EDN1_RAT
ID EDN1_RAT Reviewed; 202 AA.
AC P22388;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Endothelin-1;
DE Short=ET-1;
DE AltName: Full=Preproendothelin-1;
DE Short=PPET1;
DE Contains:
DE RecName: Full=Big endothelin-1;
DE Flags: Precursor;
GN Name=Edn1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1840483; DOI=10.1016/s0006-291x(05)81197-0;
RA Sakurai T., Yanagisawa M., Inoue A., Ryan U.S., Kimura S., Mitsui Y.,
RA Goto K., Masaki T.;
RT "cDNA cloning, sequence analysis and tissue distribution of rat
RT preproendothelin-1 mRNA.";
RL Biochem. Biophys. Res. Commun. 175:44-47(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 51-77.
RC STRAIN=Wistar; TISSUE=Kidney;
RX PubMed=2039460; DOI=10.1042/bj2750817;
RA Nunez D.J.R., Taylor E.A., Oh V.M.S., Schofield J.P., Brown M.J.;
RT "Endothelin-1 mRNA expression in the rat kidney.";
RL Biochem. J. 275:817-819(1991).
RN [3]
RP FUNCTION.
RC STRAIN=Sprague-Dawley;
RX PubMed=9508787; DOI=10.1007/bf03401733;
RA Ruiz-Opazo N., Hirayama K., Akimoto K., Herrera V.L.;
RT "Molecular characterization of a dual endothelin-1/Angiotensin II
RT receptor.";
RL Mol. Med. 4:96-108(1998).
RN [4]
RP CLEAVAGE OF SIGNAL PEPTIDE AFTER GLY-25, CLEAVAGE OF PROPEPTIDE AFTER
RP SER-50, CLEAVAGE OF BIG ENDOTHELIN-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=26479776; DOI=10.1021/acs.jproteome.5b00820;
RA Tsuchiya T., Osaki T., Minamino N., Sasaki K.;
RT "Peptidomics for studying limited proteolysis.";
RL J. Proteome Res. 14:4921-4931(2015).
CC -!- FUNCTION: Endothelins are endothelium-derived vasoconstrictor peptides
CC (By similarity). Probable ligand for G-protein coupled receptors EDNRA
CC and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and
CC RHOA cascade in glomerular mesangial cells (By similarity). Also binds
CC the DEAR/FBXW7-AS1 receptor (PubMed:9508787).
CC {ECO:0000250|UniProtKB:P05305, ECO:0000250|UniProtKB:P09558,
CC ECO:0000269|PubMed:9508787}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the endothelin/sarafotoxin family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M64711; AAA41129.1; -; mRNA.
DR PIR; JN0125; JN0125.
DR RefSeq; NP_036680.1; NM_012548.2.
DR RefSeq; XP_017455942.1; XM_017600453.1.
DR PDB; 3CMH; NMR; -; A=60-73.
DR PDB; 6CMH; NMR; -; A=53-73.
DR PDBsum; 3CMH; -.
DR PDBsum; 6CMH; -.
DR AlphaFoldDB; P22388; -.
DR SMR; P22388; -.
DR STRING; 10116.ENSRNOP00000019361; -.
DR PaxDb; P22388; -.
DR PRIDE; P22388; -.
DR Ensembl; ENSRNOT00000019361; ENSRNOP00000019361; ENSRNOG00000014361.
DR GeneID; 24323; -.
DR KEGG; rno:24323; -.
DR UCSC; RGD:2532; rat.
DR CTD; 1906; -.
DR RGD; 2532; Edn1.
DR eggNOG; ENOG502S1NV; Eukaryota.
DR GeneTree; ENSGT00950000183053; -.
DR HOGENOM; CLU_090013_1_0_1; -.
DR InParanoid; P22388; -.
DR OMA; RCQCANQ; -.
DR OrthoDB; 1264335at2759; -.
DR PhylomeDB; P22388; -.
DR TreeFam; TF333184; -.
DR Reactome; R-RNO-375276; Peptide ligand-binding receptors.
DR Reactome; R-RNO-416476; G alpha (q) signalling events.
DR EvolutionaryTrace; P22388; -.
DR PRO; PR:P22388; -.
DR Proteomes; UP000002494; Chromosome 17.
DR Bgee; ENSRNOG00000014361; Expressed in lung and 18 other tissues.
DR Genevisible; P22388; RN.
DR GO; GO:0045178; C:basal part of cell; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0048237; C:rough endoplasmic reticulum lumen; IDA:RGD.
DR GO; GO:0033093; C:Weibel-Palade body; IDA:RGD.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0031707; F:endothelin A receptor binding; IMP:RGD.
DR GO; GO:0031708; F:endothelin B receptor binding; IMP:RGD.
DR GO; GO:0005179; F:hormone activity; ISO:RGD.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0014824; P:artery smooth muscle contraction; IDA:RGD.
DR GO; GO:0048675; P:axon extension; ISO:RGD.
DR GO; GO:0060385; P:axonogenesis involved in innervation; ISO:RGD.
DR GO; GO:0048514; P:blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0007589; P:body fluid secretion; ISO:RGD.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0070588; P:calcium ion transmembrane transport; ISO:RGD.
DR GO; GO:0019722; P:calcium-mediated signaling; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD.
DR GO; GO:0007267; P:cell-cell signaling; ISO:RGD.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; ISO:RGD.
DR GO; GO:0071277; P:cellular response to calcium ion; IEP:RGD.
DR GO; GO:0071398; P:cellular response to fatty acid; IEP:RGD.
DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; ISO:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IEP:RGD.
DR GO; GO:0044751; P:cellular response to human chorionic gonadotropin stimulus; ISO:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IEP:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; ISO:RGD.
DR GO; GO:0071389; P:cellular response to mineralocorticoid stimulus; IEP:RGD.
DR GO; GO:0071310; P:cellular response to organic substance; ISO:RGD.
DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; ISO:RGD.
DR GO; GO:0035050; P:embryonic heart tube development; ISO:RGD.
DR GO; GO:0086100; P:endothelin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0086101; P:endothelin receptor signaling pathway involved in heart process; ISO:RGD.
DR GO; GO:0042045; P:epithelial fluid transport; IDA:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001821; P:histamine secretion; IDA:RGD.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0048016; P:inositol phosphate-mediated signaling; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0060137; P:maternal process involved in parturition; IEP:RGD.
DR GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; ISO:RGD.
DR GO; GO:0051899; P:membrane depolarization; IMP:RGD.
DR GO; GO:0042474; P:middle ear morphogenesis; ISO:RGD.
DR GO; GO:0007005; P:mitochondrion organization; ISO:RGD.
DR GO; GO:0010259; P:multicellular organism aging; IEP:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0046888; P:negative regulation of hormone secretion; IDA:RGD.
DR GO; GO:0051771; P:negative regulation of nitric-oxide synthase biosynthetic process; ISO:RGD.
DR GO; GO:0051248; P:negative regulation of protein metabolic process; IEA:Ensembl.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IDA:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0014032; P:neural crest cell development; ISO:RGD.
DR GO; GO:0014033; P:neural crest cell differentiation; ISO:RGD.
DR GO; GO:0014034; P:neural crest cell fate commitment; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISO:RGD.
DR GO; GO:0030185; P:nitric oxide transport; ISO:RGD.
DR GO; GO:0003357; P:noradrenergic neuron differentiation; ISO:RGD.
DR GO; GO:0030072; P:peptide hormone secretion; ISO:RGD.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISO:RGD.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; ISO:RGD.
DR GO; GO:0031583; P:phospholipase D-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:2001259; P:positive regulation of cation channel activity; ISO:RGD.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; ISO:RGD.
DR GO; GO:0070101; P:positive regulation of chemokine-mediated signaling pathway; ISO:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IDA:RGD.
DR GO; GO:0051482; P:positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:RGD.
DR GO; GO:0046887; P:positive regulation of hormone secretion; ISO:RGD.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; ISO:RGD.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; ISO:RGD.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IDA:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0042482; P:positive regulation of odontogenesis; IDA:RGD.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IDA:RGD.
DR GO; GO:0060585; P:positive regulation of prostaglandin-endoperoxide synthase activity; ISO:RGD.
DR GO; GO:0035815; P:positive regulation of renal sodium excretion; ISO:RGD.
DR GO; GO:0060298; P:positive regulation of sarcomere organization; ISO:RGD.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0045987; P:positive regulation of smooth muscle contraction; IDA:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0035810; P:positive regulation of urine volume; ISO:RGD.
DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IDA:BHF-UCL.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; ISO:RGD.
DR GO; GO:0010737; P:protein kinase A signaling; ISO:RGD.
DR GO; GO:0042313; P:protein kinase C deactivation; ISO:RGD.
DR GO; GO:0007205; P:protein kinase C-activating G protein-coupled receptor signaling pathway; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:RGD.
DR GO; GO:0010827; P:regulation of glucose transmembrane transport; ISO:RGD.
DR GO; GO:0006885; P:regulation of pH; ISO:RGD.
DR GO; GO:0051930; P:regulation of sensory perception of pain; IDA:RGD.
DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; ISO:RGD.
DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro.
DR GO; GO:0070294; P:renal sodium ion absorption; ISO:RGD.
DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:0043200; P:response to amino acid; IEP:RGD.
DR GO; GO:0001975; P:response to amphetamine; ISO:RGD.
DR GO; GO:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0044321; P:response to leptin; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0035994; P:response to muscle stretch; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0010193; P:response to ozone; IEP:RGD.
DR GO; GO:0034696; P:response to prostaglandin F; IEP:RGD.
DR GO; GO:1902074; P:response to salt; IEP:RGD.
DR GO; GO:0033574; P:response to testosterone; IEP:RGD.
DR GO; GO:0071559; P:response to transforming growth factor beta; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0043179; P:rhythmic excitation; ISO:RGD.
DR GO; GO:1902287; P:semaphorin-plexin signaling pathway involved in axon guidance; ISO:RGD.
DR GO; GO:0019233; P:sensory perception of pain; IDA:RGD.
DR GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR GO; GO:0042554; P:superoxide anion generation; IDA:RGD.
DR GO; GO:0097492; P:sympathetic neuron axon guidance; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0042310; P:vasoconstriction; IDA:RGD.
DR GO; GO:0014826; P:vein smooth muscle contraction; ISO:RGD.
DR InterPro; IPR020475; Endothelin.
DR InterPro; IPR019764; Endothelin_toxin_CS.
DR InterPro; IPR001928; Endothln-like_toxin.
DR PANTHER; PTHR13874; PTHR13874; 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 3D-structure; Cleavage on pair of basic residues; Disulfide bond;
KW Reference proteome; Secreted; Signal; Vasoactive; Vasoconstrictor.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:26479776"
FT PROPEP 26..50
FT /evidence="ECO:0000269|PubMed:26479776"
FT /id="PRO_0000008072"
FT PEPTIDE 53..91
FT /note="Big endothelin-1"
FT /evidence="ECO:0000269|PubMed:26479776"
FT /id="PRO_0000436399"
FT PEPTIDE 53..73
FT /note="Endothelin-1"
FT /id="PRO_0000008073"
FT PROPEP 74..202
FT /id="PRO_0000008074"
FT REGION 28..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 110..124
FT /note="Endothelin-like"
FT SITE 73..74
FT /note="Cleavage; by KEL"
FT /evidence="ECO:0000250|UniProtKB:P05305"
FT DISULFID 53..67
FT /evidence="ECO:0000250|UniProtKB:P05305"
FT DISULFID 55..63
FT /evidence="ECO:0000250|UniProtKB:P05305"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:6CMH"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:3CMH"
SQ SEQUENCE 202 AA; 23135 MW; 701886BAFD09AC4B CRC64;
MDYFPVIFSL LFVAFQGAPE TAVLGAELSP RAEKEVQSPP PSTSWRPRRS KRCSCSSLMD
KECVYFCHLD IIWVNTPERV VPYGLGSPSR SKRSLKDLLP TKTTDQGNRC QCAHQKDKKC
WNFCQADKEL RAQSTMQKGV KDFKKGKPCP KLGKKCIYQQ LVEGRKLRRL EAISNSIKTS
FRVAKLKAEL YRDQKLIHNR AH