ID EGLN1_HUMAN Reviewed; 426 AA. AC Q9GZT9; Q8N3M8; Q9BZS8; Q9BZT0; DT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 27-MAR-2024, entry version 208. DE RecName: Full=Egl nine homolog 1; DE EC=1.14.11.29 {ECO:0000269|PubMed:25129147}; DE AltName: Full=Hypoxia-inducible factor prolyl hydroxylase 2; DE Short=HIF-PH2; DE Short=HIF-prolyl hydroxylase 2; DE Short=HPH-2; DE AltName: Full=Prolyl hydroxylase domain-containing protein 2; DE Short=PHD2; DE AltName: Full=SM-20; GN Name=EGLN1 {ECO:0000312|HGNC:HGNC:1232}; Synonyms=C1orf12; GN ORFNames=PNAS-118, PNAS-137; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE RP SPECIFICITY. RX PubMed=11056053; DOI=10.1006/geno.2000.6343; RA Dupuy D., Aubert I., Duperat V.G., Petit J., Taine L., Stef M., Bloch B., RA Arveiler B.; RT "Mapping, characterization, and expression analysis of the SM-20 human RT homologue, C1orf12, and identification of a novel related gene, SCAND2."; RL Genomics 69:348-354(2000). RN [2] RP NUCLEOTIDE SEQUENCE (ISOFORM 1). RX PubMed=11574160; DOI=10.1016/s0378-1119(01)00633-3; RA Taylor M.S.; RT "Characterization and comparative analysis of the EGLN gene family."; RL Gene 275:125-132(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY, AND SUBSTRATE RP SPECIFICITY. RC TISSUE=Aorta, Colon, and Lung; RX PubMed=12788921; DOI=10.1074/jbc.m304982200; RA Hirsila M., Koivunen P., Gunzler V., Kivirikko K.I., Myllyharju J.; RT "Characterization of the human prolyl 4-hydroxylases that modify the RT hypoxia-inducible factor."; RL J. Biol. Chem. 278:30772-30780(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 160-426 (ISOFORM 1). RC TISSUE=Amygdala; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 136-426 (ISOFORM 2). RC TISSUE=Promyelocytic leukemia; RA Yu W.-Q., Sun B.-Z., Chai Y.-B., Zhu F., Liu X.-S., Li Z., Lu F., Yan W., RA Yang H., Zhao Z.-L.; RT "Human acute promyelocytic leukemia cell line NB4's apoptosis related RT genes."; RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP REVIEW. RX PubMed=11595178; DOI=10.1016/s0092-8674(01)00518-9; RA Semenza G.L.; RT "HIF-1, O(2), and the 3 PHDs: how animal cells signal hypoxia to the RT nucleus."; RL Cell 107:1-3(2001). RN [8] RP FUNCTION. RX PubMed=11595184; DOI=10.1016/s0092-8674(01)00507-4; RA Epstein A.C.R., Gleadle J.M., McNeill L.A., Hewitson K.S., O'Rourke J., RA Mole D.R., Mukherji M., Metzen E., Wilson M.I., Dhanda A., Tian Y.M., RA Masson N., Hamilton D.L., Jaakkola P., Barstead R., Hodgkin J., RA Maxwell P.H., Pugh C.W., Schofield C.J., Ratcliffe P.J.; RT "C. elegans EGL-9 and mammalian homologs define a family of dioxygenases RT that regulate HIF by prolyl hydroxylation."; RL Cell 107:43-54(2001). RN [9] RP FUNCTION, AND SUBSTRATE RECOGNITION MOTIF. RX PubMed=12181324; DOI=10.1074/jbc.m206955200; RA Huang J., Zhao Q., Mooney S.M., Lee F.S.; RT "Sequence determinants in hypoxia-inducible factor-1alpha for hydroxylation RT by the prolyl hydroxylases PHD1, PHD2, and PHD3."; RL J. Biol. Chem. 277:39792-39800(2002). RN [10] RP FUNCTION. RX PubMed=12351678; DOI=10.1073/pnas.192342099; RA Ivan M., Haberberger T., Gervasi D.C., Michelson K.S., Guenzler V., RA Kondo K., Yang H., Sorokina I., Conaway R.C., Conaway J.W., RA Kaelin W.G. Jr.; RT "Biochemical purification and pharmacological inhibition of a mammalian RT prolyl hydroxylase acting on hypoxia-inducible factor."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13459-13464(2002). RN [11] RP TISSUE SPECIFICITY. RX PubMed=12163023; DOI=10.1016/s0006-291x(02)00862-8; RA Oehme F., Ellinghaus P., Kolkhof P., Smith T.J., Ramakrishnan S., RA Huetter J., Schramm M., Flamme I.; RT "Overexpression of PH-4, a novel putative proline 4-hydroxylase, modulates RT activity of hypoxia-inducible transcription factors."; RL Biochem. Biophys. Res. Commun. 296:343-349(2002). RN [12] RP TISSUE SPECIFICITY, AND ACTIVITY REGULATION. RX PubMed=12670503; DOI=10.1016/s0006-291x(03)00453-4; RA Cioffi C.L., Qin Liu X., Kosinski P.A., Garay M., Bowen B.R.; RT "Differential regulation of HIF-1alpha prolyl-4-hydroxylase genes by RT hypoxia in human cardiovascular cells."; RL Biochem. Biophys. Res. Commun. 303:947-953(2003). RN [13] RP SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=12615973; DOI=10.1242/jcs.00318; RA Metzen E., Berchner-Pfannschmidt U., Stengel P., Marxsen J.H., Stolze I., RA Klinger M., Huang W.Q., Wotzlaw C., Hellwig-Burgel T., Jelkmann W., RA Acker H., Fandrey J.; RT "Intracellular localisation of human HIF-1 alpha hydroxylases: implications RT for oxygen sensing."; RL J. Cell Sci. 116:1319-1326(2003). RN [14] RP INDUCTION, AND SUBSTRATE SPECIFICITY. RX PubMed=15247232; DOI=10.1074/jbc.m406026200; RA Appelhoff R.J., Tian Y.M., Raval R.R., Turley H., Harris A.L., Pugh C.W., RA Ratcliffe P.J., Gleadle J.M.; RT "Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in RT the regulation of hypoxia-inducible factor."; RL J. Biol. Chem. 279:38458-38465(2004). RN [15] RP INTERACTION WITH ING4, AND FUNCTION. RX PubMed=15897452; DOI=10.1073/pnas.0502716102; RA Ozer A., Wu L.C., Bruick R.K.; RT "The candidate tumor suppressor ING4 represses activation of the hypoxia RT inducible factor (HIF)."; RL Proc. Natl. Acad. Sci. U.S.A. 102:7481-7486(2005). RN [16] RP SUBSTRATE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF RP 237-ASP--ILE-251, AND DOMAIN. RX PubMed=18063574; DOI=10.1074/jbc.m707411200; RA Flashman E., Bagg E.A., Chowdhury R., Mecinovic J., Loenarz C., RA McDonough M.A., Hewitson K.S., Schofield C.J.; RT "Kinetic rationale for selectivity toward N- and C-terminal oxygen- RT dependent degradation domain substrates mediated by a loop region of RT hypoxia-inducible factor prolyl hydroxylases."; RL J. Biol. Chem. 283:3808-3815(2008). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=19631610; DOI=10.1016/j.bbrc.2009.07.090; RA Steinhoff A., Pientka F.K., Mockel S., Kettelhake A., Hartmann E., RA Kohler M., Depping R.; RT "Cellular oxygen sensing: Importins and exportins are mediators of RT intracellular localisation of prolyl-4-hydroxylases PHD1 and PHD2."; RL Biochem. Biophys. Res. Commun. 387:705-711(2009). RN [19] RP SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=19339211; DOI=10.1016/j.bbamcr.2009.01.014; RA Yasumoto K., Kowata Y., Yoshida A., Torii S., Sogawa K.; RT "Role of the intracellular localization of HIF-prolyl hydroxylases."; RL Biochim. Biophys. Acta 1793:792-797(2009). RN [20] RP INTERACTION WITH EPAS1. RX PubMed=19208626; DOI=10.1074/jbc.m808737200; RA Furlow P.W., Percy M.J., Sutherland S., Bierl C., McMullin M.F., RA Master S.R., Lappin T.R., Lee F.S.; RT "Erythrocytosis-associated HIF-2alpha mutations demonstrate a critical role RT for residues C-terminal to the hydroxylacceptor proline."; RL J. Biol. Chem. 284:9050-9058(2009). RN [21] RP ACTIVITY REGULATION. RX PubMed=20840591; DOI=10.1111/j.1742-4658.2010.07804.x; RA Flashman E., Hoffart L.M., Hamed R.B., Bollinger J.M. Jr., Krebs C., RA Schofield C.J.; RT "Evidence for the slow reaction of hypoxia-inducible factor prolyl RT hydroxylase 2 with oxygen."; RL FEBS J. 277:4089-4099(2010). RN [22] RP POLYMORPHISM. RX PubMed=20838600; DOI=10.1371/journal.pgen.1001116; RA Bigham A., Bauchet M., Pinto D., Mao X., Akey J.M., Mei R., Scherer S.W., RA Julian C.G., Wilson M.J., Lopez Herraez D., Brutsaert T., Parra E.J., RA Moore L.G., Shriver M.D.; RT "Identifying signatures of natural selection in Tibetan and Andean RT populations using dense genome scan data."; RL PLoS Genet. 6:E1001116-E1001116(2010). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP POLYMORPHISM. RX PubMed=20466884; DOI=10.1126/science.1189406; RA Simonson T.S., Yang Y., Huff C.D., Yun H., Qin G., Witherspoon D.J., RA Bai Z., Lorenzo F.R., Xing J., Jorde L.B., Prchal J.T., Ge R.; RT "Genetic evidence for high-altitude adaptation in Tibet."; RL Science 329:72-75(2010). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [26] RP FUNCTION, AND INDUCTION. RX PubMed=21792862; DOI=10.1002/cncr.26344; RA Su Y., Loos M., Giese N., Metzen E., Buchler M.W., Friess H., Kornberg A., RA Buchler P.; RT "Prolyl hydroxylase-2 (PHD2) exerts tumor-suppressive activity in RT pancreatic cancer."; RL Cancer 118:960-972(2012). RN [27] RP INTERACTION WITH LIMD1, AND IDENTIFICATION IN A COMPLEX WITH LIMD1; VHL; RP ELOB AND CUL2. RX PubMed=22286099; DOI=10.1038/ncb2424; RA Foxler D.E., Bridge K.S., James V., Webb T.M., Mee M., Wong S.C., Feng Y., RA Constantin-Teodosiu D., Petursdottir T.E., Bjornsson J., Ingvarsson S., RA Ratcliffe P.J., Longmore G.D., Sharp T.V.; RT "The LIMD1 protein bridges an association between the prolyl hydroxylases RT and VHL to repress HIF-1 activity."; RL Nat. Cell Biol. 14:201-208(2012). RN [28] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-125, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [30] RP INTERACTION WITH HIF1A. RX PubMed=24681946; DOI=10.1038/onc.2014.76; RA Seo K.S., Park J.H., Heo J.Y., Jing K., Han J., Min K.N., Kim C., Koh G.Y., RA Lim K., Kang G.Y., Uee Lee J., Yim Y.H., Shong M., Kwak T.H., Kweon G.R.; RT "SIRT2 regulates tumour hypoxia response by promoting HIF-1alpha RT hydroxylation."; RL Oncogene 34:1354-1362(2015). RN [31] RP INTERACTION WITH CBFA2T3 AND HIF1A. RX PubMed=25974097; DOI=10.1371/journal.pone.0123725; RA Kumar P., Gullberg U., Olsson I., Ajore R.; RT "Myeloid translocation gene-16 co-repressor promotes degradation of RT hypoxia-inducible factor 1."; RL PLoS ONE 10:E0123725-E0123725(2015). RN [32] {ECO:0007744|PDB:2G19, ECO:0007744|PDB:2G1M} RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 181-417 IN COMPLEXES WITH IRON AND RP COMPETITIVE INHIBITOR, METAL-BINDING SITES, MUTAGENESIS OF TYR-303 AND RP ARG-383, SUBUNIT, AND COFACTOR. RX PubMed=16782814; DOI=10.1073/pnas.0601283103; RA McDonough M.A., Li V., Flashman E., Chowdhury R., Mohr C., Lienard B.M.R., RA Zondlo J., Oldham N.J., Clifton I.J., Lewis J., McNeill L.A., Kurzeja R.J., RA Hewitson K.S., Yang E., Jordan S., Syed R.S., Schofield C.J.; RT "Cellular oxygen sensing: crystal structure of hypoxia-inducible factor RT prolyl hydroxylase (PHD2)."; RL Proc. Natl. Acad. Sci. U.S.A. 103:9814-9819(2006). RN [33] {ECO:0007744|PDB:3HQR, ECO:0007744|PDB:3HQU} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 OF WILD TYPE AND MUTANTS RP ALA-252; ALA-254; LYS-254 AND ALA-398 IN COMPLEX WITH HIF1A, IRON, RP N-OXALYGLYCINE AND MANGANESE, METAL-BINDING SITES, AND COFACTOR. RX PubMed=19604478; DOI=10.1016/j.str.2009.06.002; RA Chowdhury R., McDonough M.A., Mecinovic J., Loenarz C., Flashman E., RA Hewitson K.S., Domene C., Schofield C.J.; RT "Structural basis for binding of hypoxia-inducible factor to the oxygen- RT sensing prolyl hydroxylases."; RL Structure 17:981-989(2009). RN [34] {ECO:0007744|PDB:2Y33, ECO:0007744|PDB:2Y34} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 181-426 IN COMPLEX WITH NITRIC RP OXIDE OR A NITRIC OXIDE TRANSFER REAGENT, IDENTIFICATION BY MASS RP SPECTROMETRY, S-NITROSYLATION AT CYS-201; CYS-208; CYS-302; CYS-323 AND RP CYS-326, AND MUTAGENESIS OF CYS-201; CYS-208; CYS-266; CYS-283; CYS-302; RP CYS-323 AND CYS-326. RX PubMed=21601578; DOI=10.1016/j.jmb.2011.04.075; RA Chowdhury R., Flashman E., Mecinovic J., Kramer H.B., Kessler B.M., RA Frapart Y.M., Boucher J.L., Clifton I.J., McDonough M.A., Schofield C.J.; RT "Studies on the reaction of nitric oxide with the hypoxia-inducible factor RT prolyl hydroxylase domain 2 (EGLN1)."; RL J. Mol. Biol. 410:268-279(2011). RN [35] {ECO:0007744|PDB:5V18} RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 181-416 IN COMPLEX WITH INHIBITOR RP AND IRON, AND COFACTOR. RX PubMed=28594552; DOI=10.1021/acs.jmedchem.7b00352; RA Ahmed S., Ayscough A., Barker G.R., Canning H.E., Davenport R., Downham R., RA Harrison D., Jenkins K., Kinsella N., Livermore D.G., Wright S., RA Ivetac A.D., Skene R., Wilkens S.J., Webster N.A., Hendrick A.G.; RT "1,2,4-Triazolo-[1,5-a]pyridine HIF Prolylhydroxylase Domain-1 (PHD-1) RT Inhibitors With a Novel Monodentate Binding Interaction."; RL J. Med. Chem. 60:5663-5672(2017). RN [36] RP VARIANT ECYT3 ARG-317, AND CHARACTERIZATION OF VARIANT ECYT3 ARG-317. RX PubMed=16407130; DOI=10.1073/pnas.0508423103; RA Percy M.J., Zhao Q., Flores A., Harrison C., Lappin T.R., Maxwell P.H., RA McMullin M.F., Lee F.S.; RT "A family with erythrocytosis establishes a role for prolyl hydroxylase RT domain protein 2 in oxygen homeostasis."; RL Proc. Natl. Acad. Sci. U.S.A. 103:654-659(2006). RN [37] RP VARIANT ECYT3 HIS-371, AND CHARACTERIZATION OF VARIANT EXCYT3 HIS-371. RX PubMed=17579185; DOI=10.1182/blood-2007-04-084434; RA Percy M.J., Furlow P.W., Beer P.A., Lappin T.R.J., McMullin M.F., Lee F.S.; RT "A novel erythrocytosis-associated PHD2 mutation suggests the location of a RT HIF binding groove."; RL Blood 110:2193-2196(2007). RN [38] RP VARIANTS GLU-4 AND SER-127, POLYMORPHISM, INTERACTION WITH PTGES3, AND RP CHARACTERIZATION OF VARIANTS GLU-4 AND SER-127. RX PubMed=24711448; DOI=10.1074/jbc.m113.541227; RA Song D., Li L.S., Arsenault P.R., Tan Q., Bigham A.W., Heaton-Johnson K.J., RA Master S.R., Lee F.S.; RT "Defective Tibetan PHD2 binding to p23 links high altitude adaption to RT altered oxygen sensing."; RL J. Biol. Chem. 289:14656-14665(2014). RN [39] RP VARIANTS GLU-4 AND SER-127, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, POLYMORPHISM, AND CHARACTERIZATION OF RP VARIANTS GLU-4 AND SER-127. RX PubMed=25129147; DOI=10.1038/ng.3067; RA Lorenzo F.R., Huff C., Myllymaeki M., Olenchock B., Swierczek S., Tashi T., RA Gordeuk V., Wuren T., Ri-Li G., McClain D.A., Khan T.M., Koul P.A., RA Guchhait P., Salama M.E., Xing J., Semenza G.L., Liberzon E., Wilson A., RA Simonson T.S., Jorde L.B., Kaelin W.G. Jr., Koivunen P., Prchal J.T.; RT "A genetic mechanism for Tibetan high-altitude adaptation."; RL Nat. Genet. 46:951-956(2014). CC -!- FUNCTION: Cellular oxygen sensor that catalyzes, under normoxic CC conditions, the post-translational formation of 4-hydroxyproline in CC hypoxia-inducible factor (HIF) alpha proteins. Hydroxylates a specific CC proline found in each of the oxygen-dependent degradation (ODD) domains CC (N-terminal, NODD, and C-terminal, CODD) of HIF1A. Also hydroxylates CC HIF2A. Has a preference for the CODD site for both HIF1A and HIF1B. CC Hydroxylated HIFs are then targeted for proteasomal degradation via the CC von Hippel-Lindau ubiquitination complex. Under hypoxic conditions, the CC hydroxylation reaction is attenuated allowing HIFs to escape CC degradation resulting in their translocation to the nucleus, CC heterodimerization with HIF1B, and increased expression of hypoxy- CC inducible genes. EGLN1 is the most important isozyme under normoxia CC and, through regulating the stability of HIF1, involved in various CC hypoxia-influenced processes such as angiogenesis in retinal and CC cardiac functionality. Target proteins are preferentially recognized CC via a LXXLAP motif. {ECO:0000269|PubMed:11595184, CC ECO:0000269|PubMed:12181324, ECO:0000269|PubMed:12351678, CC ECO:0000269|PubMed:15897452, ECO:0000269|PubMed:19339211, CC ECO:0000269|PubMed:21792862, ECO:0000269|PubMed:25129147}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2-oxoglutarate + L-prolyl-[hypoxia-inducible factor alpha CC subunit] + O2 = CO2 + succinate + trans-4-hydroxy-L-prolyl-[hypoxia- CC inducible factor alpha subunit]; Xref=Rhea:RHEA:48400, Rhea:RHEA- CC COMP:12093, Rhea:RHEA-COMP:12094, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, CC ChEBI:CHEBI:50342, ChEBI:CHEBI:61965; EC=1.14.11.29; CC Evidence={ECO:0000269|PubMed:25129147}; CC -!- COFACTOR: CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00805, ECO:0000269|PubMed:16782814, CC ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:28594552, CC ECO:0007744|PDB:2G19, ECO:0007744|PDB:3HQU, ECO:0007744|PDB:5V18}; CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE- CC ProRule:PRU00805, ECO:0000269|PubMed:16782814, CC ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:28594552, CC ECO:0007744|PDB:2G19, ECO:0007744|PDB:3HQU, ECO:0007744|PDB:5V18}; CC -!- COFACTOR: CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290; CC Evidence={ECO:0000269|PubMed:19604478}; CC -!- ACTIVITY REGULATION: Following exposure to hypoxia, activated in HeLa CC cells but not in cardiovascular cells. {ECO:0000269|PubMed:12670503, CC ECO:0000269|PubMed:20840591}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=70 nM for HIF2A {ECO:0000269|PubMed:25129147}; CC KM=150 uM for O(2) {ECO:0000269|PubMed:25129147}; CC KM=1.3 uM for 2-oxoglutarate {ECO:0000269|PubMed:25129147}; CC -!- SUBUNIT: Monomer. Interacts with ING4; the interaction inhibits the CC hydroxylation of HIF alpha proteins. Interacts with PTGES3 (via PXLE CC motif); thereby recruiting EGLN1 to the HSP90 pathway to facilitate HIF CC alpha proteins hydroxylation. Interacts with LIMD1. Found in a complex CC composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with CC EPAS1. Interacts with CBFA2T3 (PubMed:25974097). Interacts with HIF1A CC (PubMed:25974097). {ECO:0000269|PubMed:15897452, CC ECO:0000269|PubMed:16782814, ECO:0000269|PubMed:19208626, CC ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:21601578, CC ECO:0000269|PubMed:22286099, ECO:0000269|PubMed:24681946, CC ECO:0000269|PubMed:25974097}. CC -!- INTERACTION: CC Q9GZT9; Q99814: EPAS1; NbExp=3; IntAct=EBI-1174818, EBI-447470; CC Q9GZT9; Q14318: FKBP8; NbExp=6; IntAct=EBI-1174818, EBI-724839; CC Q9GZT9; Q16665: HIF1A; NbExp=4; IntAct=EBI-1174818, EBI-447269; CC Q9GZT9; Q13438: OS9; NbExp=4; IntAct=EBI-1174818, EBI-725454; CC Q9GZT9; PRO_0000037551 [Q9WMX2]; Xeno; NbExp=3; IntAct=EBI-1174818, EBI-6863748; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12615973, CC ECO:0000269|PubMed:19339211, ECO:0000269|PubMed:19631610}. Nucleus CC {ECO:0000269|PubMed:12615973, ECO:0000269|PubMed:19339211, CC ECO:0000269|PubMed:19631610}. Note=Mainly cytoplasmic. Shuttles between CC the nucleus and cytoplasm (PubMed:19631610). Nuclear export requires CC functional XPO1. {ECO:0000269|PubMed:19339211, CC ECO:0000269|PubMed:19631610}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9GZT9-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9GZT9-2; Sequence=VSP_007569; CC Name=3; CC IsoId=Q9GZT9-3; Sequence=VSP_042191; CC -!- TISSUE SPECIFICITY: According to PubMed:11056053, widely expressed with CC highest levels in skeletal muscle and heart, moderate levels in CC pancreas, brain (dopaminergic neurons of adult and fetal substantia CC nigra) and kidney, and lower levels in lung and liver. According to CC PubMed:12351678 widely expressed with highest levels in brain, kidney CC and adrenal gland. Expressed in cardiac myocytes, aortic endothelial CC cells and coronary artery smooth muscle. According to PubMed:12788921; CC expressed in adult and fetal heart, brain, liver, lung, skeletal muscle CC and kidney. Also expressed in placenta. Highest levels in adult heart, CC brain, lung and liver and fetal brain, heart spleen and skeletal CC muscle. {ECO:0000269|PubMed:11056053, ECO:0000269|PubMed:12163023, CC ECO:0000269|PubMed:12351678, ECO:0000269|PubMed:12670503, CC ECO:0000269|PubMed:12788921}. CC -!- DOMAIN: The beta(2)beta(3) 'finger-like' loop domain is important for CC substrate (HIFs' CODD/NODD) selectivity. {ECO:0000269|PubMed:18063574}. CC -!- PTM: S-nitrosylation inhibits the enzyme activity up to 60% under CC aerobic conditions. Chelation of Fe(2+) has no effect on the S- CC nitrosylation. It is uncertain whether nitrosylation occurs on Cys-323 CC or Cys-326. {ECO:0000269|PubMed:21601578}. CC -!- POLYMORPHISM: Variations in EGLN1 are associated with adaptation to CC high altitude (PubMed:20838600, PubMed:20466884, PubMed:24711448, CC PubMed:25129147). High-altitude hypoxia (reduced inspired oxygen CC tension due to decreased barometric pressure) exerts severe CC physiological stress on the human body and leads to an elevation of CC hematocrit levels and an increased number of erythrocytes CC (polycythemia) in non-adapted individuals. Genetic variations in EGLN1 CC contribute to adaptation to high altitute by maintaining hematocrit CC levels comparable to those for populations living at sea level and are CC present in two high-altitude regions where humans have lived for CC millennia, the Andean Altiplano and the Tibetan Plateau CC (PubMed:20838600, PubMed:20466884). Variants Glu-4 and Ser-127, which CC are frequently associated together and are present in the majority of CC Tibetan populations, participate in adaptation to high altitude CC (PubMed:24711448, PubMed:25129147). Molecular mechanisms explaining CC this adaptation are however unclear. According to a report, variants CC Glu-4 and Ser-127 lead to decreased interaction with PTGES3 and CC subsequent decrease of HIF alpha proteins degradation CC (PubMed:24711448). According to a second report, Glu-4 and Ser-127 CC haplotype enhances the catalytic activity under hypoxic conditions, CC promoting increased HIF alpha proteins degradation, thereby abrogating CC hypoxia-induced and HIF alpha-mediated augmentation of erythropoiesis CC and protecting Tibetans from polycythemia at high altitude CC (PubMed:25129147). {ECO:0000269|PubMed:20466884, CC ECO:0000269|PubMed:20838600, ECO:0000269|PubMed:24711448, CC ECO:0000269|PubMed:25129147, ECO:0000305}. CC -!- DISEASE: Erythrocytosis, familial, 3 (ECYT3) [MIM:609820]: An autosomal CC dominant disorder characterized by elevated serum hemoglobin and CC hematocrit, and normal serum erythropoietin levels. CC {ECO:0000269|PubMed:16407130, ECO:0000269|PubMed:17579185}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: [Isoform 2]: Inactive isoform. {ECO:0000305}. CC -!- CAUTION: It was previously reported that this protein was the ortholog CC of rat SM-20. However, EGLN3 is now considered the true ortholog of rat CC SM-20 since it shows substantially greater similarity. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAK07534.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAK07536.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44140/EGLN1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF246631; AAG34568.1; -; Genomic_DNA. DR EMBL; AF246630; AAG34568.1; JOINED; Genomic_DNA. DR EMBL; AF229245; AAG33965.1; -; mRNA. DR EMBL; AJ310543; CAC42509.1; -; mRNA. DR EMBL; AL833885; CAD38741.2; -; mRNA. DR EMBL; AF277174; AAK07534.1; ALT_INIT; mRNA. DR EMBL; AF277176; AAK07536.1; ALT_FRAME; mRNA. DR EMBL; AL117352; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL445524; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS1595.1; -. [Q9GZT9-1] DR RefSeq; NP_071334.1; NM_022051.2. [Q9GZT9-1] DR PDB; 2G19; X-ray; 1.70 A; A=181-417. DR PDB; 2G1M; X-ray; 2.20 A; A=181-426. DR PDB; 2HBT; X-ray; 1.60 A; A=188-426. DR PDB; 2HBU; X-ray; 1.85 A; A=188-426. DR PDB; 2Y33; X-ray; 2.00 A; A=181-426. DR PDB; 2Y34; X-ray; 2.01 A; A=181-426. DR PDB; 3HQR; X-ray; 2.00 A; A=181-426. DR PDB; 3HQU; X-ray; 2.30 A; A=181-426. DR PDB; 3OUH; X-ray; 2.51 A; A=181-416. DR PDB; 3OUI; X-ray; 1.70 A; A=181-392. DR PDB; 3OUJ; X-ray; 2.30 A; A=181-416. DR PDB; 4BQW; X-ray; 1.79 A; A=181-426. DR PDB; 4BQX; X-ray; 1.79 A; A=181-426. DR PDB; 4BQY; X-ray; 1.53 A; A=181-426. DR PDB; 4JZR; X-ray; 2.10 A; A=189-399. DR PDB; 4KBZ; X-ray; 2.15 A; A=184-419. DR PDB; 4UWD; X-ray; 1.72 A; A=181-426. DR PDB; 5A3U; X-ray; 3.30 A; A/B/C=181-426. DR PDB; 5L9B; X-ray; 1.95 A; A/B=181-426. DR PDB; 5L9R; X-ray; 1.81 A; A=181-426. DR PDB; 5L9V; X-ray; 1.83 A; A/B=181-426. DR PDB; 5LA9; X-ray; 2.81 A; A/B=181-426. DR PDB; 5LAS; X-ray; 2.10 A; A/B=181-426. DR PDB; 5LAT; X-ray; 1.90 A; A=181-426. DR PDB; 5LB6; X-ray; 1.70 A; A=181-426. DR PDB; 5LBB; X-ray; 1.70 A; A=181-426. DR PDB; 5LBC; X-ray; 1.82 A; A=181-426. DR PDB; 5LBE; X-ray; 1.75 A; A=181-426. DR PDB; 5LBF; X-ray; 1.90 A; A=181-426. DR PDB; 5OX5; X-ray; 2.25 A; A=181-426. DR PDB; 5OX6; X-ray; 1.99 A; A=181-426. DR PDB; 5V18; X-ray; 2.15 A; A=181-416. DR PDB; 6NMQ; X-ray; 1.58 A; A=180-392. DR PDB; 6QGV; X-ray; 1.40 A; A=181-407. DR PDB; 6ST3; X-ray; 2.43 A; A/B=181-407. DR PDB; 6YVT; X-ray; 2.85 A; A/B/C/D/E/F=181-426. DR PDB; 6YVW; X-ray; 1.97 A; A=181-426. DR PDB; 6YVX; X-ray; 1.80 A; A=181-426. DR PDB; 6YVZ; X-ray; 1.91 A; A=181-426. DR PDB; 6YW0; X-ray; 2.20 A; A=181-426. DR PDB; 6YW1; X-ray; 1.46 A; A=181-407. DR PDB; 6YW2; X-ray; 2.14 A; A=181-407. DR PDB; 6YW3; X-ray; 2.28 A; A=181-407. DR PDB; 6YW4; X-ray; 1.53 A; A=181-407. DR PDB; 6ZBN; X-ray; 2.01 A; A/B/C/D/E/F=181-407. DR PDB; 6ZBO; X-ray; 1.79 A; A/B/C/D/E/F=181-407. DR PDB; 7Q5V; X-ray; 1.17 A; A=181-407. DR PDB; 7Q5X; X-ray; 1.21 A; A=181-407. DR PDB; 7UJV; X-ray; 1.80 A; B=181-426. DR PDB; 7UMP; X-ray; 1.80 A; A=188-403. DR PDBsum; 2G19; -. DR PDBsum; 2G1M; -. DR PDBsum; 2HBT; -. DR PDBsum; 2HBU; -. DR PDBsum; 2Y33; -. DR PDBsum; 2Y34; -. DR PDBsum; 3HQR; -. DR PDBsum; 3HQU; -. DR PDBsum; 3OUH; -. DR PDBsum; 3OUI; -. DR PDBsum; 3OUJ; -. DR PDBsum; 4BQW; -. DR PDBsum; 4BQX; -. DR PDBsum; 4BQY; -. DR PDBsum; 4JZR; -. DR PDBsum; 4KBZ; -. DR PDBsum; 4UWD; -. DR PDBsum; 5A3U; -. DR PDBsum; 5L9B; -. DR PDBsum; 5L9R; -. DR PDBsum; 5L9V; -. DR PDBsum; 5LA9; -. DR PDBsum; 5LAS; -. DR PDBsum; 5LAT; -. DR PDBsum; 5LB6; -. DR PDBsum; 5LBB; -. DR PDBsum; 5LBC; -. DR PDBsum; 5LBE; -. DR PDBsum; 5LBF; -. DR PDBsum; 5OX5; -. DR PDBsum; 5OX6; -. DR PDBsum; 5V18; -. DR PDBsum; 6NMQ; -. DR PDBsum; 6QGV; -. DR PDBsum; 6ST3; -. DR PDBsum; 6YVT; -. DR PDBsum; 6YVW; -. DR PDBsum; 6YVX; -. DR PDBsum; 6YVZ; -. DR PDBsum; 6YW0; -. DR PDBsum; 6YW1; -. DR PDBsum; 6YW2; -. DR PDBsum; 6YW3; -. DR PDBsum; 6YW4; -. DR PDBsum; 6ZBN; -. DR PDBsum; 6ZBO; -. DR PDBsum; 7Q5V; -. DR PDBsum; 7Q5X; -. DR PDBsum; 7UJV; -. DR PDBsum; 7UMP; -. DR AlphaFoldDB; Q9GZT9; -. DR SMR; Q9GZT9; -. DR BioGRID; 120060; 90. DR CORUM; Q9GZT9; -. DR DIP; DIP-37495N; -. DR ELM; Q9GZT9; -. DR IntAct; Q9GZT9; 30. DR MINT; Q9GZT9; -. DR STRING; 9606.ENSP00000355601; -. DR BindingDB; Q9GZT9; -. DR ChEMBL; CHEMBL5697; -. DR DrugBank; DB00126; Ascorbic acid. DR DrugBank; DB11682; Daprodustat. DR DrugBank; DB14490; Ferrous ascorbate. DR DrugBank; DB14491; Ferrous fumarate. DR DrugBank; DB14488; Ferrous gluconate. DR DrugBank; DB14501; Ferrous glycine sulfate. DR DrugBank; DB14489; Ferrous succinate. DR DrugBank; DB08687; FG-2216. DR DrugBank; DB01592; Iron. DR DrugBank; DB07112; N-[(4-HYDROXY-8-IODOISOQUINOLIN-3-YL)CARBONYL]GLYCINE. DR DrugBank; DB04847; Roxadustat. DR DrugBank; DB12255; Vadadustat. DR DrugCentral; Q9GZT9; -. DR GuidetoPHARMACOLOGY; 2833; -. DR GlyGen; Q9GZT9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9GZT9; -. DR PhosphoSitePlus; Q9GZT9; -. DR BioMuta; EGLN1; -. DR DMDM; 32129514; -. DR EPD; Q9GZT9; -. DR jPOST; Q9GZT9; -. DR MassIVE; Q9GZT9; -. DR MaxQB; Q9GZT9; -. DR PaxDb; 9606-ENSP00000355601; -. DR PeptideAtlas; Q9GZT9; -. DR ProteomicsDB; 80138; -. [Q9GZT9-1] DR ProteomicsDB; 80139; -. [Q9GZT9-2] DR ProteomicsDB; 80140; -. [Q9GZT9-3] DR Pumba; Q9GZT9; -. DR Antibodypedia; 20799; 708 antibodies from 37 providers. DR DNASU; 54583; -. DR Ensembl; ENST00000366641.4; ENSP00000355601.3; ENSG00000135766.9. [Q9GZT9-1] DR GeneID; 54583; -. DR KEGG; hsa:54583; -. DR MANE-Select; ENST00000366641.4; ENSP00000355601.3; NM_022051.3; NP_071334.1. DR AGR; HGNC:1232; -. DR CTD; 54583; -. DR DisGeNET; 54583; -. DR GeneCards; EGLN1; -. DR HGNC; HGNC:1232; EGLN1. DR HPA; ENSG00000135766; Tissue enhanced (skeletal). DR MalaCards; EGLN1; -. DR MIM; 606425; gene. DR MIM; 609820; phenotype. DR neXtProt; NX_Q9GZT9; -. DR OpenTargets; ENSG00000135766; -. DR Orphanet; 247511; Autosomal dominant secondary polycythemia. DR PharmGKB; PA27670; -. DR VEuPathDB; HostDB:ENSG00000135766; -. DR eggNOG; KOG3710; Eukaryota. DR GeneTree; ENSGT00940000155704; -. DR HOGENOM; CLU_022206_2_2_1; -. DR InParanoid; Q9GZT9; -. DR OMA; GTESNCE; -. DR OrthoDB; 5358684at2759; -. DR PhylomeDB; Q9GZT9; -. DR TreeFam; TF314595; -. DR BRENDA; 1.14.11.2; 2681. DR BRENDA; 1.14.11.29; 2681. DR PathwayCommons; Q9GZT9; -. DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha. DR SABIO-RK; Q9GZT9; -. DR SignaLink; Q9GZT9; -. DR SIGNOR; Q9GZT9; -. DR BioGRID-ORCS; 54583; 108 hits in 1173 CRISPR screens. DR ChiTaRS; EGLN1; human. DR EvolutionaryTrace; Q9GZT9; -. DR GeneWiki; EGLN1; -. DR GenomeRNAi; 54583; -. DR Pharos; Q9GZT9; Tclin. DR PRO; PR:Q9GZT9; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9GZT9; Protein. DR Bgee; ENSG00000135766; Expressed in gastrocnemius and 147 other cell types or tissues. DR ExpressionAtlas; Q9GZT9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IDA:MGI. DR GO; GO:0019899; F:enzyme binding; ISS:BHF-UCL. DR GO; GO:0008198; F:ferrous iron binding; IDA:UniProtKB. DR GO; GO:0160082; F:hypoxia-inducible factor-proline dioxygenase activity; IDA:FlyBase. DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW. DR GO; GO:0031545; F:peptidyl-proline 4-dioxygenase activity; IBA:GO_Central. DR GO; GO:0031543; F:peptidyl-proline dioxygenase activity; TAS:HGNC-UCL. DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IBA:GO_Central. DR GO; GO:0060347; P:heart trabecula formation; IEA:Ensembl. DR GO; GO:0006879; P:intracellular iron ion homeostasis; IEA:Ensembl. DR GO; GO:0032364; P:intracellular oxygen homeostasis; IDA:HGNC-UCL. DR GO; GO:0060711; P:labyrinthine layer development; IEA:Ensembl. DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; ISS:BHF-UCL. DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:HGNC-UCL. DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:FlyBase. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0045765; P:regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0099159; P:regulation of modification of postsynaptic structure; IEA:Ensembl. DR GO; GO:0140252; P:regulation protein catabolic process at postsynapse; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IDA:HGNC-UCL. DR GO; GO:0071731; P:response to nitric oxide; IDA:UniProtKB. DR GO; GO:0060412; P:ventricular septum morphogenesis; IEA:Ensembl. DR Gene3D; 6.10.140.2220; -; 1. DR Gene3D; 2.60.120.620; q2cbj1_9rhob like domain; 1. DR IDEAL; IID00345; -. DR InterPro; IPR005123; Oxoglu/Fe-dep_dioxygenase. DR InterPro; IPR006620; Pro_4_hyd_alph. DR InterPro; IPR044862; Pro_4_hyd_alph_FE2OG_OXY. DR InterPro; IPR002893; Znf_MYND. DR PANTHER; PTHR12907:SF4; EGL NINE HOMOLOG 1; 1. DR PANTHER; PTHR12907; EGL NINE HOMOLOG-RELATED; 1. DR Pfam; PF13640; 2OG-FeII_Oxy_3; 1. DR Pfam; PF01753; zf-MYND; 1. DR SMART; SM00702; P4Hc; 1. DR SUPFAM; SSF144232; HIT/MYND zinc finger-like; 1. DR PROSITE; PS51471; FE2OG_OXY; 1. DR PROSITE; PS01360; ZF_MYND_1; 1. DR PROSITE; PS50865; ZF_MYND_2; 1. DR Genevisible; Q9GZT9; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Congenital erythrocytosis; KW Cytoplasm; Dioxygenase; Disease variant; Iron; Metal-binding; Nucleus; KW Oxidoreductase; Phosphoprotein; Reference proteome; S-nitrosylation; KW Vitamin C; Zinc; Zinc-finger. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..426 FT /note="Egl nine homolog 1" FT /id="PRO_0000206661" FT DOMAIN 291..392 FT /note="Fe2OG dioxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805" FT ZN_FING 21..58 FT /note="MYND-type; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT REGION 6..20 FT /note="Required for nuclear export" FT REGION 65..129 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 160..184 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 241..251 FT /note="Beta(2)beta(3) 'finger-like' loop" FT /evidence="ECO:0000269|PubMed:18063574" FT COMPBIAS 92..108 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 21 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 24 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 33 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 36 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 42 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 46 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 54 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 58 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134" FT BINDING 313 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:16782814, FT ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:28594552, FT ECO:0007744|PDB:2G19, ECO:0007744|PDB:3HQU, FT ECO:0007744|PDB:5V18" FT BINDING 315 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:16782814, FT ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:28594552, FT ECO:0007744|PDB:2G19, ECO:0007744|PDB:3HQU, FT ECO:0007744|PDB:5V18" FT BINDING 374 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /evidence="ECO:0000269|PubMed:16782814, FT ECO:0000269|PubMed:19604478, ECO:0000269|PubMed:28594552, FT ECO:0007744|PDB:2G19, ECO:0007744|PDB:3HQU, FT ECO:0007744|PDB:5V18" FT BINDING 383 FT /ligand="2-oxoglutarate" FT /ligand_id="ChEBI:CHEBI:16810" FT /evidence="ECO:0000305|PubMed:19604478" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 12 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 125 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 201 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:21601578" FT MOD_RES 208 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:21601578" FT MOD_RES 302 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:21601578" FT MOD_RES 323 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:21601578" FT MOD_RES 326 FT /note="S-nitrosocysteine" FT /evidence="ECO:0000269|PubMed:21601578" FT VAR_SEQ 58..175 FT /note="CQGSEGALGHGVGPHQHSGPAPPAAVPPPRAGAREPRKAAARRDNASGDAAK FT GKVKAKPPADPAAAASPCRAAAGGQGSAVAAEAEPGKEEPPARSSLFQEKANLYPPSNT FT PGDALSP -> LLGGYRFAFSWNSDERA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12788921" FT /id="VSP_042191" FT VAR_SEQ 338..359 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.6" FT /id="VSP_007569" FT VARIANT 4 FT /note="D -> E (increased protection from polycythemia at FT high altitude; when associated with S-127; FT dbSNP:rs186996510)" FT /evidence="ECO:0000269|PubMed:24711448, FT ECO:0000269|PubMed:25129147" FT /id="VAR_071858" FT VARIANT 127 FT /note="C -> S (increased protection from polycythemia at FT high altitude; when associated with E-4; dbSNP:rs12097901)" FT /evidence="ECO:0000269|PubMed:24711448, FT ECO:0000269|PubMed:25129147" FT /id="VAR_071859" FT VARIANT 317 FT /note="P -> R (in ECYT3; marked decrease in enzyme FT activity; dbSNP:rs80358193)" FT /evidence="ECO:0000269|PubMed:16407130" FT /id="VAR_027371" FT VARIANT 371 FT /note="R -> H (in ECYT3; decreased interaction with HIF1A FT and EPAS1 and decreased enzyme activity; FT dbSNP:rs119476044)" FT /evidence="ECO:0000269|PubMed:17579185" FT /id="VAR_045902" FT MUTAGEN 201 FT /note="C->A: Little change in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 208 FT /note="C->A: Little change in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 252 FT /note="R->A: Reduced C-terminal ODD domain (CODD) FT hydroxylation of HIF1A." FT MUTAGEN 254 FT /note="D->A,K: Reduced C-terminal ODD domain (CODD) FT hxdroxylation of HIF1A." FT MUTAGEN 266 FT /note="C->A: Little change in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 283 FT /note="C->A: Little change in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 302 FT /note="C->A: Slight increase in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 303 FT /note="Y->F: No effect." FT /evidence="ECO:0000269|PubMed:16782814" FT MUTAGEN 323 FT /note="C->A: Little change in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 326 FT /note="C->A: Slight increase in enzyme activity." FT /evidence="ECO:0000269|PubMed:21601578" FT MUTAGEN 383 FT /note="R->A: Reduces enzyme activity by 95%." FT /evidence="ECO:0000269|PubMed:16782814" FT HELIX 190..196 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 198..205 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 206..214 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 216..231 FT /evidence="ECO:0007829|PDB:7Q5V" FT TURN 233..235 FT /evidence="ECO:0007829|PDB:6ZBN" FT STRAND 240..242 FT /evidence="ECO:0007829|PDB:7Q5X" FT STRAND 244..246 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 255..259 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:6NMQ" FT HELIX 267..282 FT /evidence="ECO:0007829|PDB:7Q5V" FT TURN 283..286 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 287..289 FT /evidence="ECO:0007829|PDB:2G1M" FT STRAND 292..295 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 298..305 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 308..313 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 315..318 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 320..329 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 331..333 FT /evidence="ECO:0007829|PDB:4KBZ" FT HELIX 336..339 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 343..345 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 347..349 FT /evidence="ECO:0007829|PDB:7UMP" FT STRAND 354..356 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 362..367 FT /evidence="ECO:0007829|PDB:7Q5V" FT STRAND 374..392 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 393..404 FT /evidence="ECO:0007829|PDB:7Q5V" FT HELIX 407..409 FT /evidence="ECO:0007829|PDB:5V18" SQ SEQUENCE 426 AA; 46021 MW; 81A97FF772CAA14C CRC64; MANDSGGPGG PSPSERDRQY CELCGKMENL LRCSRCRSSF YCCKEHQRQD WKKHKLVCQG SEGALGHGVG PHQHSGPAPP AAVPPPRAGA REPRKAAARR DNASGDAAKG KVKAKPPADP AAAASPCRAA AGGQGSAVAA EAEPGKEEPP ARSSLFQEKA NLYPPSNTPG DALSPGGGLR PNGQTKPLPA LKLALEYIVP CMNKHGICVV DDFLGKETGQ QIGDEVRALH DTGKFTDGQL VSQKSDSSKD IRGDKITWIE GKEPGCETIG LLMSSMDDLI RHCNGKLGSY KINGRTKAMV ACYPGNGTGY VRHVDNPNGD GRCVTCIYYL NKDWDAKVSG GILRIFPEGK AQFADIEPKF DRLLFFWSDR RNPHEVQPAY ATRYAITVWY FDADERARAK VKYLTGEKGV RVELNKPSDS VGKDVF //