ID EDNRA_HUMAN Reviewed; 427 AA. AC P25101; B2R723; B4E2V6; B7Z9G6; D3DP03; E7ER36; O43441; Q16432; Q16433; AC Q8TBH2; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1992, sequence version 1. DT 27-MAR-2024, entry version 224. DE RecName: Full=Endothelin-1 receptor {ECO:0000305}; DE AltName: Full=Endothelin receptor type A {ECO:0000312|HGNC:HGNC:3179}; DE Short=ET-A; DE Short=ETA-R; DE Short=hET-AR; DE Flags: Precursor; GN Name=EDNRA {ECO:0000312|HGNC:HGNC:3179}; Synonyms=ETA, ETRA; 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] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=1719979; DOI=10.1016/s0006-291x(05)81332-4; RA Adachi M., Yang Y.Y., Furuichi Y., Miyamoto C.; RT "Cloning and characterization of cDNA encoding human A-type endothelin RT receptor."; RL Biochem. Biophys. Res. Commun. 180:1265-1272(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=1659806; DOI=10.1016/s0006-291x(05)81399-3; RA Cyr C., Huebner K., Druck T., Kris R.; RT "Cloning and chromosomal localization of a human endothelin ETA receptor."; RL Biochem. Biophys. Res. Commun. 181:184-190(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1652463; DOI=10.1016/0014-5793(91)80007-p; RA Hosoda K., Nakao K., Arai H., Suga S., Ogawa Y., Mukoyama M., Shirakami G., RA Saito Y., Nakanishi S., Imura H.; RT "Cloning and expression of human endothelin-1 receptor cDNA."; RL FEBS Lett. 287:23-26(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1291713; DOI=10.1253/jcj.56.supplementv_1303; RA Arai H., Nakao K., Hosoda K., Ogawa Y., Nakagawa O., Komatsu Y., Imura H.; RT "Molecular cloning of human endothelin receptors and their expression in RT vascular endothelial cells and smooth muscle cells."; RL Jpn. Circ. J. 56:1303-1307(1992). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8440682; DOI=10.1016/s0021-9258(18)53554-7; RA Elshourbagy N.A., Korman D.R., Wu H.L., Sylvester D.R., Lee J.A., RA Nuthalaganti P., Bergsma D.J., Kumar C.S., Nambi P.; RT "Molecular characterization and regulation of the human endothelin RT receptors."; RL J. Biol. Chem. 268:3873-3879(1993). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=1326535; DOI=10.1016/s0021-9258(19)37031-0; RA Hosoda K., Nakao K., Tamura N., Arai H., Ogawa Y., Suga S., Nakanishi S., RA Imura H.; RT "Organization, structure, chromosomal assignment, and expression of the RT gene encoding the human endothelin-A receptor."; RL J. Biol. Chem. 267:18797-18804(1992). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=1415318; DOI=10.1097/00000441-199210000-00002; RA Hayzer D.J., Rose P.M., Lynch J.S., Webb M.L., Kienzle B.K., Liu E.C., RA Bogosian E.A., Brinson E., Runge M.S.; RT "Cloning and expression of a human endothelin receptor: subtype A."; RL Am. J. Med. Sci. 304:231-238(1992). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), AND TISSUE SPECIFICITY. RC TISSUE=Lung; RX PubMed=8611157; DOI=10.1042/bj3130795; RA Miyamoto Y., Yoshimasa T., Arai H., Takaya K., Ogawa Y., Itoh H., Nakao K.; RT "Alternative RNA splicing of the human endothelin-A receptor generates RT multiple transcripts."; RL Biochem. J. 313:795-801(1996). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RA Warren C.N., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 5). RC TISSUE=Cerebellum, Testis, and Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [13] 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 [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [15] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-140 (ISOFORMS 1/2/3/4). RX PubMed=8427579; DOI=10.1006/bbrc.1993.1052; RA Yang H., Tabuchi H., Furuichi Y., Miyamoto C.; RT "Molecular characterization of the 5'-flanking region of human genomic ETA RT gene."; RL Biochem. Biophys. Res. Commun. 190:332-339(1993). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 52-427 (ISOFORM 2), AND TISSUE SPECIFICITY. RC TISSUE=Placenta; 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). RN [17] RP INTERACTION WITH HDAC7 AND KAT5. RX PubMed=11262386; DOI=10.1074/jbc.c000909200; RA Lee H.-J., Chun M., Kandror K.V.; RT "Tip60 and HDAC7 interact with the endothelin receptor a and may be RT involved in downstream signaling."; RL J. Biol. Chem. 276:16597-16600(2001). RN [18] RP INVOLVEMENT IN MFDA, AND VARIANTS MFDA PHE-129 AND LYS-303. RX PubMed=25772936; DOI=10.1016/j.ajhg.2015.01.015; RA Gordon C.T., Weaver K.N., Zechi-Ceide R.M., Madsen E.C., Tavares A.L., RA Oufadem M., Kurihara Y., Adameyko I., Picard A., Breton S., Pierrot S., RA Biosse-Duplan M., Voisin N., Masson C., Bole-Feysot C., Nitschke P., RA Delrue M.A., Lacombe D., Guion-Almeida M.L., Moura P.P., Garib D.G., RA Munnich A., Ernfors P., Hufnagel R.B., Hopkin R.J., Kurihara H., Saal H.M., RA Weaver D.D., Katsanis N., Lyonnet S., Golzio C., Clouthier D.E., Amiel J.; RT "Mutations in the endothelin receptor type A cause mandibulofacial RT dysostosis with alopecia."; RL Am. J. Hum. Genet. 96:519-531(2015). RN [19] RP VARIANT [LARGE SCALE ANALYSIS] LEU-136. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Receptor for endothelin-1. Mediates its action by association CC with G proteins that activate a phosphatidylinositol-calcium second CC messenger system. The rank order of binding affinities for ET-A is: ET1 CC > ET2 >> ET3. CC -!- SUBUNIT: Interacts with HDAC7 and KAT5. {ECO:0000269|PubMed:11262386}. CC -!- INTERACTION: CC P25101; P49407: ARRB1; NbExp=3; IntAct=EBI-6624559, EBI-743313; CC P25101; P32121: ARRB2; NbExp=2; IntAct=EBI-6624559, EBI-714559; CC P25101; P05305: EDN1; NbExp=2; IntAct=EBI-6624559, EBI-715181; CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P25101-1; Sequence=Displayed; CC Name=2; Synonyms=Delta-3; CC IsoId=P25101-2; Sequence=VSP_011059, VSP_011060; CC Name=3; Synonyms=Delta-4; CC IsoId=P25101-3; Sequence=VSP_011062, VSP_011063; CC Name=4; Synonyms=Delta-3,4; CC IsoId=P25101-4; Sequence=VSP_011061; CC Name=5; CC IsoId=P25101-5; Sequence=VSP_045578; CC -!- TISSUE SPECIFICITY: Isoform 1, isoform 3 and isoform 4 are expressed in CC a variety of tissues, with highest levels in the aorta and cerebellum, CC followed by lung, atrium and cerebral cortex, lower levels in the CC placenta, kidney, adrenal gland, duodenum, colon, ventricle and liver CC but no expression in umbilical vein endothelial cells. Within the CC placenta, isoform 1, isoform 2, isoform 3 and isoform 4 are expressed CC in the villi and stem villi vessels. {ECO:0000269|PubMed:8611157, CC ECO:0000269|PubMed:9284755}. CC -!- DISEASE: Mandibulofacial dysostosis with alopecia (MFDA) [MIM:616367]: CC A form of mandibulofacial dysostosis, a disorder characterized by malar CC and mandibular hypoplasia, typically associated with abnormalities of CC the ears and eyelids. MFDA features include maxillary dysmorphism with CC dysplastic zygomatic arch, hypoplastic mandible, scalp alopecia, scant CC eyebrows and eyelashes, severe hypoplasia or aplasia of eyelids, small CC cupped dysplastic ears, conductive hearing loss, cleft palate, dental CC anomalies, micrognathia, and limited jaw mobility. CC {ECO:0000269|PubMed:25772936}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC Endothelin receptor subfamily. EDNRA sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ednra/"; 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; S63938; AAB20278.1; -; mRNA. DR EMBL; S67127; AAB20407.1; -; mRNA. DR EMBL; X61950; CAA43953.1; -; mRNA. DR EMBL; D90348; BAA14359.1; -; mRNA. DR EMBL; S57498; AAB25530.2; -; mRNA. DR EMBL; L06622; AAA58447.1; -; mRNA. DR EMBL; D11151; BAA01920.1; -; Genomic_DNA. DR EMBL; S45956; AAB23644.1; -; mRNA. DR EMBL; S81539; AAB36325.1; -; mRNA. DR EMBL; S81542; AAB36326.1; -; mRNA. DR EMBL; S81545; AAB36327.1; -; mRNA. DR EMBL; AY275462; AAP32294.1; -; mRNA. DR EMBL; AY422989; AAQ87880.1; -; Genomic_DNA. DR EMBL; AK304451; BAG65268.1; -; mRNA. DR EMBL; AK312812; BAG35670.1; -; mRNA. DR EMBL; AK315931; BAH14302.1; -; mRNA. DR EMBL; AC093908; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471056; EAX05019.1; -; Genomic_DNA. DR EMBL; CH471056; EAX05021.1; -; Genomic_DNA. DR EMBL; BC022511; AAH22511.1; -; mRNA. DR EMBL; S55772; AAB25212.1; -; Genomic_DNA. DR EMBL; AF014826; AAB94859.1; -; mRNA. DR CCDS; CCDS3769.1; -. [P25101-1] DR CCDS; CCDS54810.1; -. [P25101-4] DR PIR; A44158; A44158. DR RefSeq; NP_001159527.1; NM_001166055.1. [P25101-4] DR RefSeq; NP_001243212.1; NM_001256283.1. DR RefSeq; NP_001948.1; NM_001957.3. [P25101-1] DR PDB; 8HCQ; EM; 3.01 A; R=20-406. DR PDBsum; 8HCQ; -. DR AlphaFoldDB; P25101; -. DR SMR; P25101; -. DR BioGRID; 108231; 62. DR CORUM; P25101; -. DR DIP; DIP-48718N; -. DR IntAct; P25101; 13. DR STRING; 9606.ENSP00000315011; -. DR BindingDB; P25101; -. DR ChEMBL; CHEMBL252; -. DR DrugBank; DB04674; 2-HYDROXY-3,5-DIIODOBENZOIC ACID. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB05367; Actelion-1. DR DrugBank; DB06403; Ambrisentan. DR DrugBank; DB06199; Atrasentan. DR DrugBank; DB00559; Bosentan. DR DrugBank; DB06677; Clazosentan. DR DrugBank; DB04883; Darusentan. DR DrugBank; DB06460; Enrasentan. DR DrugBank; DB08932; Macitentan. DR DrugBank; DB06268; Sitaxentan. DR DrugBank; DB12548; Sparsentan. DR DrugBank; DB05290; SPP 301. DR DrugBank; DB06558; Tezosentan. DR DrugCentral; P25101; -. DR GuidetoPHARMACOLOGY; 219; -. DR GlyCosmos; P25101; 2 sites, No reported glycans. DR GlyGen; P25101; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; P25101; -. DR PhosphoSitePlus; P25101; -. DR SwissPalm; P25101; -. DR BioMuta; EDNRA; -. DR DMDM; 119606; -. DR jPOST; P25101; -. DR MassIVE; P25101; -. DR PaxDb; 9606-ENSP00000315011; -. DR PeptideAtlas; P25101; -. DR ProteomicsDB; 17708; -. DR ProteomicsDB; 54256; -. [P25101-1] DR ProteomicsDB; 54258; -. [P25101-3] DR ProteomicsDB; 54259; -. [P25101-4] DR Antibodypedia; 2942; 387 antibodies from 34 providers. DR DNASU; 1909; -. DR Ensembl; ENST00000324300.10; ENSP00000315011.5; ENSG00000151617.17. [P25101-1] DR Ensembl; ENST00000358556.8; ENSP00000351359.4; ENSG00000151617.17. [P25101-4] DR Ensembl; ENST00000506066.1; ENSP00000425281.1; ENSG00000151617.17. [P25101-4] DR Ensembl; ENST00000510697.5; ENSP00000427259.1; ENSG00000151617.17. [P25101-3] DR Ensembl; ENST00000511804.5; ENSP00000425354.1; ENSG00000151617.17. [P25101-5] DR Ensembl; ENST00000648866.1; ENSP00000496976.1; ENSG00000151617.17. [P25101-5] DR Ensembl; ENST00000651419.1; ENSP00000498969.1; ENSG00000151617.17. [P25101-1] DR GeneID; 1909; -. DR KEGG; hsa:1909; -. DR MANE-Select; ENST00000651419.1; ENSP00000498969.1; NM_001957.4; NP_001948.1. DR UCSC; uc003iky.4; human. [P25101-1] DR AGR; HGNC:3179; -. DR CTD; 1909; -. DR DisGeNET; 1909; -. DR GeneCards; EDNRA; -. DR HGNC; HGNC:3179; EDNRA. DR HPA; ENSG00000151617; Tissue enhanced (seminal). DR MalaCards; EDNRA; -. DR MIM; 131243; gene. DR MIM; 616367; phenotype. DR neXtProt; NX_P25101; -. DR OpenTargets; ENSG00000151617; -. DR Orphanet; 586; Cystic fibrosis. DR Orphanet; 443995; Mandibulofacial dysostosis with alopecia. DR PharmGKB; PA27617; -. DR VEuPathDB; HostDB:ENSG00000151617; -. DR eggNOG; KOG3656; Eukaryota. DR GeneTree; ENSGT01100000263512; -. DR HOGENOM; CLU_096205_1_0_1; -. DR InParanoid; P25101; -. DR OMA; YNERDPG; -. DR OrthoDB; 2905228at2759; -. DR PhylomeDB; P25101; -. DR TreeFam; TF331292; -. DR PathwayCommons; P25101; -. DR Reactome; R-HSA-375276; Peptide ligand-binding receptors. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR SignaLink; P25101; -. DR SIGNOR; P25101; -. DR BioGRID-ORCS; 1909; 8 hits in 1156 CRISPR screens. DR ChiTaRS; EDNRA; human. DR GeneWiki; Endothelin_receptor_type_A; -. DR GenomeRNAi; 1909; -. DR Pharos; P25101; Tclin. DR PRO; PR:P25101; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; P25101; Protein. DR Bgee; ENSG00000151617; Expressed in cauda epididymis and 187 other cell types or tissues. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0004962; F:endothelin receptor activity; IBA:GO_Central. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc. DR GO; GO:0007190; P:activation of adenylate cyclase activity; TAS:ProtInc. DR GO; GO:0007202; P:activation of phospholipase C activity; TAS:ProtInc. DR GO; GO:0007193; P:adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway; IEA:Ensembl. DR GO; GO:0035904; P:aorta development; IEA:Ensembl. DR GO; GO:0014824; P:artery smooth muscle contraction; IMP:BHF-UCL. DR GO; GO:0003228; P:atrial cardiac muscle tissue development; 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:0001974; P:blood vessel remodeling; IEA:Ensembl. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl. DR GO; GO:0070588; P:calcium ion transmembrane transport; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0003207; P:cardiac chamber formation; IEA:Ensembl. DR GO; GO:0003253; P:cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl. DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc. 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:0071373; P:cellular response to luteinizing hormone stimulus; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:1904888; P:cranial skeletal system development; IEA:Ensembl. DR GO; GO:0048066; P:developmental pigmentation; IBA:GO_Central. DR GO; GO:0035050; P:embryonic heart tube development; IEA:Ensembl. DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl. DR GO; GO:0086100; P:endothelin receptor signaling pathway; IBA:GO_Central. DR GO; GO:0086101; P:endothelin receptor signaling pathway involved in heart process; IEA:Ensembl. DR GO; GO:0048484; P:enteric nervous system development; IEA:InterPro. DR GO; GO:0061028; P:establishment of endothelial barrier; IEA:Ensembl. DR GO; GO:0060324; P:face development; IEA:Ensembl. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0072011; P:glomerular endothelium development; IEA:Ensembl. DR GO; GO:0003094; P:glomerular filtration; IEA:Ensembl. DR GO; GO:0030202; P:heparin metabolic process; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IDA:MGI. DR GO; GO:0003220; P:left ventricular cardiac muscle tissue morphogenesis; IEA:Ensembl. DR GO; GO:1903537; P:meiotic cell cycle process involved in oocyte maturation; IEA:Ensembl. DR GO; GO:0097152; P:mesenchymal cell apoptotic process; IEA:Ensembl. DR GO; GO:0042474; P:middle ear morphogenesis; IEA:Ensembl. DR GO; GO:0007005; P:mitochondrion organization; IEA:Ensembl. DR GO; GO:0000278; P:mitotic cell cycle; IEA:Ensembl. DR GO; GO:0014034; P:neural crest cell fate commitment; IEA:Ensembl. DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl. DR GO; GO:0016322; P:neuron remodeling; IEA:Ensembl. DR GO; GO:0003357; P:noradrenergic neuron differentiation; IEA:Ensembl. DR GO; GO:0042415; P:norepinephrine metabolic process; IEA:Ensembl. DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IEA:Ensembl. DR GO; GO:1903210; P:podocyte apoptotic process; IEA:Ensembl. DR GO; GO:0072112; P:podocyte differentiation; IEA:Ensembl. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IEA:Ensembl. DR GO; GO:2001259; P:positive regulation of cation channel activity; IDA:MGI. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:ProtInc. DR GO; GO:0010737; P:protein kinase A signaling; IDA:MGI. DR GO; GO:0071806; P:protein transmembrane transport; IEA:Ensembl. DR GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl. DR GO; GO:0010827; P:regulation of glucose transmembrane transport; IEA:Ensembl. DR GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl. DR GO; GO:1905871; P:regulation of protein localization to cell leading edge; IEA:Ensembl. DR GO; GO:0097018; P:renal albumin absorption; IEA:Ensembl. DR GO; GO:0070294; P:renal sodium ion absorption; IEA:Ensembl. DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; ISS:UniProtKB. DR GO; GO:1905144; P:response to acetylcholine; IEA:Ensembl. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; IEA:Ensembl. DR GO; GO:1902287; P:semaphorin-plexin signaling pathway involved in axon guidance; IEA:Ensembl. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006939; P:smooth muscle contraction; TAS:ProtInc. DR GO; GO:0055078; P:sodium ion homeostasis; IEA:Ensembl. DR GO; GO:0048485; P:sympathetic nervous system development; 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:0097084; P:vascular associated smooth muscle cell development; IEA:Ensembl. DR GO; GO:0042310; P:vasoconstriction; IMP:BHF-UCL. DR CDD; cd15975; 7tmA_ET-AR; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR000499; Endthln_rcpt. DR InterPro; IPR002175; ETA_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR PANTHER; PTHR46099:SF2; ENDOTHELIN-1 RECEPTOR; 1. DR PANTHER; PTHR46099; G_PROTEIN_RECEP_F1_2 DOMAIN-CONTAINING PROTEIN; 1. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00570; ENDOTHELINAR. DR PRINTS; PR00366; ENDOTHELINR. DR PRINTS; PR00237; GPCRRHODOPSN. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. DR Genevisible; P25101; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell membrane; Disease variant; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Hypotrichosis; KW Membrane; Phosphoprotein; Receptor; Reference proteome; Signal; Transducer; KW Transmembrane; Transmembrane helix. FT SIGNAL 1..20 FT /evidence="ECO:0000255" FT CHAIN 21..427 FT /note="Endothelin-1 receptor" FT /id="PRO_0000012721" FT TOPO_DOM 21..80 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 81..102 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 103..112 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 113..132 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 133..159 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 160..181 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 182..205 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 206..229 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 230..256 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 257..278 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 279..306 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 307..328 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 329..347 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 348..372 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 373..427 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT REGION 406..427 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 412..427 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 425 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P28088" FT CARBOHYD 29 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 62 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 158..239 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521" FT VAR_SEQ 1..225 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045578" FT VAR_SEQ 141..249 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:8611157" FT /id="VSP_011061" FT VAR_SEQ 141..161 FT /note="LLAGRWPFDHNDFGVFLCKLF -> VQSSCLLESCSGNWDSFGNCH (in FT isoform 2)" FT /evidence="ECO:0000303|PubMed:9284755" FT /id="VSP_011059" FT VAR_SEQ 162..427 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9284755" FT /id="VSP_011060" FT VAR_SEQ 183..187 FT /note="RYRAV -> SSTKM (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8611157" FT /id="VSP_011062" FT VAR_SEQ 188..427 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8611157" FT /id="VSP_011063" FT VARIANT 129 FT /note="Y -> F (in MFDA; dbSNP:rs786205230)" FT /evidence="ECO:0000269|PubMed:25772936" FT /id="VAR_073788" FT VARIANT 136 FT /note="I -> L (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035758" FT VARIANT 303 FT /note="E -> K (in MFDA; dbSNP:rs876657388)" FT /evidence="ECO:0000269|PubMed:25772936" FT /id="VAR_073789" FT CONFLICT 110 FT /note="C -> Y (in Ref. 7; AAB23644)" FT /evidence="ECO:0000305" FT CONFLICT 115 FT /note="P -> H (in Ref. 14; AAH22511)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="V -> A (in Ref. 5; AAA58447)" FT /evidence="ECO:0000305" FT CONFLICT 232 FT /note="R -> K (in Ref. 11; BAH14302)" FT /evidence="ECO:0000305" FT CONFLICT 234 FT /note="E -> G (in Ref. 5; AAA58447)" FT /evidence="ECO:0000305" FT CONFLICT 280 FT /note="C -> G (in Ref. 5; AAA58447)" FT /evidence="ECO:0000305" FT CONFLICT 300 FT /note="Q -> H (in Ref. 11; BAG65268)" FT /evidence="ECO:0000305" FT CONFLICT 322 FT /note="L -> V (in Ref. 14; AAH22511)" FT /evidence="ECO:0000305" FT CONFLICT 345 FT /note="S -> G (in Ref. 11; BAG65268)" FT /evidence="ECO:0000305" FT CONFLICT 409 FT /note="N -> D (in Ref. 14; AAH22511)" FT /evidence="ECO:0000305" FT HELIX 77..108 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 114..142 FT /evidence="ECO:0007829|PDB:8HCQ" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 152..158 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 161..188 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 200..221 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 246..252 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 255..263 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 265..282 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 298..329 FT /evidence="ECO:0007829|PDB:8HCQ" FT HELIX 340..372 FT /evidence="ECO:0007829|PDB:8HCQ" SQ SEQUENCE 427 AA; 48722 MW; 207272D4A231404F CRC64; METLCLRASF WLALVGCVIS DNPERYSTNL SNHVDDFTTF RGTELSFLVT THQPTNLVLP SNGSMHNYCP QQTKITSAFK YINTVISCTI FIVGMVGNAT LLRIIYQNKC MRNGPNALIA SLALGDLIYV VIDLPINVFK LLAGRWPFDH NDFGVFLCKL FPFLQKSSVG ITVLNLCALS VDRYRAVASW SRVQGIGIPL VTAIEIVSIW ILSFILAIPE AIGFVMVPFE YRGEQHKTCM LNATSKFMEF YQDVKDWWLF GFYFCMPLVC TAIFYTLMTC EMLNRRNGSL RIALSEHLKQ RREVAKTVFC LVVIFALCWF PLHLSRILKK TVYNEMDKNR CELLSFLLLM DYIGINLATM NSCINPIALY FVSKKFKNCF QSCLCCCCYQ SKSLMTSVPM NGTSIQWKNH DQNNHNTDRS SHKDSMN //