Importin: Difference between revisions

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== Function ==
== Function ==


'''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.  '''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.  See also [[Protein Transport Membrane Protein]].
'''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.   
*'''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<ref>PMID:36103578</ref>. 
*'''IPO-7'''  drives the nuclear import of the regulator of mechanotransduction pathway YAP<ref>PMID:35246520</ref>.
*'''IPO-9''' binds histones H2A and H2B for nuclear import<ref>PMID:30855230</ref>.
*'''IPO-13''' has a role in oxidative stress-dependent nuclear export<ref>PMID:34625540</ref>.
 
See also [[Protein Transport Membrane Protein]].


== Disease ==
== Disease ==
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== Structural highlights ==
== Structural highlights ==
</StructureSection>


==3D structures of importin==
==3D structures of importin==
[[Importin 3D structures]]


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
{{#tree:id=OrganizedByTopic|openlevels=0|
 
*IPO-α
 
**[[1ial]] – mIPO NLS-binding domain – mouse<br />
**[[1bk5]] – yIPO NLS-binding domain - yeast<br />
**[[4tnm]] – IPO armadillo repeat domain – ''Arabidopsis thaliana''<br />
 
*''IPO-α complex with NLS peptide''
 
**[[1ejl]] – mIPO NLS-binding domain + SV40 large T antigen<br />
**[[1ejy]] – mIPO NLS-binding domain + nucleoplasmin <br />
**[[2ynr]] – mIPO NLS-binding domain + B54NLS <br />
**[[2yns]] – rIPO NLS-binding domain + B54NLS - rice<br />
**[[1bk6]] – yIPO NLS-binding domain + SV40 large T antigen<br />
**[[1ee4]] – yIPO NLS-binding domain (mutant) + c-Myc<br />
**[[1ee5]] – yIPO NLS-binding domain (mutant) + nucleoplasmin<br />
**[[1un0]], [[2c1t]] – yIPO NLS-binding domain (mutant) + Nup2<br />
**[[5h2x]], [[5h2w]] – yIPO NLS-binding domain + ubiquitin-like specific protease<br />
**[[4xzr]] – yIPO NLS-binding domain + HEH1<br />
**[[4pvz]] – yIPO NLS-binding domain + HEH2<br />
**[[4rxh]] – IPO NLS-binding domain + SV40 large T antigen – ''Neurospora crassa''<br />
 
*''IPO-α complex with protein''
 
**[[1wa5]] – yIPO NLS-binding domain + GTPase Ran + IPO-α re-exporter<br />
 
*IPO-α 1
 
**[[3wpt]] – hIPO NLS-binding domain - human<br />
**[[4b8j]] – rIPO <br />
 
*''IPO-α 1 complex with NLS peptide''
 
**[[4mz5]], [[4mz6]] – mIPO NLS-binding domain + dUTPase<br />
**[[4oih]] – mIPO NLS-binding domain + guanine nucleotide exchange factor SRM1<br />
**[[5svz]] – mIPO NLS-binding domain + TAT NLS motif<br />
**[[5wum]], [[5wun]], [[5x8n]] – mIPO NLS-binding domain + Epstein Barr antigen<br />
**[[5huw]] – mIPO NLS-binding domain + HSVI large terminase<br />
**[[5huy]] – mIPO NLS-binding domain + HSMV small terminase<br />
**[[5hhg, [[5fc8]] – mIPO NLS-binding domain + dengue 2 NS5<br />
**[[5ekg]], [[5ekf]], [[5e6q]] – mIPO NLS-binding domain + XPG2<br />
**[[5d5k]] – mIPO NLS-binding domain + PARP 2<br />
**[[5ctt]] – mIPO NLS-binding domain + SART3/TIP110<br />
**[[5b56]] – mIPO NLS-binding domain + HIV-1 VPR<br />
**[[4zdu]] – mIPO NLS-binding domain + influenza nucleoprotein<br />
**[[4yi0]] – mIPO NLS-binding domain + Nup121<br />
**[[5klr]], [[5klt]] – mIPO NLS-binding domain + NLS <br />
**[[5k9s]] – mIPO NLS-binding domain + HNF-b <br />
**[[4b18]] – hIPO NLS-binding domain + telomerase reverse transcriptase<br />
**[[4wv6]] – hIPO NLS-binding domain + TFIID<br />
**[[4b8o]] – rIPO NLS-binding domain + SV40<br />
**[[4b8p]] – rIPO NLS-binding domain + A89<br />
**[[4bpl]] – rIPO NLS-binding domain + nucleoplasmin<br />
**[[4bqk]] – rIPO NLS-binding domain + VirD2<br />
 
*''IPO-α 1 complex with protein''
 
**[[2jdq]] – hIPO NLS-binding domain + polymerase basic protein  2 C terminal<br />
**[[3tj3]] – hIPO NLS-binding domain + Nup50 N terminal<br />
**[[2jdq]] – hIPO NLS-binding domain + telomerase reverse transcriptase peptide<br />
**[[4uaf]] – mIPO NLS-binding domain + influenza RNA polymerase<br />
 
*IPO-α 2
 
**[[3tpo]] – mIPO<br />
**[[1iq1]] – mIPO NLS-binding + autoinhibitory peptide domains<br />
**[[4e4v]] – hIPO NLS-binding domain (mutant) <br />
 
*''IPO-α 2 complex with NLS peptide''
 
**[[1pjm]] – mIPO NLS-binding domain + retinoblastoma-associated protein<br />
**[[1pjn]] – mIPO NLS-binding domain + histone-binding protein N1/N2<br />
**[[1q1s]], [[1q1t]] – mIPO NLS-binding domain + SV40 large T antigen<br />
**[[1y2a]], [[3q5u]] – mIPO NLS-binding domain + phospholipid scramblase <br />
**[[2c1m]] – mIPO NLS-binding domain + Nup50<br />
**[[3btr]] – mIPO NLS-binding domain + androgen receptor<br />
**[[3knd]] – mIPO NLS-binding domain + targeting protein for KXLP2<br />
**[[3l3q]] – mIPO NLS-binding domain + library peptide<br />
**[[3oqs]] – mIPO NLS-binding domain + CLIC4<br />
**[[3rz9]] – mIPO NLS-binding domain + KU80<br />
**[[3rzx]] – mIPO NLS-binding domain + KU70<br />
**[[3tpm]] – mIPO NLS-binding domain + MAL<br />
**[[3ve6]] – mIPO NLS-binding domain + Venezuelan equine encephalitis virus<br />
**[[3uvu]] – mIPO NLS-binding domain + flap endonuclease<br />
**[[3ukw]], [[3ukx]] – mIPO NLS-binding domain + BIMAX<br />
**[[3uky]], [[3ukz]], [[3ul0]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
**[[3ul1]] – mIPO NLS-binding domain + nucleoplasmin <br />
**[[4htv]] – mIPO NLS-binding domain + capsid protein <br />
**[[4ba3]] – mIPO NLS-binding domain + A89NLS <br />
**[[3zio]], [[3zip]], [[3ziq]], [[3zir]] – mIPO NLS-binding domain + minor site-specific NLS <br />
**[[3zin]] – mIPO NLS-binding domain + nucleolar RNA helicase<br />
 
*''IPO-α 2 complex with protein''
 
**[[3fex]], [[3fey]] – mIPO NLS-binding domain + nuclear CAP-binding protein<br />
 
*IPO-α 3
 
**[[4uae]] – hIPO NLS-binding domain + influenza RNA polymerase<br />
 
*IPO-α 6
 
**[[4u2x]] – hIPO C terminal + ebola VP24<br />
 
*IPO-α 7
 
**[[4uad]] – hIPO NLS-binding domain + influenza RNA polymerase<br />
 
*IPO-β
 
**[[4xrk]] – IPO – ''Chaetomium thermophilum'' <br />
 
*IPO-β 1 (karyopherin β 1)
 
**[[3nd2]] – yIPO <br />
**[[1gcj]] – mIPO N terminal<br />
 
*''IPO-β 1 complex with protein''
 
**[[1qgx]], [[1qgr]] – hIPO + IPO-α 2 IBB domain<br />
**[[1ibr]] – hIPO + GTPase Ran<br />
**[[2bku]], [[3ea5]] – yIPO + GTPase Ran<br />
**[[1f59]], [[1o6p]], [[1o6o]] – hIPO + FXFG nucleoporin repeats<br />
**[[1m5n]] – hIPO HEAT repeats 1-11 + parathyroid hormone-related protein NLS peptide<br />
**[[2p8q]], [[2q5d]], [[2qna]], [[3lww]] – hIPO + RNA U transporter N terminal<br />
**[[1qgr]], [[3w5k]] – hIPO + zinc finger protein SNAI1<br />
**[[2bpt]] – yIPO + Nup1<br />
**[[1ukl]] – mIPO + SREBP-2<br />
 
*IPO-β 2 (Transportin 1)
 
**[[2z5j]], [[2qmr]] – hIPO <br />
 
*''IPO-β 2 complex with protein''
 
**[[2h4m]], [[2ot8]], [[2z5n]] – hIPO + hnRNP peptide<br />
**[[2z5k]], [[2z5m]] – hIPO + nuclear RNA export factor peptide<br />
**[[2z5o]] – hIPO + JKTBP peptide<br />
**[[4fdd]], [[4jlq]], [[4oo6]] – hIPO + RNA binding protein peptide<br />
**[[4fq3]] – hIPO + FUS peptide<br />
**[[5tqc]] – hIPO + RPL4 peptide<br />
**[[5j3v]] – hIPO + histone H3 peptide<br />
 
*IPO-β 3 (Karyopherin β 3)
 
**[[3w3t]] – yIPO <br />
**[[3w3u]], [[3w3v]] – yIPO (mutant)<br />
**[[3w3w]] – yIPO + STE12P<br />
**[[3w3x]] – yIPO + PHO4<br />
**[[3w3y]] – yIPO + Nup53P<br />
**[[3w3z]] – yIPO + RANGTP<br />
**[[5h2v]] – yIPO + ubiquitin-like specific protease<br />
**[[4zj7]] – yIPO + CDC14<br />
 
*IPO-12 (Transportin-3)
 
**[[4c0p]] – hIPO <br />
**[[4c0o]] – hIPO + serine/arginine-rich splicing factor<br />
**[[4c0q]], [[4ol0]] – hIPO + GTPase Ran<br />
 
*IPO-13 (karyopherin 13)
 
**[[2x19]] – hIPO + GTPase Ran<br />
**[[2xwu]] – hIPO + UBC9<br />
**[[3zjy]] – hIPO + GTPase Ran + EIF-1A<br />
}}


== References ==
== References ==

Latest revision as of 13:14, 2 July 2024


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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Michal Harel, Joel L. Sussman
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