EGL9_CAEEL
ID EGL9_CAEEL Reviewed; 723 AA.
AC G5EBV0; G5ECV8; G5EE79; G5EEP8; Q56W01;
DT 24-JUN-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 77.
DE RecName: Full=Hypoxia-inducible factor prolyl hydroxylase {ECO:0000250|UniProtKB:Q9GZT9};
DE Short=HIF-PH {ECO:0000303|PubMed:11595184};
DE EC=1.14.11.29 {ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:19737748};
DE AltName: Full=Egg-laying defective protein 9 {ECO:0000312|WormBase:F22E12.4a};
DE AltName: Full=Hypoxia-inducible factor-proline dioxygenase {ECO:0000305};
GN Name=egl-9 {ECO:0000312|WormBase:F22E12.4a};
GN ORFNames=F22E12.4 {ECO:0000312|WormBase:F22E12.4a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAD56365.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=Bristol N2 {ECO:0000303|PubMed:10611362};
RX PubMed=10611362; DOI=10.1073/pnas.96.26.15202;
RA Darby C., Cosma C.L., Thomas J.H., Manoil C.;
RT "Lethal paralysis of Caenorhabditis elegans by Pseudomonas aeruginosa.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:15202-15207(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, ACTIVITY REGULATION, DOMAIN, AND MUTAGENESIS OF HIS-487.
RX PubMed=19737748; DOI=10.1534/genetics.109.107284;
RA Shao Z., Zhang Y., Powell-Coffman J.A.;
RT "Two distinct roles for EGL-9 in the regulation of HIF-1-mediated gene
RT expression in Caenorhabditis elegans.";
RL Genetics 183:821-829(2009).
RN [3] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4] {ECO:0000305}
RP FUNCTION.
RX PubMed=11813735; DOI=10.1093/genetics/104.4.619;
RA Trent C., Tsuing N., Horvitz H.R.;
RT "Egg-laying defective mutants of the nematode Caenorhabditis elegans.";
RL Genetics 104:619-647(1983).
RN [5] {ECO:0000305}
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION.
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 [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=11591663; DOI=10.1128/jb.183.21.6207-6214.2001;
RA Gallagher L.A., Manoil C.;
RT "Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide
RT poisoning.";
RL J. Bacteriol. 183:6207-6214(2001).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=12686697; DOI=10.1152/physiolgenomics.00179.2002;
RA Treinin M., Shliar J., Jiang H., Powell-Coffman J.A., Bromberg Z.,
RA Horowitz M.;
RT "HIF-1 is required for heat acclimation in the nematode Caenorhabditis
RT elegans.";
RL Physiol. Genomics 14:17-24(2003).
RN [8] {ECO:0000305}
RP INDUCTION BY HYPOXIA.
RX PubMed=15781453; DOI=10.1074/jbc.m501894200;
RA Shen C., Nettleton D., Jiang M., Kim S.K., Powell-Coffman J.A.;
RT "Roles of the HIF-1 hypoxia-inducible factor during hypoxia response in
RT Caenorhabditis elegans.";
RL J. Biol. Chem. 280:20580-20588(2005).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=16091039; DOI=10.1111/j.1365-2958.2005.04739.x;
RA Anyanful A., Dolan-Livengood J.M., Lewis T., Sheth S., Dezalia M.N.,
RA Sherman M.A., Kalman L.V., Benian G.M., Kalman D.;
RT "Paralysis and killing of Caenorhabditis elegans by enteropathogenic
RT Escherichia coli requires the bacterial tryptophanase gene.";
RL Mol. Microbiol. 57:988-1007(2005).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=18477695; DOI=10.1073/pnas.0802164105;
RA Chang A.J., Bargmann C.I.;
RT "Hypoxia and the HIF-1 transcriptional pathway reorganize a neuronal
RT circuit for oxygen-dependent behavior in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7321-7326(2008).
RN [11] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20011506; DOI=10.1371/journal.ppat.1000689;
RA Bellier A., Chen C.S., Kao C.Y., Cinar H.N., Aroian R.V.;
RT "Hypoxia and the hypoxic response pathway protect against pore-forming
RT toxins in C. elegans.";
RL PLoS Pathog. 5:E1000689-E1000689(2009).
RN [12] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19372390; DOI=10.1126/science.1173507;
RA Mehta R., Steinkraus K.A., Sutphin G.L., Ramos F.J., Shamieh L.S., Huh A.,
RA Davis C., Chandler-Brown D., Kaeberlein M.;
RT "Proteasomal regulation of the hypoxic response modulates aging in C.
RT elegans.";
RL Science 324:1196-1198(2009).
RN [13] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH SWAN-1.
RX PubMed=20865124; DOI=10.1371/journal.ppat.1001075;
RA Shao Z., Zhang Y., Ye Q., Saldanha J.N., Powell-Coffman J.A.;
RT "C. elegans SWAN-1 Binds to EGL-9 and regulates HIF-1-mediated resistance
RT to the bacterial pathogen Pseudomonas aeruginosa PAO1.";
RL PLoS Pathog. 6:E1001075-E1001075(2010).
RN [14] {ECO:0000305}
RP FUNCTION, INTERACTION WITH LIN-10, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP HIS-487, AND CHARACTERIZATION OF ISOFORMS A; C AND E.
RX PubMed=22252129; DOI=10.1038/emboj.2011.499;
RA Park E.C., Ghose P., Shao Z., Ye Q., Kang L., Xu X.Z., Powell-Coffman J.A.,
RA Rongo C.;
RT "Hypoxia regulates glutamate receptor trafficking through an HIF-
RT independent mechanism.";
RL EMBO J. 31:1379-1393(2012).
RN [15] {ECO:0000305}
RP FUNCTION, INTERACTION WITH CYSL-1, AND MUTAGENESIS OF GLU-720.
RX PubMed=22405203; DOI=10.1016/j.neuron.2011.12.037;
RA Ma D.K., Vozdek R., Bhatla N., Horvitz H.R.;
RT "CYSL-1 interacts with the O2-sensing hydroxylase EGL-9 to promote H2S-
RT modulated hypoxia-induced behavioral plasticity in C. elegans.";
RL Neuron 73:925-940(2012).
RN [16] {ECO:0000305}
RP FUNCTION.
RX PubMed=22396654; DOI=10.1371/journal.pgen.1002498;
RA Ackerman D., Gems D.;
RT "Insulin/IGF-1 and hypoxia signaling act in concert to regulate iron
RT homeostasis in Caenorhabditis elegans.";
RL PLoS Genet. 8:E1002498-E1002498(2012).
RN [17] {ECO:0000305}
RP FUNCTION, AND DOMAIN.
RX PubMed=22792069; DOI=10.1371/journal.ppat.1002798;
RA Luhachack L.G., Visvikis O., Wollenberg A.C., Lacy-Hulbert A., Stuart L.M.,
RA Irazoqui J.E.;
RT "EGL-9 controls C. elegans host defense specificity through prolyl
RT hydroxylation-dependent and -independent HIF-1 pathways.";
RL PLoS Pathog. 8:E1002798-E1002798(2012).
RN [18] {ECO:0000305}
RP FUNCTION.
RX PubMed=24385935; DOI=10.1371/journal.pgen.1004063;
RA Ghose P., Park E.C., Tabakin A., Salazar-Vasquez N., Rongo C.;
RT "Anoxia-reoxygenation regulates mitochondrial dynamics through the hypoxia
RT response pathway, SKN-1/Nrf, and stomatin-like protein STL-1/SLP-2.";
RL PLoS Genet. 9:E1004063-E1004063(2013).
CC -!- FUNCTION: Cellular oxygen sensor which regulates the stability and the
CC activity of hypoxia-inducible transcription factor, hif-1. In normoxic
CC conditions, hydroxylates hif-1 targeting it for vhl-1-mediated
CC proteasomal degradation (PubMed:11595184). In addition, regulates hif-1
CC transcriptional activity in a vhl-1-independent manner and
CC independently of its hydroxylase activity (PubMed:19737748). By
CC regulating hif-1 activity, controls several cellular responses.
CC Mediates susceptibility to B.thuringiensis and V.cholerae pore-forming
CC toxins and enteropathogenic E.coli (PubMed:20011506, PubMed:16091039).
CC Mediates susceptibility to P.aeruginosa PAO1-mediated killing by
CC regulating resistance to cyanide produced by P.aeruginosa
CC (PubMed:10611362, PubMed:11591663, PubMed:20865124). Mediates
CC resistance to S.aureus-mediated killing (PubMed:22792069). In addition,
CC plays a role in heat acclimation, neuronal development, behavioral
CC responses to reoxygenation and hydrogen sulfide, iron homeostasis and
CC aging (PubMed:12686697, PubMed:18477695, PubMed:22405203,
CC PubMed:19372390, PubMed:22396654). In neurons, involved in
CC mitochondrion fusion during reoxygenation (PubMed:24385935). Involved
CC in egg laying (PubMed:10611362, PubMed:11813735).
CC {ECO:0000269|PubMed:10611362, ECO:0000269|PubMed:11591663,
CC ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:11813735,
CC ECO:0000269|PubMed:12686697, ECO:0000269|PubMed:16091039,
CC ECO:0000269|PubMed:18477695, ECO:0000269|PubMed:19372390,
CC ECO:0000269|PubMed:19737748, ECO:0000269|PubMed:20011506,
CC ECO:0000269|PubMed:20865124, ECO:0000269|PubMed:22396654,
CC ECO:0000269|PubMed:22405203, ECO:0000269|PubMed:22792069,
CC ECO:0000269|PubMed:24385935}.
CC -!- FUNCTION: [Isoform e]: Regulates the trafficking of the glutamate
CC receptor glr-1, probably independently of hif-1, by regulating lin-10
CC subcellular localization in response to oxygen levels. May hydroxylate
CC lin-10. {ECO:0000269|PubMed:22252129}.
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:11595184, ECO:0000269|PubMed:19737748};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:11595184, ECO:0000269|PubMed:19737748};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00805};
CC -!- COFACTOR:
CC Name=L-ascorbate; Xref=ChEBI:CHEBI:38290;
CC Evidence={ECO:0000269|PubMed:11595184};
CC -!- ACTIVITY REGULATION: Inhibited by Co(2+) and dimethyloxalylglycine
CC (PubMed:11595184). Inhibited by the iron chelator 2, 2'-dipyridyl
CC (PubMed:19737748). {ECO:0000269|PubMed:11595184,
CC ECO:0000269|PubMed:19737748}.
CC -!- SUBUNIT: Interacts (via catalytic domain) with lin-10 (via N-terminus);
CC the interaction regulates lin-10 subcellular localization; the
CC interaction is direct (PubMed:22252129). Interacts (via catalytic
CC domain) with swan-1 (via WD 1-3 repeats); the interaction may regulate
CC vhl-1-independent hif-1 transcriptional activity; the interaction is
CC direct (PubMed:20865124). Interacts (via C-terminus) with cysl-1; the
CC interaction is enhanced by hydrogen disulfide and activates hif-1-
CC mediated transcription; the interaction is direct (PubMed:22405203).
CC {ECO:0000269|PubMed:20865124, ECO:0000269|PubMed:22252129,
CC ECO:0000269|PubMed:22405203}.
CC -!- INTERACTION:
CC G5EBV0; Q93244: cysl-1; NbExp=3; IntAct=EBI-2004151, EBI-2413537;
CC G5EBV0; Q7K7J0: gei-18; NbExp=3; IntAct=EBI-2004151, EBI-2315822;
CC G5EBV0; Q93758: swan-1; NbExp=2; IntAct=EBI-2004151, EBI-331968;
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Cytoplasm
CC {ECO:0000269|PubMed:22252129}. Nucleus {ECO:0000269|PubMed:22252129}.
CC Cell projection, dendrite {ECO:0000269|PubMed:22252129}. Note=In
CC interneurons, localizes throughout the ventral cord dendrites.
CC {ECO:0000269|PubMed:22252129}.
CC -!- SUBCELLULAR LOCATION: [Isoform c]: Cytoplasm
CC {ECO:0000269|PubMed:22252129}. Nucleus {ECO:0000269|PubMed:22252129}.
CC Cell projection, dendrite {ECO:0000269|PubMed:22252129}. Note=In
CC interneurons, localizes throughout the ventral cord dendrites.
CC {ECO:0000269|PubMed:22252129}.
CC -!- SUBCELLULAR LOCATION: [Isoform e]: Cytoplasm
CC {ECO:0000269|PubMed:22252129}. Nucleus {ECO:0000269|PubMed:22252129}.
CC Cell projection, axon {ECO:0000269|PubMed:22252129}. Note=In
CC interneurons, localizes in puncta (which probably correspond to
CC endosomes) along the ventral cord. Localization to puncta is regulated
CC by oxygen levels. Co-localizes with lin-10 in puncta.
CC {ECO:0000269|PubMed:22252129}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=a {ECO:0000312|WormBase:F22E12.4a};
CC IsoId=G5EBV0-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F22E12.4b};
CC IsoId=G5EBV0-2; Sequence=VSP_057747, VSP_057748;
CC Name=c {ECO:0000312|WormBase:F22E12.4c};
CC IsoId=G5EBV0-3; Sequence=VSP_057745;
CC Name=d {ECO:0000312|WormBase:F22E12.4d};
CC IsoId=G5EBV0-4; Sequence=VSP_057749;
CC Name=e {ECO:0000312|WormBase:F22E12.4e};
CC IsoId=G5EBV0-5; Sequence=VSP_057746;
CC -!- TISSUE SPECIFICITY: In larvae and adults, expressed in pharyngeal and
CC body wall muscles. {ECO:0000269|PubMed:10611362}.
CC -!- INDUCTION: Induced by hypoxia. {ECO:0000269|PubMed:15781453}.
CC -!- DOMAIN: The MYND-type domain is not required for oxygen-mediated hif-1
CC degradation or for inhibiting hif-1 transcriptional activity
CC (PubMed:19737748). Susceptibility to S.aureus infection requires the
CC Ser-rich region but not the MYND-type or Fe2OG dioxygenase domains
CC (PubMed:22792069). {ECO:0000269|PubMed:19737748,
CC ECO:0000269|PubMed:22792069}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes enhanced
CC resistance to polyglutamine or amyloid-beta-mediated paralysis and an
CC increase in adult life span (PubMed:19372390). In addition, causes
CC resistance to B.thuringiensis pore-forming toxin CryA21-mediated
CC toxicity (PubMed:20011506). {ECO:0000269|PubMed:19372390,
CC ECO:0000269|PubMed:20011506}.
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DR EMBL; AF178536; AAD56365.1; -; mRNA.
DR EMBL; BX284605; CAA94893.2; -; Genomic_DNA.
DR EMBL; BX284605; CAD44114.1; -; Genomic_DNA.
DR EMBL; BX284605; CAI79247.1; -; Genomic_DNA.
DR EMBL; BX284605; CAI79160.1; -; Genomic_DNA.
DR EMBL; BX284605; CAK55177.1; -; Genomic_DNA.
DR PIR; T21276; T21276.
DR RefSeq; NP_001023832.1; NM_001028661.3.
DR RefSeq; NP_001023833.1; NM_001028662.1. [G5EBV0-3]
DR RefSeq; NP_001023834.1; NM_001028663.3. [G5EBV0-4]
DR RefSeq; NP_001041105.1; NM_001047640.2. [G5EBV0-5]
DR RefSeq; NP_741621.1; NM_171533.4. [G5EBV0-1]
DR AlphaFoldDB; G5EBV0; -.
DR SMR; G5EBV0; -.
DR IntAct; G5EBV0; 4.
DR STRING; 6239.F22E12.4a.2; -.
DR EPD; G5EBV0; -.
DR PaxDb; G5EBV0; -.
DR PeptideAtlas; G5EBV0; -.
DR PRIDE; G5EBV0; -.
DR EnsemblMetazoa; F22E12.4a.1; F22E12.4a.1; WBGene00001178. [G5EBV0-1]
DR EnsemblMetazoa; F22E12.4b.1; F22E12.4b.1; WBGene00001178. [G5EBV0-2]
DR EnsemblMetazoa; F22E12.4b.2; F22E12.4b.2; WBGene00001178. [G5EBV0-2]
DR EnsemblMetazoa; F22E12.4b.3; F22E12.4b.3; WBGene00001178. [G5EBV0-2]
DR EnsemblMetazoa; F22E12.4c.1; F22E12.4c.1; WBGene00001178. [G5EBV0-3]
DR EnsemblMetazoa; F22E12.4d.1; F22E12.4d.1; WBGene00001178. [G5EBV0-4]
DR EnsemblMetazoa; F22E12.4e.1; F22E12.4e.1; WBGene00001178. [G5EBV0-5]
DR GeneID; 179461; -.
DR KEGG; cel:CELE_F22E12.4; -.
DR CTD; 179461; -.
DR WormBase; F22E12.4a; CE27755; WBGene00001178; egl-9. [G5EBV0-1]
DR WormBase; F22E12.4b; CE31342; WBGene00001178; egl-9. [G5EBV0-2]
DR WormBase; F22E12.4c; CE38327; WBGene00001178; egl-9. [G5EBV0-3]
DR WormBase; F22E12.4d; CE38328; WBGene00001178; egl-9. [G5EBV0-4]
DR WormBase; F22E12.4e; CE40254; WBGene00001178; egl-9. [G5EBV0-5]
DR eggNOG; KOG3710; Eukaryota.
DR GeneTree; ENSGT00940000155704; -.
DR InParanoid; G5EBV0; -.
DR OMA; HRFAITI; -.
DR OrthoDB; 1604981at2759; -.
DR Reactome; R-CEL-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR SignaLink; G5EBV0; -.
DR PRO; PR:G5EBV0; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00001178; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0008198; F:ferrous iron binding; IBA:GO_Central.
DR GO; GO:0031418; F:L-ascorbic acid binding; IEA:UniProtKB-KW.
DR GO; GO:0031545; F:peptidyl-proline 4-dioxygenase activity; IDA:WormBase.
DR GO; GO:0031543; F:peptidyl-proline dioxygenase activity; IBA:GO_Central.
DR GO; GO:0071456; P:cellular response to hypoxia; IBA:GO_Central.
DR GO; GO:0018401; P:peptidyl-proline hydroxylation to 4-hydroxy-L-proline; IDA:WormBase.
DR GO; GO:0032880; P:regulation of protein localization; IMP:WormBase.
DR GO; GO:0001666; P:response to hypoxia; IMP:WormBase.
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 Pfam; PF13640; 2OG-FeII_Oxy_3; 1.
DR Pfam; PF01753; zf-MYND; 1.
DR SMART; SM00702; P4Hc; 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 Alternative splicing; Cell projection; Cytoplasm; Dioxygenase; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Reference proteome; Vitamin C;
KW Zinc; Zinc-finger.
FT CHAIN 1..723
FT /note="Hypoxia-inducible factor prolyl hydroxylase"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433363"
FT DOMAIN 468..566
FT /note="Fe2OG dioxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT ZN_FING 39..79
FT /note="MYND-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT REGION 249..275
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 294..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 678..723
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..320
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 688..704
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 39
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
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 54
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 57
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 63
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00134"
FT BINDING 487
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 489
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 548
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT BINDING 557
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00805"
FT VAR_SEQ 1..292
FT /note="MSSAPNDDCEIDKGTPSTASLFTTLMLSQPSSSTAVLQCTYCGSSCTSSQLQ
FT TCLFCGTVAYCSKEHQQLDWLTHKMICKSLQTSGMVPSNLMPQAAPAVMAPIPPTVSFD
FT DPALTTSLLLSLQNNPILNQTISNFPPTFSITSKTEPEPSIPIQIPQRISSTSTVPFSS
FT EGSAFKPYRNTHVFNSISSESMSSMCTSHEASLEHMSSASLAMFPTSSTAQSDISRLAQ
FT VLSLAGDSPASLALVTTSVPSTASTATIPPPATTTSSATSSGKSETITVGKEKIIQTDD
FT PDIQ -> MPLRTIVAPTSYGIPTPMPSQSRWKPYSKTMKPS (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_057745"
FT VAR_SEQ 1..76
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000305"
FT /id="VSP_057746"
FT VAR_SEQ 362..363
FT /note="YI -> RN (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057747"
FT VAR_SEQ 364..723
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_057748"
FT VAR_SEQ 642..662
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_057749"
FT MUTAGEN 487
FT /note="H->A: Loss of hydroxylase activity resulting in loss
FT of oxygen-mediated hif-1 degradation. Inhibition of hif-1
FT transcriptional activity, which is independent of egl-9
FT hydroxylase activity, is only slightly affected. Loss of
FT glr-1 recycling; in isoform e."
FT /evidence="ECO:0000269|PubMed:19737748,
FT ECO:0000269|PubMed:22252129"
FT MUTAGEN 720
FT /note="E->K: Loss of interaction with cysl-1 associated
FT with a loss of hypoxia-mediated inhibition of behavior
FT adaptation."
FT /evidence="ECO:0000269|PubMed:22405203"
SQ SEQUENCE 723 AA; 79743 MW; 15F65F197F9D1D52 CRC64;
MSSAPNDDCE IDKGTPSTAS LFTTLMLSQP SSSTAVLQCT YCGSSCTSSQ LQTCLFCGTV
AYCSKEHQQL DWLTHKMICK SLQTSGMVPS NLMPQAAPAV MAPIPPTVSF DDPALTTSLL
LSLQNNPILN QTISNFPPTF SITSKTEPEP SIPIQIPQRI SSTSTVPFSS EGSAFKPYRN
THVFNSISSE SMSSMCTSHE ASLEHMSSAS LAMFPTSSTA QSDISRLAQV LSLAGDSPAS
LALVTTSVPS TASTATIPPP ATTTSSATSS GKSETITVGK EKIIQTDDPD IQIIETEGGS
KPTVSRTRKR PTPSNSADPK INYKDHNKNV VYSTTLQEHQ KHLQNRGLAL SIHQAMVLRL
RYIAEHVIRS LNEFGWAVVD NFLGSDHYKF TAKEIERLYE RGLFSPGQLM EAKHKDEFHI
KDIRSDHIYW YDGYDGRAKD AATVRLLISM IDSVIQHFKK RIDHDIGGRS RAMLAIYPGN
GTRYVKHVDN PVKDGRCITT IYYCNENWDM ATDGGTLRLY PETSMTPMDI DPRADRLVFF
WSDRRNPHEV MPVFRHRFAI TIWYMDKSER DKALAKGKES DAACASKKEN DPTSSSLNSL
IGSLLRPRKN PSTHDLSKLD LRLFPSTSSD PALVSAADED RVDISADFQS TSSLAHPEST
DSGVSLSTFN VAHNHMERTT SLQSISDHFR SERSHERRSS TSSDQDLDEG LPPPPSTNPE
YYI
