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FLASH GENE

Symbol

EDN1

contributors: mct/npt/pgu - updated : 18-06-2015

HGNC name	endothelin 1
HGNC id	3176

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001955 5 - 2117 NP_001946 24.2 212 - 2000 10708518

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive esophagus       highly   liver       highly Nervous brain       moderately Homo sapiens Respiratory lung       moderately Urinary kidney       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly Muscular striatum skeletal     Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

isoforms

Precursor

prepro ET1 cleaved to Big ET1 including a ET1-like peptide, then releasing mature ET1 (EDN1)

HOMOLOGY

interspecies	homolog to rattus Edn1 (72.14 pc)
	homolog to murine Edn1 (73.63 pc)

Homologene

FAMILY

endothelin/sarafotoxin family

CATEGORY

signaling hormone growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm

basic FUNCTION	endothelin 1, vaso-constrictor/pressor peptide
	phospholipase C activator, playing a role in airways, including bronchoconstriction, airway mucus secretion, cell proliferation, and inflammation
	playing a role on epithelial ion transport in airways
	playing a direct role in HDL metabolism
	endothelial cell-derived vasoconstrictor and growth factor
	potent vasoactive peptide that is synthesized and released by the vascular endothelium and is a marker of endothelial function
	induces cortical neurite elongation through the endothelin A receptor
	may exert its vasoconstrictive effects in part by targeting KCNK3
	induces mRNA and protein secretion of CCL2 and IL6, forming an autocrine signaling pathway that stimulates collagen accumulation in the extracellular matrix
	increases collagen deposition in the extracellular matrix by inducing an autocrine signaling loop involving secretion of CCL2 and IL6
	increases CCL2 and IL6 mRNAs and peptide secretion in mesangial cells
	role of EDN1 in linking TLR7 inflammatory signaling to subsequent fibrosis
	TGFbeta-induced EDN1 expression in dermal fibroblasts and showed that the TGFB1-induced expression of profibrotic genes was dependent on EDN1
	in part because it induces the unfolded protein response in pulmonary artery smooth muscle cells, triggers proinflammatory processes that likely contribute to vascular remodeling in pulmonary hypertension
	BMPs act upstream and in parallel to EDN1 to promote ventral fates in the arches during early dorsal-ventral patterning
	would act in a cooperative manner with EDN2, giving to the villus the straight enough to withstand mechanical stress
	potent vasoconstrictor, the production of which is mainly catalyzed by endothelin-converting enzymes (
	is a potent lymphangiogenic factor that relies on the interplay with hypoxic microenvironment and with VEGFA, VEGFC, and FIGF
	induces positive inotropy (enhanced contractility) in cardiac muscle
	EDN1 affects systolic Ca2+, and myofilament Ca2+ sensitivity and PRKCE is the upstream kinase involved in all of these intracellular regulatory processes
	integral role for ectoderm-derived EDN1 in early arch morphogenesis, particularly in the intermediate domain (
	essential role of endothelin 1 (EDN1) signaling through the endothelin receptor type A (EDNRA) in patterning the mandibular portion of the first pharyngeal arch
	RETN and EDN1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively
	EDN1 activation of EDNRA signalled through ARF6, which is crucial for lipolysis

CELLULAR PROCESS	cell life, proliferation/growth
	cell communication

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

components of the endothelin system, are EDN1, EDNRB and ECE1

INTERACTION

DNA

RNA

small molecule

protein	interacting with CHGA (variation in expression of the CHGA gene influences endothelial EDN1 secretion, explained by a CHGA stimulus/EDN1 secretion coupling in endothelial cells)
	EDNRB is involved in the regulation of the growth of and in the formation of functional vessels upon activation by EDN1
	interacting with ZNF260 (ZNF260 is an obligatory effector of EDN1 signaling in cardiomyocytes)
	interacting with IL6, and CCL2 (an autocrine signaling loop involving CCL2 and IL6 contributes to EDN1-induced collagen accumulation)
	link between EDN1 and EDNRA and myelination during oligodendrocyte differentiation
	decreases ABCG1 possibly due to the enhancement of the proteosome/calpain pathway-dependent degradation of ABCG1
	PRKCA, PRKCB, stimulates collecting duct EDN1 synthesis via transcriptional activation of the EDN1 promoter (
	GDF2 induced EDN1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation
	mediates the autocrine effect of endothelin-1 (EDN1) on endothelial cell survival
	CDC42 plays an important role in trophoblast migration and is obligatory for EDN1 action
	ARRB1 is a nuclear transcriptional regulator of EDN1-induced CTNNB1 signaling
	EDN1 regulates neural crest deployment and fate to form great vessels through DLX5/DLX6-independent mechanisms
	EDN1 stimulates RETN gene expression
	ARF6 plays a role in EDN1 promoted endothelial cell migration, and acts upstream of ERK in EDN1-induced lipolysis
	NR4A1 is a novel negative regulator of EDN1 expression in vascular ECs through an inhibitory interaction with the JUN pathway
	sarcolemmal and nuclear membrane CACNA1E in vascular smooth muscle cells are involved in EDN1 modulation of vascular tone in physiology and pathology

cell & other

REGULATION

induced by

GATA2 in endothelial cells

repressed by

GPER (endogenous GPER inhibits EDN1-induced vasoconstriction, an effect that may be associated with reduced VSMC Ca(2+) sensitivity)

Other	regulated by hypoxia in non endothelial cells (through overexpression of GATA2 and HIF1A)
	up-regulated by leptin

ASSOCIATED DISORDERS

corresponding disease(s)

ACDS3

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in clear cell renal tumor patients and hypertension tumoral     --low   in papillary renal tumor constitutional   deletion     ectodermal deletion of EDN1 results in craniofacial defects with concomitant changes in the expression of early mandibular arch patterning genes ( constitutional     --over   higher expressed in Alzheimer disease than in control tissue

Susceptibility

to coronary heart disease to developing cardiac hypertrophy

Variant & Polymorphism SNP , other	decreasing HDL level and increasing coronary heart disease
	homozygosity for the -1224A/198K haplotype, is associated with the risk of developing cardiac hypertrophy

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS