Importin subunit alpha (KPNA)

Importin subunit alpha (KPNA) is a family of adaptor proteins essential for the classical nuclear import pathway, which facilitates the translocation of proteins from the cytoplasm into the nucleus (Wikipedia, 2024). It functions by recognizing and binding to the nuclear localization signal (NLS) of cargo proteins through its armadillo (ARM) repeat domain, subsequently forming a ternary complex with importin subunit beta-1 (KPNB1) (NIH, 2015). This complex then interacts with the nuclear pore complex (NPC) to deliver the cargo into the nucleoplasm, where Ran-GTP binding triggers the release of the cargo (NIH, 2007). Beyond its role in normal cellular homeostasis, importin-α is frequently hijacked by various viruses, such as HIV-1, Influenza A, and SARS-CoV-2, to transport viral genomes or proteins into the host nucleus for replication (MDPI, 2018; NIH, 2023). In oncology, specific isoforms like KPNA2 are often overexpressed in multiple cancers, including breast and lung cancer, where they facilitate the nuclear entry of oncogenic transcription factors and serve as markers of poor prognosis (NIH, 2016). Therapeutic targeting of importin-α, notably by small molecules like ivermectin, aims to competitively inhibit the NLS-binding pocket, thereby blocking the nuclear import of viral and pro-tumorigenic proteins (Semantic Scholar, 2012).

Other names

Karyopherin alphaImportin alphaSRP1RCH1QIP1PTAC58KPNA1KPNA2KPNA3KPNA4KPNA5KPNA6KPNA7

Competitive inhibition of the nuclear localization signal (NLS) binding site on importin-α, preventing the formation of the importin-α/β/cargo ternary complex and subsequent translocation into the nucleus.