KPNA4

Description

The KPNA4 (karyopherin subunit alpha 4) is a protein-coding gene located on chromosome 3.

Importin subunit alpha-3, also known as karyopherin subunit alpha-4, is a protein that in humans is encoded by the KPNA4 gene. The nuclear import of karyophilic proteins is directed by short amino acid sequences termed nuclear localization signals (NLSs). Karyopherins, or importins, are cytoplasmic proteins that recognize NLSs and dock NLS-containing proteins to the nuclear pore complex. The protein encoded by this gene shares the sequence similarity with Xenopus importin-alpha and Saccharomyces cerevisiae Srp1. This protein is found to interact with the NLSs of DNA helicase Q1 and SV40 T antigen. KPNA4 has been shown to interact with RECQL and STAT3.

KPNA4 functions as an adapter protein for nuclear receptor KPNB1 in nuclear protein import. It directly binds to substrates containing simple or bipartite NLS motifs, facilitating their transport across the nuclear pore complex (NPC). This docking process is mediated by KPNB1's interaction with nucleoporin FxFG repeats. The importin/substrate complex is then translocated through the NPC in an energy-requiring, Ran-dependent mechanism. Once inside the nucleus, Ran binds to importin-beta, causing the complex to dissociate. Importin-alpha and -beta are then re-exported to the cytoplasm, where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is controlled by the uneven distribution of GTP- and GDP-bound forms of Ran between the cytoplasm and the nucleus. In vitro studies demonstrate KPNA4's ability to recognize and mediate the nuclear import of human cytomegalovirus UL84, utilizing a non-classical NLS.

KPNA4 is also known as IPOA3, QIP1, SRP3.

Associated Diseases

WES Whole Exome Sequencing