Importin subunit alpha-1 (KPNA2) (KPNA2)

Importin subunit alpha-1 (KPNA2) is a critical adapter protein within the karyopherin alpha family, primarily responsible for the nucleocytoplasmic transport of proteins containing a nuclear localization signal (NLS) (UniProt P52294). It functions by binding to cargo proteins in the cytoplasm and subsequently associating with importin beta-1 to facilitate passage through the nuclear pore complex (NCBI Gene 3838). KPNA2 is involved in the nuclear import of several key regulatory proteins, including transcription factors like E2F1, NF-kappaB, and p53, as well as proteins involved in DNA repair and cell cycle progression (PMID: 33456565). In oncology, KPNA2 is frequently overexpressed across a wide range of malignancies, including breast, lung, and liver cancers, where its high expression levels correlate with increased tumor aggressiveness, poor patient prognosis, and resistance to therapy (PMID: 28848465). This overexpression facilitates the aberrant nuclear accumulation of oncogenic factors, thereby driving uncontrolled cell proliferation and survival. Consequently, KPNA2 has emerged as a significant therapeutic target, with research focusing on small molecule inhibitors, such as ivermectin, that can disrupt its transport activity and induce apoptosis in cancer cells (PMID: 32251768).

Other names

Karyopherin subunit alpha 2RCH1SRP1-alphaQIP2Importin alpha-2Pendulin

Inhibition of the nuclear import of cargo proteins by blocking the interaction between KPNA2 and nuclear localization signals (NLS) or the importin beta subunit.