HCSGD entry for VHL

1. General information

Official gene symbolVHL
Entrez ID7428
Gene full namevon Hippel-Lindau tumor suppressor, E3 ubiquitin protein ligase
Other gene symbolsHRCA1 RCA1 VHL1 pVHL
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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This gene isn't in PPI subnetwork.

3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0000122Negative regulation of transcription from RNA polymerase II promoterTASbiological_process
GO:0000902Cell morphogenesisNASbiological_process
GO:0001525AngiogenesisIEAbiological_process
GO:0004842Ubiquitin-protein ligase activityTASmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005634NucleusTAScellular_component
GO:0005654NucleoplasmTAScellular_component
GO:0005739MitochondrionNAScellular_component
GO:0005783Endoplasmic reticulumNAScellular_component
GO:0005829CytosolTAScellular_component
GO:0006355Regulation of transcription, DNA-templatedIMPbiological_process
GO:0006508ProteolysisTASbiological_process
GO:0006950Response to stressNASbiological_process
GO:0008134Transcription factor bindingIPImolecular_function
GO:0008285Negative regulation of cell proliferationTASbiological_process
GO:0010498Proteasomal protein catabolic processIEAbiological_process
GO:0016020MembraneIEAcellular_component
GO:0016567Protein ubiquitinationIMPbiological_process
GO:0019899Enzyme bindingIPImolecular_function
GO:0030182Neuron differentiationIEAbiological_process
GO:0030198Extracellular matrix organizationIEAbiological_process
GO:0030891VCB complexIEAcellular_component
GO:0032403Protein complex bindingIEAmolecular_function
GO:0042069Regulation of catecholamine metabolic processIEAbiological_process
GO:0043066Negative regulation of apoptotic processNASbiological_process
GO:0043534Blood vessel endothelial cell migrationIEAbiological_process
GO:0045471Response to ethanolIEAbiological_process
GO:0045597Positive regulation of cell differentiationNASbiological_process
GO:0045893Positive regulation of transcription, DNA-templatedIMPbiological_process
GO:0050821Protein stabilizationNASbiological_process
GO:0051291Protein heterooligomerizationIEAbiological_process
GO:0061418Regulation of transcription from RNA polymerase II promoter in response to hypoxiaTASbiological_process
GO:0061428Negative regulation of transcription from RNA polymerase II promoter in response to hypoxiaIDAbiological_process
GO:0070244Negative regulation of thymocyte apoptotic processIEAbiological_process
GO:0071456Cellular response to hypoxiaTASbiological_process
GO:2001233Regulation of apoptotic signaling pathwayIEAbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.26351534900.71337212110.95787701971.0000000000

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Up0.1680221056
GSE13712_SHEARDown-0.0908837239
GSE13712_STATICUp0.0469004363
GSE19018Down-0.1734739649
GSE19899_A1Up0.0025042141
GSE19899_A2Up0.3284436201
PubMed_21979375_A1Down-0.0983589338
PubMed_21979375_A2Down-0.2972606308
GSE35957Down-0.0804347589
GSE36640Up0.0577174495
GSE54402Down-0.0596137014
GSE9593Up0.1485518518
GSE43922Up0.0506688905
GSE24585Down-0.1527339210
GSE37065Down-0.0550356338
GSE28863_A1Up0.4798049355
GSE28863_A2Up0.1967261857
GSE28863_A3Up0.3899766381
GSE28863_A4Up0.1090041690
GSE48662Down-0.0593655798

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Not regulated by drugs

  • MicroRNAs

    • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-23b-3pMIMAT0000418MIRT007006Luciferase reporter assayFunctional MTI22649212
hsa-miR-122-5pMIMAT0000421MIRT023372MicroarrayFunctional MTI (Weak)17612493
hsa-miR-24-3pMIMAT0000080MIRT030519MicroarrayFunctional MTI (Weak)19748357
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    • mirRecord
No target information from mirRecord

6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 5 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

23868058Renal cell carcinoma is the most frequent form of kidney cancer in adults and inactivation of the von Hippel-Lindau (VHL) gene underlies most cases
23744542Regulation of E2F1 by the von Hippel-Lindau tumour suppressor protein predicts survival in renal cell cancer patients
23744542Biallelic mutations of the von Hippel-Lindau (VHL) gene are the most common cause of sporadic and inherited renal cell carcinoma (RCC)
23744542Loss of VHL has been reported to affect cell proliferation by deregulating cell cycle-associated proteins
23744542We report that the VHL gene product (pVHL) inhibits E2F1 expression at both mRNA and protein level in zebrafish and human RCC cells, while loss of VHL increases E2F1 expression in patient kidney tumour tissue and RCC cells, resulting in a delay of cell cycle progression
23744542RCCs from von Hippel-Lindau patients with known germline VHL mutations express significantly more E2F1 compared to sporadic RCCs with either clear-cell (cc) or non-cc histology
21746877Additionally, we found that cyclin E deregulation in mammary acini decreases, in an E2F-independent manner, expression of the EGLN1 prolyl hydroxylase that regulates HIF-1alpha degradation within the VHL ubiquitin ligase pathway
20679489Renal oxygenation suppresses VHL loss-induced senescence that is caused by increased sensitivity to oxidative stress
20679489Loss of the VHL tumor suppressor is regarded as an initiating event in the development of clear-cell renal carcinoma
20679489Surprisingly, loss of VHL induces senescence in mouse fibroblasts in vitro, a response that would restrict development of renal carcinoma in vivo
20679489Therefore, we investigated the oxygen dependence of VHL loss-induced senescence
20679489This suggests that VHL inactivation sensitizes cells to oxidative stress
20679489In support of this concept, senescence following VHL loss depends on p53 activity, which decreases under the less stressful conditions of mild hypoxia
20679489We confirmed these observations in vivo by treating kidney-specific VHL knockout animals with the potent oxidizer paraquat and observed a robust induction of cellular senescence
20679489Together, these data demonstrate that in vivo oxygenation promotes tolerance of VHL loss in renal epithelia, which may promote the development of renal carcinoma
9739015The KC12 cell line derived from a renal cell carcinoma in a patient with von Hippel-Lindau disease showed telomerase activity and loss of heterozygosity on the short arm of chromosome 3
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