EGLN1/PHD2 Antibody (366G/76/3)

PHD2 (Prolyl Hydroxylase Domain-containing protein 2) belongs to the Prolyl-4-hydroxylase domain (PHD) family of proteins and is encoded by the Egl-9 Family Hypoxia Inducible Factor 1 (EGLN1) gene (1). Human EGLN1/PHD2 is a ubiquitously expressed enzyme that is 426 amino acids (aa) long with a theoretical molecular weight of ~46 kDa. Structurally PHD2 contains a nuclear export signal (NES, aa 6-20), an N-terminal MYND zinc finger domain (aa 21-58), and a C-terminal catalytic domain (aa 291-392) (2, 3). Functionally, PHD2 serves as an oxygen sensor and is responsible for post-translational modification of Hypoxia-inducible factor alpha (HIF-1alpha), a component of a transcriptional complex involved in oxygen homeostasis (1-3). During normoxia, PHD2 is responsible for oxygen-dependent hydroxylation of HIF-1alpha proline residue 402, 564, or both (3). The hydroxylation event promotes the binding of von Hippel-Lindau protein (VHL) and targets HIF1-alpha for ubiquitination and degradation (4, 5).

EGLN1/PHD2 has been implicated in several critical processes including erythropoiesis, angiogenesis, and metabolism as well as various pathologies such as cancer (2, 5, 6). Studies in mice have found that somatic deletion of PHD2 resulted in higher vascular endothelial growth factor A (VEGF-A) levels, increased blood vessel formation, and more erythropoietin (EPO), leading to severe polycythemia or erythrocytosis (high red blood cell (RBC) volume) (6). Another study revealed that specific point mutations in EGLN1/PHD2 led to elevated EPO and RBC mass associated with hemorrhages and strokes (6). Accordingly, given the known role of PHD2 in inhibition of EPO production, PHD2 inhibitors are being studied as a potential therapeutic for anemia (6). Additionally, dysregulation in EGLN1, and specifically the PHD2-VHL-HIF-1alpha pathway, has been associated with the development of pheochromocytomas (PCC) and sympathetic paragangliomas (PGL), which are rare neuroendocrine tumors (2). Besides pathological features, EGLN1/PHD2 may also be important for high altitude adaptation as two coding sequence variants in PHD2 are prevalent in the Tibetan population but is very rare in people at lower altitudes (2).

Alternate names for EGLN1/PHD2 include HIF Prolyl Hydroxylase 2, PH2, Prolyl hydroxylase domain containing protein 2, HIF2PH2, HIF-Prolyl hydroxylase 2, egl nine homolog 1, and C1orf12.

References

1. Amorim-Pires, D., Peixoto, J., & Lima, J. (2016). Hypoxia Pathway Mutations in Pheochromocytomas and Paragangliomas. Cytogenetic and genome research. https://doi.org/10.1159/000457479

2. Gardie, B., Percy, M. J., Hoogewijs, D., Chowdhury, R., Bento, C., Arsenault, P. R., Richard, S., Almeida, H., Ewing, J., Lambert, F., McMullin, M. F., Schofield, C. J., & Lee, F. S. (2014). The role of PHD2 mutations in the pathogenesis of erythrocytosis. Hypoxia (Auckland, N.Z.). https://doi.org/10.2147/HP.S54455

3. Minervini, G., Quaglia, F., & Tosatto, S. C. (2015). Insights into the proline hydroxylase (PHD) family, molecular evolution and its impact on human health. Biochimie. https://doi.org/10.1016/j.biochi.2015.07.009

4. Semenza G. L. (2007). Hypoxia-inducible factor 1 (HIF-1) pathway. Science's STKE : signal transduction knowledge environment. https://doi.org/10.1126/stke.4072007cm8

5. Chan, D. A., & Giaccia, A. J. (2010). PHD2 in tumour angiogenesis. British journal of cancer. https://doi.org/10.1038/sj.bjc.6605682

6. Meneses, A. M., & Wielockx, B. (2016). PHD2: from hypoxia regulation to disease progression. Hypoxia (Auckland, N.Z.). https://doi.org/10.2147/HP.S53576

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

We have publications tested in 3 confirmed species: Human, Mouse, Rat.

We have publications tested in 2 applications: IHC-P, WB.

Showing Publications 1 - 9 of 9.

Publications using NBP1-30328	Applications	Species
Xiang L, Wei H, Ye W et al. Prolyl hydroxylase 2 inhibits glycolytic activity in colorectal cancer via the NF??B signaling pathway International journal of oncology 2024-01-01 [PMID: 37975227] (WB, Human)	WB	Human
Pavlakis D, Kampantais S, Gkagkalidis K et al. Hypoxia-Inducible Factor 2a Expression Is Positively Correlated With Gleason Score in Prostate Cancer Technology in cancer research & treatment 2021-03-23 [PMID: 33752529] (IHC-P, Human)	IHC-P	Human
Rane A, Rajagopalan S et al. Hsp90 Co-chaperone p23 contributes to dopaminergic mitochondrial stress via stabilization of PHD2: Implications for Parkinson's disease. Neurotoxicology 2018-01-03 [PMID: 29471019] (WB, Rat)	WB	Rat
Capitanio D, Fania C et al. TCA cycle rewiring fosters metabolic adaptation to oxygen restriction in skeletal muscle from rodents and humans. Sci Rep 2017-08-29 [PMID: 28852047] (WB, Mouse)	WB	Mouse
Casciello F, Al-Ejeh F, Kelly G et al. G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 2017-06-19 [PMID: 28630300]
Jubb AM, Turley H, Moeller HC, Steers G, Han C, Li JL, Leek R, Tan EY, Singh B, Mortensen NJ, Noguera-Troise I, Pezzella F, Gatter KC, Thurston G, Fox SB, Harris AL. Expression of delta-like ligand 4 (Dll4) and markers of hypoxia in colon cancer. Br J Cancer;101(10):1749-57. 2009-11-17 [PMID: 19844231] (IHC-P, Human)	IHC-P	Human
Soilleux EJ, Turley H, Tian YM et al. Use of novel monoclonal antibodies to determine the expression and distribution of the hypoxia regulatory factors PHD-1, PHD-2, PHD-3 and FIH in normal and neoplastic human tissues. Histopathology. 2005-12-01 [PMID: 16324198] (IHC-P, Human)	IHC-P	Human
Stolze IP, Tian YM, Appelhoff RJ et al. Genetic analysis of the role of the asparaginyl hydroxylase factor inhibiting hypoxia-inducible factor (FIH) in regulating hypoxia-inducible factor (HIF) transcriptional target genes [corrected]. J Biol Chem. 2004-10-01 [PMID: 15302861] (WB, Human)	WB	Human
Appelhoff RJ et al. Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. J Bil Chem 279: 38458-38465. 2004-01-01 [PMID: 15247232] (WB, Human)	WB	Human

Array NBP1-30328

• EGLN1/PHD2 Antibodies
• EGLN1/PHD2 Lysate
• EGLN1/PHD2 Proteins