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VHL 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. 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 PHF17. 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. Expressed in the adult and fetal brain and kidney. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Tumor suppressor; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 3p25.3
Cellular Component: cytosol; endoplasmic reticulum; membrane; mitochondrion; nucleoplasm; nucleus; VCB complex
Molecular Function: enzyme binding; protein binding; transcription factor binding; ubiquitin-protein transferase activity
Biological Process: cell morphogenesis; negative regulation of apoptosis; negative regulation of cell proliferation; negative regulation of JAK-STAT cascade; negative regulation of transcription from RNA polymerase II promoter; positive regulation of cell differentiation; positive regulation of transcription, DNA-templated; post-translational protein modification; protein stabilization; protein ubiquitination; proteolysis; regulation of transcription, DNA-templated
Disease: Erythrocytosis, Familial, 2; Pheochromocytoma; Renal Cell Carcinoma, Nonpapillary; Von Hippel-lindau Syndrome
Reference #:  P40337 (UniProtKB)
Alt. Names/Synonyms: elongin binding protein; HRCA1; Protein G7; pVHL; RCA1; VHL; VHL1; Von Hippel-Lindau disease tumor suppressor; von Hippel-Lindau tumor suppressor
Gene Symbols: VHL
Molecular weight: 24,153 Da
Basal Isoelectric point: 4.7  Predict pI for various phosphorylation states
CST Pathways:  Angiogenesis
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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