Transportin-3

Transportin-3 (TNPO3) is a protein that plays a crucial role in the transport of molecules within cells. It is a member of the importin-beta family of nuclear transport receptors and is involved in the nucleocytoplasmic transport of various cargoes, including proteins and ribonucleoprotein complexes.

Function[edit | edit source]

Transportin-3 functions as a carrier protein, shuttling molecules between the nucleus and the cytoplasm. It recognizes specific nuclear localization signals (NLS) on cargo molecules and facilitates their import into the nucleus. Similarly, it recognizes nuclear export signals (NES) on cargo molecules and mediates their export from the nucleus to the cytoplasm.

Structure[edit | edit source]

Transportin-3 is a large protein consisting of multiple domains. It contains an N-terminal importin-beta binding domain, which allows it to interact with importin-beta and form a complex for cargo transport. It also has a central region that contains multiple HEAT (Huntingtin, elongation factor 3, protein phosphatase 2A, and TOR1) repeats, which are involved in protein-protein interactions. The C-terminal region of Transportin-3 contains a Ran-binding domain, which enables it to interact with the small GTPase Ran and regulate cargo release.

Role in Disease[edit | edit source]

Transportin-3 has been implicated in various diseases. Mutations in the TNPO3 gene have been associated with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These mutations disrupt the normal function of Transportin-3, leading to impaired nucleocytoplasmic transport and subsequent cellular dysfunction.

Interactions[edit | edit source]

Transportin-3 interacts with a wide range of cargo molecules, including transcription factors, RNA-binding proteins, and viral proteins. Some notable interactions include its association with the transcription factor NFAT (nuclear factor of activated T-cells), which regulates gene expression in immune cells. Transportin-3 also interacts with the HIV-1 protein Rev, facilitating the nuclear export of viral RNA.