Gene content    
VHL ( by HUGO)
Von Hippel-Lindau Tumor Suppressor, E3 Ubiquitin Protein...
Tumor suppressor gene
Von Hippel-Lindau Tumor Suppressor
E3 Ubiquitin Protein Ligase
Protein G7
pVHL
Von Hippel-Lindau Syndrome
Von Hippel-Lindau Tumor Suppressor
HRCA1
RCA1
VHL1
Elongin Binding Protein
Von Hippel-Lindau Disease Tumor Suppressor
NCBI: 3p25.3    Ensembl: 3p25.3
VHL_HUMANSize: 213 amino acidsMass: 24153 Da

  • Subunit: Component of the VCB (VHL-Elongin BC-CUL2) complex; this complex acts as a ubiquitin-ligase E3 and directs proteasome-dependent degradation of targeted proteins. Interacts with CUL2; this interaction is dependent on the integrity of the trimeric VBC complex. Interacts (via the beta domain) with HIF1A (via the NTAD domain); this interaction mediates degradation of HIF1A in normoxia and, in hypoxia, prevents ubiqitination and degradation of HIF1A by mediating hypoxia-induced translocation to the nucleus, a process which requires a hypoxia-dependent regulatory signal. Interacts with ADRB2; the interaction, in normoxia, is dependent on hydroxylation of ADRB2 and the subsequent VCB-mediated ubiquitination and degradation of ADRB2. Under hypoxia, hydroxylation, interaction with VHL, ubiquitination and subsequent degradation of ADRB2 are dramatically decreased. Interacts with RNF139, USP33 and JADE1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, TCEB2 AND CUL2. Isoform 1 and isoform 3 interact with LIMD1 (via LIM zinc-binding 2), AJUBA (via LIM domains) and WTIP (via LIM domains). Interacts with EPAS1 Developmental stage: At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis and lung. Differentially expressed within renal tubules Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for VHL (see all 14): 1LM8 (3D) [IMAGE] 1LQB (3D) [IMAGE] 1VCB (3D) [IMAGE] 3ZRC (3D) [IMAGE] 3ZRF (3D) [IMAGE] 3ZTC (3D) [IMAGE]
  • Tissue specificity: Expressed in the adult and fetal brain and kidney [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including VHL: Ubiquitination (Ubiquitylation) Pathway in human mouse rat Oncogenes & Tumor Suppressor Genes in human mouse rat Apoptosis 384HT in
  • Function:
    UniProtKB/Swiss-Prot Summary: VHL_HUMAN, P40337 Function: Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Seems to act as 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

    • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR002714Tumour_suppress_VHL-diseaseTumor suppressor protein, von Hippel-Lindau diseaseFamily

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process cell morphogenesis NAS GOA 12169691
    negative regulation of apoptotic process NAS GOA 12169691
    negative regulation of cell proliferation TAS GOA 7660130
    negative regulation of transcription from RNA polymerase II promoter TAS GOA 7660122
    positive regulation of cell differentiation NAS GOA 12169691
    positive regulation of transcription, DNA-templated IMP GOA 17973242
    protein stabilization NAS GOA 12169691
    protein ubiquitination IMP GOA 12169691
    proteolysis TAS GOA 10353251
    regulation of transcription, DNA-templated IMP GOA 15824735
    Cellular Component endoplasmic reticulum NAS GOA 12169691
    mitochondrion NAS GOA 12169691
    Molecular Function enzyme binding IPI GOA 11641274
    protein binding IPI GOA 11292862
    transcription factor binding IPI GOA 11641274

    Disorder & Mutation    
    Source Disease
    SWISS-PROTPheochromocytoma (PCC) [MIM:171300]: A catecholamine-producing tumor of chromaffin tissue of the adrenal medulla or sympathetic paraganglia. The cardinal symptom, reflecting the increased secretion of epinephrine and norepinephrine, is hypertension, which may be persistent or intermittent. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
    SWISS-PROTvon Hippel-Lindau disease (VHLD) [MIM:193300]: VHLD is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign neoplasms, most frequently retinal, cerebellar and spinal hemangioblastoma, renal cell carcinoma (RCC), pheochromocytoma, and pancreatic tumors. VHL type 1 is without pheochromocytoma, type 2 is with pheochromocytoma. VHL type 2 is further subdivided into types 2A (pheochromocytoma, retinal angioma, and hemangioblastomas without renal cell carcinoma and pancreatic cyst) and 2B (pheochromocytoma, retinal angioma, and hemangioblastomas with renal cell carcinoma and pancreatic cyst). Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTErythrocytosis, familial, 2 (ECYT2) [MIM:263400]: An autosomal recessive disorder characterized by an increase in serum red blood cell mass, hypersensitivity of erythroid progenitors to erythropoietin, increased erythropoietin serum levels, and normal oxygen affinity. Patients with ECYT2 carry a high risk for peripheral thrombosis and cerebrovascular events. Note=The disease is caused by mutations affecting the gene represented in this entry

    VHL cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene