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Prolyl Hydroxylase Domain-Containing Protein 2 (PHD2)
- Target
- PHD2
- Molecular classification
- Enzyme, Dioxygenase, Fe(II)/α-ketoglutarate-dependent dioxygenase
01
Overview
Prolyl Hydroxylase Domain-Containing Protein 2 (PHD2) is a key oxygen-sensing enzyme that regulates the stability of hypoxia-inducible factor alpha (HIF-α) proteins. It catalyzes the proline hydroxylation of HIF-α, targeting it for degradation under normoxic conditions. PHD2 plays a crucial role in cellular adaptation to hypoxia by controlling the expression of genes involved in angiogenesis, erythropoiesis, and glycolysis. Dysregulation of PHD2 is implicated in various diseases, including cancer and immune disorders.
- Other names
- HIF-PH2EGLN1Egl nine homolog 1
02
Mechanism of action
Inhibition of proline hydroxylation on HIF-α, leading to HIF-α stabilization and increased transcriptional activity.
03
Biological functions
Oxygen sensingRegulation of HIF-α stabilityRegulation of cellular adaptation to hypoxiaErythropoiesisAngiogenesisGlycolysisImmune homeostasis
04
Disease associations
CancerHypoxia-related disordersImmune disordersErythropoiesis disorders
05
Safety considerations
Potential for off-target effects due to homology with other PHDsUnpredictable effects on erythropoiesis and angiogenesisDisruption of normal oxygen sensing pathways
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