Egl Nine Homolog 1 (EGLN1)

ECYT3; HIFPH2; PHD2; C1orf12; SM20; ZMYND6; HIF Prolyl Hydroxylase 2; Prolyl hydroxylase domain-containing protein 2; Hypoxia-inducible factor prolyl hydroxylase 2

SPN	M922
HGNC	1232
MGI	1932286
PubMed	20956315
RGD	631375
UniProt	Q9GZT9
Wiki	EGLN1

EGLN1 catalyzes the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins. HIF is a transcriptional complex that plays a central role in mammalian oxygen homeostasis. This protein functions as a cellular oxygen sensor, and under normal oxygen concentration, modification by prolyl hydroxylation is a key regulatory event that targets HIF subunits for proteasomal destruction via the von Hippel-Lindau ubiquitylation complex. The genes encoding these proteins were cloned and termed PHD1, PHD2, and PHD3 by the authors. Direct modulation of recombinant enzyme activity by graded hypoxia, iron chelation, and cobaltous ions mirrored the characteristics of HIF induction in vivo, fulfilling requirements for these enzymes being oxygen sensors that regulate HIF.

Reference

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Genomics 69:348-354(2000) [PubMed] [Europe PMC] [Abstract]

"Characterization and comparative analysis of the EGLN gene family."
Gene 275:125-132(2001) [PubMed] [Europe PMC] [Abstract]

"Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor."
J. Biol. Chem. 278:30772-30780(2003) [PubMed] [Europe PMC] [Abstract]

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Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]

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Cell 107:1-3(2001) [PubMed] [Europe PMC] [Abstract]

"C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation."
Cell 107:43-54(2001) [PubMed] [Europe PMC] [Abstract]

"Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation by the prolyl hydroxylases PHD1, PHD2, and PHD3."
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Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002) [PubMed] [Europe PMC] [Abstract]

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J. Cell Sci. 116:1319-1326(2003) [PubMed] [Europe PMC] [Abstract]

"Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor."
J. Biol. Chem. 279:38458-38465(2004) [PubMed] [Europe PMC] [Abstract]

"The candidate tumor suppressor ING4 represses activation of the hypoxia inducible factor (HIF)."
Proc. Natl. Acad. Sci. U.S.A. 102:7481-7486(2005) [PubMed] [Europe PMC] [Abstract]

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"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Cellular oxygen sensing: Importins and exportins are mediators of intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2."
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"Role of the intracellular localization of HIF-prolyl hydroxylases."
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"Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role for residues C-terminal to the hydroxylacceptor proline."
J. Biol. Chem. 284:9050-9058(2009) [PubMed] [Europe PMC] [Abstract]

"Evidence for the slow reaction of hypoxia-inducible factor prolyl hydroxylase 2 with oxygen."
FEBS J. 277:4089-4099(2010) [PubMed] [Europe PMC] [Abstract]

"Identifying signatures of natural selection in Tibetan and Andean populations using dense genome scan data."
PLoS Genet. 6:E1001116-E1001116(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Genetic evidence for high-altitude adaptation in Tibet."
Science 329:72-75(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in pancreatic cancer."
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"The LIMD1 protein bridges an association between the prolyl hydroxylases and VHL to repress HIF-1 activity."
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"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha hydroxylation."
Oncogene 34:1354-1362(2015) [PubMed] [Europe PMC] [Abstract]

"Cellular oxygen sensing: crystal structure of hypoxia-inducible factor prolyl hydroxylase (PHD2)."
Proc. Natl. Acad. Sci. U.S.A. 103:9814-9819(2006) [PubMed] [Europe PMC] [Abstract]

"Structural basis for binding of hypoxia-inducible factor to the oxygen-sensing prolyl hydroxylases."
Structure 17:981-989(2009) [PubMed] [Europe PMC] [Abstract]

"Studies on the reaction of nitric oxide with the hypoxia-inducible factor prolyl hydroxylase domain 2 (EGLN1)."
J. Mol. Biol. 410:268-279(2011) [PubMed] [Europe PMC] [Abstract]

"A family with erythrocytosis establishes a role for prolyl hydroxylase domain protein 2 in oxygen homeostasis."
Proc. Natl. Acad. Sci. U.S.A. 103:654-659(2006) [PubMed] [Europe PMC] [Abstract]

"A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove."
Blood 110:2193-2196(2007) [PubMed] [Europe PMC] [Abstract]

"Defective Tibetan PHD2 binding to p23 links high altitude adaption to altered oxygen sensing."
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"A genetic mechanism for Tibetan high-altitude adaptation."
Nat. Genet. 46:951-956(2014) [PubMed] [Europe PMC] [Abstract]