Property Summary

NCBI Gene PubMed Count 74
PubMed Score 0.00
PubTator Score 66.91

Knowledge Summary


No data available




Accession Q96KS0 A8K5S0 Q8WWY4 Q9BV14
Symbols EIT6


  Ortholog (1)

Species Source Disease
Chimp OMA EggNOG

 GO Component (2)

Protein-protein Interaction (4)

Gene RIF (44)

26997627 siRNA-mediated knockdown of PHD1 inhibited glucose-stimulated insulin secretion in pancreatic Beta cells.
26644182 PHD1 is phosphorylated by CDK2, CDK4 and CDK6 at Serine 130.
26492917 EglN2 associates with the NRF1-PGC1alpha complex and controls mitochondrial function in breast cancer
25609945 rs3733829 in the EGLN2 gene is significantly associated with the risk of COPD in Chinese populations of Hainan province.
25263965 Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia
24935227 PHD1 could induce cell cycle arrest in lung cancer cells, resulting in the suppression of cell proliferation.
24894671 Data indicate that the prolyl hydrolase 1 (PHD1) rs10680577 polymorphism is associated with the risk of non-small cell lung cancer in a Chinese population.
24644426 PHD-1 played an important role in hypoxic response pathway of trophoblast through modulating the level of HIF-2alpha.
24517638 study conducted to investigate the association between gastric cancer (GC) susceptibility with a 4-bp insertion/deletion polymorphism (rs10680577) in the proximal promoter of EGLN2; findings showed that the heterozygote and the homozygote 4-bp del/del confer a significantly increased risk of GC
24195777 The diminished expression of PHD1 and PHD2 and elevated level of FIH protein in cancerous tissue compared to histopathologically unchanged colonic mucosa was not associated with DNA methylation within the CpG islands of the PHD1, PHD2 and FIH genes.
24045616 Results show that variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk.
23932902 By modulating Cep192 levels, PHD1 thereby affects the processes of centriole duplication and centrosome maturation and contributes to the regulation of cell-cycle progression.
23531419 Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse prognosis in renal cell carcinoma.
23077531 Principal component analysis of the covariance matrix of free AIRE-PHD1 highlights the presence of a "flapping" movement, which is blocked in an open conformation upon binding to H3K4me0.
23026137 Findings provided strong evidence for the hypothesis that rs10680577 contributes to hepatocarcinogenesis, possibly by affecting RERT-lncRNA structure and subsequently EGLN2 expression.
22859986 miR-205 serves a protective role against both oxidative and endoplasmic reticulum stresses via the suppression of EGLN2 and subsequent decrease in intracellular reactive oxygen species.
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
21951999 Coexistence of PHD1 stabilized ATF4, as opposed to the destabilization of ATF4 by PHD3.
21887331 PHD1 and PHD2 are independent negative prognostic factors in NSCLC.
21877141 PHD1 expression correlated with high proliferation, and these tumors were mainly estrogen receptor-negative.
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.
20978146 Elevated PHD1 concomitant with decreased PHD2 are causatively related to Rpb1 hydroxylation and oncogenesis in human renal clear cell carcinomas with WT VHL gene.
20959442 Observational study of gene-disease association. (HuGE Navigator)
20840881 human prolyl hydroxylase might play an important role in determining the physiology and structure of the corpora lutea during the menstrual cycle and early pregnancy
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.
20600011 role for PHD1 as a positive regulator of intestinal epithelial cell apoptosis in the inflamed colon
20574001 Prolyl hydroxylase-dependent (but hypoxia inducible factor HIF-1alpha and -2alpha-independent) activation of hypoxia-induced monocyte-endothelial adhesion assigns a new function to monocytic ICAM-1 under acute hypoxic conditions.
20418890 Meta-analysis and genome-wide association study of gene-disease association. (HuGE Navigator)
19631610 these findings provide new insights into the mechanisms of the regulation of the oxygen sensor cascade of PHD1 and PHD2 in different cellular compartments.
19339211 Results describe the localization signal of HIF-prolyl hydroxylases (PHDs) 1-3, and their intracellular localization in response to hypoxia.
19229863 Prolyl hydroxylase inhibitor reduced mitochondrial cytochrome c release, nuclear translocation of apoptosis inducing factor (AIF), and promoted Akt phosphorylation
19147576 Authors identify an interaction between melanoma antigen-11 (MAGE-11) cancer-testis antigen and the major HIF-alpha hydroxylating enzyme PHD2.
19134330 The expression imbalance of HPH1 and FIH-1 in placenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1alpha.
18927305 Overexpression of the oxygen sensor PHD-1 is associated with tumor aggressiveness in pancreatic endocrine tumors.
18773095 The identification of EGLN2 as a significantly deregulated gene that maps within the paired chromosome region directly implicates defects in the oxygen-sensing network to the biology of renal oncocytoma.
18710826 Results describe the expression, purification and characterization of the human prolyl hydroxylase PHD1 in Escherichia coli.
17114296 hypoxia releases repression of NFkappaB activity through decreased prolyl hydroxylase-dependent hydroxylation of IKKbeta
17101781 Multiple mitochondrial products, including tricarboxylic acid intermediates and reactive oxygen species, can coordinate PHD activity, HIF stabilization, and cellular responses to O(2) depletion.
16649251 Understanding the mechanisms by which nickel can inhibit HIF-PHD's and stabilize HIF-1alpha may be important in the treatment of cancer and ischemic diseases.
16509823 defines the existence of two species of PHD1 and provide evidence that they are generated by alternative translational initiation
15247232 PHD1, PHD2, and PHD3 have roles in the regulation of hypoxia-inducible factor
15156561 effect of WT or mutated VHL on PHD 1, 2, and 3
12351678 identified a human homolog of Caenorhabditis elegans Egl9 as a HIF prolyl hydroxylase

AA Sequence


Text Mined References (79)

PMID Year Title
26997627 2016 Role of prolyl hydroxylase domain proteins in the regulation of insulin secretion.
26644182 2016 CDK-dependent phosphorylation of PHD1 on serine 130 alters its substrate preference in cells.
26492917 2015 EglN2 associates with the NRF1-PGC1? complex and controls mitochondrial function in breast cancer.
25609945 2015 EGLN2 and RNF150 genetic variants are associated with chronic obstructive pulmonary disease risk in the Chinese population.
25263965 2015 Germ-line PHD1 and PHD2 mutations detected in patients with pheochromocytoma/paraganglioma-polycythemia.
24935227 2014 Over-expression of prolyl hydroxylase-1 blocks NF-?B-mediated cyclin D1 expression and proliferation in lung carcinoma cells.
24894671 2014 Polymorphism in PHD1 gene and risk of non-small cell lung cancer in a Chinese population.
24644426 2014 Study on the expressions of PHD and HIF in placentas from normal pregnant women and patients with preeclampsia.
24517638 2014 An insertion/deletion polymorphism within the proximal promoter of EGLN2 is associated with susceptibility for gastric cancer in the Chinese population.
24195777 2013 Expression and DNA methylation levels of prolyl hydroxylases PHD1, PHD2, PHD3 and asparaginyl hydroxylase FIH in colorectal cancer.
24045616 2014 Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms.
23932902 2013 PHD1 links cell-cycle progression to oxygen sensing through hydroxylation of the centrosomal protein Cep192.
23531419 2013 Onconeuronal antigen Cdr2 correlates with HIF prolyl-4-hydroxylase PHD1 and worse prognosis in renal cell carcinoma.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23077531 2012 Exploring PHD fingers and H3K4me0 interactions with molecular dynamics simulations and binding free energy calculations: AIRE-PHD1, a comparative study.
23026137 2012 An insertion/deletion polymorphism within RERT-lncRNA modulates hepatocellular carcinoma risk.
22955912 2012 Transmembrane prolyl 4-hydroxylase is a fourth prolyl 4-hydroxylase regulating EPO production and erythropoiesis.
22859986 2012 Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.
22395314 2012 Molecular oxygen sensing: implications for visceral surgery.
22343896 2012 Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation.
22286099 2012 The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity.
22080838 2012 A genome-wide association study of COPD identifies a susceptibility locus on chromosome 19q13.
21951999 2011 PHD1 interacts with ATF4 and negatively regulates its transcriptional activity without prolyl hydroxylation.
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.
21410436 2011 Biochemical characterization of human HIF hydroxylases using HIF protein substrates that contain all three hydroxylation sites.
20978146 2010 von Hippel-Lindau-dependent patterns of RNA polymerase II hydroxylation in human renal clear cell carcinomas.
20959442 2011 Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility.
20840881 2011 Prolyl hydroxylase in human corpora lutea during menstrual cycle and early pregnancy.
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.
20600011 2010 Loss of prolyl hydroxylase-1 protects against colitis through reduced epithelial cell apoptosis and increased barrier function.
20574001 2010 Acute hypoxia induces HIF-independent monocyte adhesion to endothelial cells through increased intercellular adhesion molecule-1 expression: the role of hypoxic inhibition of prolyl hydroxylase activity for the induction of NF-kappa B.
20418890 2010 Genome-wide meta-analyses identify multiple loci associated with smoking behavior.
19631610 2009 Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2.
19587290 2009 Selective inhibition of hypoxia-inducible factor (HIF) prolyl-hydroxylase 1 mediates neuroprotection against normoxic oxidative death via HIF- and CREB-independent pathways.
19339211 2009 Role of the intracellular localization of HIF-prolyl hydroxylases.
19229863 2009 Prolyl hydroxylase inhibitor dimethyloxalylglycine enhances mesenchymal stem cell survival.
19147576 2009 Melanoma antigen-11 inhibits the hypoxia-inducible factor prolyl hydroxylase 2 and activates hypoxic response.
19134330 2008 [Clinical significance of hypoxia inducible factor-prolyl hydroxylase 1 and factor inhibiting hypoxia inducible factor-1 expression in placentas of women with severe pre-eclampsia].
18927305 2008 Overexpression of the oxygen sensors PHD-1, PHD-2, PHD-3, and FIH Is associated with tumor aggressiveness in pancreatic endocrine tumors.
18773095 2008 Somatic pairing of chromosome 19 in renal oncocytoma is associated with deregulated EGLN2-mediated [corrected] oxygen-sensing response.
18710826 2008 Expression, purification and characterization of human PHD1 in Escherichia coli.
17974005 2007 The full-ORF clone resource of the German cDNA Consortium.
17353276 2007 The peptidyl prolyl cis/trans isomerase FKBP38 determines hypoxia-inducible transcription factor prolyl-4-hydroxylase PHD2 protein stability.
17114296 2006 Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkappaB activity.
17101781 2007 Multiple factors affecting cellular redox status and energy metabolism modulate hypoxia-inducible factor prolyl hydroxylase activity in vivo and in vitro.
16649251 2006 Soluble nickel inhibits HIF-prolyl-hydroxylases creating persistent hypoxic signaling in A549 cells.
16511565 2006 Metastasis-associated protein 1 enhances stability of hypoxia-inducible factor-1alpha protein by recruiting histone deacetylase 1.
16509823 2006 Characterization of different isoforms of the HIF prolyl hydroxylase PHD1 generated by alternative initiation.
16381901 2006 The LIFEdb database in 2006.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15489336 2004 From ORFeome to biology: a functional genomics pipeline.
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.
15247232 2004 Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor.
15231748 2004 Functional proteomics mapping of a human signaling pathway.
15156561 2004 Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors.
15057824 2004 The DNA sequence and biology of human chromosome 19.
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.
12351678 2002 Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor.
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.
12039559 2002 The use of dioxygen by HIF prolyl hydroxylase (PHD1).
12004076 2002 Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling.
11850811 2002 Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression).
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.
11292862 2001 HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing.
11292861 2001 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation.
11256614 2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing.
11230166 2001 Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs.
11076863 2000 DNA cloning using in vitro site-specific recombination.