YC-1, guanylyl cyclase activator

Supplementary information

This supplementary information is collated from multiple sources and compiled automatically.

HIF-2-alpha also known as EPAS1 is a transcription factor that plays an important role in the cellular response to hypoxia. It forms a heterodimer with ARNT (aryl hydrocarbon receptor nuclear translocator) to regulate the expression of genes involved in oxygen homeostasis. HIF-2-alpha like its closely related counterpart HIF-1 alpha primarily resides in the nucleus. The protein has a molecular mass of approximately 118 kDa. It expresses in various tissues including lungs heart and liver with higher levels during low oxygen tension.

Biological function summary

HIF-2-alpha functions as a regulator of genes essential in angiogenesis and erythropoiesis. It often interacts with the coactivator CREBBP (CREB-binding protein) and KAT3B (also known as p300) forming a transcriptional complex that enhances gene transcription. The activity of HIF-2-alpha influences several processes such as endothelial function and cellular proliferation. Smad3 a member of the SMAD family of proteins occasionally cooperates with HIF-2-alpha in signaling cascades related to extracellular matrix production.

Pathways

HIF-2-alpha plays a significant role in the hypoxia-inducible factor (HIF) pathway which is important in oxygen sensing and homeostasis. This protein contributes to the regulation of genes like vascular endothelial growth factor (VEGF) and erythropoietin (EPO) under hypoxic conditions. Additionally HIF-2-alpha intertwines with the TGF-beta signaling pathway where it interacts with other proteins like Smad3 facilitating cellular responses to environmental changes.

Aberrant HIF-2-alpha activity has links to conditions such as renal cell carcinoma and pulmonary hypertension. Altered regulation of HIF-2-alpha influences tumorigenesis and vascular abnormalities. Connections with proteins like CREBBP and p300 may affect gene transcription related to these diseases. Changes in HIF-2-alpha expression can contribute to an abnormal response to hypoxia promoting disease progression.