Importin

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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). IPO 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. See also [[Protein Transport Membrane Protein]].
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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. '''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]].
== 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 ==
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</StructureSection>
 
==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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{{#tree:id=OrganizedByTopic|openlevels=0|
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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 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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}}
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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. ↑ 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

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman

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