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Protein

Endothelin-1 receptor

Gene

EDNRA

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.

GO - Molecular functioni

  • endothelin receptor activity Source: UniProtKB
  • phosphatidylinositol phospholipase C activity Source: ProtInc

GO - Biological processi

  • activation of adenylate cyclase activity Source: ProtInc
  • activation of phospholipase C activity Source: ProtInc
  • artery smooth muscle contraction Source: BHF-UCL
  • cell proliferation Source: UniProtKB
  • enteric nervous system development Source: InterPro
  • glucose transport Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • head development Source: Ensembl
  • heart development Source: Ensembl
  • in utero embryonic development Source: Ensembl
  • negative regulation of cAMP biosynthetic process Source: Ensembl
  • neural crest cell development Source: Ensembl
  • patterning of blood vessels Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • regulation of blood pressure Source: InterPro
  • respiratory gaseous exchange Source: UniProtKB
  • response to hypoxia Source: Ensembl
  • signal transduction Source: ProtInc
  • smooth muscle contraction Source: UniProtKB
  • vasoconstriction Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151617-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiP25101.

Names & Taxonomyi

Protein namesi
Recommended name:
Endothelin-1 receptor
Alternative name(s):
Endothelin A receptor
Short name:
ET-A
Short name:
ETA-R
Short name:
hET-AR
Gene namesi
Name:EDNRA
Synonyms:ETA, ETRA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:3179. EDNRA.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 80ExtracellularSequence analysisAdd BLAST60
Transmembranei81 – 102Helical; Name=1Sequence analysisAdd BLAST22
Topological domaini103 – 112CytoplasmicSequence analysis10
Transmembranei113 – 132Helical; Name=2Sequence analysisAdd BLAST20
Topological domaini133 – 159ExtracellularSequence analysisAdd BLAST27
Transmembranei160 – 181Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini182 – 205CytoplasmicSequence analysisAdd BLAST24
Transmembranei206 – 229Helical; Name=4Sequence analysisAdd BLAST24
Topological domaini230 – 256ExtracellularSequence analysisAdd BLAST27
Transmembranei257 – 278Helical; Name=5Sequence analysisAdd BLAST22
Topological domaini279 – 306CytoplasmicSequence analysisAdd BLAST28
Transmembranei307 – 328Helical; Name=6Sequence analysisAdd BLAST22
Topological domaini329 – 347ExtracellularSequence analysisAdd BLAST19
Transmembranei348 – 372Helical; Name=7Sequence analysisAdd BLAST25
Topological domaini373 – 427CytoplasmicSequence analysisAdd BLAST55

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Involvement in diseasei

Mandibulofacial dysostosis with alopecia (MFDA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of mandibulofacial dysostosis, a disorder characterized by malar and mandibular hypoplasia, typically associated with abnormalities of the ears and eyelids. MFDA features include maxillary dysmorphism with dysplastic zygomatic arch, hypoplastic mandible, scalp alopecia, scant eyebrows and eyelashes, severe hypoplasia or aplasia of eyelids, small cupped dysplastic ears, conductive hearing loss, cleft palate, dental anomalies, micrognathia, and limited jaw mobility.
See also OMIM:616367
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073788129Y → F in MFDA. 1 PublicationCorresponds to variant rs786205230dbSNPEnsembl.1
Natural variantiVAR_073789303E → K in MFDA. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi1909.
MalaCardsiEDNRA.
MIMi616367. phenotype.
OpenTargetsiENSG00000151617.
PharmGKBiPA27617.

Chemistry databases

ChEMBLiCHEMBL252.
DrugBankiDB00945. Acetylsalicylic acid.
DB06403. Ambrisentan.
DB00559. Bosentan.
DB08932. MACITENTAN.
DB06268. Sitaxentan.
GuidetoPHARMACOLOGYi219.

Polymorphism and mutation databases

BioMutaiEDNRA.
DMDMi119606.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000001272121 – 427Endothelin-1 receptorAdd BLAST407

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi29N-linked (GlcNAc...)Sequence analysis1
Glycosylationi62N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi158 ↔ 239PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP25101.
PeptideAtlasiP25101.
PRIDEiP25101.

PTM databases

iPTMnetiP25101.
PhosphoSitePlusiP25101.
SwissPalmiP25101.

Expressioni

Tissue specificityi

Isoform 1, isoform 3 and isoform 4 are expressed in a variety of tissues, with highest levels in the aorta and cerebellum, followed by lung, atrium and cerebral cortex, lower levels in the placenta, kidney, adrenal gland, duodenum, colon, ventricle and liver but no expression in umbilical vein endothelial cells. Within the placenta, isoform 1, isoform 2, isoform 3 and isoform 4 are expressed in the villi and stem villi vessels.2 Publications

Gene expression databases

BgeeiENSG00000151617.
CleanExiHS_EDNRA.
GenevisibleiP25101. HS.

Organism-specific databases

HPAiCAB018957.
HPA013774.
HPA014087.

Interactioni

Subunit structurei

Interacts with HDAC7 and KAT5.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
EDN1P053052EBI-6624559,EBI-715181

Protein-protein interaction databases

BioGridi108231. 21 interactors.
DIPiDIP-48718N.
IntActiP25101. 1 interactor.
STRINGi9606.ENSP00000315011.

Chemistry databases

BindingDBiP25101.

Structurei

3D structure databases

ProteinModelPortaliP25101.
SMRiP25101.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRA sub-subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119177.
HOGENOMiHOG000169267.
HOVERGENiHBG051443.
InParanoidiP25101.
KOiK04197.
OMAiSIQWKNQ.
OrthoDBiEOG091G0CJV.
PhylomeDBiP25101.
TreeFamiTF331292.

Family and domain databases

InterProiIPR000499. Endthln_rcpt.
IPR002175. ETA_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00570. ENDOTHELINAR.
PR00366. ENDOTHELINR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P25101-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
METLCLRASF WLALVGCVIS DNPERYSTNL SNHVDDFTTF RGTELSFLVT
60 70 80 90 100
THQPTNLVLP SNGSMHNYCP QQTKITSAFK YINTVISCTI FIVGMVGNAT
110 120 130 140 150
LLRIIYQNKC MRNGPNALIA SLALGDLIYV VIDLPINVFK LLAGRWPFDH
160 170 180 190 200
NDFGVFLCKL FPFLQKSSVG ITVLNLCALS VDRYRAVASW SRVQGIGIPL
210 220 230 240 250
VTAIEIVSIW ILSFILAIPE AIGFVMVPFE YRGEQHKTCM LNATSKFMEF
260 270 280 290 300
YQDVKDWWLF GFYFCMPLVC TAIFYTLMTC EMLNRRNGSL RIALSEHLKQ
310 320 330 340 350
RREVAKTVFC LVVIFALCWF PLHLSRILKK TVYNEMDKNR CELLSFLLLM
360 370 380 390 400
DYIGINLATM NSCINPIALY FVSKKFKNCF QSCLCCCCYQ SKSLMTSVPM
410 420
NGTSIQWKNH DQNNHNTDRS SHKDSMN
Length:427
Mass (Da):48,722
Last modified:May 1, 1992 - v1
Checksum:i207272D4A231404F
GO
Isoform 2 (identifier: P25101-2) [UniParc]FASTAAdd to basket
Also known as: Delta-3

The sequence of this isoform differs from the canonical sequence as follows:
     141-161: LLAGRWPFDHNDFGVFLCKLF → VQSSCLLESCSGNWDSFGNCH
     162-427: Missing.

Show »
Length:161
Mass (Da):17,820
Checksum:iB6227E27C1B05915
GO
Isoform 3 (identifier: P25101-3) [UniParc]FASTAAdd to basket
Also known as: Delta-4

The sequence of this isoform differs from the canonical sequence as follows:
     183-187: RYRAV → SSTKM
     188-427: Missing.

Show »
Length:187
Mass (Da):20,763
Checksum:i60E5564BDE6D7A96
GO
Isoform 4 (identifier: P25101-4) [UniParc]FASTAAdd to basket
Also known as: Delta-3,4

The sequence of this isoform differs from the canonical sequence as follows:
     141-249: Missing.

Show »
Length:318
Mass (Da):36,489
Checksum:i0423FAA16DB6A9BF
GO
Isoform 5 (identifier: P25101-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-225: Missing.

Note: No experimental confirmation available.
Show »
Length:202
Mass (Da):23,803
Checksum:i01C9764279D905CD
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti110C → Y in AAB23644 (PubMed:1415318).Curated1
Sequence conflicti115P → H in AAH22511 (PubMed:15489334).Curated1
Sequence conflicti207V → A in AAA58447 (PubMed:8440682).Curated1
Sequence conflicti232R → K in BAH14302 (PubMed:14702039).Curated1
Sequence conflicti234E → G in AAA58447 (PubMed:8440682).Curated1
Sequence conflicti280C → G in AAA58447 (PubMed:8440682).Curated1
Sequence conflicti300Q → H in BAG65268 (PubMed:14702039).Curated1
Sequence conflicti322L → V in AAH22511 (PubMed:15489334).Curated1
Sequence conflicti345S → G in BAG65268 (PubMed:14702039).Curated1
Sequence conflicti409N → D in AAH22511 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073788129Y → F in MFDA. 1 PublicationCorresponds to variant rs786205230dbSNPEnsembl.1
Natural variantiVAR_035758136I → L in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_073789303E → K in MFDA. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0455781 – 225Missing in isoform 5. 1 PublicationAdd BLAST225
Alternative sequenceiVSP_011061141 – 249Missing in isoform 4. 1 PublicationAdd BLAST109
Alternative sequenceiVSP_011059141 – 161LLAGR…LCKLF → VQSSCLLESCSGNWDSFGNC H in isoform 2. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_011060162 – 427Missing in isoform 2. 1 PublicationAdd BLAST266
Alternative sequenceiVSP_011062183 – 187RYRAV → SSTKM in isoform 3. 1 Publication5
Alternative sequenceiVSP_011063188 – 427Missing in isoform 3. 1 PublicationAdd BLAST240

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S63938 mRNA. Translation: AAB20278.1.
S67127 mRNA. Translation: AAB20407.1.
X61950 mRNA. Translation: CAA43953.1.
D90348 mRNA. Translation: BAA14359.1.
S57498 mRNA. Translation: AAB25530.2.
L06622 mRNA. Translation: AAA58447.1.
D11151 Genomic DNA. Translation: BAA01920.1.
S45956 mRNA. Translation: AAB23644.1.
S81539 mRNA. Translation: AAB36325.1.
S81542 mRNA. Translation: AAB36326.1.
S81545 mRNA. Translation: AAB36327.1.
AY275462 mRNA. Translation: AAP32294.1.
AY422989 Genomic DNA. Translation: AAQ87880.1.
AK304451 mRNA. Translation: BAG65268.1.
AK312812 mRNA. Translation: BAG35670.1.
AK315931 mRNA. Translation: BAH14302.1.
AC093908 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX05019.1.
CH471056 Genomic DNA. Translation: EAX05021.1.
BC022511 mRNA. Translation: AAH22511.1.
S55772 Genomic DNA. Translation: AAB25212.1.
AF014826 mRNA. Translation: AAB94859.1.
CCDSiCCDS3769.1. [P25101-1]
CCDS54810.1. [P25101-4]
CCDS58927.1. [P25101-5]
PIRiA44158.
RefSeqiNP_001159527.1. NM_001166055.1. [P25101-4]
NP_001243212.1. NM_001256283.1. [P25101-5]
NP_001948.1. NM_001957.3. [P25101-1]
UniGeneiHs.183713.

Genome annotation databases

EnsembliENST00000324300; ENSP00000315011; ENSG00000151617. [P25101-1]
ENST00000358556; ENSP00000351359; ENSG00000151617. [P25101-4]
ENST00000506066; ENSP00000425281; ENSG00000151617. [P25101-4]
ENST00000510697; ENSP00000427259; ENSG00000151617. [P25101-3]
ENST00000511804; ENSP00000425354; ENSG00000151617. [P25101-5]
GeneIDi1909.
KEGGihsa:1909.
UCSCiuc003iky.4. human. [P25101-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S63938 mRNA. Translation: AAB20278.1.
S67127 mRNA. Translation: AAB20407.1.
X61950 mRNA. Translation: CAA43953.1.
D90348 mRNA. Translation: BAA14359.1.
S57498 mRNA. Translation: AAB25530.2.
L06622 mRNA. Translation: AAA58447.1.
D11151 Genomic DNA. Translation: BAA01920.1.
S45956 mRNA. Translation: AAB23644.1.
S81539 mRNA. Translation: AAB36325.1.
S81542 mRNA. Translation: AAB36326.1.
S81545 mRNA. Translation: AAB36327.1.
AY275462 mRNA. Translation: AAP32294.1.
AY422989 Genomic DNA. Translation: AAQ87880.1.
AK304451 mRNA. Translation: BAG65268.1.
AK312812 mRNA. Translation: BAG35670.1.
AK315931 mRNA. Translation: BAH14302.1.
AC093908 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX05019.1.
CH471056 Genomic DNA. Translation: EAX05021.1.
BC022511 mRNA. Translation: AAH22511.1.
S55772 Genomic DNA. Translation: AAB25212.1.
AF014826 mRNA. Translation: AAB94859.1.
CCDSiCCDS3769.1. [P25101-1]
CCDS54810.1. [P25101-4]
CCDS58927.1. [P25101-5]
PIRiA44158.
RefSeqiNP_001159527.1. NM_001166055.1. [P25101-4]
NP_001243212.1. NM_001256283.1. [P25101-5]
NP_001948.1. NM_001957.3. [P25101-1]
UniGeneiHs.183713.

3D structure databases

ProteinModelPortaliP25101.
SMRiP25101.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108231. 21 interactors.
DIPiDIP-48718N.
IntActiP25101. 1 interactor.
STRINGi9606.ENSP00000315011.

Chemistry databases

BindingDBiP25101.
ChEMBLiCHEMBL252.
DrugBankiDB00945. Acetylsalicylic acid.
DB06403. Ambrisentan.
DB00559. Bosentan.
DB08932. MACITENTAN.
DB06268. Sitaxentan.
GuidetoPHARMACOLOGYi219.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP25101.
PhosphoSitePlusiP25101.
SwissPalmiP25101.

Polymorphism and mutation databases

BioMutaiEDNRA.
DMDMi119606.

Proteomic databases

PaxDbiP25101.
PeptideAtlasiP25101.
PRIDEiP25101.

Protocols and materials databases

DNASUi1909.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324300; ENSP00000315011; ENSG00000151617. [P25101-1]
ENST00000358556; ENSP00000351359; ENSG00000151617. [P25101-4]
ENST00000506066; ENSP00000425281; ENSG00000151617. [P25101-4]
ENST00000510697; ENSP00000427259; ENSG00000151617. [P25101-3]
ENST00000511804; ENSP00000425354; ENSG00000151617. [P25101-5]
GeneIDi1909.
KEGGihsa:1909.
UCSCiuc003iky.4. human. [P25101-1]

Organism-specific databases

CTDi1909.
DisGeNETi1909.
GeneCardsiEDNRA.
HGNCiHGNC:3179. EDNRA.
HPAiCAB018957.
HPA013774.
HPA014087.
MalaCardsiEDNRA.
MIMi131243. gene.
616367. phenotype.
neXtProtiNX_P25101.
OpenTargetsiENSG00000151617.
PharmGKBiPA27617.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000119177.
HOGENOMiHOG000169267.
HOVERGENiHBG051443.
InParanoidiP25101.
KOiK04197.
OMAiSIQWKNQ.
OrthoDBiEOG091G0CJV.
PhylomeDBiP25101.
TreeFamiTF331292.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000151617-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-416476. G alpha (q) signalling events.
SIGNORiP25101.

Miscellaneous databases

GeneWikiiEndothelin_receptor_type_A.
GenomeRNAii1909.
PROiP25101.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151617.
CleanExiHS_EDNRA.
GenevisibleiP25101. HS.

Family and domain databases

InterProiIPR000499. Endthln_rcpt.
IPR002175. ETA_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00570. ENDOTHELINAR.
PR00366. ENDOTHELINR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiEDNRA_HUMAN
AccessioniPrimary (citable) accession number: P25101
Secondary accession number(s): B2R723
, B4E2V6, B7Z9G6, D3DP03, E7ER36, O43441, Q16432, Q16433, Q8TBH2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: November 30, 2016
This is version 175 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.