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   24-JAN-2024, entry version 194.
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   GlyGen; P20800; 4 sites, 1 O-linked glycan (4 sites).
DR   iPTMnet; P20800; -.
DR   PhosphoSitePlus; P20800; -.
DR   BioMuta; EDN2; -.
DR   DMDM; 119615; -.
DR   MassIVE; P20800; -.
DR   PaxDb; 9606-ENSP00000361668; -.
DR   PeptideAtlas; P20800; -.
DR   Antibodypedia; 32186; 228 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   AGR; HGNC:3177; -.
DR   CTD; 1907; -.
DR   DisGeNET; 1907; -.
DR   GeneCards; EDN2; -.
DR   HGNC; HGNC:3177; EDN2.
DR   HPA; ENSG00000127129; Tissue enhanced (cervix, esophagus, 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; 4317037at2759; -.
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; 12 hits in 1147 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 cell types or tissues.
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:0007166; P:cell surface receptor signaling pathway; IC:BHF-UCL.
DR   GO; GO:0009932; P:cell tip growth; IEA:Ensembl.
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:0006874; P:intracellular calcium ion homeostasis; IBA:GO_Central.
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:0050850; P:positive regulation of calcium-mediated signaling; IDA:BHF-UCL.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; 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   PANTHER; PTHR13874; ENDOTHELIN; 1.
DR   PANTHER; PTHR13874:SF9; ENDOTHELIN-2; 1.
DR   Pfam; PF00322; Endothelin; 1.
DR   PRINTS; PR00365; ENDOTHELIN.
DR   SMART; SM00272; END; 2.
DR   PROSITE; PS00270; ENDOTHELIN; 2.
DR   Genevisible; P20800; HS.
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
//