Anti-phospho-PHD2 (Ser 125) Antibody, clone 4

Egl nine homolog 1 (UniProt: Q9GZT9; also known as EC:1.14.11.29, Hypoxia-inducible factor prolyl hydroxylase 2, HIF-PH2, HIF-prolyl hydroxylase 2, HPH-2, Prolyl hydroxylase domain-containing protein 2, PHD2, SM-20) is encoded by the EGLN1 (also known as C1orf12, PNAS-118, PNAS-137) gene (GeneID: 54583) in human. PHD2 acts as a cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. It is widely expressed with highest levels in skeletal muscle and heart, moderate levels in pancreas, brain and kidney, and lower levels in lung and liver. PHD2 is mainly cytoplasmic, but it shuttles between the nucleus and cytoplasm. It hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1alpha and is also reported to hydroxylate HIF2alpha. PHD2 is reported to be phosphorylated on serine 125 by p70S6K and this phosphorylation increased its ability to degrade HIF1alpha. PHD2 exhibits a preference for the CODD site for both HIF1alpha and HIF1beta. Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus and heterodimerization with HIF1beta. It is one of the most important isozyme under normoxia and, through regulating the stability of HIF1, it is involved in various hypoxia-influenced processes such as angiogenesis in retinal and cardiac functionality. Defects in EGLN1 gene cause familial type erythrocytosis, an autosomal dominant disorder that is characterized by increased serum red blood cell mass, elevated serum hemoglobin and hematocrit, and normal serum erythropoietin levels. (Ref.: Di Conza, G., et al. (2017). Cell Rep. 18(7): 1699-1712).