KPNA6

KPNA6 (Karyopherin alpha 6), also known as importin alpha 7, is a protein that in humans is encoded by the KPNA6 gene. This protein is part of the karyopherin alpha family and plays a critical role in the nuclear import of proteins. It functions as an adaptor that mediates the nuclear import of various proteins by recognizing nuclear localization signals (NLSs) and facilitating their transport through the nuclear pore complex in a process that requires the RanGTPase cycle.

Function

KPNA6 is involved in the nuclear import of proteins by acting as an adapter between the nuclear localization signals (NLS) of target proteins and the nuclear transport receptor, importin-beta. This interaction is essential for the translocation of proteins from the cytoplasm into the nucleus, a fundamental process in cellular regulation and signaling. KPNA6 recognizes classical NLS motifs, which are typically rich in basic amino acids, through its armadillo repeat domain. Once KPNA6 binds to its cargo protein, it associates with importin-beta to form a trimeric complex. This complex is then translocated through the nuclear pore complex into the nucleus. Inside the nucleus, RanGTP binds to the complex, causing disassembly and release of the cargo protein.

Clinical Significance

Alterations in the expression or function of KPNA6 have been implicated in various diseases, including cancer. Overexpression of KPNA6 has been observed in certain types of cancers and is associated with poor prognosis. It is thought that the increased nuclear import of oncogenic proteins mediated by KPNA6 may contribute to tumorigenesis. Additionally, KPNA6 has been studied in the context of viral infections, where it may facilitate the nuclear import of viral proteins, aiding in viral replication.

Structure

The KPNA6 protein contains an N-terminal importin-beta binding (IBB) domain, which is responsible for its interaction with importin-beta. The central and C-terminal regions of KPNA6 consist of armadillo (ARM) repeats, which are involved in the recognition of NLS motifs in cargo proteins. The structure of KPNA6, like other members of the karyopherin alpha family, is adapted for its role in protein transport, allowing it to interact with a wide range of NLS-containing proteins.

Gene

The KPNA6 gene is located on chromosome 1q32.1 and consists of multiple exons. The gene undergoes alternative splicing, resulting in different isoforms of the KPNA6 protein, which may have distinct functions or regulatory mechanisms.

See Also

• Nuclear localization signal
• Importin
• RanGTPase
• Nuclear pore complex
• Armadillo repeat