Property Summary

NCBI Gene PubMed Count 83
PubMed Score 102.88
PubTator Score 88.43

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (18)

Protein-protein Interaction (7)

Gene RIF (60)

PMID Text
26997627 In pancreatic Beta cells, knock-down of PHD3 inhibited glucose-stimulated insulin secretion.
26940742 The selective efficacy of PZ was further demonstrated at the cellular level by observing inhibition of the PHD3-dependent DNA damage response pathway without stabilization of HIF-1alpha.
26372732 Loss of PHD3 expression is associated with breast cancer.
26223520 The data demonstrates that PHD3 can drive cell cycle entry at the G1/S transition through decreasing the half-life of p27 that occurs by attenuating p27S10 phosphorylation.
25542265 The enhanced expression of PHD3 might likely contribute to the poor neovascularization and affect the biological characterization in PDAC cancer cells
25420773 PHD3 loss sustains cell proliferation through the control of EGFR.
25420589 PHD3 controls EGFR activity by acting as a scaffolding protein that associates with the endocytic adaptor Eps15 and promotes the internalization of EGFR.
25380826 PHD3 SUMOylation occurs at a cluster of four lysines at the C-terminal end of the protein. Furthermore, PHD3 SUMOylation by SUMO2 or SUMO3 contributes to PHD3-mediated repression of HIF1-dependent transcriptional activity.
25088999 PHD3 depletion did not affect the expression of the PDH-E1alpha, E1beta, and E2 subunits, or the phosphorylation status of E1alpha, but destabilized the PDH complex (PDC), resulting in less functional PDC.
25081707 HIFPH3 expression in human non-small cell lung cancer lesions is significantly higher than that in para-cancerous and normal lung tissues and is positively associated with lymph node metastasis and microvessel density.
25079693 A novel role for PHD3 as a negative regulator of cell motility through posttranslational modification of nonmuscle actins.
24477694 PHD3 has an antiproliferative function independent of HIF protein status in renal cell carcinoma (RCC), indicating a novel expression mechanism and function of PHD3.
24367580 the relationship between PHD3 expression and epithelial-to-mesenchymal transition
24195777 reduced PHD3 expression in cancerous tissue was accompanied by methylation of the CpG rich region located within the first exon and intron of the PHD3 gene.
23886708 PHD-3 mediates specific HIF1-alpha proline 567 hydroxylation, which can function as a new player in the VHL/HIF-1alpha interactions.
23732909 EGLN3 inhibits cIAP1-mediated IKK-gamma ubiquitination by interfering with the interaction between IKK-gamma and cIAP1.
23601303 Studies suggest that hypoxia, HIF-1 alpha, PHD3 and pVHL could be considered as potential therapeutic targets for lung cancer pathogenesis and progression.
23533015 LOw expression of PHD3 is associated with gastric cancer.
23345396 The data demonstrate p62 is a critical regulator of the hypoxia response and PHD3 activity, by inducing PHD3 aggregation and degradation under normoxia.
22948157 Prolyl hydroxylase 3 (PHD3) modulates catabolic effects of tumor necrosis factor-alpha (TNF-alpha) on cells of the nucleus pulposus through co-activation of nuclear factor kappaB (NF-kappaB)/p65 signaling.
22905089 Egln3 suppresses glioma progression
22898032 Our study has provided preliminary materials and data for further investigation of the effect of PHD3 on HepG2 cells
22797300 identification of HCLK2 as a substrate of PHD3 reveals the mechanism through which hypoxia inhibits the DDR, suggesting hydroxylation of HCLK2 is a potential therapeutic target for regulating the ATR/CHK1/p53 pathway
22778395 These results indicate that EGLN3 gene expression in macrophages is dependent on activin A
22395314 Here, we outline specific functions of PHD enzymes in surgically relevant pathological conditions, and discuss how these functions might be exploited in order to support the treatment of surgically relevant diseases.
22343896 (R)-2HG, but not (S)-2HG, stimulates EGLN activity, leading to diminished HIF levels, which enhances the proliferation and soft agar growth of human astrocytes
22290580 Overexpression of PHD3 is a favorable prognosticator for gastric cancer.
22087251 a block in G1 to S transition in carcinoma cells under PHD3 inhibition
21887331 High tumor cell expression of PHD3 (P= 0.058) and FIH (P= 0.15) did not, however, reach statistical significance
21877141 PHD3 may be an important regulator of apoptosis and it is mainly found in tumors with good prognosis.
21748337 The expression of PHD genes and their relationship with the tumor behavior and apoptosis-associated factors in non-small cell lung cancer, was investigated.
21620138 Interaction of PKM2 with prolyl hydroxylase 3 (PHD3) enhances PKM2 binding to HIF-1alpha and PKM2 coactivator function; PKM2 participates in a positive feedback loop that promotes HIF-1 transactivation and reprograms glucose metabolism in cancer cells.
21575608 these results suggest that PHD3 targets Pax2 for destruction.
21483450 The oxygen sensor PHD3 limits glycolysis under hypoxia via direct binding to pyruvate kinase
21421125 Prolyl hydroxylases (PHD3) regulate the transcriptional activity of HIF-1alpha. This could be potentially inhibited by polynitrogen compounds.
21317538 PHD3 has a role in regulating neutrophil survival in hypoxia
21297970 PHD3 expression is silenced by aberrant CpG methylation in a subset of human carcinoma cell lines of diverse origin and this aberrant cytosine methylation status is the mechanism by which these cancer cell lines fail to upregulate PHD3 mRNA
20978507 Essential functions of PHD3 in pncreatic tumour growth, apoptosis and angiogenesis.
20959442 Observational study of gene-disease association. (HuGE Navigator)
20727020 Methylation-induced epigenetic silencing of PHD1, PHD2, PHD3 and FIH is unlikely to underlie up-regulated HIF-1alpha expression in human breast cancer but may play a role in other tumour types.
20599946 hPRP19 interacts with PHD3 to suppress the cell death under hypoxic conditions by limiting the function of PHD3 which leads to caspase activation
20379614 Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
20028863 our findings recognize the PHD/HIF regulatory axis as a novel therapeutic target to disable a tumor's ability to adjust to hypoxic conditions and control cell survival
19786027 PHD3 appears to be a tumor suppressor in colorectal cancer cells that inhibits IKKbeta/NF-kappaB signaling, independent of its hydroxylase activity.
19737309 The CpG island of EGLN3 is frequently methylated in plasma cell dyscrasias and B-cell lymphomas. loss of EGLN3 is an important epigenetic event not only in plasma cell neoplasias but also in B-cell neoplasias.
19724277 BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression.
19584355 interaction of pVHL with beta(2)AR is dependent on proline hydroxylation (proline-382 and -395) and the dioxygenase EGLN3 interacts directly with the beta(2)AR to serve as an endogenous beta(2)AR prolyl hydroxylase.
19574556 Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent mechanism in human endothelial cells.
19339211 Results describe the localization signal of HIF-prolyl hydroxylases (PHDs) 1-3, and their intracellular localization in response to hypoxia.
18954447 Data show that PDK1 and HIF prolyl hydroxylase 3 mRNA expressions are lowest in children of chronic mountain sickness fathers at altitude.
18927305 Overexpression of the oxygen sensor PHD-3 is associated with tumor aggressiveness in pancreatic endocrine tumors.
18347341 Chronic hypoxia not only increases the pool of PHDs but also overactivates the three PHD isoforms.
18337469 The data demonstrates the cellular oxygen sensor PHD3 as a regulator of protein aggregation in response to varying oxygen availability.
17684156 PHD-dependent oxygen-sensing recruits both the hypoxia-inducible factor (HIF) and ATF-4 systems.
17003045 The role of Siah2 phosphorylation in the regulation of its activity toward PHD3 is reported.
16958618 Mechanism underlying the regulation of PHD3 availability and activity in hypoxia by the E3 ligase Siah2.
16098468 EglN3 acts downstream of c-Jun and is specifically required among the three EglN family members for neuronal apoptosis.
15251459 results indicate that PHD3 is a TRiC substrate, providing another step at which PHD3 activity may be regulated
15247232 PHD1, PHD2, and PHD3 have roles in the regulation of hypoxia-inducible factor
15156561 siRNA targeted degradation of HIF-1alpha and HIF-2alpha results in decreased hypoxia-induced PHD3 expression

AA Sequence

MPLGHIMRLDLEKIALEYIVPCLHEVGFCYLDNFLGEVVGDCVLERVKQLHCTGALRDGQLAGPRAGVSK      1 - 70
RHLRGDQITWIGGNEEGCEAISFLLSLIDRLVLYCGSRLGKYYVKERSKAMVACYPGNGTGYVRHVDNPN     71 - 140
GDGRCITCIYYLNKNWDAKLHGGILRIFPEGKSFIADVEPIFDRLLFFWSDRRNPHEVQPSYATRYAMTV    141 - 210
WYFDAEERAEAKKKFRNLTRKTESALTED                                             211 - 239
//

Text Mined References (85)

PMID Year Title
26997627 2016 Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion.
26972000 2016 Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways.
26940742 2016 Pyrithione Zn selectively inhibits hypoxia-inducible factor prolyl hydroxylase PHD3.
26372732 2015 Distinct breast cancer stem/progenitor cell populations require either HIF1? or loss of PHD3 to expand under hypoxic conditions.
26223520 2015 Hypoxia inducible prolyl hydroxylase PHD3 maintains carcinoma cell growth by decreasing the stability of p27.
25542265 2015 Increased expression of PHD3 represses the HIF-1 signaling pathway and contributes to poor neovascularization in pancreatic ductal adenocarcinoma.
25420773 2014 Loss of PHD3 allows tumours to overcome hypoxic growth inhibition and sustain proliferation through EGFR.
25420589 2014 PHD3 regulates EGFR internalization and signalling in tumours.
25416956 2014 A proteome-scale map of the human interactome network.
25380826 2015 PHD3-SUMO conjugation represses HIF1 transcriptional activity independently of PHD3 catalytic activity.
25088999 2014 Prolyl-hydroxylase PHD3 interacts with pyruvate dehydrogenase (PDH)-E1? and regulates the cellular PDH activity.
25081707 2014 Expression of hypoxia-inducible factor prolyl hydroxylase 3 HIFPH3 in human non-small cell lung cancer (NSCLC) and its correlation with prognosis.
25079693 2014 PHD3-mediated prolyl hydroxylation of nonmuscle actin impairs polymerization and cell motility.
24477694 2014 Hypoxia-inducible factor (HIF)-independent expression mechanism and novel function of HIF prolyl hydroxylase-3 in renal cell carcinoma.
24367580 2013 Prolyl-4-hydroxylase 3 (PHD3) expression is downregulated during epithelial-to-mesenchymal transition.
24195777 2013 Expression and DNA methylation levels of prolyl hydroxylases PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer.
23886708 2013 In silico investigation of PHD-3 specific HIF1-? proline 567 hydroxylation: a new player in the VHL/HIF-1? interaction pathway?
23732909 2013 EGLN3 inhibition of NF-?B is mediated by prolyl hydroxylase-independent inhibition of I?B kinase ? ubiquitination.
23601303 2013 [Advances of hypoxia and lung cancer].
23533015 2014 Prolyl hydroxylase 3 inhibited the tumorigenecity of gastric cancer cells.
23345396 2013 p62/SQSTM1 regulates cellular oxygen sensing by attenuating PHD3 activity through aggregate sequestration and enhanced degradation.
22955912 2012 Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.
22948157 2012 Prolyl hydroxylase 3 (PHD3) modulates catabolic effects of tumor necrosis factor-? (TNF-?) on cells of the nucleus pulposus through co-activation of nuclear factor ?B (NF-?B)/p65 signaling.
22905089 2012 Suppression of glioma progression by Egln3.
22898032 2012 Construction of a recombinant eukaryotic expression vector containing PHD3 gene and its expression in HepG2 cells.
22797300 2012 PHD3-dependent hydroxylation of HCLK2 promotes the DNA damage response.
22778395 2012 The prolyl hydroxylase PHD3 identifies proinflammatory macrophages and its expression is regulated by activin A.
22395314 2012 Molecular oxygen sensing: implications for visceral surgery.
22343896 2012 Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation.
22290580 2012 Overexpression of the HIF hydroxylase PHD3 is a favorable prognosticator for gastric cancer.
22286099 2012 The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
22087251 2011 Prolyl hydroxylase PHD3 enhances the hypoxic survival and G1 to S transition of carcinoma cells.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21887331 2011 Overexpression of the HIF hydroxylases PHD1, PHD2, PHD3 and FIH are individually and collectively unfavorable prognosticators for NSCLC survival.
21877141 2012 Expressions of individual PHDs associate with good prognostic factors and increased proliferation in breast cancer patients.
21748337 2011 The expression of prolyl hydroxylase domain enzymes are up-regulated and negatively correlated with Bcl-2 in non-small cell lung cancer.
21620138 2011 Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1.
21575608 2011 Prolyl hydroxylase domain protein 3 targets Pax2 for destruction.
21483450 2011 The oxygen sensor PHD3 limits glycolysis under hypoxia via direct binding to pyruvate kinase.
21421125 2011 Effects of polynitrogen compounds on the activity of recombinant human HIF-1? prolyl hydroxylase 3 in E. coli.
21410436 2011 Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites.
21317538 2011 Prolyl hydroxylase 3 (PHD3) is essential for hypoxic regulation of neutrophilic inflammation in humans and mice.
21297970 2011 Aberrant promoter CpG methylation is a mechanism for impaired PHD3 expression in a diverse set of malignant cells.
20978507 2010 PHD3 regulates differentiation, tumour growth and angiogenesis in pancreatic cancer.
20959442 2011 Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.
20849813 2010 Prolyl hydroxylase 3 interacts with Bcl-2 to regulate doxorubicin-induced apoptosis in H9c2 cells.
20727020 2010 DNA methylation analysis of the HIF-1? prolyl hydroxylase domain genes PHD1, PHD2, PHD3 and the factor inhibiting HIF gene FIH in invasive breast carcinomas.
20599946 2010 Human PRP19 interacts with prolyl-hydroxylase PHD3 and inhibits cell death in hypoxia.
20379614 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
20028863 2010 Prolyl hydroxylases 2 and 3 act in gliomas as protective negative feedback regulators of hypoxia-inducible factors.
19786027 2010 Prolyl hydroxylase-3 is down-regulated in colorectal cancer cells and inhibits IKKbeta independent of hydroxylase activity.
19737309 2010 The prolyl-hydroxylase EGLN3 and not EGLN1 is inactivated by methylation in plasma cell neoplasia.
19724277 2009 BRCA1 tumours correlate with a HIF-1alpha phenotype and have a poor prognosis through modulation of hydroxylase enzyme profile expression.
19584355 2009 Oxygen-regulated beta(2)-adrenergic receptor hydroxylation by EGLN3 and ubiquitylation by pVHL.
19574556 2009 Interferon-gamma induces prolyl hydroxylase (PHD)3 through a STAT1-dependent mechanism in human endothelial cells.
19339211 2009 Role of the intracellular localization of HIF-prolyl hydroxylases.
18954447 2008 Abnormal energy regulation in early life: childhood gene expression may predict subsequent chronic mountain sickness.
18927305 2008 Overexpression of the oxygen sensors PHD-1, PHD-2, PHD-3, and FIH Is associated with tumor aggressiveness in pancreatic endocrine tumors.
18347341 2008 PHDs overactivation during chronic hypoxia "desensitizes" HIFalpha and protects cells from necrosis.
18337469 2008 Prolyl hydroxylase PHD3 activates oxygen-dependent protein aggregation.
17684156 2007 Oxygen-dependent ATF-4 stability is mediated by the PHD3 oxygen sensor.
17353276 2007 The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability.
17003045 2006 Regulation of the ring finger E3 ligase Siah2 by p38 MAPK.
16958618 2007 Hypoxia-induced assembly of prolyl hydroxylase PHD3 into complexes: implications for its activity and susceptibility for degradation by the E3 ligase Siah2.
16511565 2006 Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1.
16407229 2006 The novel WD-repeat protein Morg1 acts as a molecular scaffold for hypoxia-inducible factor prolyl hydroxylase 3 (PHD3).
16098468 2005 Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer.
15721254 2005 OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15474027 2004 Determination and comparison of specific activity of the HIF-prolyl hydroxylases.
15251459 2004 The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin.
15247232 2004 Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor.
15156561 2004 Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12788921 2003 Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor.
12670503 2003 Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells.
12615973 2003 Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12181324 2002 Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3.
12163023 2002 Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors.
11598268 2001 A conserved family of prolyl-4-hydroxylases that modify HIF.
11595184 2001 C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation.
11595178 2001 HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus.
11574160 2001 Characterization and comparative analysis of the EGLN gene family.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.