FUNCTION: SwissProt: Q99814 # Transcription factor involved in the induction of oxygen regulated genes. Binds to core DNA sequence 5'-[AG]CGTG-3' within the hypoxia response element (HRE) of target gene promoters. Regulates the vascular endothelial growth factor (VEGF) expression and seems to be implicated in the development of blood vessels and the tubular system of lung. May also play a role in the formation of the endothelium that gives rise to the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase expression. Activation seems to require recruitment of transcriptional coactivators such as CREBPB and probably EP300. Interaction with redox regulatory protein APEX seems to activate CTAD.
SIZE: 870 amino acids; 96459 Da
SUBUNIT: Efficient DNA binding requires dimerization with another bHLH protein. Heterodimerizes with ARNT. Interacts with CREBBP (By similarity).
SUBCELLULAR LOCATION: Nucleus (Potential).
TISSUE SPECIFICITY: Expressed in most tissues, with highest levels in placenta, lung and heart. Selectively expressed in endothelial cells.
PTM: In normoxia, is probably hydroxylated on Pro-405 and Pro-531 by EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity). & In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably abrogating interaction with CREBBP and EP300 and preventing transcriptional activation (By similarity). & Phosphorylated on multiple sites in the CTAD (By similarity).
SIMILARITY: SwissProt: Q99814 ## Contains 1 basic helix-loop-helix (bHLH) domain. & Contains 1 PAC (PAS-associated C-terminal) domain. & Contains 2 PAS (PER-ARNT-SIM) domains.