EGLN2 explained

Egl nine homolog 2 is a protein that in humans is encoded by the EGLN2 gene.^[1] ELGN2 is an alpha-ketoglutarate-dependent hydroxylase, a superfamily of non-haem iron-containing proteins.

The hypoxia inducible factor (HIF) is a transcriptional complex which is involved in oxygen homeostasis. At normal oxygen levels, the alpha subunit of HIF is targeted for degradation by prolyl hydroxylation. This gene encodes an enzyme responsible for this posttranslational modification. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Further reading

• Semenza GL . HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the nucleus . Cell . 107 . 1 . 1–3 . 2001 . 11595178 . 10.1016/S0092-8674(01)00518-9 . 14922615 . free .
• Hartley JL, Temple GF, Brasch MA . DNA Cloning Using In Vitro Site-Specific Recombination . Genome Res. . 10 . 11 . 1788–95 . 2001 . 11076863 . 10.1101/gr.143000 . 310948 .
• Wiemann S, Weil B, Wellenreuther R . Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs . Genome Res. . 11 . 3 . 422–35 . 2001 . 11230166 . 10.1101/gr.GR1547R . 311072 . etal.
• Jaakkola P, Mole DR, Tian YM . Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation . Science . 292 . 5516 . 468–72 . 2001 . 11292861 . 10.1126/science.1059796 . etal. 2001Sci...292..468J . 20914281 . free .
• Ivan M, Kondo K, Yang H . HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing . Science . 292 . 5516 . 464–8 . 2001 . 11292862 . 10.1126/science.1059817 . etal. 2001Sci...292..464I . 33725562 . free .
• Taylor MS . Characterization and comparative analysis of the EGLN gene family . Gene . 275 . 1 . 125–32 . 2001 . 11574160 . 10.1016/S0378-1119(01)00633-3 .
• Epstein AC, Gleadle JM, McNeill LA . C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation . Cell . 107 . 1 . 43–54 . 2001 . 11595184 . 10.1016/S0092-8674(01)00507-4 . 18372306 . etal. free .
• Bruick RK, McKnight SL . A conserved family of prolyl-4-hydroxylases that modify HIF . Science . 294 . 5545 . 1337–40 . 2001 . 11598268 . 10.1126/science.1066373 . 2001Sci...294.1337B . 9695199 .
• Seth P, Krop I, Porter D, Polyak K . Novel estrogen and tamoxifen induced genes identified by SAGE (Serial Analysis of Gene Expression) . Oncogene . 21 . 5 . 836–43 . 2002 . 11850811 . 10.1038/sj.onc.1205113 . free .
• Min JH, Yang H, Ivan M . Structure of an HIF-1alpha -pVHL complex: hydroxyproline recognition in signaling . Science . 296 . 5574 . 1886–9 . 2002 . 12004076 . 10.1126/science.1073440 . etal. 2002Sci...296.1886M . 19641938 . free .
• McNeill LA, Hewitson KS, Gleadle JM . The use of dioxygen by HIF prolyl hydroxylase (PHD1) . Bioorg. Med. Chem. Lett. . 12 . 12 . 1547–50 . 2002 . 12039559 . 10.1016/S0960-894X(02)00219-6 . etal.
• Oehme F, Ellinghaus P, Kolkhof P . Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates activity of hypoxia-inducible transcription factors . Biochem. Biophys. Res. Commun. . 296 . 2 . 343–9 . 2002 . 12163023 . 10.1016/S0006-291X(02)00862-8 . etal.
• Ivan M, Haberberger T, Gervasi DC . Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor . Proc. Natl. Acad. Sci. U.S.A. . 99 . 21 . 13459–64 . 2002 . 12351678 . 10.1073/pnas.192342099 . 129695 . etal. 2002PNAS...9913459I . free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . etal . 2002PNAS...9916899M. free .
• Metzen E, Berchner-Pfannschmidt U, Stengel P . Intracellular localisation of human HIF-1 alpha hydroxylases: implications for oxygen sensing . J. Cell Sci. . 116 . Pt 7 . 1319–26 . 2003 . 12615973 . 10.1242/jcs.00318 . etal. free .
• Cioffi CL, Liu XQ, Kosinski PA . Differential regulation of HIF-1 alpha prolyl-4-hydroxylase genes by hypoxia in human cardiovascular cells . Biochem. Biophys. Res. Commun. . 303 . 3 . 947–53 . 2003 . 12670503 . 10.1016/S0006-291X(03)00453-4 . etal.
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Aprelikova O, Chandramouli GV, Wood M . Regulation of HIF prolyl hydroxylases by hypoxia-inducible factors . J. Cell. Biochem. . 92 . 3 . 491–501 . 2004 . 15156561 . 10.1002/jcb.20067 . 24455956 . etal.
• Colland F, Jacq X, Trouplin V . Functional Proteomics Mapping of a Human Signaling Pathway . Genome Res. . 14 . 7 . 1324–32 . 2004 . 15231748 . 10.1101/gr.2334104 . 442148 . etal.

Notes and References

1. Web site: Entrez Gene: EGLN2 egl nine homolog 2 (C. elegans).