EPAS1_HUMAN
ID EPAS1_HUMAN Reviewed; 870 AA.
AC Q99814; Q86VA2; Q99630;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 03-JUL-2003, sequence version 3.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Endothelial PAS domain-containing protein 1;
DE Short=EPAS-1;
DE AltName: Full=Basic-helix-loop-helix-PAS protein MOP2;
DE AltName: Full=Class E basic helix-loop-helix protein 73;
DE Short=bHLHe73;
DE AltName: Full=HIF-1-alpha-like factor;
DE Short=HLF;
DE AltName: Full=Hypoxia-inducible factor 2-alpha;
DE Short=HIF-2-alpha;
DE Short=HIF2-alpha;
DE AltName: Full=Member of PAS protein 2;
DE AltName: Full=PAS domain-containing protein 2;
GN Name=EPAS1; Synonyms=BHLHE73, HIF2A, MOP2, PASD2;
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 [MRNA].
RX PubMed=9000051; DOI=10.1101/gad.11.1.72;
RA Tian H., McKnight S.L., Russell D.W.;
RT "Endothelial PAS domain protein 1 (EPAS1), a transcription factor
RT selectively expressed in endothelial cells.";
RL Genes Dev. 11:72-82(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hepatoma;
RX PubMed=9079689; DOI=10.1074/jbc.272.13.8581;
RA Hogenesch J.B., Chan W.K., Jackiw V.H., Brown R.C., Gu Y.-Z.,
RA Pray-Grant M., Perdew G.H., Bradfield C.A.;
RT "Characterization of a subset of the basic-helix-loop-helix-PAS superfamily
RT that interacts with components of the dioxin signaling pathway.";
RL J. Biol. Chem. 272:8581-8593(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP TRANSACTIVATION DOMAINS NTAD AND CTAD, INTERACTION WITH APEX1, AND
RP MUTAGENESIS OF CYS-844.
RX PubMed=10202154; DOI=10.1093/emboj/18.7.1905;
RA Ema M., Hirota K., Mimura J., Abe H., Yodoi J., Sogawa K., Poellinger L.,
RA Fujii-Kuriyama Y.;
RT "Molecular mechanisms of transcription activation by HLF and HIF1alpha in
RT response to hypoxia: their stabilization and redox signal-induced
RT interaction with CBP/p300.";
RL EMBO J. 18:1905-1914(1999).
RN [5]
RP INTERACTION WITH EGLN1 AND VHL, VARIANT ECYT4 LEU-534, AND CHARACTERIZATION
RP OF VARIANTS ECYT4 LEU-534; VAL-535 AND ARG-537.
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 [6] {ECO:0007744|PDB:2A24}
RP STRUCTURE BY NMR OF 356-470 IN COMPLEX WITH ARNT, AND INTERACTION WITH
RP ARNT.
RX PubMed=16181639; DOI=10.1016/j.jmb.2005.08.043;
RA Card P.B., Erbel P.J., Gardner K.H.;
RT "Structural basis of ARNT PAS-B dimerization: use of a common beta-sheet
RT interface for hetero- and homodimerization.";
RL J. Mol. Biol. 353:664-677(2005).
RN [7]
RP VARIANTS ECYT4 VAL-535 AND ARG-537.
RX PubMed=18378852; DOI=10.1182/blood-2008-02-137703;
RA Percy M.J., Beer P.A., Campbell G., Dekker A.W., Green A.R., Oscier D.,
RA Rainey M.G., van Wijk R., Wood M., Lappin T.R., McMullin M.F., Lee F.S.;
RT "Novel exon 12 mutations in the HIF2A gene associated with
RT erythrocytosis.";
RL Blood 111:5400-5402(2008).
RN [8]
RP INTERACTION WITH KAPOSI'S SARCOMA-ASSOCIATED HERPESVIRUS/HHV-8 PROTEIN
RP ORF34 (MICROBIAL INFECTION).
RX PubMed=31189709; DOI=10.1128/jvi.00764-19;
RA Haque M., Kousoulas K.G.;
RT "The Kaposi's Sarcoma-Associated Herpesvirus ORF34 Protein Interacts and
RT Stabilizes HIF-2alpha via Binding to the HIF-2alpha bHLH and PAS Domains.";
RL J. Virol. 93:0-0(2019).
RN [9]
RP VARIANT ECYT4 TRP-537, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP CHARACTERIZATION OF VARIANT ECYT4 TRP-537.
RX PubMed=18184961; DOI=10.1056/nejmoa073123;
RA Percy M.J., Furlow P.W., Lucas G.S., Li X., Lappin T.R., McMullin M.F.,
RA Lee F.S.;
RT "A gain-of-function mutation in the HIF2A gene in familial
RT erythrocytosis.";
RL N. Engl. J. Med. 358:162-168(2008).
RN [10]
RP VARIANTS ECYT4 THR-535 AND LEU-540, AND CHARACTERIZATION OF VARIANT ECYT4
RP LEU-540.
RX PubMed=22367913; DOI=10.1002/ajh.23123;
RA Percy M.J., Chung Y.J., Harrison C., Mercieca J., Hoffbrand A.V.,
RA Dinardo C.L., Santos P.C., Fonseca G.H., Gualandro S.F., Pereira A.C.,
RA Lappin T.R., McMullin M.F., Lee F.S.;
RT "Two new mutations in the HIF2A gene associated with erythrocytosis.";
RL Am. J. Hematol. 87:439-442(2012).
CC -!- FUNCTION: Transcription factor involved in the induction of oxygen
CC regulated genes. Heterodimerizes with ARNT; heterodimer binds to core
CC DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of
CC target gene promoters (By similarity). Regulates the vascular
CC endothelial growth factor (VEGF) expression and seems to be implicated
CC in the development of blood vessels and the tubular system of lung. May
CC also play a role in the formation of the endothelium that gives rise to
CC the blood brain barrier. Potent activator of the Tie-2 tyrosine kinase
CC expression. Activation requires recruitment of transcriptional
CC coactivators such as CREBBP and probably EP300. Interaction with redox
CC regulatory protein APEX1 seems to activate CTAD (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P97481}.
CC -!- SUBUNIT: Interacts with HIF3A (By similarity). Efficient DNA binding
CC requires dimerization with another bHLH protein. Heterodimerizes with
CC ARNT; heterodimer binds to core DNA sequence 5'-TACGTG-3' within the
CC hypoxia response element (HRE) of target gene promoters
CC (PubMed:16181639). Interacts with CREBBP (By similarity). Interacts
CC with EGLN1. Interacts with VHL (PubMed:19208626).
CC {ECO:0000250|UniProtKB:P97481, ECO:0000269|PubMed:10202154,
CC ECO:0000269|PubMed:16181639, ECO:0000269|PubMed:19208626}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Kaposi's sarcoma-
CC associated herpesvirus/HHV-8 protein ORF34; this interaction results in
CC increased stability of EPAS1 and thus activation of its transcriptional
CC activity. {ECO:0000269|PubMed:31189709}.
CC -!- INTERACTION:
CC Q99814; P27540: ARNT; NbExp=8; IntAct=EBI-447470, EBI-80809;
CC Q99814; O00327-8: ARNTL; NbExp=3; IntAct=EBI-447470, EBI-11991546;
CC Q99814; Q8WYA1-3: ARNTL2; NbExp=3; IntAct=EBI-447470, EBI-12268276;
CC Q99814; Q96RK4: BBS4; NbExp=2; IntAct=EBI-447470, EBI-1805814;
CC Q99814; Q9GZT9: EGLN1; NbExp=3; IntAct=EBI-447470, EBI-1174818;
CC Q99814; P60228: EIF3E; NbExp=10; IntAct=EBI-447470, EBI-347740;
CC Q99814; O60573: EIF4E2; NbExp=2; IntAct=EBI-447470, EBI-398610;
CC Q99814; P09467: FBP1; NbExp=4; IntAct=EBI-447470, EBI-712740;
CC Q99814; P61244: MAX; NbExp=2; IntAct=EBI-447470, EBI-751711;
CC Q99814; Q9BWF3-1: RBM4; NbExp=6; IntAct=EBI-447470, EBI-15621561;
CC Q99814; P08047: SP1; NbExp=2; IntAct=EBI-447470, EBI-298336;
CC Q99814; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-447470, EBI-14096082;
CC Q99814; P40818: USP8; NbExp=2; IntAct=EBI-447470, EBI-1050865;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P97481,
CC ECO:0000255|PROSITE-ProRule:PRU00981}. Nucleus speckle
CC {ECO:0000250|UniProtKB:P97481}. Note=Colocalizes with HIF3A in the
CC nucleus and speckles. {ECO:0000250|UniProtKB:P97481}.
CC -!- TISSUE SPECIFICITY: Expressed in most tissues, with highest levels in
CC placenta, lung and heart. Selectively expressed in endothelial cells.
CC -!- PTM: In normoxia, is probably hydroxylated on Pro-405 and Pro-531 by
CC EGLN1/PHD1, EGLN2/PHD2 and/or EGLN3/PHD3. The hydroxylated prolines
CC promote interaction with VHL, initiating rapid ubiquitination and
CC subsequent proteasomal degradation. Under hypoxia, proline
CC hydroxylation is impaired and ubiquitination is attenuated, resulting
CC in stabilization (By similarity). {ECO:0000250}.
CC -!- PTM: In normoxia, is hydroxylated on Asn-847 by HIF1AN thus probably
CC abrogating interaction with CREBBP and EP300 and preventing
CC transcriptional activation. {ECO:0000250}.
CC -!- PTM: Phosphorylated on multiple sites in the CTAD. {ECO:0000250}.
CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of
CC asparagine is (S) stereospecific within HIF CTAD domains.
CC {ECO:0000250}.
CC -!- DISEASE: Erythrocytosis, familial, 4 (ECYT4) [MIM:611783]: An autosomal
CC dominant disorder characterized by elevated serum hemoglobin and
CC hematocrit, and normal platelet and leukocyte counts.
CC {ECO:0000269|PubMed:18184961, ECO:0000269|PubMed:18378852,
CC ECO:0000269|PubMed:19208626, ECO:0000269|PubMed:22367913}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
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DR EMBL; U81984; AAB41495.1; -; mRNA.
DR EMBL; U51626; AAC51212.1; -; mRNA.
DR EMBL; BC051338; AAH51338.1; -; mRNA.
DR CCDS; CCDS1825.1; -.
DR RefSeq; NP_001421.2; NM_001430.4.
DR PDB; 1P97; NMR; -; A=240-350.
DR PDB; 2A24; NMR; -; A=242-348.
DR PDB; 3F1N; X-ray; 1.48 A; A=239-350.
DR PDB; 3F1O; X-ray; 1.60 A; A=239-350.
DR PDB; 3F1P; X-ray; 1.17 A; A=239-350.
DR PDB; 3H7W; X-ray; 1.65 A; A=239-350.
DR PDB; 3H82; X-ray; 1.50 A; A=239-350.
DR PDB; 4GHI; X-ray; 1.50 A; A=239-350.
DR PDB; 4GS9; X-ray; 1.72 A; A=239-350.
DR PDB; 4PKY; X-ray; 3.20 A; G=239-350.
DR PDB; 4XT2; X-ray; 1.70 A; A/C=239-350.
DR PDB; 5KIZ; NMR; -; A=239-349.
DR PDB; 5TBM; X-ray; 1.85 A; A=239-348.
DR PDB; 5UFP; X-ray; 1.90 A; A=239-348.
DR PDB; 6BVB; X-ray; 2.00 A; H=523-540.
DR PDB; 6CZW; X-ray; 1.60 A; A=239-350.
DR PDB; 6D09; X-ray; 1.85 A; A=239-350.
DR PDB; 6D0B; X-ray; 1.60 A; A=239-350.
DR PDB; 6D0C; X-ray; 1.50 A; A=239-350.
DR PDB; 6I7Q; X-ray; 1.80 A; H=523-541.
DR PDB; 6I7R; X-ray; 1.95 A; H=523-542.
DR PDB; 6X21; X-ray; 1.54 A; A=239-348.
DR PDB; 6X28; X-ray; 1.92 A; A=239-348.
DR PDB; 6X2H; X-ray; 2.00 A; A=239-348.
DR PDB; 6X37; X-ray; 1.94 A; A=239-348.
DR PDB; 6X3D; X-ray; 2.00 A; A=239-348.
DR PDBsum; 1P97; -.
DR PDBsum; 2A24; -.
DR PDBsum; 3F1N; -.
DR PDBsum; 3F1O; -.
DR PDBsum; 3F1P; -.
DR PDBsum; 3H7W; -.
DR PDBsum; 3H82; -.
DR PDBsum; 4GHI; -.
DR PDBsum; 4GS9; -.
DR PDBsum; 4PKY; -.
DR PDBsum; 4XT2; -.
DR PDBsum; 5KIZ; -.
DR PDBsum; 5TBM; -.
DR PDBsum; 5UFP; -.
DR PDBsum; 6BVB; -.
DR PDBsum; 6CZW; -.
DR PDBsum; 6D09; -.
DR PDBsum; 6D0B; -.
DR PDBsum; 6D0C; -.
DR PDBsum; 6I7Q; -.
DR PDBsum; 6I7R; -.
DR PDBsum; 6X21; -.
DR PDBsum; 6X28; -.
DR PDBsum; 6X2H; -.
DR PDBsum; 6X37; -.
DR PDBsum; 6X3D; -.
DR AlphaFoldDB; Q99814; -.
DR SMR; Q99814; -.
DR BioGRID; 108348; 158.
DR CORUM; Q99814; -.
DR DIP; DIP-32857N; -.
DR ELM; Q99814; -.
DR IntAct; Q99814; 56.
DR MINT; Q99814; -.
DR STRING; 9606.ENSP00000263734; -.
DR BindingDB; Q99814; -.
DR ChEMBL; CHEMBL1744522; -.
DR DrugBank; DB15463; Belzutifan.
DR GuidetoPHARMACOLOGY; 3148; -.
DR iPTMnet; Q99814; -.
DR PhosphoSitePlus; Q99814; -.
DR BioMuta; EPAS1; -.
DR DMDM; 32470617; -.
DR jPOST; Q99814; -.
DR MassIVE; Q99814; -.
DR MaxQB; Q99814; -.
DR PaxDb; Q99814; -.
DR PeptideAtlas; Q99814; -.
DR PRIDE; Q99814; -.
DR ProteomicsDB; 78489; -.
DR Antibodypedia; 29965; 744 antibodies from 39 providers.
DR DNASU; 2034; -.
DR Ensembl; ENST00000263734.5; ENSP00000263734.3; ENSG00000116016.14.
DR GeneID; 2034; -.
DR KEGG; hsa:2034; -.
DR MANE-Select; ENST00000263734.5; ENSP00000263734.3; NM_001430.5; NP_001421.2.
DR UCSC; uc002ruv.3; human.
DR CTD; 2034; -.
DR DisGeNET; 2034; -.
DR GeneCards; EPAS1; -.
DR HGNC; HGNC:3374; EPAS1.
DR HPA; ENSG00000116016; Tissue enhanced (lung, placenta).
DR MalaCards; EPAS1; -.
DR MIM; 603349; gene.
DR MIM; 611783; phenotype.
DR neXtProt; NX_Q99814; -.
DR OpenTargets; ENSG00000116016; -.
DR Orphanet; 247511; Autosomal dominant secondary polycythemia.
DR Orphanet; 324299; Multiple paragangliomas associated with polycythemia.
DR Orphanet; 276621; Sporadic pheochromocytoma/secreting paraganglioma.
DR PharmGKB; PA27809; -.
DR VEuPathDB; HostDB:ENSG00000116016; -.
DR eggNOG; KOG3558; Eukaryota.
DR GeneTree; ENSGT00940000155930; -.
DR HOGENOM; CLU_010044_3_1_1; -.
DR InParanoid; Q99814; -.
DR OMA; QPTPQHC; -.
DR OrthoDB; 547545at2759; -.
DR PhylomeDB; Q99814; -.
DR TreeFam; TF317772; -.
DR PathwayCommons; Q99814; -.
DR Reactome; R-HSA-1234158; Regulation of gene expression by Hypoxia-inducible Factor.
DR Reactome; R-HSA-1234174; Cellular response to hypoxia.
DR Reactome; R-HSA-1234176; Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha.
DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells.
DR Reactome; R-HSA-8849473; PTK6 Expression.
DR Reactome; R-HSA-8951664; Neddylation.
DR Reactome; R-HSA-9664873; Pexophagy.
DR SignaLink; Q99814; -.
DR SIGNOR; Q99814; -.
DR BioGRID-ORCS; 2034; 19 hits in 1078 CRISPR screens.
DR ChiTaRS; EPAS1; human.
DR EvolutionaryTrace; Q99814; -.
DR GeneWiki; EPAS1; -.
DR GenomeRNAi; 2034; -.
DR Pharos; Q99814; Tchem.
DR PRO; PR:Q99814; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q99814; protein.
DR Bgee; ENSG00000116016; Expressed in right lung and 201 other tissues.
DR ExpressionAtlas; Q99814; baseline and differential.
DR Genevisible; Q99814; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IGI:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:UniProtKB.
DR GO; GO:0001892; P:embryonic placenta development; IEA:Ensembl.
DR GO; GO:0002070; P:epithelial cell maturation; IEA:Ensembl.
DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl.
DR GO; GO:0055072; P:iron ion homeostasis; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl.
DR GO; GO:0042789; P:mRNA transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0048625; P:myoblast fate commitment; ISS:BHF-UCL.
DR GO; GO:0042415; P:norepinephrine metabolic process; IEA:Ensembl.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl.
DR GO; GO:2000434; P:regulation of protein neddylation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0043619; P:regulation of transcription from RNA polymerase II promoter in response to oxidative stress; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IDA:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0043129; P:surfactant homeostasis; IEA:Ensembl.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR CDD; cd00130; PAS; 2.
DR Gene3D; 4.10.280.10; -; 1.
DR IDEAL; IID00629; -.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR014887; HIF-1_TAD_C.
DR InterPro; IPR021537; HIF_alpha_subunit.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR InterPro; IPR001067; Nuc_translocat.
DR InterPro; IPR001610; PAC.
DR InterPro; IPR000014; PAS.
DR InterPro; IPR035965; PAS-like_dom_sf.
DR InterPro; IPR013767; PAS_fold.
DR InterPro; IPR013655; PAS_fold_3.
DR Pfam; PF11413; HIF-1; 1.
DR Pfam; PF08778; HIF-1a_CTAD; 1.
DR Pfam; PF00989; PAS; 1.
DR Pfam; PF08447; PAS_3; 1.
DR PRINTS; PR00785; NCTRNSLOCATR.
DR SMART; SM00353; HLH; 1.
DR SMART; SM00086; PAC; 1.
DR SMART; SM00091; PAS; 2.
DR SUPFAM; SSF47459; SSF47459; 1.
DR SUPFAM; SSF55785; SSF55785; 2.
DR TIGRFAMs; TIGR00229; sensory_box; 2.
DR PROSITE; PS50888; BHLH; 1.
DR PROSITE; PS50112; PAS; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Angiogenesis; Congenital erythrocytosis;
KW Developmental protein; Differentiation; Disease variant; DNA-binding;
KW Host-virus interaction; Hydroxylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..870
FT /note="Endothelial PAS domain-containing protein 1"
FT /id="PRO_0000127419"
FT DOMAIN 14..67
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT DOMAIN 84..154
FT /note="PAS 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 230..300
FT /note="PAS 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00140"
FT DOMAIN 304..347
FT /note="PAC"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..53
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:P97481"
FT REGION 171..192
FT /note="Required for heterodimer formation with ARNT"
FT /evidence="ECO:0000250|UniProtKB:P97481"
FT REGION 460..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 496..542
FT /note="NTAD"
FT REGION 830..870
FT /note="CTAD"
FT COMPBIAS 462..486
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 405
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 531
FT /note="4-hydroxyproline"
FT /evidence="ECO:0000250"
FT MOD_RES 840
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P97481"
FT MOD_RES 847
FT /note="(3S)-3-hydroxyasparagine"
FT /evidence="ECO:0000250"
FT VARIANT 534
FT /note="P -> L (in ECYT4; impairs interaction with EGLN1 and
FT VHL)"
FT /evidence="ECO:0000269|PubMed:19208626"
FT /id="VAR_067358"
FT VARIANT 535
FT /note="M -> T (in ECYT4)"
FT /evidence="ECO:0000269|PubMed:22367913"
FT /id="VAR_067359"
FT VARIANT 535
FT /note="M -> V (in ECYT4; impairs interaction with EGLN1;
FT dbSNP:rs137853037)"
FT /evidence="ECO:0000269|PubMed:18378852,
FT ECO:0000269|PubMed:19208626"
FT /id="VAR_067360"
FT VARIANT 537
FT /note="G -> R (in ECYT4; impairs interaction with EGLN1 and
FT VHL; dbSNP:rs137853036)"
FT /evidence="ECO:0000269|PubMed:18378852,
FT ECO:0000269|PubMed:19208626"
FT /id="VAR_067361"
FT VARIANT 537
FT /note="G -> W (in ECYT4; gain of function; affects
FT hydroxylation; dbSNP:rs137853036)"
FT /evidence="ECO:0000269|PubMed:18184961"
FT /id="VAR_042443"
FT VARIANT 540
FT /note="F -> L (in ECYT4; affects the interaction with EGLN1
FT and VHL)"
FT /evidence="ECO:0000269|PubMed:22367913"
FT /id="VAR_067362"
FT VARIANT 766
FT /note="T -> P (in dbSNP:rs59901247)"
FT /id="VAR_061261"
FT VARIANT 785
FT /note="P -> T (in dbSNP:rs61518065)"
FT /id="VAR_061262"
FT MUTAGEN 844
FT /note="C->S: Abolishes hypoxia-inducible transcriptional
FT activation of ctaD."
FT /evidence="ECO:0000269|PubMed:10202154"
FT CONFLICT 60
FT /note="A -> E (in Ref. 1; AAB41495)"
FT /evidence="ECO:0000305"
FT CONFLICT 539
FT /note="D -> G (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 601
FT /note="H -> R (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 693
FT /note="D -> N (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 716
FT /note="E -> K (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 722
FT /note="L -> P (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="F -> L (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 769
FT /note="P -> S (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 844
FT /note="C -> R (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT CONFLICT 847
FT /note="N -> K (in Ref. 2; AAC51212)"
FT /evidence="ECO:0000305"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:3F1P"
FT STRAND 243..248
FT /evidence="ECO:0007829|PDB:3F1P"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:2A24"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:3F1P"
FT HELIX 260..265
FT /evidence="ECO:0007829|PDB:3F1P"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:3F1P"
FT HELIX 277..280
FT /evidence="ECO:0007829|PDB:3F1P"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:3F1P"
FT HELIX 286..299
FT /evidence="ECO:0007829|PDB:3F1P"
FT STRAND 300..303
FT /evidence="ECO:0007829|PDB:3F1P"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:3F1P"
FT STRAND 314..327
FT /evidence="ECO:0007829|PDB:3F1P"
FT TURN 329..331
FT /evidence="ECO:0007829|PDB:3F1P"
FT STRAND 334..343
FT /evidence="ECO:0007829|PDB:3F1P"
SQ SEQUENCE 870 AA; 96459 MW; 4838989598234FC1 CRC64;
MTADKEKKRS SSERRKEKSR DAARCRRSKE TEVFYELAHE LPLPHSVSSH LDKASIMRLA
ISFLRTHKLL SSVCSENESE AEADQQMDNL YLKALEGFIA VVTQDGDMIF LSENISKFMG
LTQVELTGHS IFDFTHPCDH EEIRENLSLK NGSGFGKKSK DMSTERDFFM RMKCTVTNRG
RTVNLKSATW KVLHCTGQVK VYNNCPPHNS LCGYKEPLLS CLIIMCEPIQ HPSHMDIPLD
SKTFLSRHSM DMKFTYCDDR ITELIGYHPE ELLGRSAYEF YHALDSENMT KSHQNLCTKG
QVVSGQYRML AKHGGYVWLE TQGTVIYNPR NLQPQCIMCV NYVLSEIEKN DVVFSMDQTE
SLFKPHLMAM NSIFDSSGKG AVSEKSNFLF TKLKEEPEEL AQLAPTPGDA IISLDFGNQN
FEESSAYGKA ILPPSQPWAT ELRSHSTQSE AGSLPAFTVP QAAAPGSTTP SATSSSSSCS
TPNSPEDYYT SLDNDLKIEV IEKLFAMDTE AKDQCSTQTD FNELDLETLA PYIPMDGEDF
QLSPICPEER LLAENPQSTP QHCFSAMTNI FQPLAPVAPH SPFLLDKFQQ QLESKKTEPE
HRPMSSIFFD AGSKASLPPC CGQASTPLSS MGGRSNTQWP PDPPLHFGPT KWAVGDQRTE
FLGAAPLGPP VSPPHVSTFK TRSAKGFGAR GPDVLSPAMV ALSNKLKLKR QLEYEEQAFQ
DLSGGDPPGG STSHLMWKRM KNLRGGSCPL MPDKPLSANV PNDKFTQNPM RGLGHPLRHL
PLPQPPSAIS PGENSKSRFP PQCYATQYQD YSLSSAHKVS GMASRLLGPS FESYLLPELT
RYDCEVNVPV LGSSTLLQGG DLLRALDQAT
