Karyopherin subunit alpha 3 (KPNA3)

Karyopherin subunit alpha 3 (KPNA3), commonly known as importin alpha-3, is a nuclear transport protein belonging to the importin alpha family, functioning as an adapter that recognizes nuclear localization signals (NLSs) on cargo proteins[2]. It forms a complex with importin beta (KPNB1), facilitating the translocation of large proteins through the nuclear pore complex in a Ran-dependent GTPase cycle[2]. KPNA3 is critically involved in the nuclear import of various proteins, including those implicated in neurodegenerative diseases. In the context of spinocerebellar ataxia type 3 (SCA3), KPNA3 mediates the import of polyglutamine-expanded ataxin-3, promoting its nuclear aggregation and toxicity, which are central to disease pathogenesis[1]. Experimental inhibition or knockdown of KPNA3 has been shown to rescue neurodegenerative phenotypes in in vivo models, highlighting its significance as a therapeutic target for disorders characterized by abnormal nuclear import and protein aggregation[1]. KPNA3 may play roles in infectious disease pathways and other disorders involving nucleocytoplasmic transport.

Other names

Importin subunit alpha-4IMA3Importin alpha-3Importin α3

Inhibition or modulation of KPNA3 can reduce abnormal nuclear import of disease-related proteins such as ataxin-3, alleviating toxicity and aggregation implicated in neurodegenerative diseases[1].