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Beschreibung

Importin subunit alpha-3 (UniProt O35343, also known as Importin alpha Q1, Karyopherin subunit alpha-4, Qip1) is encoded by the Kpna4 (also known as Qip1) gene (Gene ID 16649) in murine species. The transport of macromolecules between cytoplasm and nucleus is mediated by importins and exportins and regulated by the small GTPase Ran. Importins bind their cargoes with either nuclear localization signal (NLS) or M9 domain-containing hnRNP proteins in the cytoplasm, while exportins target their substrates via their nuclear export signal (NES) or M9 domain inside the nucleus. Qip1/KPNA4 belongs to the importin- /karyopherin- (KPNA) family of adaptor proteins that interact with both monopartite and bipartite types of classical nuclear localization signals (cNLSs). The seven KPNA family members are divided into the 1 (KPNA1/5/6), 2 (KPNA2/7), and 3 (KPNA3/4) subfamilies based on structural and functional similarities. KPNA members mediate substrate cargo nuclear import by bridging substrate cargo and the Ran-karyopherin- complex. Both KPNA3 and Qip1/KPNA4 are reported to target methyl-CpG-binding protein 2 (MeCp2) bipartite NLS (255-RKAEADPQAIPKKRGRK-271). Qip1/KPNA4 can ineract with both wild-type and MeCp2 R270X mutants found in Rett syndrome (RTT) patients, while KPNA3 binds only wild-type, but not MeCp2 R270X mutants. Human and murine Qip1 contains an NLS (a.a. 43-52) in its importin- -binding (IBB) domain (a.a. 2-58), followed by ten ARM domains (a.a. 66-485), one majore and one minor NLS-binding site (a.a. 137-229 and a.a. 306-394).