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 '''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]].
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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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== 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 NLS-binding domain – mouse<br />
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**[[1bk5]] – yIPO NLS-binding domain - yeast<br />
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**[[4tnm]] – IPO armadillo repeat domain – ''Arabidopsis thaliana''<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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**[[2yns]] – rIPO NLS-binding domain + B54NLS - rice<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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**[[5h2x]], [[5h2w]] – yIPO NLS-binding domain + ubiquitin-like specific protease<br />
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**[[4xzr]] – yIPO NLS-binding domain + HEH1<br />
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**[[4pvz]] – yIPO NLS-binding domain + HEH2<br />
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**[[4rxh]] – NcIPO NLS-binding domain + SV40 large T antigen – ''Neurospora crassa''<br />
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**[[5vqi]] – NcIPO NLS-binding domain + NIT2<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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**[[5t94]] – yIPO NLS-binding domain + guanine nucleotide exchange factor <br />
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**[[5mfm]] – yIPO NLS-binding domain + YIIIM6AII <br />
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*IPO-α 1
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**[[3wpt]] – hIPO NLS-binding domain - human<br />
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**[[4b8j]] – rIPO <br />
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**[[6bvt]] – mIPO NLS-binding domain <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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**[[5svz]] – mIPO NLS-binding domain + TAT NLS motif<br />
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**[[5wum]], [[5wun]], [[5x8n]] – mIPO NLS-binding domain + Epstein Barr antigen<br />
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**[[5huw]] – mIPO NLS-binding domain + HSVI large terminase<br />
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**[[5huy]] – mIPO NLS-binding domain + HSMV small terminase<br />
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**[[5hhg]], [[5fc8]] – mIPO NLS-binding domain + dengue 2 NS5<br />
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**[[5ekg]], [[5ekf]], [[5e6q]] – mIPO NLS-binding domain + XPG2<br />
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**[[5d5k]] – mIPO NLS-binding domain + PARP 2<br />
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**[[5ctt]] – mIPO NLS-binding domain + SART3/TIP110<br />
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**[[5b56]] – mIPO NLS-binding domain + HIV-1 VPR<br />
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**[[4zdu]] – mIPO NLS-binding domain + influenza nucleoprotein<br />
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**[[4yi0]] – mIPO NLS-binding domain + Nup121<br />
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**[[5klr]], [[5klt]] – mIPO NLS-binding domain + NLS <br />
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**[[5k9s]] – mIPO NLS-binding domain + HNF-b <br />
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**[[4b18]] – hIPO NLS-binding domain + telomerase reverse transcriptase<br />
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**[[4wv6]] – hIPO NLS-binding domain + TFIID<br />
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**[[6bw0]] – hIPO NLS-binding domain + Nipa virus peptide<br />
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**[[6bw1]] – hIPO NLS-binding domain + Hendra virus peptide<br />
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**[[5w41]] – mIPO NLS-binding domain + Zika virus peptide <br />
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**[[5v5o]], [[5v5p]] – mIPO NLS-binding domain + influenza virus peptide <br />
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**[[5umz]] – mIPO NLS-binding domain + TNRC6A peptide <br />
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**[[5u5p]], [[5u5r]] – mIPO NLS-binding domain + MLH1 peptide <br />
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**[[5gxw]] – mIPO NLS-binding domain + NUMA peptide <br />
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**[[5w4e]], [[5w4f]], [[5w4g]] – hIPO NLS-binding domain + polymerase peptide<br />
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**[[5h43]] – hIPO NLS-binding domain + histone acetyltransferase KAT8<br />
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**[[4b8o]] – rIPO NLS-binding domain + SV40<br />
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**[[4b8p]] – rIPO NLS-binding domain + A89<br />
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**[[4bpl]] – rIPO NLS-binding domain + nucleoplasmin<br />
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**[[4bqk]] – rIPO NLS-binding domain + VirD2<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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**[[4uaf]] – mIPO NLS-binding domain + influenza RNA polymerase<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) <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-α 3
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**[[6bvz]] – hIPO NLS-binding domain <br />
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**[[4uae]] – hIPO NLS-binding domain + influenza RNA polymerase<br />
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**[[6bw9]], [[6bwa]], [[6bwb]] – hIPO NLS-binding domain + Hendra virus peptide<br />
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**[[6bvv]] – hIPO NLS-binding domain + Nipa virus peptide<br />
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**[[5xzx]] – hIPO NLS-binding domain + RAN-binding protein peptide<br />
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**[[5tbk]] – hIPO NLS-binding domain + regulator of chromosome condensation <br />
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*IPO-α 6
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**[[4u2x]] – hIPO C terminal + ebola VP24<br />
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*IPO-α 7
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**[[4uad]] – hIPO NLS-binding domain + influenza RNA polymerase<br />
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*IPO-β
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**[[4xrk]] – IPO – ''Chaetomium thermophilum'' <br />
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*IPO-β 1 (karyopherin 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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**[[5owu]] – 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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**[[5yvg]], [[5yvh]] – hIPO + FUS <br />
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**[[5vyh]], [[5vyi]] – hIPO + FUS peptide<br />
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**[[4fq3]] – hIPO + FUS peptide<br />
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**[[5tqc]] – hIPO + RPL4 peptide<br />
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**[[5j3v]] – hIPO + histone H3 peptide<br />
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*IPO-β 3 (Karyopherin β 3)
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**[[3w3t]] – yIPO <br />
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**[[3w3u]], [[3w3v]] – yIPO (mutant)<br />
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**[[3w3w]] – yIPO + STE12P<br />
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**[[3w3x]] – yIPO + PHO4<br />
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**[[3w3y]] – yIPO + Nup53P<br />
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**[[3w3z]] – yIPO + RANGTP<br />
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**[[5h2v]] – yIPO + ubiquitin-like specific protease<br />
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**[[4zj7]] – yIPO + CDC14<br />
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*IPO-4B
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**[[5xah]] – hIPO residues 668-1081 <br />
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**[[5xbk]] – hIPO residues 668-1081 + histone H3 peptide <br />
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*IPO-12 (Transportin-3)
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**[[4c0p]] – hIPO <br />
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**[[4c0o]] – hIPO + serine/arginine-rich splicing factor<br />
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**[[4c0q]], [[4ol0]] – hIPO + GTPase Ran<br />
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*IPO-13 (karyopherin 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. 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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