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


== Relevance ==
== 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<ref>PMID:25656054</ref>.


== Structural highlights ==
== Structural highlights ==


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


Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
</StructureSection>
 
'''IPO-α'''
 
[[1ial]] – mIPO residues 44-496 – mouse<br />
[[1bk5]] – yIPO NLS-binding domain - yeast<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 />
[[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 />
 
''IPO-α complex with protein''
 
[[1wa5]] – yIPO NLS-binding domain + GTPase Ran + IPO-α re-exporter<br />
 
'''IPO-α 1'''
 
''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 />
 
''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 />
 
'''IPO-α 2'''
 
[[3tpo]] – mIPO<br />
[[1iq1]] – mIPO NLS-binding + autoinhibitory peptide domains<br />
[[4e4v]] – hIPO NLS-binding domain (mutant) - human <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-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 />
 
'''IPO-13'''
 
[[2x19]] – hIPO + GTPase Ran<br />
[[2xwu]] – hIPO + UBC9<br />
[[3zjy]] – hIPO + GTPase Ran + EIF-1A<br />
 


== References ==
== References ==

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Joel L. Sussman