IPO5 explained

Importin-5 is a protein that in humans is encoded by the IPO5 gene.^{[1] [2] [3]} The protein encoded by this gene is a member of the importin beta family. Structurally, the protein adopts the shape of a right hand solenoid and is composed of 24 HEAT repeats.^[4]

Function

Nuclear transport, a signal- and energy-dependent process, takes place through nuclear pore complexes embedded in the nuclear envelope. The import of proteins containing a nuclear localization signal (NLS) requires the NLS import receptor, a heterodimer of importin alpha and beta subunits also known as karyopherins. Importin alpha binds the NLS-containing cargo in the cytoplasm and importin beta docks the complex at the cytoplasmic side of the nuclear pore complex. In the presence of nucleoside triphosphates and the small GTP binding protein Ran, the complex moves into the nuclear pore complex and the importin subunits dissociate. Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. Interactions between importin beta and the FG repeats of nucleoporins are essential in translocation through the pore complex.^[5]

IPO5 facilitates cytoplasmic polyadenylation element-binding protein (CPEB)3 translocation by binding to RRM1 motif of CPEB3 in neurons. NMDAR signaling increases RanBP1 expression and reduces the level of cytoplasmic GTP-bound Ran. These changes enhance CPEB3–IPO5 interaction, which consequently accelerates the nuclear import of CPEB3 and promotes its nuclear function.^[6]

Further reading

• Bukrinsky MI, Haffar OK . HIV-1 nuclear import: in search of a leader . Frontiers in Bioscience . 2 . d578-87 . December 1997 . 4 . 9366553 . 10.2741/A213 . free .
• Bukrinsky MI, Haffar OK . HIV-1 nuclear import: matrix protein is back on center stage, this time together with Vpr . Molecular Medicine . 4 . 3 . 138–43 . March 1998 . 9562972 . 2230352 . 10.1007/BF03401911 .
• Christophe D, Christophe-Hobertus C, Pichon B . Nuclear targeting of proteins: how many different signals? . Cellular Signalling . 12 . 5 . 337–41 . May 2000 . 10822175 . 10.1016/S0898-6568(00)00077-2 .
• Chook YM, Blobel G . Karyopherins and nuclear import . Current Opinion in Structural Biology . 11 . 6 . 703–15 . December 2001 . 11751052 . 10.1016/S0959-440X(01)00264-0 .
• Bukrinsky MI, Sharova N, Dempsey MP, Stanwick TL, Bukrinskaya AG, Haggerty S, Stevenson M . Active nuclear import of human immunodeficiency virus type 1 preintegration complexes . Proceedings of the National Academy of Sciences of the United States of America . 89 . 14 . 6580–4 . July 1992 . 1631159 . 49545 . 10.1073/pnas.89.14.6580 . 1992PNAS...89.6580B . free .
• Bukrinsky MI, Haggerty S, Dempsey MP, Sharova N, Adzhubel A, Spitz L, Lewis P, Goldfarb D, Emerman M, Stevenson M . 6 . A nuclear localization signal within HIV-1 matrix protein that governs infection of non-dividing cells . Nature . 365 . 6447 . 666–9 . October 1993 . 8105392 . 10.1038/365666a0 . 9524217 . 1993Natur.365..666B . 25678 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . September 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Gallay P, Hope T, Chin D, Trono D . HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway . Proceedings of the National Academy of Sciences of the United States of America . 94 . 18 . 9825–30 . September 1997 . 9275210 . 23276 . 10.1073/pnas.94.18.9825 . 1997PNAS...94.9825G . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Henderson BR, Percipalle P . Interactions between HIV Rev and nuclear import and export factors: the Rev nuclear localisation signal mediates specific binding to human importin-beta . Journal of Molecular Biology . 274 . 5 . 693–707 . December 1997 . 9405152 . 10.1006/jmbi.1997.1420 .
• Efthymiadis A, Briggs LJ, Jans DA . The HIV-1 Tat nuclear localization sequence confers novel nuclear import properties . The Journal of Biological Chemistry . 273 . 3 . 1623–8 . January 1998 . 9430704 . 10.1074/jbc.273.3.1623 . free .
• Vodicka MA, Koepp DM, Silver PA, Emerman M . HIV-1 Vpr interacts with the nuclear transport pathway to promote macrophage infection . Genes & Development . 12 . 2 . 175–85 . January 1998 . 9436978 . 316441 . 10.1101/gad.12.2.175 .
• Popov S, Rexach M, Zybarth G, Reiling N, Lee MA, Ratner L, Lane CM, Moore MS, Blobel G, Bukrinsky M . 6 . Viral protein R regulates nuclear import of the HIV-1 pre-integration complex . The EMBO Journal . 17 . 4 . 909–17 . February 1998 . 9463369 . 1170440 . 10.1093/emboj/17.4.909 .
• Popov S, Rexach M, Ratner L, Blobel G, Bukrinsky M . Viral protein R regulates docking of the HIV-1 preintegration complex to the nuclear pore complex . The Journal of Biological Chemistry . 273 . 21 . 13347–52 . May 1998 . 9582382 . 10.1074/jbc.273.21.13347 . free .
• Fouchier RA, Meyer BE, Simon JH, Fischer U, Albright AV, González-Scarano F, Malim MH . Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex . Journal of Virology . 72 . 7 . 6004–13 . July 1998 . 9621063 . 110405 . 10.1128/JVI.72.7.6004-6013.1998 .

Notes and References

1. Yaseen NR, Blobel G . Cloning and characterization of human karyopherin beta3 . Proceedings of the National Academy of Sciences of the United States of America . 94 . 9 . 4451–6 . April 1997 . 9114010 . 20743 . 10.1073/pnas.94.9.4451 . 1997PNAS...94.4451Y . free .
2. Deane R, Schäfer W, Zimmermann HP, Mueller L, Görlich D, Prehn S, Ponstingl H, Bischoff FR . 6 . Ran-binding protein 5 (RanBP5) is related to the nuclear transport factor importin-beta but interacts differently with RanBP1 . Molecular and Cellular Biology . 17 . 9 . 5087–96 . September 1997 . 9271386 . 232359 . 10.1128/mcb.17.9.5087 .
3. Deng T, Engelhardt OG, Thomas B, Akoulitchev AV, Brownlee GG, Fodor E . Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex . Journal of Virology . 80 . 24 . 11911–9 . December 2006 . 17005651 . 1676300 . 10.1128/JVI.01565-06 .
4. Swale C, Da Costa B, Sedano L, Garzoni F, McCarthy AA, Berger I, Bieniossek C, Ruigrok RW, Delmas B, Crépin T . 6 . X-ray Structure of the Human Karyopherin RanBP5, an Essential Factor for Influenza Polymerase Nuclear Trafficking . Journal of Molecular Biology . 432 . 10 . 3353–3359 . May 2020 . 32222384 . 10.1016/j.jmb.2020.03.021 . 219670671 .
5. Web site: Entrez Gene: RANBP5 RAN binding protein 5.
6. Chao HW, Lai YT, Lu YL, Lin CL, Mai W, Huang YS . NMDAR signaling facilitates the IPO5-mediated nuclear import of CPEB3 . Nucleic Acids Research . 40 . 17 . 8484–98 . September 2012 . 22730302 . 3458550 . 10.1093/nar/gks598 .