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

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Code CSB-EP025852HU
Size US$2466
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  • (Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.

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Product Details

Purity Greater than 85% as determined by SDS-PAGE.
Target Names VHL
Uniprot No. P40337
Research Area Cancer
Alternative Names Elongin binding protein; G7 protein; HRCA 1; HRCA1; Protein G7; pVHL; RCA 1; RCA1; VHL 1; VHL; VHL_HUMAN; VHL1; VHLH; Von Hippel Lindau; Von Hippel Lindau disease tumor suppressor; von Hippel Lindau syndrome; von Hippel Lindau tumor suppressor; Von Hippel Lindau tumor suppressor, E3 ubiquitin protein ligase; Von Hippel-Lindau disease tumor suppressor
Species Homo sapiens (Human)
Source E.coli
Expression Region 1-213aa
Target Protein Sequence MPRRAENWDEAEVGAEEAGVEEYGPEEDGGEESGAEESGPEESGPEELGAEEEMEAGRPRPVLRSVNSREPSQVIFCNRSPRVVLPVWLNFDGEPQPYPTLPPGTGRRIHSYRGHLWLFRDAGTHDGLLVNQTELFVPSLNVDGQPIFANITLPVYTLKERCLQVVRSLVKPENYRRLDIVRSLYEDLEDHPNVQKDLERLTQERIAHQRMGD
Note: The complete sequence including tag sequence, target protein sequence and linker sequence could be provided upon request.
Mol. Weight 28.2 kDa
Protein Length Full Length
Tag Info N-terminal 6xHis-tagged
Form 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.
Buffer If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution 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°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.
Troubleshooting
and FAQs
Protein FAQs
Storage Condition Store at -20°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.
Shelf Life 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.
Lead Time Basically, we can dispatch the products out in 3-7 working days after receiving your orders. Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.
Notes 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.

Target Data

Function 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.
Gene References into Functions
  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
  51. Newcastle disease virus infection diminished hypoxia-induced HIF-1alpha accumulation in cancer cell lines through proteasomal pathways independent of VHL and p53. PMID: 27902314
  52. Data found that non-inactivated VHL expression level was associated with high expression level of PD-L1 and poor prognosis in clear cell renal cell carcinoma. PMID: 27623354
  53. Age-specific risk for CNS hemangioblastoma was significantly higher in subjects carrying missense mutations in alpha domain in exon 1; beta domain in exon 3 of von Hippel-Lindau tumor suppressor within the HIF-alpha binding site. PMID: 27439424
  54. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC PMID: 27485825
  55. Our aim was to identify VHL gene mutations in Argentinian patients who fulfilled the clinical criteria for type 1 VHL disease and in patients with VHL-associated manifestations. VHL mutations were detected in 16/19 (84.2%) patients in Group 1 and included: gross deletions (4/16); nonsense mutations (6/16); frameshift mutations (4/16); missense mutations (1/16); and splicing mutations (1/16). Three mutations were novel. PMID: 27617348
  56. Mutations in the VHL gene is associated with von Hippel-Lindau syndrome. PMID: 27527340
  57. The von Hippel-Lindau protein (pVHL) bound directly to hydroxylated Akt and inhibited Akt activity. PMID: 27563096
  58. VHL-deficient renal cancer cells gain resistance to mitochondria-activating apoptosis inducers by activating AKT through the IGF1R-PI3K pathway PMID: 27460078
  59. VHL promoter hypermethylation, which may play an important role in carcinogenesis of renal cell carcinoma (RCC), is significantly associated with an increased risk of RCC. PMID: 27997886
  60. VHLalpha isoform inhibits Warburg effect via modulation of PKM splicing. PMID: 27473082
  61. The VHL short variant is involved in protein quality control during translation. PMID: 27196060
  62. Study identified VHL as a direct target of miR-101 and demonstrated that miR-101 could increase HIF1alpha protein levels by repressing VHL in normoxia condition. PMID: 26841847
  63. VHL inactivation is associated with gastrointestinal stromal tumors. PMID: 25987131
  64. indicate that HIF-1alpha/pVHL/Hsp90 interactions may be implicated in biology of different types of brain tumors through different signaling mechanisms PMID: 26592496
  65. misfolded TDP-43 is cleared by VHL/CUL2 in a step-wise manner via fragmentation. PMID: 26751167
  66. Overexpression of VHL is associated with multiple myeloma. PMID: 26735336
  67. HBV induces the HIF2alpha expression through its encoded protein HBx. This upregulates the HIF-2alpha expression by binding to the pVHL activating the NF-kappaB signaling pathway PMID: 26647960
  68. proteome and phospho-proteomic analysis of isogenic 786-O renal cell carcinoma (+/-VHL) cells to compare signatures that reflect hypoxia and/or loss of VHL protein PMID: 26506913
  69. Pars plana vitrectomy in advanced VHL eye disease can improve or preserve visual function, but postoperative progression of ocular VHL disease can be accelerated in cases where retinotomy is performed. PMID: 26308528
  70. AR-suppressed miRNA-145 is a key player in renal cell carcinoma progression by regulating HIF2alpha/VEGF/MMP9/CCND1 expression levels, irrespective of VHL status. PMID: 26304926
  71. VHL was shown to influence cellular metabolism through its effect on HIF proteins as well as by affecting activity of other factors. PMID: 26620126
  72. Data indicate that mutant VHL can protect HIF1alpha from SART1-dependent degradation in normoxic conditions, but this protection is lost in hypoxic settings, favoring hypoxia-dependent ccRCC proliferation. PMID: 25915846
  73. VHLp19 has a role for regulating EPO levels that VHLp30 does not have, whereas VHLp30 is really the tumor suppressor isoform. PMID: 26224408
  74. Of note, we also observed that the shorter pVHL19 isoform shows an unexpected high tendency to form homodimers, suggesting an additional isoform-specific binding specialization. PMID: 26211615
  75. pVHL interacts with CERKL and ubiquitinates it for oxygen dependent proteasomal degradation. PMID: 26296657
  76. APOE, VHL and MTHFR gene polymorphisms were related to the risk of renal cell carcinoma PMID: 26191297
  77. A previously unclassified variant in the von Hippel Lindau disease gene (c.361G>C) is identified in a family with the disease. PMID: 25557216
  78. Distinct von Hippel-Lindau gene and hypoxia-regulated alterations in gene and protein expression patterns of renal cell carcinoma are accompanied with distinct metabolic changes. PMID: 25890500
  79. 14 (51.9%) patients had a germline mutation in the succinate dehydrogenase subunit B gene (SDHB), and 3 (11.1%) had mutations in the von Hippel-Lindau gene PMID: 25683602
  80. Hereditary pheochromocytoma / paraganglioma associated with VHL gene mutations has more aggressive course,bilateral adrenal involvement, higher recurrence rate, younger age at disease manifestations. PMID: 26591561
  81. Novel frameshift mutation in the VHL gene of the family members that contributes to VHL was detected. PMID: 25966224
  82. ID2 binds to the VHL ubiquitin ligase complex, displaces VHL-associated Cullin 2, and impairs HIF2alpha ubiquitylation and degradation PMID: 26735018
  83. Decreased VHL expression is associated with tumor progression in papillary thyroid carcinoma. PMID: 25490036
  84. ZBRK1 suppresses renal cancer progression perhaps by regulating VHL expression through formation of a complex with VHL and p300 in renal cancer PMID: 25749518
  85. HBV up-regulated miR-331-3p expression in HCC cell lines and miR-331-3p could inhibit VHL expression by directly targeting its 3'-UTR PMID: 25750939
  86. RSUME is expressed in VHL tumors and inhibits VHL and regulates its tumor suppressor function. PMID: 25500545
  87. VHL gene abnormalities were identified in the Chinese family with non-syndromic PCCs. PMID: 25773797
  88. The crystal structure of VHL bound to a Cul2 N-terminal domain, Elongin B, and Elongin C. PMID: 25661653
  89. pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation PMID: 26179906
  90. This is also the first nonsense mutation to manifest as VHL disease type 2 in ethnic Chinese PMID: 25069792
  91. Interaction between Nm23 and the tumor suppressor VHL PMID: 24915993
  92. Thirty-two percent (16/50) of patients were found to be positive for mutations including mutations among RET (n=4), VHL (n=6), SDHB (n=3), and SDHD (n=3) genes. PMID: 24977658
  93. Thus, Fulvestrant but not Tamoxifen, antagonist against ER-alpha, can restore the Taxol sensitivity in VHL- or BRCA1-deficient cells. Our results suggest that pVHL-mediated ER-alpha suppression is important for regulation of MTOC as well as drug resistance. PMID: 25499220
  94. Results from mutational analysis and genetic association studies in a Chinese family with Von Hippel-Lindau syndrome identified a novel small duplication creating a premature stop signal, resulting in severely truncated VHL protein. PMID: 25501229
  95. results confirmed that the existence of G allele in both rs779805 and rs1642742 in the von Hippel-Lindau tumor suppressor gene is of importance in renal cell carcinoma tumorigenesis PMID: 25217002
  96. VHL can inhibit SARS-CoV replication by regulating nsp16 ubiquitination and promoting its degradation. PMID: 25732088
  97. Molecular dynamics of hif-1alpha and VHL may determine the success of antineoplastic strategies in hypoxia-reoxygenation as predicted by computational modeling. PMID: 25338163
  98. Deep-coverage sequence analysis techniques uncovered VHL alterations within the neoplastic fraction of tumors. Findings support the role of VHL inactivation in the pathogenesis of familial and sporadic hemangioblastomas. PMID: 25589003
  99. This is the first report that identifies molecular aberrations in the VHL gene from a South Asian population. PMID: 24727139
  100. NEK8 may be a new target gene of HIFs; pVHL can down-regulate NEK8 via HIFs to maintain the primary cilia structure in human renal cancer cells PMID: 25451921

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Involvement in disease Pheochromocytoma (PCC); von Hippel-Lindau disease (VHLD); Erythrocytosis, familial, 2 (ECYT2); Renal cell carcinoma (RCC)
Subcellular Location 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, SUBCELLULAR LOCATION: Isoform 3: Cytoplasm, Nucleus
Protein Families VHL family
Tissue Specificity Expressed in the adult and fetal brain and kidney.
Database Links

HGNC: 12687

OMIM: 144700

KEGG: hsa:7428

STRING: 9606.ENSP00000256474

UniGene: Hs.517792

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