID:30855230 doi:http://dx.doi.org/10.7554/eLife.43630
  5. ↑ Gajewska KA, Lescesen H, Ramialison M, Wagstaff KM, Jans DA. Nuclear transporter Importin-13 plays a key role in the oxidative stress transcriptional response. Nat Commun. 2021 Oct 8;12(1):5904. PMID:34625540 doi:10.1038/s41467-021-26125-x
  6. ↑ Pumroy RA, Cingolani G. Diversification of importin-alpha isoforms in cellular trafficking and disease states. Biochem J. 2015 Feb 15;466(1):13-28. doi: 10.1042/BJ20141186. PMID:25656054 doi:http://dx.doi.org/10.1042/BJ20141186

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