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;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00805,
CC ECO:0000269|PubMed:16782814, ECO:0000269|PubMed:19604478,
CC ECO:0000269|PubMed:28594552, ECO:0007744|PDB:2G19,
CC 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 ---------------------------------------------------------------------------
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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 Genevisible; Q9GZT9; HS.
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.
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
//
