Transportin-1 (TNPO1)

Transportin-1 (TNPO1, also known as karyopherin beta-2) is a nuclear import receptor belonging to the karyopherin beta family[1][3][4][6]. It mediates the import of proteins with non-classical proline-tyrosine nuclear localization signals (PY-NLS) and related motifs, including RNA-binding proteins (such as FUS, hnRNPs), transcription factors, and other regulatory proteins[1][3][4][5][6]. TNPO1 recognizes diverse cargoes through both well-characterized PY-NLS motifs and less understood non-PY-NLS mechanisms, adapting by engaging distinct structural epitopes[3][5][6]. Its nuclear transport activity is essential for proper subcellular localization and function of its cargoes; disruption leads to cellular aggregation, stress responses, and has been implicated in neurodegenerative disorders (notably ALS and FTD), as well as in oncogenic and viral processes[1][3][6]. TNPO1 is highly regulated by post-translational modifications, and beyond nuclear transport, it also moonlights in protein targeting to subcellular compartments, ciliary import, and in modulating aggregation-prone protein phase separation[3][6]. There are no clinically approved drugs directly targeting TNPO1, but the protein is a prominent research focus as a potential therapeutic node in protein mislocalization pathologies and viral infections[5].

Other names

Karyopherin beta-2Kapβ2Importin beta-2KPNB2M9 region interaction proteinImportin 2IPO2TRNMIPMIP1

Blockade/inhibition of nuclear import function (e.g., competitive inhibition of PY-NLS binding)