KPNA5

Description

The KPNA5 (karyopherin subunit alpha 5) is a protein-coding gene located on chromosome 6.

Importin subunit alpha-6 is a protein that in humans is encoded by the KPNA5 gene. The transport of molecules between the nucleus and the cytoplasm in eukaryotic cells is mediated by the nuclear pore complex (NPC) which consists of 60-100 proteins and is probably 120 million daltons in molecular size. Small molecules (up to 70 kD) can pass through the nuclear pore by nonselective diffusion; larger molecules are transported by an active process. Most nuclear proteins contain short basic amino acid sequences known as nuclear localization signals (NLSs).

KPNA5, also known as importin subunit alpha-6, acts as an adapter protein for the nuclear receptor KPNB1 in nuclear protein import. It directly binds to substrates containing either simple or bipartite NLS motifs. The importin/substrate complex docks to the nuclear pore complex (NPC) via KPNB1's interaction with nucleoporin FxFG repeats. Subsequently, the complex translocates through the pore using a Ran-dependent, energy-requiring mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta, causing the complex to dissociate. Importin-alpha and -beta are then re-exported from the nucleus to the cytoplasm, where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be driven by the unequal distribution of GTP- and GDP-bound forms of Ran between the nucleus and cytoplasm. KPNA5 mediates the nuclear import of STAT1 homodimers and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1 and STAT2 through ARM repeats 8-9. It also recognizes influenza A virus nucleoprotein through ARM repeat 7-9. In vitro studies indicate that KPNA5 mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.

KPNA5 is also known as IPOA6, SRP6.

Associated Diseases

WES Whole Exome Sequencing