ID EDN1_RABIT Reviewed; 202 AA. AC P29560; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 02-SEP-2026, entry version 139. 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 Oryctolagus cuniculus (Rabbit). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus. OX NCBI_TaxID=9986; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1339290; DOI=10.1016/0167-4781(92)90499-p; RA Marsden P.A., Sultan P., Cybulsky M., Gimbrone M.A. Jr., Brenner B.M., RA Collins T.; RT "Nucleotide sequence of endothelin-1 cDNA from rabbit endothelial cells."; RL Biochim. Biophys. Acta 1129:249-250(1992). 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 (By similarity). Promotes mesenteric CC arterial wall remodeling via activation of ROCK signaling and CC subsequent colocalization of NFATC3 with F-actin filaments (By CC similarity). NFATC3 then translocates to the nucleus where it CC subsequently promotes the transcription of the smooth muscle CC hypertrophy and differentiation marker ACTA2 (By similarity). CC {ECO:0000250|UniProtKB:P05305, ECO:0000250|UniProtKB:P09558, CC ECO:0000250|UniProtKB:P22387}. 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; X59931; CAA42555.1; -; mRNA. DR PIR; S20609; S20609. DR RefSeq; NP_001095166.1; NM_001101696.1. DR AlphaFoldDB; P29560; -. DR FunCoup; P29560; 57. DR STRING; 9986.ENSOCUP00000011526; -. DR PaxDb; 9986-ENSOCUP00000011526; -. DR Ensembl; ENSOCUT00000013396.4; ENSOCUP00000011526.2; ENSOCUG00000013396.4. DR GeneID; 100009270; -. DR KEGG; ocu:100009270; -. DR CTD; 1906; -. DR eggNOG; ENOG502S1NV; Eukaryota. DR GeneTree; ENSGT00950000183053; -. DR HOGENOM; CLU_090013_1_0_1; -. DR InParanoid; P29560; -. DR OMA; TDHRNRC; -. DR OrthoDB; 8873756at2759; -. DR Proteomes; UP000001811; Chromosome 12. DR Bgee; ENSOCUG00000013396; Expressed in upper lobe of left lung and 17 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell. DR GO; GO:0005125; F:cytokine activity; IEA:Ensembl. DR GO; GO:0031707; F:endothelin A receptor binding; IEA:Ensembl. DR GO; GO:0031708; F:endothelin B receptor binding; IEA:Ensembl. DR GO; GO:0005179; F:hormone activity; IEA:Ensembl. DR GO; GO:0014824; P:artery smooth muscle contraction; IEA:Ensembl. DR GO; GO:0048675; P:axon extension; IEA:Ensembl. DR GO; GO:0060385; P:axonogenesis involved in innervation; IEA:Ensembl. DR GO; GO:0070588; P:calcium ion transmembrane transport; IEA:Ensembl. DR GO; GO:0019722; P:calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0141156; P:cAMP/PKA signal transduction; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl. DR GO; GO:0071372; P:cellular response to follicle-stimulating hormone stimulus; IEA:Ensembl. DR GO; GO:0044751; P:cellular response to human chorionic gonadotropin stimulus; IEA:Ensembl. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl. DR GO; GO:0097237; P:cellular response to toxic substance; IEA:Ensembl. DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl. DR GO; GO:0086100; P:endothelin receptor signaling pathway; IEA:Ensembl. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0072011; P:glomerular endothelium development; IEA:Ensembl. DR GO; GO:0003094; P:glomerular filtration; IEA:Ensembl. DR GO; GO:0003015; P:heart process; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl. DR GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0160195; P:negative regulation of phospholipase C/protein kinase C signal transduction; IEA:Ensembl. DR GO; GO:0051248; P:negative regulation of protein metabolic process; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0014034; P:neural crest cell fate commitment; IEA:Ensembl. DR GO; GO:0030185; P:nitric oxide transport; IEA:Ensembl. DR GO; GO:0003357; P:noradrenergic neuron differentiation; IEA:Ensembl. DR GO; GO:0030072; P:peptide hormone secretion; IEA:Ensembl. DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IEA:Ensembl. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IEA:Ensembl. DR GO; GO:0072112; P:podocyte differentiation; IEA:Ensembl. DR GO; GO:1905653; P:positive regulation of artery morphogenesis; IEA:Ensembl. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IEA:Ensembl. DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IEA:Ensembl. DR GO; GO:0030335; P:positive regulation of cell migration; IEA:Ensembl. DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl. DR GO; GO:0010460; P:positive regulation of heart rate; IEA:Ensembl. DR GO; GO:0046887; P:positive regulation of hormone secretion; IEA:Ensembl. DR GO; GO:0046330; P:positive regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0045840; P:positive regulation of mitotic nuclear division; IEA:Ensembl. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB. DR GO; GO:0060298; P:positive regulation of sarcomere organization; IEA:Ensembl. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0003100; P:regulation of systemic arterial blood pressure by endothelin; IEA:Ensembl. DR GO; GO:0019229; P:regulation of vasoconstriction; IEA:InterPro. DR GO; GO:0070294; P:renal sodium ion absorption; IEA:Ensembl. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0071526; P:semaphorin-plexin signaling pathway; IEA:Ensembl. DR GO; GO:0023019; P:signal transduction involved in regulation of gene expression; IEA:Ensembl. DR GO; GO:0097492; P:sympathetic neuron axon guidance; IEA:Ensembl. DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0014826; P:vein smooth muscle contraction; IEA:Ensembl. DR InterPro; IPR020475; Endothelin. DR InterPro; IPR019764; Endothelin_toxin_CS. DR InterPro; IPR001928; Endothln-like_toxin. DR PANTHER; PTHR13874; ENDOTHELIN; 1. DR PANTHER; PTHR13874:SF10; ENDOTHELIN-1; 1. DR Pfam; PF00322; Endothelin; 1. DR PRINTS; PR00365; ENDOTHELIN. DR SMART; SM00272; END; 2. DR PROSITE; PS00270; ENDOTHELIN; 2. PE 2: Evidence at transcript level; KW Cleavage on pair of basic residues; Disulfide bond; Reference proteome; KW Secreted; Signal; Vasoactive; Vasoconstrictor. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT PROPEP 24..50 FT /evidence="ECO:0000250|UniProtKB:P22388" FT /id="PRO_0000008069" FT PEPTIDE 53..91 FT /note="Big endothelin-1" FT /evidence="ECO:0000250|UniProtKB:P22388" FT /id="PRO_0000436398" FT PEPTIDE 53..73 FT /note="Endothelin-1" FT /id="PRO_0000008070" FT PROPEP 74..202 FT /id="PRO_0000008071" FT REGION 24..49 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" SQ SEQUENCE 202 AA; 22828 MW; 22B41EA286D51286 CRC64; MDYFSMMVSL LLVAFHGAPE TAASGTELST GAENPGEKPP ASAPWRPRRS KRCSCSSLMD KECVYFCHLD IIWVNTPGHI VPYGLGSPSR SKRSLKDLFP TRAAYHKNRC QCTSPHDKKC WNFCQAGTEL RAQETMEKGR NNLKKGKDCS KLGKKCILQK LMQGRKIRRL EAISNSIKTS FHAAQLRAQL HREQKVTHNR TH //