XPO4 (Exportin-4) is a member of the karyopherin-β family of nuclear transport receptors, primarily responsible for mediating the export of specific protein cargoes from the nucleus to the cytoplasm. It plays a critical role in maintaining cellular homeostasis by regulating the nucleocytoplasmic shuttling of transcription factors, tumor suppressors, and RNA-binding proteins. Unlike other exportins such as XPO1/CRM1. XPO4 specifically recognizes cargoes bearing a unique nuclear export signal (NES), including SMAD transcription factors (e.g., SMAD2/3) and SOX family proteins, which are pivotal in TGF-β signaling, embryonic development, and cancer progression.
The recombinant XPO4 protein is engineered using expression systems like *E. coli* or mammalian cells, enabling large-scale production of functional, purified XPO4 for research and therapeutic applications. Its recombinant form retains the ability to bind cargoes and RanGTP, a small GTPase essential for the transport cycle. Structural studies reveal that XPO4 contains characteristic HEAT repeats, facilitating interactions with cargoes and regulatory partners.
Dysregulation of XPO4 is implicated in diseases such as cancer, fibrosis, and neurodegenerative disorders. For instance, aberrant XPO4 activity may disrupt SMAD localization, contributing to TGF-β-driven metastasis or fibrosis. Conversely, XPO4 can act as a tumor suppressor by exporting oncogenic proteins. This dual role underscores its context-dependent functionality.
Recombinant XPO4 is widely used to study nuclear transport mechanisms, screen for small-molecule inhibitors, and develop targeted therapies. Recent efforts focus on modulating XPO4 to restore normal protein trafficking in pathological conditions. However, its therapeutic potential remains under exploration compared to XPO1. highlighting the need for further mechanistic and clinical studies.
以下是关于b3GAT2重组蛋白的3篇代表性文献摘要(注：文献为虚构示例，仅供格式参考)：
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1. **文献名称**：*Recombinant human β3GAT2 expression and enzymatic characterization in glycosaminoglycan synthesis*
**作者**：Smith A, et al.
**摘要**：本研究成功在大肠杆菌中表达并纯化了具有活性的重组人b3GAT2蛋白，证实其催化葡萄糖醛酸转移至糖胺聚糖核心结构的关键功能，为体外合成硫酸乙酰肝素提供了工具酶。
2. **文献名称**：*Structural insights into β3GAT2 substrate specificity via X-ray crystallography*
**作者**：Zhang L, et al.
**摘要**：通过解析重组b3GAT2的晶体结构，揭示了其底物结合口袋的关键氨基酸残基，解释了该酶对不同糖链受体的选择性机制，为设计特异性抑制剂奠定基础。
3. **文献名称**：*Role of recombinant β3GAT2 in modulating cancer cell adhesion*
**作者**：Tanaka K, et al.
**摘要**：利用重组b3GAT2蛋白处理肿瘤细胞，发现其通过调控细胞表面硫酸软骨素的合成，显著抑制癌细胞迁移和侵袭能力，提示其在癌症治疗中的潜在应用价值。
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**提示**：实际文献需通过PubMed或Google Scholar检索关键词“b3GAT2 recombinant”“β3-glucuronyltransferase 2”获取。可重点关注蛋白表达、酶学机制或疾病关联方向的研究。
**Background of b3GAT2 Recombinant Protein**
β3-glucuronyltransferase 2 (b3GAT2), also known as GlcAT-II, is a member of the glycosyltransferase 43 (GT43) family within the CAZy database. It catalyzes the transfer of glucuronic acid (GlcA) from UDP-GlcA to terminal galactose residues in glycosaminoglycan (GAG) biosynthesis, a critical step in forming proteoglycans like heparan sulfate and chondroitin sulfate. These sulfated polysaccharides play essential roles in cell signaling, extracellular matrix organization, and interactions with growth factors or receptors.
b3GAT2 is particularly associated with the biosynthesis of linker regions in GAG chains, acting early in the pathway to initiate chain elongation. Its activity influences the structural diversity of GAGs, which impacts cellular processes such as neuronal development, immune response, and tissue homeostasis. Dysregulation of b3GAT2 has been linked to pathological conditions, including cancer metastasis (due to altered cell adhesion) and congenital disorders affecting connective tissues.
Recombinant b3GAT2 protein is produced using heterologous expression systems (e.g., *E. coli* or mammalian cells) to study its enzymatic mechanisms, substrate specificity, and interactions. Purified b3GAT2 enables *in vitro* reconstitution of GAG synthesis pathways, aiding drug discovery for GAG-related diseases. Structural studies using recombinant protein have revealed insights into its catalytic domain and binding sites, though challenges remain in resolving full-length structures due to its membrane-associated nature.
Current research focuses on b3GAT2’s role in neurological disorders and its potential as a therapeutic target. Recombinant variants are also explored for biotechnological applications, such as engineering GAG-like polymers for biomaterials. Further studies aim to clarify its regulation and tissue-specific functions, advancing understanding of glycobiology and disease mechanisms.
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