Karyopherin alpha 2

Karyopherin alpha 2 (KPNA2), also known as importin alpha 1, is a protein that in humans is encoded by the KPNA2 gene. This protein is a member 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 proteins by binding to their nuclear localization signals (NLS) and to the nuclear transport receptor, karyopherin beta, facilitating their translocation through the nuclear pore complex.

Function

KPNA2 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, karyopherin beta 1. This interaction is essential for the translocation of proteins from the cytoplasm into the nucleus, a process that is fundamental for the regulation of numerous cellular functions including cell cycle progression, DNA replication, and repair. KPNA2 recognizes classical NLS motifs, which are typically rich in basic amino acids, through its NLS-binding site.

Structure

The structure of KPNA2 is characterized by a series of armadillo (ARM) repeats, which are involved in the interaction with the NLS motifs of cargo proteins. These ARM repeats form a superhelical structure that creates a large groove, serving as the binding site for the NLS motifs.

Clinical Significance

Alterations in the expression levels of KPNA2 have been associated with various types of cancer, including breast cancer, prostate cancer, and glioma. Overexpression of KPNA2 has been correlated with poor prognosis in several cancers, suggesting its potential role as a biomarker for cancer diagnosis and prognosis. Furthermore, KPNA2 has been implicated in the regulation of cell proliferation and apoptosis, highlighting its importance in cancer biology and the potential for targeting KPNA2 in cancer therapy.

Interaction

KPNA2 interacts with a variety of proteins, including karyopherin beta 1, which is involved in the nuclear-cytoplasmic transport, and numerous proteins containing classical nuclear localization signals. Through these interactions, KPNA2 plays a crucial role in the regulation of nuclear import of proteins involved in essential cellular processes.

See also

• Karyopherin
• Nuclear localization signal
• Nuclear pore complex
• Cell cycle
• DNA replication