Recombinant Human Von Hippel-Lindau disease tumor suppressor (VHL),Biotinylated

^{In
Stock}

貨號：

CSB-EP025852HU-B
說明書：

MSDS Datasheet
規格：
圖片：
(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
其他：

產品詳情
產品評價
相關產品
靶點詳情

產品詳情

純度：

Greater than 85% as determined by SDS-PAGE.
基因名：

VHL
Uniprot No.：

P40337
種屬：

Homo sapiens (Human)
蛋白長度：

Full Length
來源：

E.coli
分子量：

71.9 kDa
表達區域：

1-213aa
氨基酸序列

MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.
蛋白標簽：

N-terminal MBP-tagged and C-terminal 6xHis-Avi-tagged
產品提供形式：

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.
緩沖液：

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
復溶：

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20℃/-80℃. Our default final concentration of glycerol is 50%. Customers could use it as reference.
儲存條件：

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
保質期：

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.
貨期：

3-7 business days
注意事項：

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Datasheet & COA：

Please contact us to get it.

產品評價

靶點詳情

功能：

Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions. Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases. Ubiquitinates, in an oxygen-responsive manner, ADRB2.
基因功能參考文獻：
1. The sporadic hemangioblastoma can occur rarely without a somatic biallelic VHL mutation. The VHL protein was earlier found to be associated with the deposition of matrix fibronectin (FN) protein in the renal extracellular matrix. PMID: 29813026
2. aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in clear cell renal cell carcinoma cells. PMID: 28643803
3. Study suggests that reduced expression of PBRM1 and VHL in clear cell renal cell carcinoma is correlated with an increased tumor aggressiveness. Low VHL expression identified as a risk factor for worse patient overall survival. PMID: 29169846
4. The results of the present study also demonstrated a mutation in VHL associated with the VHL syndrome phenotype, which may be of future therapeutic benefit for the diagnosis of VHL syndrome. PMID: 29749453
5. Overexpression of VHL was more successful at inhibiting fibrosis compared with silencing HIF-1a plus HIF-2a. Normoxia-active HIF-1a or HIF-2a prevented the inhibitory effect of VHL on liver fibrosis, indicating that attenuating fibrosis via VHL is HIF-1a- and HIF-2a-dependent to some extent. PMID: 28112200
6. The inverse correlation between the VHL gene expression profile and alisertib sensitivity was further confirmed in human cancer xenografts models. Taken together, these results suggested that VHL loss could potentially serve as a biomarker for predicting the efficacy of AURKA inhibitors. PMID: 29845253
7. JMJD6 regulates VHL gene expression in the human placenta. VHL downregulation in preeclampsia is dependent on decreased JMJD6 demethylase activity due to hypoxia and reduced Fe2+ bioavailability. PMID: 29373688
8. Low VHL expression is associated with papillary thyroid carcinoma. PMID: 29340905
9. that the reduced expression of LimD1 and VHL might have synergistic effect on induction of HIF1alpha resulting increased cellular proliferation and progression of the disease. PMID: 29033184
10. A two-hit loss involving VHL predicted for clear-cell renal cell carcinoma(ccRCC ) and a better prognosis, whereas mutations in PTEN, TP53, or RELN predicted for Sarcomatoid clear-cell renal cell carcinoma and worse prognosis. PMID: 28710314
11. we report a rare case of renal-cell carcinoma and hereditary polycythemia. Genotyping revealed that the patient carried both a germline HIF2A mutation and a somatic VHL mutation. Both mutations result in overactivation of HIF2A and its downstream target genes PMID: 29172931
12. The co-transfection of VHL and PLN in HEK293 cells decreased PLN expression under oxidative stress, whereas knockdown of VHL increased PLN expression both under normal and oxidative stress conditions. PMID: 29068413
13. missense mutations in the VHL gene during sporadic CCRCC were studied to evaluate their specific localization in relation to binding sites for the proteins interacting with VHL. PMID: 28853079
14. epigenomic profiling of clear cell renal cell carcinoma (ccRCC) establishes a compendium of somatically altered cis-regulatory elements, uncovering new potential targets including ZNF395. Loss of VHL, a ccRCC signature event, causes pervasive enhancer malfunction, with binding of enhancer-centric HIF2a and recruitment of histone acetyltransferase p300 at preexisting lineage-specific promoter-enhancer complexes PMID: 28893800
15. Biochemical analyses demonstrate that Daam2 associates with VHL and facilitates its ubiquitination and degradation. PMID: 29053101
16. VHLdb presently contains 478 interactors, of which 117 have been manually curated, and 1,074 mutations. This makes it the largest available database for pVHL-related information PMID: 27511743
17. A mouse model based on concurrent ectopic expression of constitutively active Notch1 (NICD1) and deletion of the Vhl gene show the existence of nests of dysplastic cells in the kidney with a clear cytoplasm as a consequence of lipid accumulation, thus displaying a one important hallmark of human clear cell renal cell carcinoma. PMID: 27491826
18. VHL mutation is associated with paediatric pheochromocytoma and paraganglioma. PMID: 28432847
19. pVHL loss causes the transcriptional activation of hypoxia-inducible factor (HIF) target genes, including many genes that encode histone lysine demethylases. PMID: 28701475
20. VHL expression was associated with the presence of mutations, and the absence of expression was associated with nuclear grade and the presence of metastasis in clear cell renal cell carcinoma patients. PMID: 27836247
21. HIF-1alpha/miR-210 pathway is strongly activated in VHL mutated paragangliomas, weakly activated in SDHx mutated PGLs, and not activated in VHLdel- and SDHxwt/VHLwt-PGLs. PMID: 28036268
22. VHL missense mutations in the p53 binding domain show different effects on p53 signaling and HIFalpha degradation in clear cell renal cell carcinoma, enhancing tumor cell survival. PMID: 28052007
23. the structural model of the HIF2a-pVHL complex presented in this study enhances understanding of how HIF2a is captured by pVHL. Moreover, the important contact amino acids that we identified may be useful in the development of drugs to treat HIF2a-related diseases. PMID: 27902963
24. these findings demonstrate that USP9X is a novel regulator of Von Hippel-Lindau protein stability, and USP9X may be a therapeutic target for treatment of Von Hippel-Lindau protein-related tumors PMID: 27517496
25. To the best of our knowledge, this is the first report of the coexistence of VHL disease and CPT2 deficiency in the same individual. Based on findings from animal models, the case illustrates that mutations in the VHL gene might protect against renal damage caused by CPT2 gene mutations. PMID: 27034144
26. Our work provides the first evidence that VHL mutations positively correlate with PD-L1 expression in ccRCC and may influence the response to ccRCC anti-PD-L1/PD-1 immunotherapy. PMID: 26707870
27. VHL is one of the commonly disrupted genes in patients with Sarcomatoid Renal Cell Carcinoma. PMID: 26895810
28. This article puts together the sequential pathogenesis of VHL mutant Clear cell renal cell carcinoma (ccRCC) by elaborating these mechanisms and the interplay of oncogenic pathways, epigenetics, metabolism and immune evasion, with a perspective on potential therapeutic strategies. PMID: 27329246
29. VHL promoter region 7896829 which was hypermethylated with sunitinib treatment in metastatic clear cell renal cancer PMID: 27029034
30. Positive staining for pVHL was observed in cancerous areas but not in normal tissues in patients with tongue cancer PMID: 28549422
31. miR-92 can target the VHL transcript to repress its expression. PMID: 28952293
32. VHL gene expression is deregulated in the majority of papillary thyroid cancer tissues. PMID: 28089820
33. kidney-specific deletion of Vhl and Pbrm1, but not either gene alone, results in bilateral, multifocal, transplantable clear cell kidney cancers. PMID: 28329682
34. Loss of VHL gene is associated with paragangliomas. PMID: 28099933
35. It has been proposed that the archetypal linker protein Rootletin maintains centrosome cohesion in part through inhibition of VHL-mediated Cep68 degradation. PMID: 28089774
36. Results show that VHL missense mutations may exert mild, moderate or strong impact on protein stability. Besides the HIF binding domain, other pVHL binding sites seem to be non-randomly altered by missense mutations in sporadic clear cell renal cell carcinoma. PMID: 27530247
37. Data identify VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions. PMID: 28114281
38. Moderate/strong NEMO protein expression is more frequent in VHL wild-type ccRCCs. PMID: 26500060
39. The Absence of MCM7 weakened the interaction between Cep68 and VHL, whereas MCM7 overexpression facilitated the Cep68-VHL association. PMID: 28578000
40. this meta-analysis indicates that VHL gene alteration has no prognostic or predictive value in patients with clear cell renal cell carcinoma PMID: 28103578
41. Low VHL expression is associated with Clear cell renal cell carcinoma. PMID: 27841867
42. The negative feedback modulation between LncRNA-SARCC/AR complex and HIF-2alpha signaling may then lead to differentially modulated RCC progression in a VHL-dependent manner. Together, these results may provide us a new therapeutic approach via targeting this newly identified signal from LncRNA-SARCC to AR-mediated HIF-2alpha/C-MYC signals against RCC progression. PMID: 26973243
43. Our study reveals a novel mechanism regulating VHL proteostasis and function, which is significant for identifying new drug targets and developing new therapeutic approaches targeting VHL deficiency in VHL diseases. PMID: 26973240
44. The prefoldin subunit Pac10 (the human homolog VBP-1 binds to pVHL) is required for pVHL stability. Reduction of soluble functional pVHL might be crucial in VHL-related diseases. PMID: 27179072
45. Up-regulation of 14-3-3zeta in response to pVHL is important for the recruitment of PI3K to the cell membrane and for stabilization of soluble beta-catenin. PMID: 28666999
46. pVHL mediates K63-linked ubiquitination of IKKbeta, which plays a role in the regulation of IKK/NF-kappaB signalling. PMID: 27693634
47. VHL hypermethylation was significantly correlated with SLE. PMID: 27940592
48. by modulating hypoxia-inducible factor activity via up-regulation of VHL, FOXO3a (foxo3b) plays an important role in survival in response to hypoxic stress. PMID: 27777301
49. Results show that pVHL interacts with B-Myb for proteasomal degradation. This regulation of B-Myb by pVHL plays a critical role in von Hippel-Lindau disease. PMID: 27090638
50. The von Hippel-Lindau protein (pVHL)-dependent degradation of HIF-2a participates in the regulation of ERalpha expression. Additionally, HIF-2a forms a protein complex with ERa, and amino acids 396-823 of HIF-2a physically interact with the ligand-binding domain of ERa PMID: 27323688
顯示更多

收起更多
相關疾病：

Pheochromocytoma (PCC); von Hippel-Lindau disease (VHLD); Erythrocytosis, familial, 2 (ECYT2); Renal cell carcinoma (RCC)
亞細胞定位：

[Isoform 1]: Cytoplasm. Membrane; Peripheral membrane protein. Nucleus. Note=Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.; [Isoform 3]: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the cytoplasm but not membrane-associated.
蛋白家族：

VHL family
組織特異性：

Expressed in the adult and fetal brain and kidney.
數據庫鏈接：

HGNC: 12687

OMIM: 144700

KEGG: hsa:7428

STRING: 9606.ENSP00000256474

UniGene: Hs.517792