HHAH2A

HHAH2A, also known as Hypoxia Inducible Factor 1 Alpha Subunit, is a protein-coding gene. It is a transcription factor that plays a crucial role in cellular response to low oxygen conditions, a state known as hypoxia. When oxygen levels decrease, HHAH2A becomes stabilized and translocates to the nucleus where it binds to specific DNA sequences. This binding initiates the transcription of a wide array of genes involved in adaptation to hypoxia. These genes regulate various physiological processes, including angiogenesis (the formation of new blood vessels), erythropoiesis (red blood cell production), glucose metabolism, and cell survival.

The HHAH2A protein is a key component of the hypoxia-inducible factor (HIF) complex, which is a heterodimer composed of an alpha subunit (HIF-1A) and a beta subunit (HIF-1B). Under normal oxygen conditions, the alpha subunit is rapidly degraded by a process called prolyl hydroxylation, which targets it for ubiquitination and proteasomal degradation. However, during hypoxia, the prolyl hydroxylases are inhibited, leading to the stabilization of HIF-1A. This stabilized HIF-1A can then dimerize with HIF-1B and activate target genes. Dysregulation of HHAH2A is implicated in various diseases, including cancer, where it promotes tumor growth and metastasis by facilitating angiogenesis and survival under hypoxic tumor environments. It is also involved in cardiovascular diseases and inflammatory conditions.