VHL
Developmental stage
At 4-10 weeks pc, strong expression in the developing central nervous system, kidneys, testis and lung. Differentially expressed within renal tubules.
Domain
The Elongin BC complex binding domain is also known as BC-box with the consensus [APST]-L-x(3)-C-x(3)-[AILV].
Function
Involved in the ubiquitination and subsequent proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:10944113, PubMed:17981124, PubMed:19584355). Seems to act as a target recruitment subunit in the E3 ubiquitin ligase complex and recruits hydroxylated hypoxia-inducible factor (HIF) under normoxic conditions (PubMed:10944113, PubMed:17981124). Involved in transcriptional repression through interaction with HIF1A, HIF1AN and histone deacetylases (PubMed:10944113, PubMed:17981124). Ubiquitinates, in an oxygen-responsive manner, ADRB2 (PubMed:19584355). Acts as a negative regulator of mTORC1 by promoting ubiquitination and degradation of RPTOR (PubMed:34290272).
Involvement in disease
Pheochromocytoma
PCC
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
von Hippel-Lindau disease
VHLD
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).
None
The disease is caused by variants affecting the gene represented in this entry.
Erythrocytosis, familial, 2
ECYT2
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Renal cell carcinoma
RCC
Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. It is subclassified into clear cell renal carcinoma (non-papillary carcinoma), papillary renal cell carcinoma, chromophobe renal cell carcinoma, collecting duct carcinoma with medullary carcinoma of the kidney, and unclassified renal cell carcinoma. Clear cell renal cell carcinoma is the most common subtype.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein ubiquitination.
Sequence Similarities
Belongs to the VHL family.
Tissue Specificity
Expressed in the adult and fetal brain and kidney.
Cellular localization
- Isoform 1
- Cytoplasm
- Cell membrane
- Peripheral membrane protein
- Endoplasmic reticulum
- Nucleus
- Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated (PubMed:9751722). Colocalizes with ADRB2 at the cell membrane (PubMed:19584355).
- Isoform 3
- Cytoplasm
- Nucleus
- Equally distributed between the nucleus and the cytoplasm but not membrane-associated.
Alternative names
von Hippel-Lindau disease tumor suppressor, Protein G7, pVHL, VHL