Importin

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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. 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[2].

Structural highlights

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

3D structures of importin3D structures of importin

Updated on 15-June-2017 {{#tree:id=OrganizedByTopic|openlevels=0|

  • IPO-α
    • 1ial – mIPO NLS-binding domain – mouse
    • 1bk5 – yIPO NLS-binding domain - yeast
    • 4tnm – IPO armadillo repeat domain – Arabidopsis thaliana
  • IPO-α complex with NLS peptide
    • 1ejl – mIPO NLS-binding domain + SV40 large T antigen
    • 1ejy – mIPO NLS-binding domain + nucleoplasmin
    • 2ynr – mIPO NLS-binding domain + B54NLS
    • 2yns – rIPO NLS-binding domain + B54NLS - rice
    • 1bk6 – yIPO NLS-binding domain + SV40 large T antigen
    • 1ee4 – yIPO NLS-binding domain (mutant) + c-Myc
    • 1ee5 – yIPO NLS-binding domain (mutant) + nucleoplasmin
    • 1un0, 2c1t – yIPO NLS-binding domain (mutant) + Nup2
    • 5h2x, 5h2w – yIPO NLS-binding domain + ubiquitin-like specific protease
    • 4xzr – yIPO NLS-binding domain + HEH1
    • 4pvz – yIPO NLS-binding domain + HEH2
    • 4rxh – IPO NLS-binding domain + SV40 large T antigen – Neurospora crassa
  • IPO-α complex with protein
    • 1wa5 – yIPO NLS-binding domain + GTPase Ran + IPO-α re-exporter
  • IPO-α 1
    • 3wpt – hIPO NLS-binding domain - human
    • 4b8j – rIPO
  • IPO-α 1 complex with NLS peptide
    • 4mz5, 4mz6 – mIPO NLS-binding domain + dUTPase
    • 4oih – mIPO NLS-binding domain + guanine nucleotide exchange factor SRM1
    • 5svz – mIPO NLS-binding domain + TAT NLS motif
    • 5wum, 5wun, 5x8n – mIPO NLS-binding domain + Epstein Barr antigen
    • 5huw – mIPO NLS-binding domain + HSVI large terminase
    • 5huy – mIPO NLS-binding domain + HSMV small terminase
    • [[5hhg, 5fc8 – mIPO NLS-binding domain + dengue 2 NS5
    • 5ekg, 5ekf, 5e6q – mIPO NLS-binding domain + XPG2
    • 5d5k – mIPO NLS-binding domain + PARP 2
    • 5ctt – mIPO NLS-binding domain + SART3/TIP110
    • 5b56 – mIPO NLS-binding domain + HIV-1 VPR
    • 4zdu – mIPO NLS-binding domain + influenza nucleoprotein
    • 4yi0 – mIPO NLS-binding domain + Nup121
    • 5klr, 5klt – mIPO NLS-binding domain + NLS
    • 5k9s – mIPO NLS-binding domain + HNF-b
    • 4b18 – hIPO NLS-binding domain + telomerase reverse transcriptase
    • 4wv6 – hIPO NLS-binding domain + TFIID
    • 4b8o – rIPO NLS-binding domain + SV40
    • 4b8p – rIPO NLS-binding domain + A89
    • 4bpl – rIPO NLS-binding domain + nucleoplasmin
    • 4bqk – rIPO NLS-binding domain + VirD2
  • IPO-α 1 complex with protein
    • 2jdq – hIPO NLS-binding domain + polymerase basic protein 2 C terminal
    • 3tj3 – hIPO NLS-binding domain + Nup50 N terminal
    • 2jdq – hIPO NLS-binding domain + telomerase reverse transcriptase peptide
    • 4uaf – mIPO NLS-binding domain + influenza RNA polymerase
  • IPO-α 2
    • 3tpo – mIPO
    • 1iq1 – mIPO NLS-binding + autoinhibitory peptide domains
    • 4e4v – hIPO NLS-binding domain (mutant)
  • IPO-α 2 complex with NLS peptide
    • 1pjm – mIPO NLS-binding domain + retinoblastoma-associated protein
    • 1pjn – mIPO NLS-binding domain + histone-binding protein N1/N2
    • 1q1s, 1q1t – mIPO NLS-binding domain + SV40 large T antigen
    • 1y2a, 3q5u – mIPO NLS-binding domain + phospholipid scramblase
    • 2c1m – mIPO NLS-binding domain + Nup50
    • 3btr – mIPO NLS-binding domain + androgen receptor
    • 3knd – mIPO NLS-binding domain + targeting protein for KXLP2
    • 3l3q – mIPO NLS-binding domain + library peptide
    • 3oqs – mIPO NLS-binding domain + CLIC4
    • 3rz9 – mIPO NLS-binding domain + KU80
    • 3rzx – mIPO NLS-binding domain + KU70
    • 3tpm – mIPO NLS-binding domain + MAL
    • 3ve6 – mIPO NLS-binding domain + Venezuelan equine encephalitis virus
    • 3uvu – mIPO NLS-binding domain + flap endonuclease
    • 3ukw, 3ukx – mIPO NLS-binding domain + BIMAX
    • 3uky, 3ukz, 3ul0 – mIPO NLS-binding domain + nuclear CAP-binding protein
    • 3ul1 – mIPO NLS-binding domain + nucleoplasmin
    • 4htv – mIPO NLS-binding domain + capsid protein
    • 4ba3 – mIPO NLS-binding domain + A89NLS
    • 3zio, 3zip, 3ziq, 3zir – mIPO NLS-binding domain + minor site-specific NLS
    • 3zin – mIPO NLS-binding domain + nucleolar RNA helicase
  • IPO-α 2 complex with protein
    • 3fex, 3fey – mIPO NLS-binding domain + nuclear CAP-binding protein
  • IPO-α 3
    • 4uae – hIPO NLS-binding domain + influenza RNA polymerase
  • IPO-α 6
    • 4u2x – hIPO C terminal + ebola VP24
  • IPO-α 7
    • 4uad – hIPO NLS-binding domain + influenza RNA polymerase
  • IPO-β
    • 4xrk – IPO – Chaetomium thermophilum
  • IPO-β 1 (karyopherin β 1)
  • IPO-β 1 complex with protein
    • 1qgx, 1qgr – hIPO + IPO-α 2 IBB domain
    • 1ibr – hIPO + GTPase Ran
    • 2bku, 3ea5 – yIPO + GTPase Ran
    • 1f59, 1o6p, 1o6o – hIPO + FXFG nucleoporin repeats
    • 1m5n – hIPO HEAT repeats 1-11 + parathyroid hormone-related protein NLS peptide
    • 2p8q, 2q5d, 2qna, 3lww – hIPO + RNA U transporter N terminal
    • 1qgr, 3w5k – hIPO + zinc finger protein SNAI1
    • 2bpt – yIPO + Nup1
    • 1ukl – mIPO + SREBP-2
  • IPO-β 2 (Transportin 1)
  • IPO-β 2 complex with protein
    • 2h4m, 2ot8, 2z5n – hIPO + hnRNP peptide
    • 2z5k, 2z5m – hIPO + nuclear RNA export factor peptide
    • 2z5o – hIPO + JKTBP peptide
    • 4fdd, 4jlq, 4oo6 – hIPO + RNA binding protein peptide
    • 4fq3 – hIPO + FUS peptide
    • 5tqc – hIPO + RPL4 peptide
    • 5j3v – hIPO + histone H3 peptide
  • IPO-β 3 (Karyopherin β 3)
    • 3w3t – yIPO
    • 3w3u, 3w3v – yIPO (mutant)
    • 3w3w – yIPO + STE12P
    • 3w3x – yIPO + PHO4
    • 3w3y – yIPO + Nup53P
    • 3w3z – yIPO + RANGTP
    • 5h2v – yIPO + ubiquitin-like specific protease
    • 4zj7 – yIPO + CDC14
  • IPO-12 (Transportin-3)
    • 4c0p – hIPO
    • 4c0o – hIPO + serine/arginine-rich splicing factor
    • 4c0q, 4ol0 – hIPO + GTPase Ran
  • IPO-13 (karyopherin 13)
    • 2x19 – hIPO + GTPase Ran
    • 2xwu – hIPO + UBC9
    • 3zjy – hIPO + GTPase Ran + EIF-1A

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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. 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