GenomeNet

Database: UniProt
Entry: Q99814
LinkDB: Q99814
Original site: Q99814 
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   07-OCT-2020, entry version 214.
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 APEX, 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:0000244|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   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   [9]
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 APEX 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   -!- INTERACTION:
CC       Q99814; P27540: ARNT; NbExp=7; 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; P84022: SMAD3; NbExp=2; IntAct=EBI-447470, EBI-347161;
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 mutations affecting the gene represented in this
CC       entry.
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   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   SMR; Q99814; -.
DR   BioGRID; 108348; 129.
DR   CORUM; Q99814; -.
DR   DIP; DIP-32857N; -.
DR   ELM; Q99814; -.
DR   IntAct; Q99814; 38.
DR   MINT; Q99814; -.
DR   STRING; 9606.ENSP00000263734; -.
DR   BindingDB; Q99814; -.
DR   ChEMBL; CHEMBL1744522; -.
DR   DrugBank; DB15463; PT2977.
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; 698 antibodies.
DR   Ensembl; ENST00000263734; ENSP00000263734; ENSG00000116016.
DR   GeneID; 2034; -.
DR   KEGG; hsa:2034; -.
DR   UCSC; uc002ruv.3; human.
DR   CTD; 2034; -.
DR   DisGeNET; 2034; -.
DR   EuPathDB; HostDB:ENSG00000116016.13; -.
DR   GeneCards; EPAS1; -.
DR   HGNC; HGNC:3374; EPAS1.
DR   HPA; ENSG00000116016; Tissue enhanced (lung).
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   eggNOG; KOG3558; Eukaryota.
DR   GeneTree; ENSGT00940000155930; -.
DR   HOGENOM; CLU_010044_3_1_1; -.
DR   InParanoid; Q99814; -.
DR   KO; K09095; -.
DR   OMA; TKWPVGD; -.
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; 11 hits in 877 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 visceral pleura and 243 other tissues.
DR   ExpressionAtlas; Q99814; baseline and differential.
DR   Genevisible; Q99814; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0000790; C:nuclear chromatin; ISA:NTNU_SB.
DR   GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
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:0035035; F:histone acetyltransferase binding; IPI:UniProtKB.
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:0008134; F:transcription factor binding; IPI:BHF-UCL.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR   GO; GO:0048469; P:cell maturation; 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: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: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:0043687; P:post-translational protein modification; TAS:Reactome.
DR   GO; GO:0016567; P:protein ubiquitination; TAS:Reactome.
DR   GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0061418; P:regulation of transcription from RNA polymerase II promoter in response to hypoxia; TAS:Reactome.
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; cd00083; HLH; 1.
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 mutation; DNA-binding;
KW   Hydroxylation; Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW   Repeat; Transcription; Transcription regulation; 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          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          496..542
FT                   /note="NTAD"
FT   REGION          830..870
FT                   /note="CTAD"
FT   COMPBIAS        474..480
FT                   /note="Poly-Ser"
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:0000244|PDB:3F1P"
FT   STRAND          243..248
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   TURN            250..252
FT                   /evidence="ECO:0000244|PDB:2A24"
FT   STRAND          253..257
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   HELIX           260..265
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   HELIX           269..272
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   HELIX           277..280
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   HELIX           283..285
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   HELIX           286..299
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   STRAND          300..303
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   STRAND          307..310
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   STRAND          314..327
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   TURN            329..331
FT                   /evidence="ECO:0000244|PDB:3F1P"
FT   STRAND          334..343
FT                   /evidence="ECO:0000244|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
//
DBGET integrated database retrieval system