KPNA4

KPNA4 (Karyopherin Alpha 4), also known as importin alpha 3, is a protein that in humans is encoded by the KPNA4 gene. This protein is part of the karyopherin alpha family, which plays a critical role in the nuclear import pathway. The nuclear import pathway is essential for the transport of proteins from the cytoplasm into the nucleus, a process that is fundamental for cellular function and regulation.

Function

KPNA4 functions as an adaptor that mediates the nuclear import of proteins by ferrying them through the nuclear pore complex. It recognizes nuclear localization signals (NLS) on the cargo proteins and interacts with the nuclear transport receptor, importin beta, forming a trimeric complex. This complex is then transported through the nuclear pore. Once inside the nucleus, RanGTP binds to the complex, causing disassembly and release of the cargo protein.

Structure

The KPNA4 protein is composed of several armadillo (ARM) repeats, which are involved in protein-protein interactions. These ARM repeats form a superhelical structure that creates a major groove for NLS recognition. The specific recognition of NLS motifs by KPNA4 is crucial for the selective import of proteins into the nucleus.

Clinical Significance

Alterations in the expression or function of KPNA4 have been implicated in various diseases. For example, dysregulation of KPNA4 has been associated with cancer progression, as it may affect the nuclear import of proteins that regulate cell cycle and apoptosis. Additionally, mutations in the KPNA4 gene could potentially disrupt the nuclear import pathway, leading to diseases caused by the mislocalization of critical regulatory proteins.

Research

Research on KPNA4 continues to uncover its role in cellular processes and its potential as a therapeutic target. Studies have focused on understanding the detailed mechanism of nuclear import, the specific interactions between KPNA4 and its cargo proteins, and the regulation of KPNA4 expression and function.

See Also

• Nuclear pore
• Nuclear localization signal
• Importin
• RanGTP