Affinage

EGLN1

Egl nine homolog 1 · UniProt Q9GZT9

Length
426 aa
Mass
46.0 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EGLN1/PHD2 is an iron(II)- and 2-oxoglutarate-dependent prolyl hydroxylase that serves as the principal cellular oxygen sensor, hydroxylating specific prolyl residues on HIF-1α and HIF-2α to target them for proteolysis; loss-of-function studies establish PHD2 as the dominant HIF prolyl hydroxylase under normoxia and in vivo (PMID:15247232, PMID:18096761). It preferentially hydroxylates the HIF-1α CODD site ~20-fold over NODD, a selectivity governed primarily by differential substrate binding affinity (PMID:23787140). Because PHD2 is itself transcribed from a hypoxia-responsive promoter directly bound by HIF-1, the enzyme operates within a negative-feedback loop that restrains the HIF response (PMID:15563275), and additional layers of control include DAP5/eIF2β-dependent translation of PHD2 mRNA during hypoxia (PMID:29530922). PHD2 activity is tuned by a dense array of post-translational and metabolic inputs: activating S125 phosphorylation by the mTOR/P70S6K axis opposed by PP2A-B55α dephosphorylation (PMID:28199842), ERK phosphorylation that blocks HIF-1α binding (PMID:31285371), inhibitory K297 methylation by SET7 (PMID:35452683), activating persulfidation at Cys21/Cys33 by CBS-derived H2S (PMID:32937467), inactivating oxidative disulfide homodimerization (PMID:26740011), and direct competitive inhibition at the α-ketoglutarate site by lactate (PMID:36064857). Beyond HIF-α, PHD2 hydroxylates non-HIF substrates that connect it to diverse cellular programs: filamin A to control dendritic spine maturation (PMID:26972007), thyroid hormone receptor-α to regulate phospholamban and cardiac stress tolerance (PMID:26075818), the PP2A subunit B55α to govern apoptosis under glucose starvation (PMID:28329677), and mitochondrial AMPKα within a CaMKK2-containing complex to maintain metabolic homeostasis in hypoxia (PMID:37661833). The enzyme links to the HSP90 chaperone pathway through its N-terminal MYND zinc finger, which binds a PXLE motif in the co-chaperones p23 and FKBP38 to facilitate HIF-α hydroxylation and regulate PHD2 stability (PMID:19546213, PMID:23413029), and it shuttles between cytoplasm and nucleus via CRM1-dependent export (PMID:19631610). In vivo, PHD2 is the master regulator of erythropoiesis and cardiac homeostasis (PMID:18096761), tumor and ischemic vascular normalization and arteriogenesis (PMID:19217150, PMID:21983962), pulmonary vascular remodeling through HIF-2α (PMID:27143681), and the hypoxic ventilatory response via the PHD2/HIF-2α couple in the carotid body (PMID:26337139). The Tibetan D4E/C127S haplotype is a loss-of-function allele that impairs p23 binding, blunting the HIF pathway and the hypoxic ventilatory/inflammatory response to facilitate high-altitude adaptation (PMID:32414920, PMID:34102396).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2000 High

    Before its enzymatic identity was known, EGLN1 (SM-20) was found to localize to mitochondria and drive neuronal apoptosis, establishing an early functional readout that would later be reconciled with its dioxygenase role.

    Evidence fusion-protein import assays, co-localization, and caspase-inhibitor rescue in NGF-deprived neurons and PC12 cells

    PMID:11060309 PMID:12675908

    Open questions at the time
    • did not identify the enzymatic activity or molecular substrate
    • relationship between pro-apoptotic activity and prolyl hydroxylase function unresolved
  2. 2004 High

    Defining EGLN1 as the dominant cellular HIF prolyl hydroxylase answered which enzyme sets normoxic HIF-α levels and revealed site- and isoform-selectivity.

    Evidence isoform-specific siRNA knockdown with HIF-α hydroxylation site readouts across multiple cell types

    PMID:15247232

    Open questions at the time
    • kinetic basis of site selectivity not yet defined
    • did not address regulation of PHD2 itself
  3. 2005 High

    Identifying PHD2 as a direct HIF-1 target gene with a functional HRE explained how the oxygen-sensing system self-limits through negative feedback.

    Evidence promoter luciferase reporters, EMSA, and transcript analysis of the downstream CpG-island promoter

    PMID:15563275 PMID:16157596

    Open questions at the time
    • mechanism of HIF-independent transcriptional repression by PHD2 not fully defined
  4. 2007 High

    Conditional mouse knockout established PHD2 as the primary HIF prolyl hydroxylase in vivo and tied it to erythropoiesis and cardiac homeostasis.

    Evidence Cre-lox conditional Egln1 inactivation with phenotypic and gene-expression profiling

    PMID:18096761

    Open questions at the time
    • did not resolve which HIF isoform mediates each phenotype
    • tissue-specific contributions not dissected
  5. 2009 High

    Cell-type-specific PHD2 haplodeficiency revealed roles in endothelial vascular normalization and macrophage-driven arteriogenesis, including HIF-independent NF-κB-dependent outputs.

    Evidence Phd2(+/-) tumor and ischemia mouse models with HIF and NF-κB pathway epistasis and cytokine assays

    PMID:19217150 PMID:19477431

    Open questions at the time
    • direct substrate underlying NF-κB/HIF-independent effects not identified
  6. 2009 High

    Mapping the N-terminal MYND zinc finger as a protein-interaction module connected PHD2 to chaperone-pathway partners and to non-canonical trafficking control.

    Evidence peptide arrays, FRET, co-IP, fractionation for FKBP38 binding, plus CRM1-inhibition and importin-competition for nucleocytoplasmic shuttling

    PMID:19546213 PMID:19631610

    Open questions at the time
    • functional consequence of nuclear pool of PHD2 unresolved
    • FKBP38-dependent stability mechanism not linked to specific physiology
  7. 2013 High

    Biochemical and structural studies quantified CODD-over-NODD selectivity and defined inhibitor-binding chemistry of the catalytic site.

    Evidence kinetic competition assays, HDX-MS, and X-ray crystallography of PHD2-inhibitor complexes

    PMID:23787140 PMID:24055079

    Open questions at the time
    • structural basis for non-HIF substrate recognition not addressed
  8. 2013 Medium

    Defining the PXLE motif shared by p23 and FKBP38, and later by HSP90, mechanistically linked PHD2 to the HSP90 chaperone machinery as a determinant of HIF-α hydroxylation.

    Evidence co-IP, PXLE motif identification, and p23 knockdown with HIF-1α readouts; ANG1-TIE2 feed-forward loop in macrophages

    PMID:23413029 PMID:23616286

    Open questions at the time
    • how chaperone binding mechanistically enhances catalysis not defined
    • single-lab characterization of the p23 dependency
  9. 2015 High

    Identifying filamin A and cancer-associated fibroblast deactivation extended PHD2 function to HIF-independent substrate hydroxylation and tumor-stroma mechanics.

    Evidence site-directed mutagenesis of FLNA prolines, ubiquitination and spine imaging; CAF traction-force microscopy with HIF-1α epistasis

    PMID:26323721 PMID:26972007

    Open questions at the time
    • physiological contexts of FLNA hydroxylation beyond neurons not mapped
  10. 2016 High

    A wave of in vivo and biochemical studies expanded the PHD2 substrate/regulatory repertoire (TR-α, oxidative dimerization, S125 phosphorylation) and dissected organ-specific HIF isoform dependencies in pulmonary, ventilatory, ischemic, and metabolic settings.

    Evidence double conditional KOs (Phd2/Phd3, Egln1/Hif1a, Egln1/Hif2a), in vitro hydroxylation of TR-α, cysteine mutagenesis, phospho-specific assays, parabiosis and metabolomics, Seahorse metabolic profiling

    PMID:26075818 PMID:26337139 PMID:26740011 PMID:26919427 PMID:27143681 PMID:27795296 PMID:27919930 PMID:28199842

    Open questions at the time
    • integration of competing post-translational inputs in a single cell type unresolved
    • relative contribution of each non-HIF substrate to organ phenotypes unclear
  11. 2018 Medium

    Discovery of DAP5/eIF2β-dependent translation of PHD2 mRNA added a translational safeguard limiting HIF-1α accumulation during hypoxic protein-synthesis repression.

    Evidence DAP5 knockdown, polysome profiling of PHD2 mRNA, and DAP5:eIF2β co-IP

    PMID:29530922

    Open questions at the time
    • single-lab characterization
    • in vivo relevance of translational control not established
  12. 2020 High

    Persulfidation by CBS-derived H2S and genetic confirmation of the Tibetan allele as a p23-pathway loss-of-function variant clarified how PHD2 activity is metabolically and evolutionarily tuned for hypoxic adaptation.

    Evidence persulfidation assays with Cys21/Cys33 mutagenesis and zebrafish rescue; Tibetan Phd2 and p23-mutant knockin mice with plethysmography; endothelial Cav1/NOS rescue in renal/pulmonary injury models

    PMID:31996410 PMID:32414920 PMID:32937467 PMID:35798360

    Open questions at the time
    • interplay between persulfidation and other cysteine-based redox regulation not resolved
  13. 2022 High

    Direct lactate competition at the αKG site and SET7-mediated K297 methylation revealed PHD2 as a direct metabolic and epigenetic sensor coupling energy state to HIF signaling and inflammation.

    Evidence direct binding/competition kinetics with purified PHD2, in vitro methylation assays with K297 mutants, and PHD2-deficient macrophage rescue; Tibetan-variant monocyte immunophenotyping

    PMID:34102396 PMID:35452683 PMID:36064857

    Open questions at the time
    • quantitative hierarchy among lactate, methylation, and phosphorylation inputs unknown
  14. 2023 High

    Identification of mitochondrial AMPKα as a substrate within a CaMKK2-EglN1-AMPKα complex and osteocyte control of FGF23 placed PHD2 at the interface of organelle-localized metabolic signaling and systemic phosphate/iron homeostasis.

    Evidence mitochondrial proteomics, in vitro AMPKα hydroxylation, β2β3 loop deletion mutants and xenografts; osteocyte-specific Phd2 KO with ATAC/RNAseq and HIF-1α rescue

    PMID:36650133 PMID:37661833

    Open questions at the time
    • structural basis of mitochondrial recruitment via β2β3 loop not solved
    • generality of mitochondrial AMPKα hydroxylation across tissues untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many competing post-translational, redox, and metabolic regulators of PHD2 are integrated in real time within a single cell, and how substrate choice between HIF-α and the growing set of non-HIF substrates is determined, remain open.
  • no unified model reconciling phosphorylation, methylation, persulfidation, dimerization, and lactate inhibition
  • substrate-selection rules for non-HIF targets undefined
  • structural determinants of organelle-specific PHD2 activity unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0016787 hydrolase activity 2 GO:0140299 molecular sensor activity 2
Localization
GO:0005739 mitochondrion 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 3 R-HSA-8953897 Cellular responses to stimuli 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
EPAS1FKBP38FLNAHIF1AHSP90PPP2R2APTGES3THRA
Complex memberships
CaMKK2-EglN1-AMPKα mitochondrial complex

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 PHD2 (EGLN1) hydroxylates specific prolyl residues on both HIF-1α and HIF-2α subunits in an oxygen-dependent manner, targeting them for proteolysis. siRNA-based knockdown demonstrated that PHD2 is the primary contributor to HIF regulation under normoxic conditions, and that PHD2 shows specificity for different prolyl hydroxylation sites within each HIF-α subunit and some selectivity between HIF-1α and HIF-2α isoforms. siRNA knockdown, isoform-specific PHD suppression assays in multiple cell types The Journal of biological chemistry High 15247232
2005 The PHD2 gene is transcribed exclusively from a downstream CpG island promoter that contains a functional hypoxia-responsive element (HRE). HIF-1 binds this HRE as demonstrated by EMSA, and the promoter is induced by hypoxia in luciferase reporter assays, establishing PHD2 as a direct HIF target gene and part of a negative-feedback loop. Promoter luciferase reporter assays, EMSA, sequence analysis, RT-PCR The Biochemical journal High 15563275
2005 EGLN1/PHD2 represses HIF-1α transcriptional activity in hypoxia independently of promoting its proteolysis. Ectopic EGLN1 expression inhibited HIF-1α transcriptional activity without altering its protein levels in VHL-deficient cells, indicating a discrete transcriptional repression activity separate from the hydroxylation/degradation mechanism. Ectopic overexpression in VHL-deficient cells, luciferase reporter assays for HIF-1α transcriptional activity, siRNA knockdown The Journal of biological chemistry Medium 16157596
2000 SM-20 (EGLN1) protein localizes to mitochondria via a functional N-terminal mitochondrial targeting sequence (first 25 amino acids), and promotes caspase-3-dependent apoptosis in NGF-deprived neurons. An N-terminally truncated form loses mitochondrial restriction but retains the ability to induce cell death, demonstrating that mitochondrial localization is not required for pro-apoptotic activity. Immunofluorescence co-localization with mitochondrial markers, SM-20/DHFR fusion protein import assays, caspase inhibitor experiments, cytochrome c fractionation The Journal of biological chemistry High 11060309
2007 Conditional inactivation of PHD2 (Egln1) in mice is sufficient to activate a subset of HIF target genes including erythropoietin, causing striking polycythemia and premature mortality from dilated cardiomyopathy, demonstrating PHD2 is the primary HIF prolyl hydroxylase in vivo. Conditional gene knockout in mice (Cre-lox), phenotypic analysis, gene expression profiling Blood High 18096761
2009 PHD2 haplodeficiency in endothelial cells normalizes tumor vasculature, improves tumor perfusion and oxygenation, and inhibits metastasis. The mechanism involves HIF-driven upregulation of soluble VEGFR-1 and VE-cadherin, redirecting endothelial tip cell specification toward a quiescent phalanx formation. PHD2(+/-) mouse tumor implantation model, gene expression analysis, HIF pathway epistasis Cell High 19217150
2009 PHD2 regulates tumor angiogenesis and bone marrow-derived cell (BMDC) mobilization through IL-8 and angiogenin in a HIF-independent but NF-κB-dependent manner. PHD2 levels are decreased in human cancers versus normal tissue. PHD2 knockdown/overexpression in cancer cells, cytokine assays (ELISA), NF-κB pathway analysis Cancer cell Medium 19477431
2009 FKBP38 interacts with PHD2 via a glutamate-rich N-terminal domain in FKBP38 and the MYND-type zinc finger domain in PHD2's N-terminus. This interaction regulates PHD2 protein stability through a ubiquitin-independent proteasomal pathway dependent on membrane-anchored FKBP38. PHD2 subcellular localization overlaps with FKBP38 at the endoplasmic reticulum and mitochondria, with an additional cytoplasmic fraction. Peptide array binding assays, fluorescence spectroscopy, FRET, biochemical fractionation, immunofluorescence, co-immunoprecipitation The Journal of biological chemistry High 19546213
2009 PHD2 nuclear export requires CRM1 and the N-terminal 100 amino acids of PHD2. PHD2 cycles between nucleus and cytoplasm, and its nuclear import is independent of classical importin α/β receptors (unlike PHD1 which has a classical NLS-dependent import). Subcellular fractionation, CRM1 inhibition (leptomycin B), importin knockdown/competition assays, live cell imaging Biochemical and biophysical research communications Medium 19631610
2011 PHD2 haplodeficiency in macrophages skews them toward a pro-arteriogenic M2-like phenotype, promoting collateral artery growth via increased release of arteriogenic factors and smooth muscle cell recruitment. The mechanism relies on activation of the canonical NF-κB pathway in PHD2-haplodeficient macrophages. Phd2(+/-) mice, hindlimb ischemia model, macrophage-specific Phd2 deletion, NF-κB pathway analysis, macrophage depletion and transfer experiments Nature High 21983962
2013 PHD2's N-terminal MYND-type zinc finger domain binds a conserved Pro-Xaa-Leu-Glu (PXLE) motif in the HSP90 co-chaperones p23 and FKBP38. p23 knockdown augments hypoxia-induced HIF-1α levels and HIF target gene expression, indicating that the PHD2:p23 interaction facilitates HIF-α hydroxylation by linking PHD2 to the HSP90 chaperone pathway. Co-immunoprecipitation, PXLE motif identification, p23 siRNA knockdown, HIF-1α protein level measurement The Journal of biological chemistry Medium 23413029
2014 The Tibetan PHD2 haplotype (D4E/C127S) strikingly diminishes PHD2 interaction with the HSP90 co-chaperone p23 via its PXLE motif, impairing PHD2-mediated downregulation of the HIF pathway. Both substitutions are required for the defective p23 binding. HSP90 itself also contains a PXLE motif that binds PHD2, but this interaction is maintained with the Tibetan haplotype. Co-immunoprecipitation, in vitro binding assays, HIF pathway reporter assays with Tibetan vs. wild-type PHD2 The Journal of biological chemistry Medium 24711448
2015 PHD2 hydroxylates proline residues P2309 and P2316 in the actin cross-linker filamin A (FLNA) under normoxia, leading to VHL-mediated ubiquitination and proteasomal degradation of FLNA. In hypoxia, PHD2 inactivation stabilizes FLNA, causing immature filopodium-like dendritic protrusions and reduced synaptic density independently of HIF signaling. Silencing FLNA rescues the immature spine phenotype caused by PHD2 inhibition. PHD2 siRNA, chemical PHD inhibition, site-directed mutagenesis of FLNA proline residues, ubiquitination assays, dendritic spine imaging, electrophysiology Cell reports High 26972007
2016 PHD2 is phosphorylated at serine 125 (S125) by the mTOR downstream kinase P70S6K, increasing its ability to degrade HIF-1α. Under hypoxia, mTOR blockade by REDD1 restrains P70S6K and permits PP2A (via its regulatory subunit B55α) to directly dephosphorylate PHD2 at S125, reducing PHD2 activity and boosting HIF-1α accumulation to promote autophagy-dependent cell survival in colorectal cancer cells. Kinase assays, phospho-specific antibodies, mTOR/PP2A inhibitors, B55α knockdown, in vivo xenograft models, patient tissue analysis Cell reports High 28199842
2016 PHD2 undergoes disulfide bond-mediated homo-dimerization in response to oxidative stress (oxidizing agents and oncogenic H-RasV12 signaling), and this dimerization inactivates PHD2, stabilizing HIF-1α. Cysteine residues in the double-stranded β-helix fold at the catalytic site mediate the oxidative dimerization. This mechanism links oncogenic RAS signaling to HIF-1α activation and aerobic glycolysis. Non-reducing SDS-PAGE, mutagenesis of cysteine residues, co-IP for dimer detection, antioxidant rescue experiments, PHD2 knockdown controls Scientific reports Medium 26740011
2016 Combined deletion of Phd2 and Phd3 in mice dramatically decreases phospholamban (PLN) expression, causes sustained CaMKII activation, and sensitizes mice to chronic β-adrenergic stress-induced myocardial injury. Mechanistically, PHD2 and PHD3 interact with and hydroxylate thyroid hormone receptor-α (TR-α) at two proline residues; PHD inhibition increases TR-α interaction with the corepressor NCOR2, suppressing PLN transcription. Double Phd2/Phd3 conditional knockout, co-IP of TR-α with PHD2/PHD3, in vitro prolyl hydroxylation assay of TR-α, transcript analysis, cardiac physiology The Journal of clinical investigation High 26075818
2016 PHD2 deficiency in endothelial/hematopoietic cells (Egln1Tie2 mice) causes severe pulmonary arterial hypertension with obliterative vascular remodeling via HIF-2α. Genetic deletion of both Egln1 and Hif2a (but not Hif1a) normalized the PAH phenotype. PHD2-deficient endothelial cells promote smooth muscle cell proliferation partly through HIF-2α-activated CXCL12 expression; genetic Cxcl12 deletion attenuated PAH. Tissue-specific double conditional knockout (Egln1/Hif1a and Egln1/Hif2a), Cxcl12 genetic deletion, hemodynamic measurements, histology Circulation High 27143681
2016 PHD2 is a regulator of glycolytic reprogramming in macrophages. PHD2-deficient macrophages show increased anaerobic glycolysis with increased PDK1 protein levels and decreased pyruvate dehydrogenase activity. Inhibition of PDK1 or knockout of HIF-1α reversed the metabolic phenotype, placing PHD2 upstream of HIF-1α/PDK1 in macrophage metabolic control. PHD2 knockout bone marrow-derived macrophages and RAW cells, metabolic phenotyping (Seahorse), HIF-1α knockout rescue, PDK1 inhibition Molecular and cellular biology Medium 27795296
2016 PHD2 inhibition in pulmonary artery smooth muscle cells (PASMC) induces HIF-1α and promotes proliferation; SMC-specific PHD2 knockout exacerbates hypoxia-induced pulmonary hypertension and vascular remodeling in mice. The 3'-UTR of PHD2 contains a functional miR-17/20a binding site, and miR-17/20a suppresses PHD2 to upregulate HIF-1α and drive proliferation. SMC-specific PHD2 knockout mice, miR-17/20 inhibitors/mimics, 3'-UTR reporter assays, pulmonary hypertension hemodynamics Journal of the American Heart Association Medium 27919930
2017 PHD2 hydroxylates the PP2A regulatory subunit B55α at proline 319, triggering its degradation. Under glucose starvation, PHD2-mediated B55α hydroxylation and degradation promotes apoptosis. PHD2 silencing rescues B55α from degradation and prevents apoptosis, while B55α knockdown restores apoptosis in PHD2-deficient cells, identifying B55α as a PHD2 substrate linking PHD2 to cell death responses under nutrient stress. PHD2 overexpression/silencing, site-directed mutagenesis of B55α proline 319, co-IP, in vitro hydroxylation, xenograft models Cell reports High 28329677
2019 ERK directly phosphorylates PHD2, and this phosphorylation prevents PHD2 from binding to HIF-1α, thereby inhibiting HIF-1α hydroxylation and increasing HIF-1α stability. TGFβ1 activates this ERK/PHD2 signaling axis in platinum-resistant ovarian cancer to promote platinum resistance by stabilizing HIF-1α. In vitro kinase assay (ERK phosphorylating PHD2), co-IP of PHD2/HIF-1α, HIF-1α stability assays, TGFβ1 pathway inhibitors, in vivo xenograft models Clinical cancer research Medium 31285371
2020 Cystathionine β-synthase (CBS) produces H2S which persulfidates PHD2 at Cys21 and Cys33 in the zinc finger motif, augmenting its prolyl hydroxylase activity. Depletion of H2S (by hypoxia or CBS inhibition) reduces PHD2 persulfidation and inhibits its activity, resulting in HIF-1α stabilization. Point mutations at these cysteines confirmed their functional importance. Biochemical persulfidation assays, CBS knockdown/inhibition, site-directed mutagenesis of Cys21/Cys33, in vitro PHD2 activity assays, zebrafish CBS depletion model, H2S rescue experiments Science advances High 32937467
2020 Additional PHD2 mutations at or near Asp-4 or Cys-127 (beyond the Tibetan D4E/C127S haplotype) impair interaction with the HSP90 cochaperone p23 in vitro. Mice carrying the Tibetan Phd2 allele display augmented hypoxic ventilatory response, and this phenotype is also produced by a p23 mutation that abrogates the PHD2:p23 interaction, confirming the Tibetan allele is a loss-of-function allele acting through the p23/HSP90 pathway. In vitro p23 binding assays with mutant PHD2, Tibetan Phd2 knockin mice, p23 mutant mice, plethysmography (hypoxic ventilatory response), HIF pathway analysis Proceedings of the National Academy of Sciences of the United States of America High 32414920
2013 PHD2 shows substrate preference for the CODD (C-terminal oxygen degradation domain) of HIF-1α by approximately 20-fold over NODD. Kinetic competition assays and amide H/D exchange reveal that electrostatics influence this selectivity, and that both substrates stabilize the β2β3 loop to a similar extent; differences in substrate selectivity arise primarily from differential binding affinities rather than differential loop closure. In vitro kinetic competition assays, varied ionic strength, amide H/D exchange monitored by mass spectrometry Journal of inorganic biochemistry High 23787140
2013 Novel crystal structure of PHD2 enzyme complexed with a 2,8-diazaspiro[4.5]decan-1-one inhibitor reveals previously unobserved binding interactions: hydrogen bond with Arg322, π-cation interaction with Arg322, π-π stacking with Trp389 and His313, without the salt bridge to Arg383 seen in all prior complex structures. X-ray crystallography of PHD2-inhibitor complex, structure-activity relationship studies Bioorganic & medicinal chemistry High 24055079
2016 Endothelial PHD2 deficiency induces obliterative pulmonary vascular remodeling and PAH through suppression of caveolin-1 (Cav1), which augments nitrative stress via endothelial NOS activation. Genetic restoration of Cav1 in Egln1Tie2 mice normalized nitrative stress and reduced PAH, while NOS3 knockdown or superoxide dismutase mimetic also inhibited the vascular remodeling. Egln1Tie2 mouse model, Cav1 genetic rescue, endothelial NOS3 knockdown via CRISPR-Cas9 nanoparticle delivery, SOD mimetic treatment, hemodynamic measurements The European respiratory journal Medium 35798360
2016 PHD2 deficiency in endothelial cells and carotid bodies increases ventilatory sensitivity to hypoxia and causes carotid body hyperplasia through HIF-2α but not HIF-1α. Inducible inactivation of HIF-2α impairs ventilatory acclimatization to chronic hypoxia, establishing the PHD2/HIF-2α enzyme-substrate couple as the key mediator of hypoxic ventilatory responses. Tamoxifen-inducible Phd2 knockout, HIF-1α and HIF-2α conditional knockout epistasis, plethysmography, BrdU proliferation assays in carotid bodies The Journal of physiology High 26337139
2016 Inhibition of Egln1 systemically or in skeletal muscles protects mice against myocardial ischemia-reperfusion injury. The protection is mediated by a secreted factor: Egln1 loss causes accumulation of circulating α-ketoglutarate (αKG), which drives hepatic production and secretion of kynurenic acid (KYNA), which is necessary and sufficient to mediate cardiac ischemic protection. Somatic Egln1 gene deletion, pharmacological inhibition (PHD inhibitor), parabiosis experiments, metabolomics (αKG measurement), KYNA supplementation and depletion experiments Cell High 26919427
2022 Lactate, at physiological concentrations, directly binds to the catalytic domain of PHD2 in competition with α-ketoglutarate, inhibiting PHD2 activity and stabilizing HIF-1α. Lactate-induced IL-1β production was abolished in PHD2-deficient macrophages, identifying PHD2 as a direct metabolic sensor of lactate that connects chronic inflammation to energy metabolism. Direct binding assay (lactate to PHD2 catalytic domain), competitive inhibition kinetics vs. α-ketoglutarate, PHD2-deficient macrophage rescue experiments, in vivo adipocyte-specific LDHA deletion mouse model Nature communications High 36064857
2022 SET7, a lysine monomethylase, catalyzes EGLN1 methylation at lysine 297, repressing EGLN1 prolyl hydroxylase activity toward HIF-1α. A methylation mimic mutant of EGLN1 loses the capability to suppress hypoxia signaling, leading to enhanced cell proliferation and increased oxygen consumption rate. In vitro methylation assay (SET7 acting on EGLN1), site-directed mutagenesis of K297, PHD2 activity assays, HIF-1α hydroxylation measurement, cell proliferation and metabolic assays The Journal of biological chemistry High 35452683
2018 DAP5 (Death-associated protein 5) regulates HIF-1α abundance by enabling DAP5:eIF2β complex-dependent translation of PHD2 during hypoxia. DAP5 depletion caused a surge in HIF-1α levels due to reduced PHD2 translation, revealing a translational control mechanism that safeguards against excessive HIF-1α accumulation during hypoxia-associated protein synthesis repression. DAP5 siRNA knockdown, polysome profiling for PHD2 mRNA, co-IP of DAP5:eIF2β, HIF-1α protein measurement, PHD2 reporter constructs Molecular and cellular biology Medium 29530922
2023 EglN1/PHD2 accumulates on mitochondria under hypoxia via its β2β3 loop substrate-binding region, where it interacts with and prolyl-hydroxylates AMPKα under normoxia, causing their rapid dissociation and release from mitochondria. Under hypoxia, the EglN1-AMPKα interaction is maintained, and a CaMKK2-EglN1-AMPKα complex forms on mitochondria, activating AMPKα phosphorylation to maintain metabolic homeostasis and support breast tumor growth. Mitochondrial proteomic profiling, co-IP of EglN1-AMPKα on mitochondria, in vitro prolyl hydroxylation assay of AMPKα, β2β3 loop deletion mutants, CaMKK2 co-IP, xenograft tumor growth assays The EMBO journal High 37661833
2023 Osteocyte PHD2 (Egln1) controls FGF23 production: conditional osteocyte-specific Phd2 deletion upregulates Fgf23 through HIF-1α-dependent mechanisms. PHD2-knockout osteocyte-like cells lose iron-mediated suppression of Fgf23 that cannot be compensated by PHD1 or PHD3, and in vivo CKD models show suppressed Phd1-3 consistent with FGF23 upregulation, linking the oxygen/iron-sensing PHD2 axis to phosphate homeostasis. Osteocyte-specific Phd2 conditional knockout, CRISPR Phd2-KO osteocyte cell lines, ATACseq/RNAseq, HIF1α blockade rescue, chronic kidney disease mouse model Bone research Medium 36650133
2003 Induction of SM-20 (EGLN1) expression in PC12 cells leads to increased cytochrome c levels, accumulation of cytochrome c in the cytosol, and caspase-dependent cell death, establishing a mechanism by which SM-20 promotes neuronal apoptosis through the cytochrome c/caspase pathway. Doxycycline-inducible SM-20 PC12 cell line, subcellular fractionation of cytochrome c, caspase activity assays, caspase inhibitor (zVAD-FMK) rescue Journal of neurochemistry Medium 12675908
2015 PHD2 inhibition in cancer-associated fibroblasts (CAFs) phenocopies the effects of chronic hypoxia: PHD2 loss leads to HIF-1α stabilization, reduced αSMA and periostin expression, decreased myosin II activity, loss of contractile force, and reduced ECM remodeling. This deactivates CAFs and impairs CAF-mediated cancer cell invasion and metastasis. These effects require HIF-1α, as simultaneous HIF-1α depletion prevents the PHD2 loss phenotype. PHD2 RNAi and chemical inhibition (DMOG) in CAFs, orthotopic breast cancer model, αSMA/periostin expression analysis, traction force microscopy, HIF-1α siRNA epistasis EMBO reports Medium 26323721
2013 PHD2 repression in macrophages is induced by angiopoietin-1 (ANG1)-mediated signaling during femoral artery occlusion. ANG1-dependent PHD2 repression initiates a feed-forward loop mediated by induction of the ANG receptor TIE2 in macrophages. TIE2 induction is required for proarteriogenic macrophage functions enabling collateral vessel formation. ANG1 blockade (soluble trap), Phd2 gene silencing in macrophages, macrophage depletion/transfer, TIE2 gene silencing, hindlimb ischemia model EMBO molecular medicine Medium 23616286
2020 Endothelial PHD2 deletion protects against renal ischemia-reperfusion injury by suppressing proinflammatory gene expression and inflammatory cell recruitment in a manner dependent on HIF-1 but not HIF-2. In vitro experiments implicated a humoral factor in the anti-inflammatory effects of endothelial PHD2/HIF-1 signaling. Endothelial-specific Phd2 deletion, double KO with HIF-1 or HIF-2, inducible endothelial Phd2 deletion in adult mice, renal ischemia-reperfusion injury model, inflammatory cell quantification Journal of the American Society of Nephrology Medium 31996410
2021 The gain-of-function Tibetan PHD2 D4E;C127S variant suppresses hypoxia-induced inflammatory responses in monocytes: PHD2D4E;C127S monocytes show reduced secretion of IL-6 and IL-1β, impaired chemotaxis, and downmodulation of RELA, JUN, STAT1, ATF2 and CXCR4. U937 monocytic cells engineered to express PHD2D4E;C127S confirmed these findings at the protein level under hypoxia. αKG supplementation (augmenting PHD2 activity) also diminished inflammatory responses in vitro and reduced leukocyte infiltration in lungs of hypoxia-exposed mice. Flow cytometry immunophenotyping of homozygous Tibetan PHD2 variant carriers, nCounter gene expression analysis, engineered U937 cell lines expressing Tibetan variant vs. WT PHD2, in vivo hypoxia mouse model with αKG supplementation EBioMedicine Medium 34102396

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. The Journal of biological chemistry 905 15247232
2009 Heterozygous deficiency of PHD2 restores tumor oxygenation and inhibits metastasis via endothelial normalization. Cell 646 19217150
2008 PHD2 mutation and congenital erythrocytosis with paraganglioma. The New England journal of medicine 259 19092153
2011 Macrophage skewing by Phd2 haplodeficiency prevents ischaemia by inducing arteriogenesis. Nature 251 21983962
2007 Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood 247 18096761
2016 Prolyl-4 Hydroxylase 2 (PHD2) Deficiency in Endothelial Cells and Hematopoietic Cells Induces Obliterative Vascular Remodeling and Severe Pulmonary Arterial Hypertension in Mice and Humans Through Hypoxia-Inducible Factor-2α. Circulation 213 27143681
2009 Tumor vasculature is regulated by PHD2-mediated angiogenesis and bone marrow-derived cell recruitment. Cancer cell 194 19477431
2005 Regulation of the prolyl hydroxylase domain protein 2 (phd2/egln-1) gene: identification of a functional hypoxia-responsive element. The Biochemical journal 173 15563275
2022 Adipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2. Nature communications 149 36064857
2016 Oxidative Dimerization of PHD2 is Responsible for its Inactivation and Contributes to Metabolic Reprogramming via HIF-1α Activation. Scientific reports 147 26740011
2015 Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis. EMBO reports 141 26323721
2013 Identification of a Tibetan-specific mutation in the hypoxic gene EGLN1 and its contribution to high-altitude adaptation. Molecular biology and evolution 123 23666208
2016 EGLN1 Inhibition and Rerouting of α-Ketoglutarate Suffice for Remote Ischemic Protection. Cell 111 26919427
2014 Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia. Journal of molecular medicine (Berlin, Germany) 108 25263965
2012 Gene-targeting of Phd2 improves tumor response to chemotherapy and prevents side-toxicity. Cancer cell 106 22897855
2010 EGLN1 involvement in high-altitude adaptation revealed through genetic analysis of extreme constitution types defined in Ayurveda. Proceedings of the National Academy of Sciences of the United States of America 104 20956315
2017 The mTOR and PP2A Pathways Regulate PHD2 Phosphorylation to Fine-Tune HIF1α Levels and Colorectal Cancer Cell Survival under Hypoxia. Cell reports 102 28199842
2009 Binding of the CHD4 PHD2 finger to histone H3 is modulated by covalent modifications. The Biochemical journal 93 19624289
2005 Suppression of hypoxia-inducible factor 1alpha (HIF-1alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1. The Journal of biological chemistry 93 16157596
2015 Hypoxia-inducible miR-182 enhances HIF1α signaling via targeting PHD2 and FIH1 in prostate cancer. Scientific reports 87 26205124
2006 Overexpression and nuclear translocation of hypoxia-inducible factor prolyl hydroxylase PHD2 in head and neck squamous cell carcinoma is associated with tumor aggressiveness. Clinical cancer research : an official journal of the American Association for Cancer Research 81 16489060
2000 SM-20 is a novel mitochondrial protein that causes caspase-dependent cell death in nerve growth factor-dependent neurons. The Journal of biological chemistry 81 11060309
2015 Regulation of ventilatory sensitivity and carotid body proliferation in hypoxia by the PHD2/HIF-2 pathway. The Journal of physiology 77 26337139
1999 Expression of the SM-20 gene promotes death in nerve growth factor-dependent sympathetic neurons. Journal of neurochemistry 71 10386996
2012 Expression of prolyl hydroxylases (PHDs) is selectively controlled by HIF-1 and HIF-2 proteins in nucleus pulposus cells of the intervertebral disc: distinct roles of PHD2 and PHD3 proteins in controlling HIF-1α activity in hypoxia. The Journal of biological chemistry 70 22451659
2010 Prolyl-4-hydroxylase PHD2- and hypoxia-inducible factor 2-dependent regulation of amphiregulin contributes to breast tumorigenesis. Oncogene 68 20856199
2015 The Cancer Cell Oxygen Sensor PHD2 Promotes Metastasis via Activation of Cancer-Associated Fibroblasts. Cell reports 66 26235614
2006 Induction of human endometrial cancer cell senescence through modulation of HIF-1alpha activity by EGLN1. International journal of cancer 65 16161047
2014 Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing. The Journal of biological chemistry 63 24711448
2017 Gain-of-function EGLN1 prolyl hydroxylase (PHD2 D4E:C127S) in combination with EPAS1 (HIF-2α) polymorphism lowers hemoglobin concentration in Tibetan highlanders. Journal of molecular medicine (Berlin, Germany) 61 28233034
2009 Hypoxia-inducible factor prolyl-4-hydroxylase PHD2 protein abundance depends on integral membrane anchoring of FKBP38. The Journal of biological chemistry 61 19546213
2016 PHD2: from hypoxia regulation to disease progression. Hypoxia (Auckland, N.Z.) 60 27800508
2010 PHD2 in tumour angiogenesis. British journal of cancer 60 20461086
2019 Hydrogen sulfide inhibits cigarette smoke-induced inflammation and injury in alveolar epithelial cells by suppressing PHD2/HIF-1α/MAPK signaling pathway. International immunopharmacology 59 31771816
2016 miR-17/20 Controls Prolyl Hydroxylase 2 (PHD2)/Hypoxia-Inducible Factor 1 (HIF1) to Regulate Pulmonary Artery Smooth Muscle Cell Proliferation. Journal of the American Heart Association 52 27919930
2013 Prolyl hydroxylase domain protein 2 (PHD2) binds a Pro-Xaa-Leu-Glu motif, linking it to the heat shock protein 90 pathway. The Journal of biological chemistry 52 23413029
2016 The Oxygen Sensor PHD2 Controls Dendritic Spines and Synapses via Modification of Filamin A. Cell reports 51 26972007
2020 Cystathione β-synthase regulates HIF-1α stability through persulfidation of PHD2. Science advances 49 32937467
2019 Association of EGLN1 gene with high aerobic capacity of Peruvian Quechua at high altitude. Proceedings of the National Academy of Sciences of the United States of America 49 31712437
2020 Inhibition of Endothelial PHD2 Suppresses Post-Ischemic Kidney Inflammation through Hypoxia-Inducible Factor-1. Journal of the American Society of Nephrology : JASN 47 31996410
2019 ERK Regulates HIF1α-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 45 31285371
2007 Disturbance in the HIF-1alpha pathway associated with erythrocytosis: further evidences brought by frameshift and nonsense mutations in the prolyl hydroxylase domain protein 2 (PHD2) gene. Blood cells, molecules & diseases 45 17933562
2013 Expression and DNA methylation levels of prolyl hydroxylases PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer. BMC cancer 44 24195777
2014 The role of PHD2 mutations in the pathogenesis of erythrocytosis. Hypoxia (Auckland, N.Z.) 43 27774468
2013 EGLN1 variants influence expression and SaO2 levels to associate with high-altitude pulmonary oedema and adaptation. Clinical science (London, England : 1979) 41 23130672
2021 The DpdtbA induced EMT inhibition in gastric cancer cell lines was through ferritinophagy-mediated activation of p53 and PHD2/hif-1α pathway. Journal of inorganic biochemistry 40 33713969
2019 Genome-Wide Interrogation of Human Cancers Identifies EGLN1 Dependency in Clear Cell Ovarian Cancers. Cancer research 40 30898838
2009 The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia. European journal of haematology 40 19737309
2019 Convergent evolution on the hypoxia-inducible factor (HIF) pathway genes EGLN1 and EPAS1 in high-altitude ducks. Heredity 39 30631144
2013 Gambogic acid inhibits angiogenesis through inhibiting PHD2-VHL-HIF-1α pathway. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 39 23501055
2014 Intermediary metabolite precursor dimethyl-2-ketoglutarate stabilizes hypoxia-inducible factor-1α by inhibiting prolyl-4-hydroxylase PHD2. PloS one 38 25420025
2013 PHD2 regulates arteriogenic macrophages through TIE2 signalling. EMBO molecular medicine 38 23616286
2003 SM-20, EGL-9, and the EGLN family of hypoxia-inducible factor prolyl hydroxylases. Molecules and cells 37 14503838
2020 Tibetan PHD2, an allele with loss-of-function properties. Proceedings of the National Academy of Sciences of the United States of America 35 32414920
2019 PHD2 exerts anti-cancer and anti-inflammatory effects in colon cancer xenografts mice via attenuating NF-κB activity. Life sciences 35 31838134
2003 Induction of SM-20 in PC12 cells leads to increased cytochrome c levels, accumulation of cytochrome c in the cytosol, and caspase-dependent cell death. Journal of neurochemistry 35 12675908
2002 Angiotensin II's antiproliferative effects mediated through AT2-receptors depend on down-regulation of SM-20. Laboratory investigation; a journal of technical methods and pathology 35 12379765
2011 Prolyl hydroxylase domain protein 2 (PHD2) mediates oxygen-induced retinopathy in neonatal mice. The American journal of pathology 34 21435465
2009 Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2. Biochemical and biophysical research communications 34 19631610
1996 SM-20 is a novel 40-kd protein whose expression in the arterial wall is restricted to smooth muscle. Laboratory investigation; a journal of technical methods and pathology 34 8606489
2014 HIF-1-PHD2 axis controls expression of syndecan 4 in nucleus pulposus cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 32 24558194
2014 Conditional disruption of the prolyl hydroxylase domain-containing protein 2 (Phd2) gene defines its key role in skeletal development. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 32 24753072
2018 Acceleration of Diabetic Wound Healing with PHD2- and miR-210-Targeting Oligonucleotides. Tissue engineering. Part A 31 29644938
2013 Wound healing improvement with PHD-2 silenced fibroblasts in diabetic mice. PloS one 31 24376825
2000 Mapping, characterization, and expression analysis of the SM-20 human homologue, c1orf12, and identification of a novel related gene, SCAND2. Genomics 30 11056053
2020 Myocardium-targeted transplantation of PHD2 shRNA-modified bone mesenchymal stem cells through ultrasound-targeted microbubble destruction protects the heart from acute myocardial infarction. Theranostics 29 32308762
2016 PHD2 Is a Regulator for Glycolytic Reprogramming in Macrophages. Molecular and cellular biology 29 27795296
2012 GNAS1 and PHD2 short-interfering RNA support bone regeneration in vitro and in an in vivo sheep model. Clinical orthopaedics and related research 28 22833384
2011 Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer. Cancer 28 21792862
2022 Endothelial PHD2 deficiency induces nitrative stress via suppression of caveolin-1 in pulmonary hypertension. The European respiratory journal 27 35798360
2019 Systemic silencing of PHD2 causes reversible immune regulatory dysfunction. The Journal of clinical investigation 27 31162141
2017 PHD2 Targeting Overcomes Breast Cancer Cell Death upon Glucose Starvation in a PP2A/B55α-Mediated Manner. Cell reports 27 28329677
2015 Molecular characterization and mRNA expression of HIF-prolyl hydroxylase-2 (phd2) in hypoxia-sensing pathways from Megalobrama amblycephala. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 27 25868626
2015 PHD2/3-dependent hydroxylation tunes cardiac response to β-adrenergic stress via phospholamban. The Journal of clinical investigation 27 26075818
2019 Genetic variants at the EGLN1 locus associated with high-altitude adaptation in Tibetans are absent or found at low frequency in highland Andeans. Annals of human genetics 26 30719713
2011 An activator of PHD2, KRH102140, decreases angiogenesis via inhibition of HIF-1α. Cell biochemistry and function 26 21287578
2018 A redox ruthenium compound directly targets PHD2 and inhibits the HIF1 pathway to reduce tumor angiogenesis independently of p53. Cancer letters 25 30339780
1999 SM-20 is a novel growth factor-responsive gene regulated during skeletal muscle development and differentiation. Gene expression 25 10543731
2015 Conditional Deletion of Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Gene Reveals Its Essential Role in Chondrocyte Function and Endochondral Bone Formation. Endocrinology 24 26562260
2018 Gamma linolenic acid regulates PHD2 mediated hypoxia and mitochondrial apoptosis in DEN induced hepatocellular carcinoma. Drug design, development and therapy 23 30587920
2014 Variants of the low oxygen sensors EGLN1 and HIF-1AN associated with acute mountain sickness. International journal of molecular sciences 23 25431923
2021 Gain-of-function Tibetan PHD2D4E;C127S variant suppresses monocyte function: A lesson in inflammatory response to inspired hypoxia. EBioMedicine 20 34102396
2018 Regulation of Hypoxia-Inducible Factor 1α during Hypoxia by DAP5-Induced Translation of PHD2. Molecular and cellular biology 20 29530922
2023 Osteocyte Egln1/Phd2 links oxygen sensing and biomineralization via FGF23. Bone research 19 36650133
2022 PHD2 deletion in endothelial or arterial smooth muscle cells reveals vascular cell type-specific responses in pulmonary hypertension and fibrosis. Angiogenesis 18 34997404
2017 Conditional Deletion of the Phd2 Gene in Articular Chondrocytes Accelerates Differentiation and Reduces Articular Cartilage Thickness. Scientific reports 18 28349987
2022 A novel PHD2 inhibitor acteoside from Cistanche tubulosa induces skeletal muscle mitophagy to improve cancer-related fatigue. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 35658245
2016 Short Hairpin RNA Silencing of PHD-2 Improves Neovascularization and Functional Outcomes in Diabetic Wounds and Ischemic Limbs. PloS one 16 26967994
2013 Substrate preference of the HIF-prolyl hydroxylase-2 (PHD2) and substrate-induced conformational change. Journal of inorganic biochemistry 16 23787140
2009 Defects in embryonic development of EGLN1/PHD2 knockdown transgenic mice are associated with induction of Igfbp in the placenta. Biochemical and biophysical research communications 16 19683511
2023 Characterization of genetic variants in the EGLN1/PHD2 gene identified in a European collection of patients with erythrocytosis. Haematologica 15 37317877
2023 A mitochondrial EglN1-AMPKα axis drives breast cancer progression by enhancing metabolic adaptation to hypoxic stress. The EMBO journal 15 37661833
2022 Differential methylation in EGLN1 associates with blood oxygen saturation and plasma protein levels in high-altitude pulmonary edema. Clinical epigenetics 15 36180894
2018 Hepatic PHD2/HIF-1α axis is involved in postexercise systemic energy homeostasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 15 29601782
2018 Inhibition of the Oxygen Sensor PHD2 Enhances Tissue-Engineered Endochondral Bone Formation. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 15 30452097
2016 Erythrocytosis due to PHD2 Mutations: A Review of Clinical Presentation, Diagnosis, and Genetics. Case reports in hematology 15 27034858
2022 EGLN1 prolyl hydroxylation of hypoxia-induced transcription factor HIF1α is repressed by SET7-catalyzed lysine methylation. The Journal of biological chemistry 14 35452683
2021 Endothelial cell PHD2-HIF1α-PFKFB3 contributes to right ventricle vascular adaptation in pulmonary hypertension. American journal of physiology. Lung cellular and molecular physiology 14 34346780
2016 Prolyl Hydroxylase Domain-Containing Protein 2 (Phd2) Regulates Chondrocyte Differentiation and Secondary Ossification in Mice. Scientific reports 14 27775044
2013 Novel complex crystal structure of prolyl hydroxylase domain-containing protein 2 (PHD2): 2,8-Diazaspiro[4.5]decan-1-ones as potent, orally bioavailable PHD2 inhibitors. Bioorganic & medicinal chemistry 14 24055079

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