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   11-NOV-2015, entry version 147.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; 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.,
RA   Onda H., 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
RT   precursor 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;
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
RT   adenocarcinoma 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.,
RA   Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA   Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA   McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA   Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA   Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA   Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA   Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA   Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA   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.,
RA   Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA   Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA   Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA   Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA   Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA   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.,
RA   Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA   Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA   Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA   Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   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.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   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
RT   project: 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/jc.82.9.3116;
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
RT   cells from human placenta: a new ETA receptor messenger ribonucleic
RT   acid is generated by alternative splicing of exon 3.";
RL   J. Clin. Endocrinol. Metab. 82:3116-3123(1997).
CC   -!- FUNCTION: Endothelins are endothelium-derived vasoconstrictor
CC       peptides.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed in lung, but not in placental stem
CC       villi 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; CAI14535.1; -; 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   UniGene; Hs.1407; -.
DR   ProteinModelPortal; P20800; -.
DR   STRING; 9606.ENSP00000361668; -.
DR   BioMuta; EDN2; -.
DR   DMDM; 119615; -.
DR   PaxDb; P20800; -.
DR   PRIDE; P20800; -.
DR   DNASU; 1907; -.
DR   Ensembl; ENST00000372587; ENSP00000361668; ENSG00000127129.
DR   GeneID; 1907; -.
DR   KEGG; hsa:1907; -.
DR   UCSC; uc001cgx.3; human.
DR   CTD; 1907; -.
DR   GeneCards; EDN2; -.
DR   HGNC; HGNC:3177; EDN2.
DR   HPA; HPA028459; -.
DR   MIM; 131241; gene.
DR   neXtProt; NX_P20800; -.
DR   PharmGKB; PA27615; -.
DR   eggNOG; ENOG410J1XQ; Eukaryota.
DR   eggNOG; ENOG410YUMW; LUCA.
DR   GeneTree; ENSGT00530000063310; -.
DR   HOGENOM; HOG000231110; -.
DR   HOVERGEN; HBG051441; -.
DR   InParanoid; P20800; -.
DR   KO; K16367; -.
DR   OMA; PTAWCSV; -.
DR   OrthoDB; EOG7F7WBX; -.
DR   PhylomeDB; P20800; -.
DR   TreeFam; TF333184; -.
DR   Reactome; R-HSA-375276; Peptide ligand-binding receptors.
DR   Reactome; R-HSA-416476; G alpha (q) signalling events.
DR   GeneWiki; Endothelin_2; -.
DR   GenomeRNAi; 1907; -.
DR   NextBio; 7761; -.
DR   PMAP-CutDB; P20800; -.
DR   PRO; PR:P20800; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; P20800; -.
DR   CleanEx; HS_EDN2; -.
DR   Genevisible; P20800; HS.
DR   GO; GO:0005829; C:cytosol; IDA:GOC.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0005622; C:intracellular; IDA:GOC.
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:0014824; P:artery smooth muscle contraction; IDA:BHF-UCL.
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:0019221; P:cytokine-mediated signaling pathway; IDA:BHF-UCL.
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 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; Bibrotoxin/Sarafotoxin-D.
DR   InterPro; IPR019764; Endothelin_toxin_CS.
DR   InterPro; IPR001928; Endothln-like_toxin.
DR   InterPro; IPR015658; ET-2.
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; Complete proteome;
KW   Direct protein sequencing; Disulfide bond; Polymorphism;
KW   Reference proteome; Secreted; Signal; Vasoactive; Vasoconstrictor.
FT   SIGNAL        1     24       {ECO:0000255}.
FT   PROPEP       25     46
FT                                /FTId=PRO_0000008093.
FT   PEPTIDE      49     69       Endothelin-2.
FT                                /FTId=PRO_0000008094.
FT   PROPEP       70    178
FT                                /FTId=PRO_0000008095.
FT   REGION       96    111       Endothelin-like.
FT   SITE         69     70       Cleavage; by KEL.
FT   DISULFID     49     63       {ECO:0000250}.
FT   DISULFID     51     59       {ECO:0000250}.
FT   VARIANT     131    131       F -> L (in dbSNP:rs5798).
FT                                /FTId=VAR_033914.
FT   VARIANT     168    168       P -> L (in dbSNP:rs11572371).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=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
//