Prolyl hydroxylase domain proteins HIF PHD1, HIF PHD2 and HIF PHD3 (known as PHD1, PHD2 and PHD3 in rodents, respectively) can hydroxylate HIF-α subunits. Hypoxia-inducible factor (HIF) is a transcriptional regulator important in several aspects of oxygen homeostasis. The prolyl hydroxylases catalyze the posttranslational formation of 4-hydroxyproline in HIF-α proteins. HIF PHD1, which is widely expressed, with highest levels of expression in testis, functions as a cellular oxygen sensor and is important in cell growth regulation. HIF PHD1 can localize to the nucleus or the cytoplasm and is also detected in hormone responsive tissues, such as normal and cancerous mammary, ovarian and prostate epithelium. HIF PHD1 is encoded by EGLN2, which maps to chromosome 19q13.3. HIF PHD2 is regarded as the main cellular oxygen sensor, as RNA interference against HIF PHD2, but not HIF PHD1 or HIF PHD3, is enough to stabilize HIF-1α in normoxia. HIF PHD2, a direct HIF target gene, is expressed mainly in skeletal muscle, heart, kidney and brain. HIF PHD3 may play a role in the regulation of cell growth in muscle cells and in apoptosis in neuronal tissue. HIF PHD3 is widely expressed, although the highest levels can be detected in placenta and he
