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.
Molecular Function: protein binding; enzyme binding; ubiquitin-protein ligase activity; protein complex binding; transcription factor binding
Biological Process: proteasomal protein catabolic process; extracellular matrix organization and biogenesis; protein stabilization; blood vessel endothelial cell migration; protein heterooligomerization; positive regulation of transcription, DNA-dependent; regulation of catecholamine metabolic process; cell morphogenesis; protein ubiquitination; negative regulation of transcription from RNA polymerase II promoter; proteolysis; neuron differentiation; negative regulation of cell proliferation; response to ethanol; regulation of transcription, DNA-dependent; response to stress; angiogenesis; positive regulation of cell differentiation; negative regulation of apoptosis
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.