InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: VHL

Summary

InnateDB Protein

IDBP-17821.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

VHL

Protein Name

von Hippel-Lindau tumor suppressor

Synonyms

HRCA1; pVHL; RCA1; VHL1;

Species

Homo sapiens

Ensembl Protein

ENSP00000256474

InnateDB Gene

IDBG-17819 (VHL)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10944113, ECO:0000269PubMed:17981124, ECO:0000269PubMed:19584355}.

Subcellular Localization

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.Isoform 3: Cytoplasm. Nucleus. Note=Equally distributed between the nucleus and the cytoplasm but not membrane-associated.

Disease Associations

Pheochromocytoma (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. {ECO:0000269PubMed:12000816, ECO:0000269PubMed:14500403, ECO:0000269PubMed:9663592}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.von 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). {ECO:0000269PubMed:10408776, ECO:0000269PubMed:10533030, ECO:0000269PubMed:10627136, ECO:0000269PubMed:10635329, ECO:0000269PubMed:16502427, ECO:0000269PubMed:7728151, ECO:0000269PubMed:7987306, ECO:0000269PubMed:8493574, ECO:0000269PubMed:8592333, ECO:0000269PubMed:8634692, ECO:0000269PubMed:8730290, ECO:0000269PubMed:8825918, ECO:0000269PubMed:8956040, ECO:0000269PubMed:9452032, ECO:0000269PubMed:9452106, ECO:0000269PubMed:9829911, ECO:0000269PubMed:9829912, ECO:0000269Ref.41}. Note=The disease is caused by mutations affecting the gene represented in this entry.Erythrocytosis, 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. {ECO:0000269PubMed:12393546, ECO:0000269PubMed:12844285}. Note=The disease is caused by mutations affecting the gene represented in this entry.Renal cell carcinoma (RCC) [MIM:144700]: 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. {ECO:0000269PubMed:11986208}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in the adult and fetal brain and kidney.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 360 experimentally validated interaction(s) in this database.
They are also associated with 10 interaction(s) predicted by orthology.

Experimentally validated
Total	360 [view]
Protein-Protein	358 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	10 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008134	transcription factor binding
GO:0019899	enzyme binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0000902	cell morphogenesis
GO:0006355	regulation of transcription, DNA-templated
GO:0006508	proteolysis
GO:0006950	response to stress
GO:0008285	negative regulation of cell proliferation
GO:0016567	protein ubiquitination
GO:0043066	negative regulation of apoptotic process
GO:0045597	positive regulation of cell differentiation
GO:0045893	positive regulation of transcription, DNA-templated
GO:0050821	protein stabilization
GO:0061418	regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0061428	negative regulation of transcription from RNA polymerase II promoter in response to hypoxia
GO:0071456	cellular response to hypoxia

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005829	cytosol
GO:0016020	membrane
GO:0045111	intermediate filament cytoskeleton