Gene Report

Basic Information

Approved Symbol	EDN1
Approved Name	endothelin 1
Symbol Alias	ET1
Location	6p24.1
Position	chr6:12290529-12297427 (+)
External Links	Entrez Gene: 1906 Ensembl: ENSG00000078401 UCSC: uc003nae.4 HGNC ID: 3176
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between EDN1 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
EDN1	Guilloux JP, 2012	patients and normal controls		genes significantly affected in female MDD subjects genes significantly affected in female MDD subjects

Positive relationships between EDN1 and other components at different levels (count: 0)

Positive relationship network of EDN1 in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between EDN1 and MDD (count: 0)

Negative relationships between EDN1 and other components at different levels (count: 0)

EDN1 related SNPs in MK4MDD (count: 0)

EDN1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Endothelin-1	P05305	0(0/0)	Gene mapped

EDN1 related GO terms (count: 85)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0032269	negative regulation of cellular protein metabolic process	biological process	IDA[19767294]
GO:0042554	superoxide anion generation	biological process	IEA
GO:0045840	positive regulation of mitosis	biological process	IDA[10770212]
GO:0048661	positive regulation of smooth muscle cell proliferation	biological process	IDA[10393673]
GO:0007267	cell-cell signaling	biological process	IDA[12379507]
GO:0007589	body fluid secretion	biological process	IEA
GO:0019229	regulation of vasoconstriction	biological process	IEA
GO:0031708	endothelin B receptor binding	molecular function	IDA[10770212]
GO:0007166	cell surface receptor signaling pathway	biological process	IDA[1713452]
GO:0014824	artery smooth muscle contraction	biological process	IDA[8982507]; TAS[1725334]
GO:0005125	cytokine activity	molecular function	IDA[19767294]
GO:0007585	respiratory gaseous exchange	biological process	IEA
GO:0031583	phospholipase D-activating G-protein coupled receptor signaling pathway	biological process	IEA
GO:0045987	positive regulation of smooth muscle contraction	biological process	IEA
GO:0003100	regulation of systemic arterial blood pressure by endothelin	biological process	IDA[2649896]
GO:0005615	extracellular space	cellular component	IDA[15691296]
GO:0035810	positive regulation of urine volume	biological process	IEA
GO:0060585	positive regulation of prostaglandin-endoperoxide synthase activity	biological process	IMP[9492062]
GO:0030335	positive regulation of cell migration	biological process	IDA[9696419]
GO:0019722	calcium-mediated signaling	biological process	IDA[1917960]
GO:0014065	phosphatidylinositol 3-kinase cascade	biological process	IDA[17078114]
GO:0014826	vein smooth muscle contraction	biological process	IDA[9422810]
GO:0015758	glucose transport	biological process	IEA
GO:0035094	response to nicotine	biological process	IEA
GO:0045429	positive regulation of nitric oxide biosynthetic process	biological process	TAS[8999856]
GO:0071347	cellular response to interleukin-1	biological process	IEA
GO:0045321	leukocyte activation	biological process	TAS[16820593]
GO:0001516	prostaglandin biosynthetic process	biological process	IDA[9492062]
GO:0046887	positive regulation of hormone secretion	biological process	IDA[10770212]
GO:0009953	dorsal/ventral pattern formation	biological process	IEA
GO:0030185	nitric oxide transport	biological process	IDA[16820593]
GO:0007204	elevation of cytosolic calcium ion concentration	biological process	IDA[1917960]
GO:0042313	protein kinase C deactivation	biological process	IDA[16820593]
GO:0014032	neural crest cell development	biological process	IEA
GO:0007243	intracellular protein kinase cascade	biological process	IEA
GO:0042310	vasoconstriction	biological process	IDA[2649896]
GO:0070101	positive regulation of chemokine-mediated signaling pathway	biological process	IC[17178876]
GO:0031707	endothelin A receptor binding	molecular function	IDA[10770212]
GO:0007507	heart development	biological process	IEA
GO:0008284	positive regulation of cell proliferation	biological process	IDA[1917960]
GO:0042045	epithelial fluid transport	biological process	IEA
GO:0019233	sensory perception of pain	biological process	IEA
GO:0043179	rhythmic excitation	biological process	IEA
GO:0000122	negative regulation of transcription from RNA polymerase II promoter	biological process	IDA[19767294]
GO:0030818	negative regulation of cAMP biosynthetic process	biological process	IEA
GO:0071356	cellular response to tumor necrosis factor	biological process	IEA
GO:0051930	regulation of sensory perception of pain	biological process	IEA
GO:0030072	peptide hormone secretion	biological process	IDA[10770212]
GO:0010870	positive regulation of receptor biosynthetic process	biological process	IDA[17178876]
GO:0005737	cytoplasm	cellular component	IDA[12379507]
GO:0090023	positive regulation of neutrophil chemotaxis	biological process	IEA
GO:0032496	response to lipopolysaccharide	biological process	IEA
GO:0010613	positive regulation of cardiac muscle hypertrophy	biological process	IDA[12847114]
GO:0048016	inositol phosphate-mediated signaling	biological process	IDA[1917960]
GO:0001821	histamine secretion	biological process	IEA
GO:0034392	negative regulation of smooth muscle cell apoptotic process	biological process	IEA
GO:0043200	response to amino acid stimulus	biological process	IEA
GO:0045793	positive regulation of cell size	biological process	IDA[12847114]
GO:0060137	maternal process involved in parturition	biological process	IEA
GO:0042482	positive regulation of odontogenesis	biological process	IEA
GO:0007205	protein kinase C-activating G-protein coupled receptor signaling pathway	biological process	IEA
GO:0007186	G-protein coupled receptor signaling pathway	biological process	IDA[17078114]
GO:0051216	cartilage development	biological process	IEA
GO:0001701	in utero embryonic development	biological process	IEA
GO:0046888	negative regulation of hormone secretion	biological process	IEA
GO:0005179	hormone activity	molecular function	IDA[2649896]
GO:0005576	extracellular region	cellular component	TAS
GO:0033574	response to testosterone stimulus	biological process	IEA
GO:0060298	positive regulation of sarcomere organization	biological process	IMP[12847114]
GO:0043507	positive regulation of JUN kinase activity	biological process	IDA[12847114]
GO:0043406	positive regulation of MAP kinase activity	biological process	IDA[12847114]
GO:0006885	regulation of pH	biological process	IEA
GO:0030593	neutrophil chemotaxis	biological process	IDA[9696419]
GO:0010259	multicellular organismal aging	biological process	IEA
GO:0051771	negative regulation of nitric-oxide synthase biosynthetic process	biological process	IDA[16820593]
GO:0030195	negative regulation of blood coagulation	biological process	TAS[16820593]
GO:0001569	patterning of blood vessels	biological process	IEA
GO:0010460	positive regulation of heart rate	biological process	IDA[2649896]
GO:0051482	elevation of cytosolic calcium ion concentration involved in phospholipase C-activating G-protein coupled signaling pathway	biological process	IEA
GO:0010595	positive regulation of endothelial cell migration	biological process	TAS[8999856]
GO:0042474	middle ear morphogenesis	biological process	IEA
GO:0001666	response to hypoxia	biological process	IEA
GO:0035815	positive regulation of renal sodium excretion	biological process	IEA
GO:0016049	cell growth	biological process	IEA
GO:0051899	membrane depolarization	biological process	IEA

EDN1 related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04916	melanogenesis	Melanogenesis	Cutaneous melanin pigment plays a critical role in camouflag...... Cutaneous melanin pigment plays a critical role in camouflage, mimicry, social communication, and protection against harmful effects of solar radiation. Melanogenesis is under complex regulatory control by multiple agents. The most important positive regulator of melanogenesis is the MC1 receptor with its ligands melanocortic peptides. MC1R activates the cyclic AMP (cAMP) response-element binding protein (CREB). Increased expression of MITF and its activation by phosphorylation (P) stimulate the transcription of tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and dopachrome tautomerase (DCT), which produce melanin. Melanin synthesis takes place within specialized intracellular organelles named melanosomes. Melanin-containing melanosomes then move from the perinuclear region to the dendrite tips and are transferred to keratinocytes by a still not well-characterized mechanism. More...

EDN1 related BioCarta pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
NFAT_PATHWAY	nfat pathway	NFAT and Hypertrophy of the heart (Transcription in the broken heart)	Hypertrophy associated with both hypertension and obstructio...... Hypertrophy associated with both hypertension and obstruction to ventricular outflow leads to pathologic cardiac growth and it is associated with increase morbidity and mortality. Symptomatic ventricular disease takes a growing toll on the health of nations. As other cardiovascular diseases such as stroke and myocardial infraction are in decline as causes of mortality, the heart failure problem becomes increasingly urgent. Congenital heart defects occur in 1% of live births and fetal heart malformations are implicated in many pregnancies that end in still-birth or spontaneous abortion. The current paradigm suggests that the heart adapts to excess of hemodynamic loading by compensatory hypertrophy, which under condition of persistent stress, over time evolves into dysfunction and myocardial failure. There is considerable evidence that direct effects of increased mechanical stress are sensed within the ventricular wall and that signals critical for the generation of growth responses. Despite compelling statistics we still do not understand biochemically why heart defects are so prevalent. A single transcriptional regulator initially associated with the activation of the T-cells More...
HIF_PATHWAY	hif pathway	Hypoxia-Inducible Factor in the Cardiovascular System	Hypoxia (or low O2 levels) affects various pathologies. Firs...... Hypoxia (or low O2 levels) affects various pathologies. First, tissue ischemia, a variation in O2 tension caused by hypoxia/reoxygenation, can lead to endothelial cell changes. For example, long periods of ischemia result in endothelial changes, such as vascular leakage, resulting in varicose veins. In more severe situations, ischemia can lead to myocardial or cerebral infarction and retinal vessel occlusion. Of interest, HIF-1 is stabilized prior to induction of vascular endothelial growth factor (VEGF) expression during acute ischemia in the human heart. Second, pulmonary hypertension associated with chronic respiratory disorders results from persistent vasoconstriction and vascular remodeling. Third, hypoxic gradients created in enlarging solid tumors trigger expression of genes containing hypoxia response element (HRE)s such as those involved in angiogenesis. This allows subsequent delivery of O2, nutrients, and further tumor growth. Vascular remodeling is an important component to tumorigenesis; without proper blood supply, delivery of oxygen may occur by diffusion, but becomes inefficient in tumors greater than 1 mm in diameter. Short-term hypoxia can also elevate platelet numbers, while prolonged exposure may cause some degree of thrombocytopenia in response to increased levels of erythropoetin (EPO). Another disorder involving inadequate responses to hypoxia is preeclampsia, a pathology of pregnancy thought to be caused by improper differentiation of placental trophoblast cells due to poorly controlled O2 tension or improper hypoxia-inducible factor (HIF)-mediated responses. The primary molecular mechanism of gene activation during hypoxia is through HIF-1. Several genes involved in cellular differentiation are directly or indirectly regulated by hypoxia. These include EPO, LDH-A, ET-1, transferrin, transferrin receptor, VEGF, Flk-1, Flt-1, platelet-derived growth factor- (PDGF-), basic fibroblast growth factor (bFGF), and others genes affecting glycolysis. HIF-1 is a member of the basic helix-loop-helix (bHLH)-PAS family of transcription factors known to induce gene expression by binding to a ~50-bp HRE containing a core 5'-ACGTG-3' sequence. bHLH-PAS proteins heterodimerize to form transcription complexes that regulate O2 homeostasis, circadian rhythms, neurogenesis, and toxin metabolism. Three bHLH-PAS proteins in vertebrates respond to hypoxia: HIF-1 , EPAS (HIF-2 ), and HIF-3. These dimerize with ARNT (aryl hydrocarbon receptor nuclear translocator protein), ARNT-2, or ARNT-3. HIF-1 is ubiquitinated and subsequently degraded in less than 5 minutes under normoxic conditions. Although several candidate O2-sensing molecules have emerged in the literature, the molecular basis of how cells sense O2 levels is poorly characterized. pVHL, the protein product of a tumor-suppressor gene responsible for von Hippel Lindau disease, is implicated in this O2-sensing system by its association with HIF-1 , targeting it for ubiquitin-mediated degradation. Similarly, F-box-containing proteins recognize substrates of the ubiquitin ligases, targeting them for phosphorylation-dependent ubiquitination and proteosomal degradation. In addition to F-boxes, most of these proteins also contain a WD40 or a leucine-rich repeat (LLR) domain that presumably functions as a Ser/Thr binding module. A second family of proteins assisting the ubiquitin ligases share a region designated SOCS-box (originally from the suppressor of cytokine signaling proteins SOCS). Under low O2 (<5% O2) HIF-1 is stabilized leading to the formation of a functional transcription factor complex with ARNT. This complex is the master regulator of O2 homeostasis and induces a network of genes involved in angiogenesis, erythropoiesis, and glucose metabolism. More...
CARDIACEGF_PATHWAY	cardiacegf pathway	Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy	One of responses to increased blood pressure is cardiac hype...... One of responses to increased blood pressure is cardiac hypertrophy through increased size of ventricular myocardial cells leading to increased thickness of the ventricular walls. Cardiac hypertrophy allows the heart to handle the increased stress caused by elevated blood pressure but is also a risk factor associated with heart disease. Cardiac hypertrophy results from cross-talk between G-protein coupled receptor signaling and the EGF receptor pathway. Several GPCR ligands are known to stimulate cardiac hypertrophy, including factors that regulate blood pressure such as angiotensin II and endothelin- 1. These factors stimulate phospholipase C through Gq activation, and the production of 1P3 and diacylglycerol second messengers. PKC-delta is activated by DAG and interacts with the metalloproteinase ADAM12. ADAM12 cleaves the membrane-bound HB-EGF to release soluble EGF ligand that activates EGF receptor in myocardial cells. EGF receptor activation downstream through small G proteins and the MAP kinase pathway ultimately leads to cardiac hypertrophy. Signals by GPCR ligands such as angiotensin II result in transcriptional translation of immediate early genes like fos and other genes involved in long-term remodeling of heart tissue and the physiological response to stress in the heart such as the atrial natriuretic factor. Factors such as the AKT kinase, reactive oxygen species (ROS) and NE-kB also are involved in signaling that leads to hypertrophy, although their role is not yet clear. Blocking this pathway at various steps may prevent heart disease through the prevention of cardiac hypertrophy, but may also have other consequences. More...

EDN1 related Reactome pathways (count: 5)

ID	Name	Description
Gene mapped Reactome pathways
REACT_14819	peptide ligand_binding_receptors	These receptors, a subset of the Class A/1 (Rhodopsin-like) ...... These receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins. More...
REACT_14828	class a1_rhodopsin_like_receptors	Rhodopsin-like receptors. They represent members which inclu...... Rhodopsin-like receptors. They represent members which include hormone, light and neurotransmitter receptors and encompass a wide range of functions including many autocrine, paracrine and endocrine processes. More...
REACT_19184	downstream events_in_gpcr_signaling	G protein-coupled receptors. The beta:gamma G-protein dimer ...... G protein-coupled receptors. The beta:gamma G-protein dimer is also involved in downstream signaling , and some receptors form part of metastable complexes of receptor and accessory proteins such as the arrestins. GPCRs are involved in many diverse signaling events , using a variety of pathways that include modulation of adenylyl cyclase, phospholipase C, the mitogen activated protein kinases (MAPKs), extracellular signal regulated kinase (ERK) c-Jun-NH2-terminal kinase (JNK) and p38 MAPK. More...
REACT_18283	g alpha_q_signalling_events	The classic signalling route for G alpha (q) is activation o...... The classic signalling route for G alpha (q) is activation of phospholipase C beta thereby triggering phosphoinositide hydrolysis, calcium mobilization and protein kinase C activation. This provides a path to calcium-regulated kinases and phosphatases, GEFs, MAP kinase cassettes and other proteins that mediate cellular responses ranging from granule secretion, integrin activation, and aggregation in platelets. Gq participates in many other signalling events including direct interaction with RhoGEFs that stimulate RhoA activity and inhibition of PI3K. Both in vitro and in vivo, the G-protein Gq seems to be the predominant mediator of the activation of platelets. More...
REACT_21340	gpcr ligand_binding	There are more than 800 G-protein coupled receptor. GPCRs ar...... There are more than 800 G-protein coupled receptor. GPCRs are receptors for a diverse range of ligands from large proteins to photons and have an equal diverstiy of ligand-binding mechanisms. Classical GPCR signaling involves signal transduction via heterotrimeric G-proteins, however many G-protein independent mechanisms have been reported. More...

EDN1 related interactors from protein-protein interaction data in HPRD (count: 10)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
EDN1	COPS6	No	yeast 2-hybrid	16169070
EDN1	EDNRA	No	in vivo	10770212
EDN1	BAT3	No	yeast 2-hybrid	16169070
EDN1	UBQLN4	No	yeast 2-hybrid	16713569
EDN1	CMA1	No	in vitro	9257865
EDN1	EDNRB	No	in vitro;in vivo	12972292
EDN1	KEL	No	in vitro	10438732
EDN1	ECE1	No	in vitro;in vivo	10438732 , 10620363 , 9595387
EDN1	ADM	No	in vivo	11410113
EDN1	MME	No	in vitro	2201681

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways