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Importin

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(New page: <StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain complex with nucleoplasmin peptide (PDB code 1ee5).' scene=''> == Fun...)
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<StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain (grey) complex with nucleoplasmin peptide (green) (PDB code [[1ee5]]).' scene=''>
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<StructureSection load='1ee5' size='340' side='right' caption='Structure of yeast importin α NLS-binding domain complex with nucleoplasmin peptide (PDB code [[1ee5]]).' scene=''>
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== Function ==
== Function ==
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'''Importins''' (IPO) mediate the import of cellular proteins into the nucleus by binding to the nuclear localization signal (NLS). IMP has 2 subunits: α and β. IPO-α is an adaptor protein which binds the NLS. Proteins can contain one or two NLS motifs. IPO-α contains several armadillo repeats with two NLS-binding sites and an IPO-β binding site (IBB). IPO-β contains 19 HEAT repeats. Many nuclear proteins contain Phe-Gly sequences which can bind to HEAT repeats and thus be transported.
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'''Importins''' (IPO) mediate the import of cellular proteins into the nucleus by binding to the '''N'''uclear '''L'''ocalization '''S'''ignal (NLS). IPO has 2 subunits: α and β. '''IPO-α''' is an adaptor protein which binds the NLS<ref>PMID:9759490</ref>. IPOs can contain one or two NLS motifs.
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*'''IPO-α''' contains several armadillo repeats with two NLS-binding sites and an IPO-β binding (IBB) site.
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*'''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.
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*'''IPO-4''' binds histones H3 and H4 and histone chaperone ASF1 for nuclear import<ref>PMID:36103578</ref>.
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*'''IPO-7''' drives the nuclear import of the regulator of mechanotransduction pathway YAP<ref>PMID:35246520</ref>.
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*'''IPO-9''' binds histones H2A and H2B for nuclear import<ref>PMID:30855230</ref>.
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*'''IPO-13''' has a role in oxidative stress-dependent nuclear export<ref>PMID:34625540</ref>.
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See also [[Protein Transport Membrane Protein]].
== Disease ==
== Disease ==
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IPO-α isoform expression is altered in many kinds of cancer.
== Relevance ==
== Relevance ==
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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<ref>PMID:25656054</ref>.
== Structural highlights ==
== Structural highlights ==
==3D structures of importin==
==3D structures of importin==
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[[Importin 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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'''IPO-α'''
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[[1ial]] – mIPO residues 44-496 – mouse<br />
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[[1bk5]] – yIPO NLS-binding domain - yeast<br />
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''IPO-α complex with NLS peptide''
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[[1ejl]] – mIPO NLS-binding domain + SV40 large T antigen<br />
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[[1ejy]] – mIPO NLS-binding domain + nucleoplasmin <br />
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[[2ynr]] – mIPO NLS-binding domain + B54NLS <br />
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[[1bk6]] – yIPO NLS-binding domain + SV40 large T antigen<br />
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[[1ee4]] – yIPO NLS-binding domain (mutant) + c-Myc<br />
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[[1ee5]] – yIPO NLS-binding domain (mutant) + nucleoplasmin<br />
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[[1un0]], [[2c1t]] – yIPO NLS-binding domain (mutant) + Nup2<br />
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''IPO-α complex with protein''
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[[1wa5]] – yIPO NLS-binding domain + GTPase Ran + IPO-α re-exporter<br />
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'''IPO-α 1'''
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''IPO-α 1 complex with NLS peptide''
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[[4mz5]], [[4mz6]] – mIPO NLS-binding domain + dUTPase<br />
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[[4oih]] – mIPO NLS-binding domain + guanine nucleotide exchange factor SRM1<br />
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''IPO-α 1 complex with protein''
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[[2jdq]] – hIPO NLS-binding domain + polymerase basic protein 2 C terminal<br />
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[[3tj3]] – hIPO NLS-binding domain + Nup50 N terminal<br />
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[[2jdq]] – hIPO NLS-binding domain + telomerase reverse transcriptase peptide<br />
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'''IPO-α 2'''
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[[3tpo]] – mIPO<br />
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[[1iq1]] – mIPO NLS-binding + autoinhibitory peptide domains<br />
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[[4e4v]] – hIPO NLS-binding domain (mutant) - human <br />
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''IPO-α 2 complex with NLS peptide''
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[[1pjm]] – mIPO NLS-binding domain + retinoblastoma-associated protein<br />
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[[1pjn]] – mIPO NLS-binding domain + histone-binding protein N1/N2<br />
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[[1q1s]], [[1q1t]] – mIPO NLS-binding domain + SV40 large T antigen<br />
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[[1y2a]], [[3q5u]] – mIPO NLS-binding domain + phospholipid scramblase <br />
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[[2c1m]] – mIPO NLS-binding domain + Nup50<br />
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[[3btr]] – mIPO NLS-binding domain + androgen receptor<br />
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[[3knd]] – mIPO NLS-binding domain + targeting protein for KXLP2<br />
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[[3l3q]] – mIPO NLS-binding domain + library peptide<br />
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[[3oqs]] – mIPO NLS-binding domain + CLIC4<br />
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[[3rz9]] – mIPO NLS-binding domain + KU80<br />
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[[3rzx]] – mIPO NLS-binding domain + KU70<br />
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[[3tpm]] – mIPO NLS-binding domain + MAL<br />
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[[3ve6]] – mIPO NLS-binding domain + Venezuelan equine encephalitis virus<br />
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[[3uvu]] – mIPO NLS-binding domain + flap endonuclease<br />
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[[3ukw]], [[3ukx]] – mIPO NLS-binding domain + BIMAX<br />
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[[3uky]], [[3ukz]], [[3ul0]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
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[[3ul1]] – mIPO NLS-binding domain + nucleoplasmin <br />
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[[4htv]] – mIPO NLS-binding domain + capsid protein <br />
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[[4ba3]] – mIPO NLS-binding domain + A89NLS <br />
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[[3zio]], [[3zip]], [[3ziq]], [[3zir]] – mIPO NLS-binding domain + minor site-specific NLS <br />
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[[3zin]] – mIPO NLS-binding domain + nucleolar RNA helicase<br />
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''IPO-α 2 complex with protein''
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[[3fex]], [[3fey]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
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'''IPO-β 1'''
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[[3nd2]] – yIPO <br />
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[[1gcj]] – mIPO N terminal<br />
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''IPO-β 1 complex with protein''
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[[1qgx]], [[1qgr]] – hIPO + IPO-α 2 IBB domain<br />
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[[1ibr]] – hIPO + GTPase Ran<br />
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[[2bku]], [[3ea5]] – yIPO + GTPase Ran<br />
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[[1f59]], [[1o6p]], [[1o6o]] – hIPO + FXFG nucleoporin repeats<br />
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[[1m5n]] – hIPO HEAT repeats 1-11 + parathyroid hormone-related protein NLS peptide<br />
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[[2p8q]], [[2q5d]], [[2qna]], [[3lww]] – hIPO + RNA U transporter N terminal<br />
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[[1qgr]], [[3w5k]] – hIPO + zinc finger protein SNAI1<br />
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[[2bpt]] – yIPO + Nup1<br />
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[[1ukl]] – mIPO + SREBP-2<br />
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'''IPO-β 2 (Transportin 1)'''
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[[2z5j]], [[2qmr]] – hIPO <br />
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''IPO-β 2 complex with protein''
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[[2h4m]], [[2ot8]], [[2z5n]] – hIPO + hnRNP peptide<br />
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[[2z5k]], [[2z5m]] – hIPO + nuclear RNA export factor peptide<br />
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[[2z5o]] – hIPO + JKTBP peptide<br />
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[[4fdd]], [[4jlq]], [[4oo6]] – hIPO + RNA binding protein peptide<br />
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[[4fq3]] – hIPO + FUS peptide<br />
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'''IPO-13'''
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[[2x19]] – hIPO + GTPase Ran<br />
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[[2xwu]] – hIPO + UBC9<br />
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[[3zjy]] – hIPO + GTPase Ran + EIF-1A<br />
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== References ==
== References ==

Current revision

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

References

  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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