NXT2 Human
Description
Introduction to NXT2 Human
NXT2 (Nuclear Transport Factor 2 Like Export Factor 2), also known as NTF2-related export protein 2 or P15-2, is a recombinant protein critical for nucleocytoplasmic RNA transport in eukaryotic cells . It belongs to the NXT family and shares functional homology with NXT1, though NXT2 exhibits testis-enriched expression, suggesting specialized roles in spermatogenesis . The recombinant human NXT2 protein is typically produced in E. coli with an N-terminal His-tag and purified via chromatography, making it a valuable tool for biochemical and functional studies .
RNA Export and Protein Regulation
NXT2 regulates nuclear export of NES-containing proteins and mRNA by interacting with NXF proteins (NXF1, NXF2, NXF3, NXF5) . Its NTF2-like domain mediates binding to NXF2 and NXF3, enabling cargo transport through nuclear pore complexes .
Tissue-Specific Functions
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Testis Dominance: Enriched expression in human testis, critical for spermatogenesis .
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Embryonic Development: Maintains morphogenetic integrity in vertebrate heart development .
Key Protein Interactions
Male Infertility and Genetic Variants
Recent studies identified loss-of-function NXT2 variants in infertile men, linking impaired RNA export to reduced germ cell development . Key findings:
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NXT2 Deficiency: Leads to near-complete absence of germ cells in testicular biopsies .
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NXF3 Deficiency: Disrupts later spermatogenesis stages, causing qualitative sperm defects .
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Mechanism: NTF2 domain mutations abrogate NXF2/NXF3 binding, halting RNA transport .
Research Applications
NXT2 is used in:
Product Specs
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Q&A
FAQs on NXT2 in Human Biology: Academic Research Perspectives
Advanced Research Questions
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How do loss-of-function (LoF) variants in NXT2 or NXF3 contribute to male infertility, and what are the conflicting findings across studies?
LoF variants in NXT2 are linked to non-obstructive azoospermia (NOA) due to germ cell depletion, while NXF3 LoF causes severe oligoasthenozoospermia . Contradictions arise in murine models: Nxt2 knockout mice remain fertile, highlighting primate-specific adaptations . Researchers address this by analyzing human-induced pluripotent stem cell (iPSC)-derived germ cells with CRISPR-edited NXT2 variants. -
What evolutionary evidence supports the functional divergence of NXT2 between humans and mice?
Phylogenetic analyses reveal: -
How does the NXT2 interactome adapt to support RNA export in the testis, and what methodological challenges exist in characterizing it?
The testis-specific NXT2 interactome includes NXF2/3 and lacks canonical NXF1 . Challenges include:
Data Contradictions and Resolution Strategies
Methodological Recommendations
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For functional studies: Prioritize CRISPR-Cas9 editing in human testicular organoids over murine models .
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For interaction mapping: Use crosslinking AP-MS in native testicular cells to preserve transient complexes .
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For clinical correlations: Integrate RNA-seq from NOA patients with proteomic data to identify NXT2-dependent pathways .
Product Science Overview
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.
