Tag Info: N-terminal 6xHis-tagged. MW: 28.2 kDa. Function: 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. Involvement in disease: Pheochromocytoma (PCC); von Hippel-Lindau disease (VHLD); Erythrocytosis, familial, 2 (ECYT2); Renal cell carcinoma (RCC) . Subcellular Location: 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, SUBCELLULAR LOCATION: Isoform 3: Cytoplasm, Nucleus.Protein Families: VHL family.Tissue Specificity: Expressed in the adult and fetal brain and kidney.