EDN2_HUMAN
ID EDN2_HUMAN Reviewed; 178 AA.
AC P20800; Q5T1R3;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Endothelin-2;
DE Short=ET-2;
DE AltName: Full=Preproendothelin-2;
DE Short=PPET2;
DE Flags: Precursor;
GN Name=EDN2;
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=1701397; DOI=10.1016/0014-5793(90)81348-r;
RA Ohkubo S., Ogi K., Hosoya M., Matsumoto H., Suzuki N., Kimura C., Onda H.,
RA Fujino M.;
RT "Specific expression of human endothelin-2 (ET-2) gene in a renal
RT adenocarcinoma cell line. Molecular cloning of cDNA encoding the precursor
RT of ET-2 and its characterization.";
RL FEBS Lett. 274:136-140(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1840558; DOI=10.1016/0888-7543(91)90505-9;
RA Bloch K.D., Hong C.C., Eddy R.L. Jr., Shows T.B., Quertermous T.;
RT "cDNA cloning and chromosomal assignment of the endothelin 2 gene:
RT vasoactive intestinal contractor peptide is rat endothelin 2.";
RL Genomics 10:236-242(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1725387; DOI=10.1097/00005344-199100177-00011;
RA Onda H., Ohkubo S., Kosaka T., Yasuhara T., Ogi K., Hosoya M.,
RA Matsumoto H., Suzuki N., Kitada C., Ishibashi Y., Kimura C., Kubo K.,
RA Fujino M.;
RT "Expression of endothelin-2 (ET-2) gene in a human renal adenocarcinoma
RT cell line: purification and cDNA cloning of ET-2.";
RL J. Cardiovasc. Pharmacol. 17:S39-S43(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-168.
RG NIEHS SNPs program;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
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 GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Kidney, and Stomach;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 22-73.
RX PubMed=2649896; DOI=10.1073/pnas.86.8.2863;
RA Inoue A., Yanagisawa M., Kimura S., Kasuya Y., Miyauchi T., Goto K.,
RA Masaki T.;
RT "The human endothelin family: three structurally and pharmacologically
RT distinct isopeptides predicted by three separate genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 86:2863-2867(1989).
RN [9]
RP PARTIAL PROTEIN SEQUENCE, CLEAVAGE BY KELL, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=10438732;
RA Lee S., Lin M., Mele A., Cao Y., Farmar J., Russo D., Redman C.;
RT "Proteolytic processing of big endothelin-3 by the kell blood group
RT protein.";
RL Blood 94:1440-1450(1999).
RN [10]
RP TISSUE SPECIFICITY.
RX PubMed=9284755; DOI=10.1210/jcem.82.9.4209;
RA Bourgeois C., Robert B., Rebourcet R., Mondon F., Mignot T.-M.,
RA Duc-Goiran P., Ferre F.;
RT "Endothelin-1 and ETA receptor expression in vascular smooth muscle cells
RT from human placenta: a new ETA receptor messenger ribonucleic acid is
RT generated by alternative splicing of exon 3.";
RL J. Clin. Endocrinol. Metab. 82:3116-3123(1997).
CC -!- FUNCTION: Endothelins are endothelium-derived vasoconstrictor peptides.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in lung, but not in placental stem villi
CC vessels or cultured placental villi smooth muscle cells.
CC {ECO:0000269|PubMed:9284755}.
CC -!- SIMILARITY: Belongs to the endothelin/sarafotoxin family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/edn2/";
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DR EMBL; X55177; CAA38962.1; -; mRNA.
DR EMBL; M65199; AAA52404.1; -; mRNA.
DR EMBL; AY518541; AAR89914.1; -; Genomic_DNA.
DR EMBL; AL445933; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX07175.1; -; Genomic_DNA.
DR EMBL; BC034393; AAH34393.1; -; mRNA.
DR EMBL; M25550; AAA52340.1; -; Genomic_DNA.
DR CCDS; CCDS462.1; -.
DR PIR; A39070; A39070.
DR RefSeq; NP_001289198.1; NM_001302269.1.
DR RefSeq; NP_001947.1; NM_001956.4.
DR AlphaFoldDB; P20800; -.
DR STRING; 9606.ENSP00000361668; -.
DR iPTMnet; P20800; -.
DR PhosphoSitePlus; P20800; -.
DR BioMuta; EDN2; -.
DR DMDM; 119615; -.
DR MassIVE; P20800; -.
DR PaxDb; P20800; -.
DR PeptideAtlas; P20800; -.
DR PRIDE; P20800; -.
DR Antibodypedia; 32186; 187 antibodies from 26 providers.
DR DNASU; 1907; -.
DR Ensembl; ENST00000372587.5; ENSP00000361668.4; ENSG00000127129.10.
DR GeneID; 1907; -.
DR KEGG; hsa:1907; -.
DR MANE-Select; ENST00000372587.5; ENSP00000361668.4; NM_001956.5; NP_001947.1.
DR UCSC; uc001cgx.4; human.
DR CTD; 1907; -.
DR DisGeNET; 1907; -.
DR GeneCards; EDN2; -.
DR HGNC; HGNC:3177; EDN2.
DR HPA; ENSG00000127129; Tissue enhanced (esophagus, intestine, vagina).
DR MIM; 131241; gene.
DR neXtProt; NX_P20800; -.
DR OpenTargets; ENSG00000127129; -.
DR PharmGKB; PA27615; -.
DR VEuPathDB; HostDB:ENSG00000127129; -.
DR eggNOG; ENOG502S5KM; Eukaryota.
DR GeneTree; ENSGT00950000183053; -.
DR HOGENOM; CLU_090013_2_1_1; -.
DR InParanoid; P20800; -.
DR OMA; PTAWCSV; -.
DR OrthoDB; 1264335at2759; -.
DR PhylomeDB; P20800; -.
DR TreeFam; TF333184; -.
DR PathwayCommons; P20800; -.
DR Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR Reactome; R-HSA-416476; G alpha (q) signalling events.
DR SignaLink; P20800; -.
DR BioGRID-ORCS; 1907; 11 hits in 1070 CRISPR screens.
DR GeneWiki; Endothelin_2; -.
DR GenomeRNAi; 1907; -.
DR Pharos; P20800; Tbio.
DR PRO; PR:P20800; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P20800; protein.
DR Bgee; ENSG00000127129; Expressed in lower esophagus mucosa and 112 other tissues.
DR Genevisible; P20800; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR GO; GO:0031708; F:endothelin B receptor binding; IPI:BHF-UCL.
DR GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0014824; P:artery smooth muscle contraction; IDA:BHF-UCL.
DR GO; GO:0048675; P:axon extension; IEA:Ensembl.
DR GO; GO:0019722; P:calcium-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IC:BHF-UCL.
DR GO; GO:0009932; P:cell tip growth; IEA:Ensembl.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IBA:GO_Central.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043542; P:endothelial cell migration; IEA:Ensembl.
DR GO; GO:0097009; P:energy homeostasis; IEA:Ensembl.
DR GO; GO:0003058; P:hormonal regulation of the force of heart contraction; TAS:BHF-UCL.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; IDA:BHF-UCL.
DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl.
DR GO; GO:0042116; P:macrophage activation; IDA:BHF-UCL.
DR GO; GO:0048246; P:macrophage chemotaxis; IDA:BHF-UCL.
DR GO; GO:0030593; P:neutrophil chemotaxis; IDA:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:BHF-UCL.
DR GO; GO:0010460; P:positive regulation of heart rate; IDA:BHF-UCL.
DR GO; GO:0002690; P:positive regulation of leukocyte chemotaxis; IDA:BHF-UCL.
DR GO; GO:0060585; P:positive regulation of prostaglandin-endoperoxide synthase activity; IMP:BHF-UCL.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IEA:Ensembl.
DR GO; GO:0003099; P:positive regulation of the force of heart contraction by chemical signal; TAS:BHF-UCL.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IDA:BHF-UCL.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0001659; P:temperature homeostasis; IEA:Ensembl.
DR GO; GO:0042310; P:vasoconstriction; IDA:BHF-UCL.
DR GO; GO:0014826; P:vein smooth muscle contraction; IDA:BHF-UCL.
DR InterPro; IPR020475; Endothelin.
DR InterPro; IPR019764; Endothelin_toxin_CS.
DR InterPro; IPR001928; Endothln-like_toxin.
DR InterPro; IPR015658; ET-2.
DR PANTHER; PTHR13874; PTHR13874; 1.
DR PANTHER; PTHR13874:SF9; PTHR13874:SF9; 1.
DR Pfam; PF00322; Endothelin; 1.
DR PRINTS; PR00365; ENDOTHELIN.
DR SMART; SM00272; END; 2.
DR PROSITE; PS00270; ENDOTHELIN; 2.
PE 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Direct protein sequencing;
KW Disulfide bond; Reference proteome; Secreted; Signal; Vasoactive;
KW Vasoconstrictor.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT PROPEP 25..46
FT /id="PRO_0000008093"
FT PEPTIDE 49..69
FT /note="Endothelin-2"
FT /id="PRO_0000008094"
FT PROPEP 70..178
FT /id="PRO_0000008095"
FT REGION 96..111
FT /note="Endothelin-like"
FT REGION 159..178
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 69..70
FT /note="Cleavage; by KEL"
FT DISULFID 49..63
FT /evidence="ECO:0000250"
FT DISULFID 51..59
FT /evidence="ECO:0000250"
FT VARIANT 131
FT /note="F -> L (in dbSNP:rs5798)"
FT /id="VAR_033914"
FT VARIANT 168
FT /note="P -> L (in dbSNP:rs11572371)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_018817"
SQ SEQUENCE 178 AA; 19960 MW; 7711B2B6F075CFB4 CRC64;
MVSVPTTWCS VALALLVALH EGKGQAAATL EQPASSSHAQ GTHLRLRRCS CSSWLDKECV
YFCHLDIIWV NTPEQTAPYG LGNPPRRRRR SLPRRCQCSS ARDPACATFC LRRPWTEAGA
VPSRKSPADV FQTGKTGATT GELLQRLRDI STVKSLFAKR QQEAMREPRS THSRWRKR
