PHD3 (Egl Nine Homolog 3, HPH-1, Hypoxia-inducible Factor Prolyl Hydroxylase 3, HIF-PH3, HIF-prolyl Hydroxylase 3, HPH-3, Prolyl Hydroxylase Domain-containing Protein 3, EGLN3)

Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates HIF2A. Has a preference for the CODD site for both HIF1A and HIF2A. Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site. 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, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes. EGLN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM2 in hypoxia, limiting glycolysis. Under normoxia, hydroxylates and regulates the stability of ADRB2. Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex. In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity. Also essential for hypoxic regulation of neutrophilic inflammation.\n\nApplications:\nSuitable for use in ELISA and Western Blot. Other applications not tested.\n\nRecommended Dilution:\nELISA: 1:8000\nWestern Blot: 0.1-0.3ug/ml, observed in human skeletal muscle lysates on ~30kD bands\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.

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SPECIFICATIONS

Catalog Number

P3375-07C

Size

100ug

Applications

ELISA, WB

Hosts

Goat

Reactivities

Hum, Mouse, Rat, Bov, Can

Form

Supplied as a liquid in Tris saline, 0.02% sodium azide, pH 7.3, 0.5% BSA.

P Type

Pab

Purity

Purified by immunoaffinity chromatography.

References

1. Nakayama K, Gazdoiu S, Abraham R, Pan ZQ, Ronai Z. Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2. Biochem J. 2007 Jan 1;401(1):217-26.

Additional Info

Recognizes human EGLN3. Species sequence homology: Bovine, canine, mouse and rat.