Gene Symbol: Egln3
Description: egl-9 family hypoxia-inducible factor 3
Alias: 2610021G09Rik, AI505553, AI648162, Hif-p4h-3, Phd3, SM-20, egl nine homolog 3, HIF-PH3, HIF-prolyl hydroxylase 3, HPH-3, hypoxia-inducible factor prolyl hydroxylase 3, prolyl hydroxylase domain-containing protein 3
Species: mouse
Products:     Egln3

Top Publications

  1. Xue J, Li X, Jiao S, Wei Y, Wu G, Fang J. Prolyl hydroxylase-3 is down-regulated in colorectal cancer cells and inhibits IKKbeta independent of hydroxylase activity. Gastroenterology. 2010;138:606-15 pubmed publisher
    ..The PHD family comprises PHD1, PHD2, and PHD3. The enzymatic activity of PHDs is O(2)-dependent, so PHDs are believed to be oxygen sensors as well as tumor ..
  2. Takeda K, Aguila H, Parikh N, Li X, Lamothe K, Duan L, et al. Regulation of adult erythropoiesis by prolyl hydroxylase domain proteins. Blood. 2008;111:3229-35 pubmed
    ..Although Phd1(-/-) or Phd3(-/-) mice had no apparent defects, double knockout of Phd1 and Phd3 led to moderate erythrocytosis...
  3. Sciorra V, Sanchez M, Kunibe A, Wurmser A. Suppression of glioma progression by Egln3. PLoS ONE. 2012;7:e40053 pubmed publisher
    ..Here, we tested the hypothesis that Egl 9 homolog 3 (Egln3), a prolyl-hydroxylase that promotes Hif degradation, suppresses tumor progression of human and rodent glioma ..
  4. Fu J, Menzies K, Freeman R, Taubman M. EGLN3 prolyl hydroxylase regulates skeletal muscle differentiation and myogenin protein stability. J Biol Chem. 2007;282:12410-8 pubmed
    b>EGLN3, a member of the EGLN family of prolyl hydroxylases, has been shown to catalyze hydroxylation of the alpha subunit of hypoxia-inducible factor-alpha, which targets hypoxia-inducible factor-alpha for ubiquitination by a ubiquitin ..
  5. Aragones J, Schneider M, van Geyte K, Fraisl P, Dresselaers T, Mazzone M, et al. Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet. 2008;40:170-80 pubmed publisher
    ..Hypoxia tolerance relies primarily on Hif-2alpha and was not observed in heterozygous Phd2-deficient or homozygous Phd3-deficient mice. Of medical importance, conditional knockdown of Phd1 also rapidly induces hypoxia tolerance...
  6. Bishop T, Gallagher D, Pascual A, Lygate C, de Bono J, Nicholls L, et al. Abnormal sympathoadrenal development and systemic hypotension in PHD3-/- mice. Mol Cell Biol. 2008;28:3386-400 pubmed publisher
    Cell culture studies have implicated the oxygen-sensitive hypoxia-inducible factor (HIF) prolyl hydroxylase PHD3 in the regulation of neuronal apoptosis...
  7. Fu J, Taubman M. Prolyl hydroxylase EGLN3 regulates skeletal myoblast differentiation through an NF-kappaB-dependent pathway. J Biol Chem. 2010;285:8927-35 pubmed publisher
    ..We have previously shown that EGLN3 promotes differentiation of C2C12 skeletal myoblasts...
  8. Adam J, Hatipoglu E, O Flaherty L, Ternette N, Sahgal N, Lockstone H, et al. Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell. 2011;20:524-37 pubmed publisher
  9. Ginouves A, Ilc K, Macías N, Pouyssegur J, Berra E. PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis. Proc Natl Acad Sci U S A. 2008;105:4745-50 pubmed publisher
    ..Hence, PHDs serve as dual enzymes, for which inactivation and later overactivation is necessary for cell survival in acute or chronic hypoxia, respectively. ..

More Information


  1. Urrutia A, Afzal A, Nelson J, Davidoff O, Gross K, Haase V. Prolyl-4-hydroxylase 2 and 3 coregulate murine erythropoietin in brain pericytes. Blood. 2016;128:2550-2560 pubmed
    ..furthermore determined that Epo transcription in brain pericytes was HIF-2 dependent and cocontrolled by PHD2 and PHD3, oxygen- and 2-oxoglutarate-dependent prolyl-4-hydroxylases that regulate HIF activity...
  2. German N, Yoon H, Yusuf R, Murphy J, Finley L, Laurent G, et al. PHD3 Loss in Cancer Enables Metabolic Reliance on Fatty Acid Oxidation via Deactivation of ACC2. Mol Cell. 2016;63:1006-20 pubmed publisher
    ..Here, we reveal that PHD3 rapidly triggers repression of FAO in response to nutrient abundance via hydroxylation of acetyl-coA carboxylase 2 (..
  3. Xie L, Pi X, Wang Z, He J, Willis M, Patterson C. Depletion of PHD3 protects heart from ischemia/reperfusion injury by inhibiting cardiomyocyte apoptosis. J Mol Cell Cardiol. 2015;80:156-65 pubmed publisher
    b>PHD3, a member of a family of Prolyl-4 Hydroxylase Domain (PHD) proteins, has long been considered a pro-apoptotic protein...
  4. Rishi M, Selvaraju V, Thirunavukkarasu M, Shaikh I, Takeda K, Fong G, et al. Deletion of prolyl hydroxylase domain proteins (PHD1, PHD3) stabilizes hypoxia inducible factor-1 alpha, promotes neovascularization, and improves perfusion in a murine model of hind-limb ischemia. Microvasc Res. 2015;97:181-8 pubmed publisher
    ..Although prolyl hydroxylase domain proteins 1 and 3 (PHD1 and PHD3) may modulate angiogenesis via regulation of hypoxia inducible factor-1α (HIF-1α), there has been no study ..
  5. Liu H, Xia Y, Li B, Pan J, Lv M, Wang X, et al. Prolyl hydroxylase 3 overexpression accelerates the progression of atherosclerosis in ApoE-/- mice. Biochem Biophys Res Commun. 2016;473:99-106 pubmed publisher
    b>PHD3 belongs to the family of 2-oxoglutarate and iron-dependent dioxygenases and is a critical regulator of HIF-1?...
  6. Moschella M, Menzies K, Tsao L, Lieb M, Kohtz J, Kohtz D, et al. SM-20 is a novel growth factor-responsive gene regulated during skeletal muscle development and differentiation. Gene Expr. 1999;8:59-66 pubmed
    ..SM-20 thus represents a novel intracellular protein that is regulated during skeletal muscle differentiation and development. ..
  7. Dykes I, van Bueren K, Ashmore R, Floss T, Wurst W, Szumska D, et al. HIC2 is a novel dosage-dependent regulator of cardiac development located within the distal 22q11 deletion syndrome region. Circ Res. 2014;115:23-31 pubmed publisher
    ..Together our data suggest that HIC2 haploinsufficiency likely contributes to the cardiac defects seen in distal 22q11 deletion syndrome. ..
  8. Chowdhury R, Leung I, Tian Y, Abboud M, Ge W, Domene C, et al. Structural basis for oxygen degradation domain selectivity of the HIF prolyl hydroxylases. Nat Commun. 2016;7:12673 pubmed publisher
    ..The results inform on how HIF target gene selectivity is achieved and will be of use in developing selective PHD inhibitors. ..
  9. Rajagopalan S, Rane A, Chinta S, Andersen J. Regulation of ATP13A2 via PHD2-HIF1α Signaling Is Critical for Cellular Iron Homeostasis: Implications for Parkinson's Disease. J Neurosci. 2016;36:1086-95 pubmed publisher
    ..Mechanistically, this was due to ATP13A2's role in maintaining lysosomal iron stores. This constitutes a novel mechanism by which alterations in ATP13A2 activity may be driving PD-related neuropathology. ..
  10. Chen R, Nagel S, Papadakis M, Bishop T, Pollard P, Ratcliffe P, et al. Roles of individual prolyl-4-hydroxylase isoforms in the first 24 hours following transient focal cerebral ischaemia: insights from genetically modified mice. J Physiol. 2012;590:4079-91 pubmed publisher
    ..Male, 8- to 12-week old PHD1?/?, PHD2+/? and PHD3?/? mice and their wild-type (WT) littermate were subjected to 45 min of middle cerebral artery occlusion (MCAO)...
  11. Zieseniss A, Hesse A, Jatho A, Krull S, Hölscher M, Vogel S, et al. Cardiomyocyte-Specific Transgenic Expression of Prolyl-4-Hydroxylase Domain 3 Impairs the Myocardial Response to Ischemia. Cell Physiol Biochem. 2015;36:843-51 pubmed publisher
    ..Whereas overexpression of PHD3 in the resting state does not significantly influence cardiac function, it is crucial for the cardiac response to ..
  12. Kikuchi D, Minamishima Y, Nakayama K. Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1? and regulates the cellular PDH activity. Biochem Biophys Res Commun. 2014;451:288-94 pubmed publisher
    ..To further understand the physiological role of PHD3, proteomics were used to identify PHD3-interacting proteins, and pyruvate dehydrogenase (PDH)-E1? was identified as ..
  13. Walmsley S, Chilvers E, Thompson A, Vaughan K, Marriott H, Parker L, et al. Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice. J Clin Invest. 2011;121:1053-63 pubmed publisher
    ..We examined PHD expression in human neutrophils and found that PHD3 was strongly induced in response to hypoxia and inflammatory stimuli in vitro and in vivo...
  14. Bondeva T, Heinzig J, Ruhe C, Wolf G. Advanced glycated end-products affect HIF-transcriptional activity in renal cells. Mol Endocrinol. 2013;27:1918-33 pubmed publisher
    ..The purpose of this study was to analyze the influence of AGEs on Morg1 expression and its correlation to PHD3 activity and HIF-transcriptional activity in various renal cell types...
  15. Taylor M. Characterization and comparative analysis of the EGLN gene family. Gene. 2001;275:125-32 pubmed
    ..Each of the human genes (EGLN1, EGLN2 and EGLN3) are of a conserved genomic structure consisting of five coding exons...
  16. Swain L, Wottawa M, Hillemann A, Beneke A, Odagiri H, Terada K, et al. Prolyl-4-hydroxylase domain 3 (PHD3) is a critical terminator for cell survival of macrophages under stress conditions. J Leukoc Biol. 2014;96:365-75 pubmed publisher
    ..Especially, PHD3 has been additionally associated with apoptotic cell death...
  17. Scholz C, Cavadas M, Tambuwala M, Hams E, Rodriguez J, von Kriegsheim A, et al. Regulation of IL-1?-induced NF-?B by hydroxylases links key hypoxic and inflammatory signaling pathways. Proc Natl Acad Sci U S A. 2013;110:18490-5 pubmed publisher
    ..Thus, we hypothesize that hydroxylases regulate IL-1? signaling and subsequent inflammatory gene expression. Furthermore, hydroxylase inhibition represents a unique approach to the inhibition of IL-1?-dependent inflammatory signaling. ..
  18. Clever D, Roychoudhuri R, Constantinides M, Askenase M, Sukumar M, Klebanoff C, et al. Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche. Cell. 2016;166:1117-1131.e14 pubmed publisher
    ..Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis. PAPERCLIP. ..
  19. Rankin E, Wu C, Khatri R, Wilson T, Andersen R, Araldi E, et al. The HIF signaling pathway in osteoblasts directly modulates erythropoiesis through the production of EPO. Cell. 2012;149:63-74 pubmed publisher
    ..Furthermore, these studies demonstrate a molecular role for osteoblastic PHD/VHL/HIF signaling that can be targeted to elevate both HSCs and erythroid progenitors in the local hematopoietic microenvironment. ..
  20. Wu C, Rankin E, Castellini L, Alcudia J, Fernandez Alcudia J, LaGory E, et al. Oxygen-sensing PHDs regulate bone homeostasis through the modulation of osteoprotegerin. Genes Dev. 2015;29:817-31 pubmed publisher
    ..Hypoxia-inducible factor (HIF) activation associated with Phd2 and Phd3 inactivation drove bone accumulation by modulating osteoblastic/osteoclastic cross-talk through the direct ..
  21. Oriowo B, Thirunavukkarasu M, Selvaraju V, Adluri R, Zhan L, Takeda K, et al. Targeted gene deletion of prolyl hydroxylase domain protein 3 triggers angiogenesis and preserves cardiac function by stabilizing hypoxia inducible factor 1 alpha following myocardial infarction. Curr Pharm Des. 2014;20:1305-10 pubmed
    ..In the settings of cardiomyopathy and ischemia-reperfusion injury, PHD3 expression is elevated, resulting in decreased HIF activation...
  22. Chen Y, Zhang H, Fong G, Xi Q, Wu G, Bai C, et al. PHD3 Stabilizes the Tight Junction Protein Occludin and Protects Intestinal Epithelial Barrier Function. J Biol Chem. 2015;290:20580-9 pubmed publisher
    ..PHDs are found involved in inflammatory bowel disease (IBD); however, the exact role of PHD3, a member of the PHD family, in IBD remains unknown...
  23. Chang E, Loh S, Ceradini D, Chang E, Lin S, Bastidas N, et al. Age decreases endothelial progenitor cell recruitment through decreases in hypoxia-inducible factor 1alpha stabilization during ischemia. Circulation. 2007;116:2818-29 pubmed
    ..Aging impairs EPC trafficking to sites of ischemia through a failure of aged tissues to normally activate the hypoxia-inducible factor 1alpha-mediated hypoxia response. ..
  24. Himmels P, Paredes I, Adler H, Karakatsani A, Luck R, Marti H, et al. Motor neurons control blood vessel patterning in the developing spinal cord. Nat Commun. 2017;8:14583 pubmed publisher
  25. Yoshinaga M, Nakatsuka Y, Vandenbon A, Ori D, Uehata T, Tsujimura T, et al. Regnase-1 Maintains Iron Homeostasis via the Degradation of Transferrin Receptor 1 and Prolyl-Hydroxylase-Domain-Containing Protein 3 mRNAs. Cell Rep. 2017;19:1614-1630 pubmed publisher
    ..We reveal that duodenal Regnase-1 controls the expression of PHD3, which impairs duodenal iron uptake via HIF2α suppression...
  26. Taniguchi C, Miao Y, Diep A, Wu C, Rankin E, Atwood T, et al. PHD inhibition mitigates and protects against radiation-induced gastrointestinal toxicity via HIF2. Sci Transl Med. 2014;6:236ra64 pubmed publisher
    ..Thus, prolyl hydroxylase inhibition represents a treatment strategy to protect against and mitigate GI toxicity from both therapeutic radiation and potentially lethal radiation exposures. ..
  27. Van Welden S, De Vos M, Wielockx B, Tavernier S, Dullaers M, Neyt S, et al. Haematopoietic prolyl hydroxylase-1 deficiency promotes M2 macrophage polarization and is both necessary and sufficient to protect against experimental colitis. J Pathol. 2017;241:547-558 pubmed publisher
    ..cell infiltration, and colonic microvascular dysfunction, whereas the response of Phd2f/+ Tie2:cre and Phd3f/f Tie2:cre mice to DSS was similar to that of their littermate controls...
  28. Duan L, Takeda K, Fong G. Hematological, hepatic, and retinal phenotypes in mice deficient for prolyl hydroxylase domain proteins in the liver. Am J Pathol. 2014;184:1240-1250 pubmed publisher
    ..In this study, albumin Cre (Alb(Cre))-mediated, hepatocyte-specific triple disruption of Phd1, Phd2, and Phd3 (Phd(1/2/3)hKO) promoted liver erythropoietin (EPO) expression 1246-fold, whereas renal EPO was down-regulated to 6...
  29. Terkhorn S, Bohensky J, Shapiro I, Koyama E, Srinivas V. Expression of HIF prolyl hydroxylase isozymes in growth plate chondrocytes: relationship between maturation and apoptotic sensitivity. J Cell Physiol. 2007;210:257-65 pubmed
    ..This loss of protective activity together with the changes mediated by HIF would be expected to generate conditions that would favor the induction of chondrocyte apoptosis. ..
  30. Segura I, Lange C, Knevels E, Moskalyuk A, Pulizzi R, Eelen G, et al. The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A. Cell Rep. 2016;14:2653-67 pubmed publisher
    ..FLNA upregulation induces more immature spines, whereas Flna silencing rescues the immature spine phenotype induced by PHD2 inhibition. ..
  31. Minamishima Y, Kaelin W. Reactivation of hepatic EPO synthesis in mice after PHD loss. Science. 2010;329:407 pubmed publisher controlled by hypoxia-inducible factor (HIF), which is inhibited by three prolyl hydroxylases (PHD1, PHD2, and PHD3). Systemic PHD2 inactivation has been found to increase renal, but not hepatic, erythropoietin production...
  32. Arsenault P, Song D, Chung Y, Khurana T, Lee F. The Zinc Finger of Prolyl Hydroxylase Domain Protein 2 Is Essential for Efficient Hydroxylation of Hypoxia-Inducible Factor α. Mol Cell Biol. 2016;36:2328-43 pubmed publisher
    ..Thus, these findings have important implications for understanding both the molecular mechanism of the hypoxic response and human adaptation to high altitude. ..
  33. Querbes W, Bogorad R, Moslehi J, Wong J, Chan A, Bulgakova E, et al. Treatment of erythropoietin deficiency in mice with systemically administered siRNA. Blood. 2012;120:1916-22 pubmed publisher
  34. Bishop T, Talbot N, Turner P, Nicholls L, Pascual A, Hodson E, et al. Carotid body hyperplasia and enhanced ventilatory responses to hypoxia in mice with heterozygous deficiency of PHD2. J Physiol. 2013;591:3565-77 pubmed publisher
    ..0015 ± 0.00019 mm(3) in controls; P < 0.01). In contrast, HVR in PHD1(-/-) and PHD3(-/-) mice was similar to littermate controls...
  35. Xie L, Pi X, Townley Tilson W, Li N, Wehrens X, Entman M, et al. PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban. J Clin Invest. 2015;125:2759-71 pubmed publisher
    ..Both PHD2 and PHD3 are highly expressed in the heart, yet their functional roles in modulating contractile function remain ..
  36. Xie L, Pi X, Mishra A, Fong G, Peng J, Patterson C. PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response. J Clin Invest. 2012;122:2827-36 pubmed publisher
    ..clock protein CLK-2 (HCLK2), associated with and was hydroxylated by prolyl hydroxylase domain protein 3 (PHD3). HCLK2 hydroxylation was necessary for its interaction with ATR and the subsequent activation of ATR/CHK1/p53...
  37. Kobayashi H, Liu Q, Binns T, Urrutia A, Davidoff O, Kapitsinou P, et al. Distinct subpopulations of FOXD1 stroma-derived cells regulate renal erythropoietin. J Clin Invest. 2016;126:1926-38 pubmed publisher the kidney and liver and is regulated by prolyl-4-hydroxylase domain (PHD) dioxygenases PHD1, PHD2, and PHD3, which function as cellular oxygen sensors...
  38. Kapitsinou P, Jaffe J, Michael M, Swan C, Duffy K, Erickson Miller C, et al. Preischemic targeting of HIF prolyl hydroxylation inhibits fibrosis associated with acute kidney injury. Am J Physiol Renal Physiol. 2012;302:F1172-9 pubmed publisher
    ..Therefore, preischemic targeting of the PHD/HIF pathway represents an effective therapeutic strategy for the prevention of CKD resulting from AKI, and it warrants further investigation in clinical trials. ..
  39. Zhu K, Jiao H, Li S, Cao H, Galson D, Zhao Z, et al. ATF4 promotes bone angiogenesis by increasing VEGF expression and release in the bone environment. J Bone Miner Res. 2013;28:1870-1884 pubmed publisher
    ..Thus, ATF4 is a new key regulator of the HIF/VEGF axis in osteoblasts in response to hypoxia and of VEGF release from bone matrix, two critical steps for bone angiogenesis. ..
  40. Guentsch A, Beneke A, Swain L, Farhat K, Nagarajan S, Wielockx B, et al. PHD2 Is a Regulator for Glycolytic Reprogramming in Macrophages. Mol Cell Biol. 2017;37: pubmed
    ..We suggest that PHD2 serves as an adjustable switch to control macrophage behavior. ..
  41. Quaegebeur A, Segura I, Schmieder R, Verdegem D, Decimo I, Bifari F, et al. Deletion or Inhibition of the Oxygen Sensor PHD1 Protects against Ischemic Stroke via Reprogramming of Neuronal Metabolism. Cell Metab. 2016;23:280-91 pubmed publisher
    ..These data identify PHD1 as a regulator of neuronal metabolism and a potential therapeutic target in ischemic stroke. ..
  42. Nakayama K, Frew I, Hagensen M, Skals M, Habelhah H, Bhoumik A, et al. Siah2 regulates stability of prolyl-hydroxylases, controls HIF1alpha abundance, and modulates physiological responses to hypoxia. Cell. 2004;117:941-52 pubmed
    ..Here, we demonstrate that the abundance of PHD1 and PHD3 are regulated via their targeting for proteasome-dependent degradation by the E3 ubiquitin ligases Siah1a/2, under ..
  43. Henze A, Garvalov B, Seidel S, Cuesta A, Ritter M, Filatova A, et al. Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR. Nat Commun. 2014;5:5582 pubmed publisher
    ..Here we show that the prolyl hydroxylase PHD3 restrains tumour growth in response to microenvironmental cues through the control of EGFR...
  44. Takeda K, Duan L, Takeda H, Fong G. Improved vascular survival and growth in the mouse model of hindlimb ischemia by a remote signaling mechanism. Am J Pathol. 2014;184:686-96 pubmed publisher
  45. Laitala A, Aro E, Walkinshaw G, Maki J, Rossi M, Heikkilä M, et al. Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis. Blood. 2012;120:3336-44 pubmed publisher
    ..Our data thus indicate that P4H-TM plays a role in the regulation of EPO production, hepcidin expression, and erythropoiesis. ..
  46. Moslehi J, Minamishima Y, Shi J, Neuberg D, Charytan D, Padera R, et al. Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation. 2010;122:1004-16 pubmed publisher
  47. Hölscher M, Silter M, Krull S, von Ahlen M, Hesse A, Schwartz P, et al. Cardiomyocyte-specific prolyl-4-hydroxylase domain 2 knock out protects from acute myocardial ischemic injury. J Biol Chem. 2011;286:11185-94 pubmed publisher
    ..This correlated with a decreased number of apoptotic cells in the infarcted myocardium in the cPhd2(-/-) mice and significantly improved cardiac function 3 weeks after myocardial infarction. ..
  48. Franke K, Kalucka J, Mamlouk S, Singh R, Muschter A, Weidemann A, et al. HIF-1? is a protective factor in conditional PHD2-deficient mice suffering from severe HIF-2?-induced excessive erythropoiesis. Blood. 2013;121:1436-45 pubmed publisher
    ..Using different genetic approaches, we show that simultaneous inactivation of PHD2 and HIF-1? resulted in a drastic PHD3 reduction with consequent overexpression of HIF-2?-related genes, neurodegeneration, and lethality...
  49. Hulley P, Bishop T, Vernet A, Schneider J, Edwards J, Athanasou N, et al. Hypoxia-inducible factor 1-alpha does not regulate osteoclastogenesis but enhances bone resorption activity via prolyl-4-hydroxylase 2. J Pathol. 2017;242:322-333 pubmed publisher
    ..b>Phd3-/- bone marrow precursors displayed accelerated early fusion, mirroring results with HIF-1α siRNA...
  50. Zhu K, Song P, Lai Y, Liu C, Xiao G. Prolyl hydroxylase domain proteins regulate bone mass through their expression in osteoblasts. Gene. 2016;594:125-130 pubmed publisher
    ..Here we deleted the expression of genes encoding PHD1, PHD2, and PHD3 in osteoblasts in mice by breeding the floxed Phd1-3 mice with Col1a1-Cre transgenic mice...
  51. Tavernier S, Vanlangenakker N, Vetters J, Carmeliet P, Janssens S, Lambrecht B. Opposing regulation and roles for PHD3 in lung dendritic cells and alveolar macrophages. J Leukoc Biol. 2017;102:1115-1126 pubmed publisher
    ..Although PHD2 and PHD3 were expressed in baseline, stimulation with house dust mite (HDM) allergen, hypoxia, and TLR4 ligands induced the ..
  52. Macías D, Fernández Agüera M, Bonilla Henao V, López Barneo J. Deletion of the von Hippel-Lindau gene causes sympathoadrenal cell death and impairs chemoreceptor-mediated adaptation to hypoxia. EMBO Mol Med. 2014;6:1577-92 pubmed publisher
    ..Therefore, in the normal sympathoadrenal setting, Vhl deletion does not give rise to tumors but impairs development and plasticity of the peripheral Oâ‚‚-sensing system required for survival in hypoxic conditions. ..
  53. Singh Y, Shi X, Zhang S, Umbach A, Chen H, Salker M, et al. Prolyl hydroxylase 3 (PHD3) expression augments the development of regulatory T cells. Mol Immunol. 2016;76:7-12 pubmed publisher
    ..In this study, we reveal that prolyl hydroxylase 3 (PHD3), which is a negative regulator of HIF-1?, is upregulated in Tregs and enhances the development of Tregs...
  54. Taniguchi C, Finger E, Krieg A, Wu C, Diep A, LaGory E, et al. Cross-talk between hypoxia and insulin signaling through Phd3 regulates hepatic glucose and lipid metabolism and ameliorates diabetes. Nat Med. 2013;19:1325-30 pubmed publisher
    ..Here, we show that acute deletion of hepatic Phd3, also known as Egln3, improves insulin sensitivity and ameliorates diabetes by specifically stabilizing Hif-2?, which then increases ..
  55. Kiss J, Mollenhauer M, Walmsley S, Kirchberg J, Radhakrishnan P, Niemietz T, et al. Loss of the oxygen sensor PHD3 enhances the innate immune response to abdominal sepsis. J Immunol. 2012;189:1955-65 pubmed publisher
    ..The HIF prolyl hydroxylase enzymes PHD1, PHD2 and PHD3 regulate the mammalian adaptive response to hypoxia; however, their significance in the innate immune response has ..
  56. Trollmann R, Rehrauer H, Schneider C, Krischke G, Huemmler N, Keller S, et al. Late-gestational systemic hypoxia leads to a similar early gene response in mouse placenta and developing brain. Am J Physiol Regul Integr Comp Physiol. 2010;299:R1489-99 pubmed publisher
    ..Our observations implicate future diagnostic options to identify fetal and cerebral tissue hypoxia. ..
  57. Minamishima Y, Moslehi J, Padera R, Bronson R, Liao R, Kaelin W. A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Mol Cell Biol. 2009;29:5729-41 pubmed publisher
    ..Among the three Phd family members, Phd2 appears to be the primary HIF prolyl hydroxylase. Phd3 is induced by HIF and, based on findings from in vitro studies, may participate in a HIF-regulatory feedback loop...
  58. Shen X, Wan C, Ramaswamy G, Mavalli M, Wang Y, Duvall C, et al. Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice. J Orthop Res. 2009;27:1298-305 pubmed publisher
    ..These results suggest that HIF activation is a viable approach to increase vascularity and bone formation following skeletal trauma. ..
  59. Aglan A, Longen S, Dehne N, Köhler Y, Hassan M, Beck M, et al. Nitric oxide mediates prolyl hydroxylase 3 expression in mesangial cells and in glomerulonephritis. J Mol Med (Berl). 2017;95:257-271 pubmed publisher
    ..and TNF-α (1 nM), a combination further referred to as cytokine mix (CM), resulted in a fivefold increase in PHD3 but not PHD1 and PHD2 mRNA expression compared to untreated controls...
  60. Takeda K, Cowan A, Fong G. Essential role for prolyl hydroxylase domain protein 2 in oxygen homeostasis of the adult vascular system. Circulation. 2007;116:774-81 pubmed
    Prolyl hydroxylase domain (PHD) proteins, including PHD1, PHD2, and PHD3, mediate oxygen-dependent degradation of hypoxia-inducible factor (HIF)-alpha subunits...
  61. Lieb M, Menzies K, Moschella M, Ni R, Taubman M. Mammalian EGLN genes have distinct patterns of mRNA expression and regulation. Biochem Cell Biol. 2002;80:421-6 pubmed
    The mammalian EGLN family contains three paralagous genes (EGLN1, EGLN2, and EGLN3) encoding prolyl hydroxylase isoforms that mediate the oxygen-dependent targeting of the transcription factor hypoxia inducible factor alpha to the ..