Transportin 1

From WikiMD's medical encyclopedia

Transportin 1, also known as TNPO1, is a protein that plays a crucial role in the transport of molecules into and out of the cell nucleus. It is a member of the importin-beta family of nuclear transport receptors and is involved in the import of various cargoes, including proteins and ribonucleoprotein complexes, into the nucleus.

Function

Transportin 1 functions as a nuclear import receptor by recognizing and binding to specific nuclear localization signals (NLS) present on cargo molecules. It then interacts with the nuclear pore complex, a large protein complex that regulates the transport of molecules between the nucleus and the cytoplasm. Through this interaction, transportin 1 facilitates the translocation of cargo molecules across the nuclear envelope.

Role in Nuclear Import

Transportin 1 is responsible for the import of a wide range of cargoes into the nucleus. It recognizes and binds to cargoes containing classical NLS, which are short amino acid sequences rich in positively charged residues. Once bound to the cargo, transportin 1 forms a complex with other proteins, such as RanGTP, to facilitate the translocation of the cargo through the nuclear pore complex.

Interactions

Transportin 1 interacts with various proteins and factors involved in nuclear transport. One of its key interactions is with Ran, a small GTPase that regulates the directionality of nuclear transport. Transportin 1 binds to RanGTP in the nucleus, which triggers the release of the cargo molecule. This interaction is essential for the proper functioning of transportin 1 in nuclear import.

Clinical Significance

Transportin 1 has been implicated in several diseases and cellular processes. It is involved in the nuclear import of viral proteins, such as HIV-1 integrase, which is essential for the replication of the virus. Inhibition of transportin 1 has been explored as a potential therapeutic strategy for viral infections.

Additionally, transportin 1 has been linked to neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in the gene encoding transportin 1 have been identified in patients with these diseases, suggesting a role in disease pathogenesis.

References


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Contributors: Prab R. Tumpati, MD