NTF2-like Export Factor 2, also known as NXT2, is a protein encoded by the NXT2 gene in humans. This protein plays a crucial role in the nucleocytoplasmic transport of macromolecules, ions, and small molecules between the cytoplasm and the nucleus. It is particularly significant in the context of mRNA nuclear export and protein export for NES-containing proteins .
NXT2 contains a nuclear transport factor 2 (NTF2) domain, which is essential for its function. The NTF2 domain is a versatile fold that can accommodate various sequences and has no characteristic sequence motif associated with it . This domain mediates the binding of NXT2 to other nuclear export factors such as NXF1, NXF2, and NXF3 .
In eukaryotic cells, the nuclear envelope acts as a barrier that separates the nucleus from the cytoplasm. The NXT2 protein is involved in the export of bulk poly(A)±mRNAs through the nuclear pore complex. It interacts with crucial components of the nuclear export machinery, including NXF1, the testis-specific NXF1 paralogs NXF2 and NXF3, and the nuclear pore complex proteins NUP93 and NUP214 .
NXT2 exhibits testis-enriched expression, suggesting a role in spermatogenesis. It is critical for the proper development of germ cells. Loss-of-function variants in NXT2 and NXF3 have been linked to impaired germ cell development and male infertility . The predominant absence of germ cells in men with NXT2 deficiency indicates its critical function during the early stages of germ cell development. In contrast, loss of NXF3 affects later stages of spermatogenesis, resulting in quantitatively and qualitatively impaired sperm production .
The study of NXT2 and its interactions with other nuclear export factors is essential for understanding the mechanisms of nucleocytoplasmic transport and its implications in various biological processes. Recombinant NXT2 protein is used in research to investigate its role in mRNA nuclear export and protein export. Understanding the function of NXT2 can provide insights into the molecular basis of male infertility and other related disorders.