VHL

Von Hippel-Lindau syndrome (VHL) is a dominantly inherited familial cancer syndrome predisposing to a variety of malignant and benign tumors. A germline mutation of this gene is the basis of familial inheritance of VHL syndrome. The protein encoded by this gene is a component of the protein complex that includes elongin B, elongin C, and cullin-2, and possesses ubiquitin ligase E3 activity. This protein is involved in the ubiquitination and degradation of hypoxia-inducible-factor (HIF), which is a transcription factor that plays a central role in the regulation of gene expression by oxygen. RNA polymerase II subunit POLR2G/RPB7 is also reported to be a target of this protein. Alternatively spliced transcript variants encoding distinct isoforms have been observed.

von Hippel-Lindau tumor suppressor

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.

Biological Process amyloid fibril formation Source:DisProt1 Publication
Biological Process cell morphogenesis Source:UniProtKB1 Publication
Biological Process cellular response to hypoxia Source:Reactome
Biological Process negative regulation of apoptotic process Source:UniProtKB1 Publication
Biological Process negative regulation of autophagy Source:DisProt1 Publication
Biological Process negative regulation of cell population proliferation Source:DisProt1 Publication
Biological Process negative regulation of gene expression Source:CAFA1 Publication
Biological Process negative regulation of receptor signaling pathway via JAK-STAT Source:CAFA1 Publication
Biological Process negative regulation of signal transduction Source:DisProt1 Publication
Biological Process negative regulation of transcription elongation by RNA polymerase II Source:UniProtKB1 Publication
Biological Process negative regulation of transcription from RNA polymerase II promoter in response to hypoxia Source:UniProtKB1 Publication
Biological Process positive regulation of cell differentiation Source:UniProtKB1 Publication
Biological Process positive regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process positive regulation of ubiquitin-dependent protein catabolic process Source:DisProt1 Publication
Biological Process protein stabilization Source:UniProtKB1 Publication
Biological Process protein ubiquitination Source:ParkinsonsUK-UCL1 Publication
Biological Process proteolysis Source:ProtInc1 Publication
Biological Process regulation of cellular response to hypoxia Source:DisProt1 Publication
Biological Process regulation of DNA-templated transcription Source:BHF-UCL1 Publication
Biological Process regulation of gene expression Source:DisProt2 Publications
Biological Process selective autophagy Source:DisProt1 Publication

Isoform 1
Cytoplasm
Membrane
Nucleus
Found predominantly in the cytoplasm and with less amounts nuclear or membrane-associated. Colocalizes with ADRB2 at the cell membrane.
Isoform 3
Cytoplasm
Nucleus
Equally distributed between the nucleus and the cytoplasm but not membrane-associated.

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.
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).
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.
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.