EDNRA

Protein identityUniProt · HPA

UniProt accession

P25101

Gene

EDNRA

Ensembl

ENSG00000151617

Chromosome

4

Canonical length

427 aa

Protein class

Disease related genes, FDA approved drug targets, G-protein coupled receptors, Human disease related genes, Predicted membrane proteins

Subcellular location

Plasma membrane,Cytosol

OverviewNCBI Gene

This gene encodes the receptor for endothelin-1, a peptide that plays a role in potent and long-lasting vasoconstriction. This receptor associates with guanine-nucleotide-binding (G) proteins, and this coupling activates a phosphatidylinositol-calcium second messenger system. Polymorphisms in this gene have been linked to migraine headache resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Canonical amino-acid sequenceUniProt

427 residues, UniProt reviewed canonical sequence.

>P25101|EDNRA
     1  METLCLRASF WLALVGCVIS DNPERYSTNL SNHVDDFTTF RGTELSFLVT THQPTNLVLP
    61  SNGSMHNYCP QQTKITSAFK YINTVISCTI FIVGMVGNAT LLRIIYQNKC MRNGPNALIA
   121  SLALGDLIYV VIDLPINVFK LLAGRWPFDH NDFGVFLCKL FPFLQKSSVG ITVLNLCALS
   181  VDRYRAVASW SRVQGIGIPL VTAIEIVSIW ILSFILAIPE AIGFVMVPFE YRGEQHKTCM
   241  LNATSKFMEF YQDVKDWWLF GFYFCMPLVC TAIFYTLMTC EMLNRRNGSL RIALSEHLKQ
   301  RREVAKTVFC LVVIFALCWF PLHLSRILKK TVYNEMDKNR CELLSFLLLM DYIGINLATM
   361  NSCINPIALY FVSKKFKNCF QSCLCCCCYQ SKSLMTSVPM NGTSIQWKNH DQNNHNTDRS
   421  SHKDSMN

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against EDNRA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

7

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

107 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about EDNRA.

Disease | AllUniProt

Conditions EDNRA is implicated in, by any mechanism.

• Mandibulofacial dysostosis with alopecia (MFDA) MIM:616367

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 143 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Mandibulofacial dysostosis with alopecia

ReferencesPubMed · IEDB

Publications for EDNRA from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.25

gnomAD pLI

0.99

gnomAD missense Z

2.8

DepMap mean gene effect

0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• activation of adenylate cyclase activity
• adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
• aorta development
• artery smooth muscle contraction
• atrial cardiac muscle tissue development
• axon extension
• axonogenesis involved in innervation
• blood vessel remodeling
• branching involved in blood vessel morphogenesis
• calcium ion transmembrane transport
• cAMP/PKA signal transduction
• canonical Wnt signaling pathway
• cardiac chamber formation
• cardiac neural crest cell migration involved in outflow tract morphogenesis
• cell population proliferation
• cellular response to follicle-stimulating hormone stimulus
• cellular response to human chorionic gonadotropin stimulus
• cellular response to luteinizing hormone stimulus
• cellular response to oxidative stress
• cellular response to toxic substance
• cranial skeletal system development
• developmental pigmentation
• embryonic heart tube development
• embryonic skeletal system development
• endothelin receptor signaling pathway
• endothelin receptor signaling pathway involved in heart process
• enteric nervous system development
• establishment of endothelial barrier
• face development
• G protein-coupled receptor signaling pathway
• gene expression
• glomerular endothelium development
• glomerular filtration
• heparin proteoglycan metabolic process
• in utero embryonic development
• intracellular calcium ion homeostasis
• left ventricular cardiac muscle tissue morphogenesis
• meiotic cell cycle process involved in oocyte maturation
• mesenchymal cell apoptotic process
• middle ear morphogenesis
• mitochondrion organization
• mitotic cell cycle
• neural crest cell fate commitment
• neuromuscular process
• neuron remodeling
• noradrenergic neuron differentiation
• norepinephrine metabolic process
• pharyngeal arch artery morphogenesis
• phospholipase C-activating G protein-coupled receptor signaling pathway
• podocyte apoptotic process
• podocyte differentiation
• positive regulation of canonical NF-kappaB signal transduction
• positive regulation of cation channel activity
• positive regulation of cytosolic calcium ion concentration
• protein transmembrane transport
• regulation of blood pressure
• regulation of D-glucose transmembrane transport
• regulation of heart rate
• renal albumin absorption
• renal sodium ion absorption
• respiratory gaseous exchange by respiratory system
• response to acetylcholine
• response to amphetamine
• response to hypoxia
• response to wounding
• semaphorin-plexin signaling pathway involved in axon guidance
• signal transduction
• smooth muscle contraction
• sodium ion homeostasis
• sympathetic nervous system development
• sympathetic neuron axon guidance
• thyroid gland development
• vascular associated smooth muscle cell development
• vasoconstriction
• regulation of protein localization to cell leading edge

Molecular functions

• endothelin receptor activity
• phosphatidylinositol-4,5-bisphosphate phospholipase C activity

Cellular components

• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• G protein-coupled receptor, rhodopsin-like
• Endothelin receptor family
• GPCR, rhodopsin-like, 7TM
• G-protein coupled endothelin receptor
• 7 transmembrane receptor (rhodopsin family)
• Endothelin receptor A

KeywordsUniProt

• Cell membrane
• Disulfide bond
• G-protein coupled receptor
• Glycoprotein
• Hypotrichosis
• Membrane
• Phosphoprotein
• Receptor
• Signal
• Transducer
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of EDNRA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HDAC7
• KAT5