| 纯度 | >90%SDS-PAGE. |
| 种属 | Human |
| 靶点 | Sharpin |
| Uniprot No | Q9H0F6 |
| 内毒素 | < 0.01EU/μg |
| 表达宿主 | E.coli |
| 表达区间 | 1-387aa |
| 氨基酸序列 | MAPPAGGAAAAASDLGSAAVLLAVHAAVRPLGAGPDAEAQLRRLQLSADPERPGRFRLELLGAGPGAVNLEWPLESVSYTIRGPTQHELQPPPGGPGTLSLHFLNPQEAQRWAVLVRGATVEGQNGSKSNSPPALGPEACPVSLPSPPEASTLKGPPPEADLPRSPGNLTEREELAGSLARAIAGGDEKGAAQVAAVLAQHRVALSVQLQEACFPPGPIRLQVTLEDAASAASAASSAHVALQVHPHCTVAALQEQVFSELGFPPAVQRWVIGRCLCVPERSLASYGVRQDGDPAFLYLLSAPREAPATGPSPQHPQKMDGELGRLFPPSLGLPPGPQPAASSLPSPLQPSWSCPSCTFINAPDRPGCEMCSTQRPCTWDPLAAAST |
| 预测分子量 | 47.4 kDa |
| 蛋白标签 | His tag N-Terminus |
| 缓冲液 | PBS, pH7.4, containing 0.01% SKL, 1mM DTT, 5% Trehalose and Proclin300. |
| 稳定性 & 储存条件 | Lyophilized protein should be stored at ≤ -20°C, stable for one year after receipt. Reconstituted protein solution can be stored at 2-8°C for 2-7 days. Aliquots of reconstituted samples are stable at ≤ -20°C for 3 months. |
| 复溶 | Always centrifuge tubes before opening.Do not mix by vortex or pipetting. It is not recommended to reconstitute to a concentration less than 100μg/ml. Dissolve the lyophilized protein in distilled water. Please aliquot the reconstituted solution to minimize freeze-thaw cycles. |
1. **文献名称**: "SHARPIN is a component of the TNF-R1 signaling complex and is required for NF-κB activation"
**作者**: Tokunaga F., et al.
**摘要**: 该研究揭示了Sharpin是线性泛素化复合物(LUBAC)的关键组分，通过促进TNF受体信号通路中NF-κB的激活，调控炎症反应和细胞存活，Sharpin缺失会导致小鼠皮肤炎症和免疫系统异常。
2. **文献名称**: "Sharpin prevents skin inflammation by inhibiting TNFR1-induced keratinocyte apoptosis"
**作者**: Kumari S., et al.
**摘要**: 研究证明Sharpin通过抑制TNF-α诱导的角质细胞凋亡维持皮肤稳态，其缺失会破坏表皮屏障功能，导致慢性炎症和自身免疫性疾病表型。
3. **文献名称**: "The E3 ligase HOIP specifies linear ubiquitination in the LUBAC complex through a unique ubiquitin-binding domain"
**作者**: Ikeda F., et al.
**摘要**: 解析了LUBAC复合物(含Sharpin)的分子机制，阐明其通过线性泛素化修饰调控NF-κB和细胞死亡信号通路，为炎症性疾病治疗提供靶点。
4. **文献名称**: "Sharpin promotes hepatocellular carcinoma progression via transactivating c-Myc and suppressing apoptosis"
**作者**: Zhang Y., et al.
**摘要**: 发现Sharpin在肝癌中高表达，通过激活c-Myc转录和抑制Bax介导的凋亡通路促进肿瘤生长与转移，提示其作为癌症治疗潜在靶点。
(注：以上文献信息为示例，实际引用需核实具体论文。)
Sharpin (SHANK-associated RH domain-interacting protein) is a multifunctional adaptor protein encoded by the UBR4 gene in humans. It is best known as a critical component of the linear ubiquitin chain assembly complex (LUBAC), an E3 ubiquitin ligase complex that regulates NF-κB signaling pathways by generating linear polyubiquitin chains on target proteins. Discovered through its interaction with the SHANK family of postsynaptic scaffolding proteins, Sharpin also plays roles in cell adhesion, apoptosis regulation, and integrin activation.
Biologically, Sharpin deficiency in mice (observed in *Cpdm* mice) leads to severe chronic proliferative dermatitis, immune system dysregulation, and defective lymphoid organ development, highlighting its importance in skin homeostasis and immune response. Its involvement in NF-κB activation connects it to inflammation, cancer progression, and resistance to apoptosis, making it a protein of interest in immunological and oncological research.
Recombinant Sharpin proteins are engineered to study these mechanisms *in vitro* or *in vivo*. Produced via bacterial (e.g., *E. coli*) or mammalian expression systems, recombinant Sharpin retains binding domains like the ubiquitin-like (UBL) domain and Npl4 zinc finger (NZF) motifs, enabling interaction with partners such as HOIP (LUBAC's catalytic subunit) and SHANK proteins. These proteins are often purified with tags (e.g., His, GST) for experimental flexibility.
Applications include investigating Sharpin's role in ubiquitination cascades, validating protein-protein interactions, and modeling diseases linked to LUBAC dysfunction, such as certain cancers and autoimmune disorders. Quality-controlled through SDS-PAGE, Western blotting, and functional assays, recombinant Sharpin serves as a tool to dissect signaling pathways and develop therapeutic strategies targeting NF-κB or ubiquitination processes.
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