Gene Report

Basic Information

Approved Symbol	ADRA2A
Approved Name	adrenoceptor alpha 2A
Previous Symbol	ADRA2, ADRA2R
Previous Name	adrenergic, alpha-2A-, receptor
Symbol Alias	ADRAR
Name Alias	alpha-2AAR subtype C10, " alpha-2A-adrenergic receptor"
Location	10q25.2
Position	chr10:112836790-112840665 (+)
External Links	Entrez Gene: 150 Ensembl: ENSG00000150594 UCSC: uc001kzo.3 HGNC ID: 281
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin; Protein mapped

Positive relationships between ADRA2A and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
ADRA2A	Klempan, 2009	patients and normal controls		Selected differentially expressed genes in BA44 to BA47 (ANO...... Selected differentially expressed genes in BA44 to BA47 (ANOVA and t-test P < 0.01, fold change 1.3t) More...

Positive relationships between ADRA2A and other components at different levels (count: 2)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
ADRA2A		Pro-opiomelanocortin(adrenocorticotropin)	protein	Haefner S, 2008	patients only	F = 4.9, d.f. = 2, p = 0.009	Male ADRA2A -1291G allele homozygotes showed significant pre...... Male ADRA2A -1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). More...
ADRA2A		Hydrocortisone(cortisol)	molecule	Haefner S, 2008	patients only	F = 6.4, d.f. = 2, p = 0.003	Male ADRA2A -1291G allele homozygotes showed significant pre...... Male ADRA2A -1291G allele homozygotes showed significant pretreatment HPA axis hyperactivity, with increased adrenocorticotropin (ACTH; F = 4.9, d.f. = 2, p = 0.009) and cortisol responses (F = 6.4, d.f. = 2, p = 0.003). More...

Positive relationship network of ADRA2A in MK4MDD

Network loading ...

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 ADRA2A and MDD (count: 0)

Negative relationships between ADRA2A and other components at different levels (count: 0)

ADRA2A related SNPs in MK4MDD (count: 0)

ADRA2A related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Alpha-2A adrenergic receptor	P08913	2(2/0)	Literature-origin

ADRA2A related GO terms (count: 63)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0016323	basolateral plasma membrane	cellular component	TAS[17655843]
GO:0030036	actin cytoskeleton organization	biological process	TAS[9624180]
GO:0005737	cytoplasm	cellular component	IDA[19477270]
GO:0005887	integral to plasma membrane	cellular component	IDA[10948191]
GO:0050995	negative regulation of lipid catabolic process	biological process	IGI[10948198]
GO:0008284	positive regulation of cell proliferation	biological process	TAS[10896916]
GO:0007266	Rho protein signal transduction	biological process	TAS[9624180]
GO:0005515	protein binding	molecular function	IPI[16531006]
GO:0032811	negative regulation of epinephrine secretion	biological process	NAS[16531006]
GO:0007565	female pregnancy	biological process	IEA
GO:0001819	positive regulation of cytokine production	biological process	IDA[17655843]
GO:0030168	platelet activation	biological process	TAS
GO:0006260	DNA replication	biological process	IEA
GO:0031692	alpha-1B adrenergic receptor binding	molecular function	ISS
GO:0051379	epinephrine binding	molecular function	IDA[10948191]
GO:0007165	signal transduction	biological process	TAS[2823383]
GO:0044281	small molecule metabolic process	biological process	TAS
GO:0046982	protein heterodimerization activity	molecular function	IPI[16605244]; ISS
GO:0004938	alpha2-adrenergic receptor activity	molecular function	IDA[10948191]; ISS[1354394]
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	biological process	IDA[17655843]
GO:0043235	receptor complex	cellular component	IDA[10948191]
GO:0005886	plasma membrane	cellular component	TAS
GO:0071883	activation of MAPK activity by adrenergic receptor signaling pathway	biological process	IDA[10948191]
GO:0051380	norepinephrine binding	molecular function	IDA[2823383]
GO:0051926	negative regulation of calcium ion transport	biological process	ISS
GO:0090303	positive regulation of wound healing	biological process	IMP[17655843]
GO:0045909	positive regulation of vasodilation	biological process	IEA
GO:0019901	protein kinase binding	molecular function	IPI[15653687]
GO:0007186	G-protein coupled receptor signaling pathway	biological process	ISS[19965390]
GO:0010700	negative regulation of norepinephrine secretion	biological process	NAS[16531006]; TAS[19477270]
GO:0050796	regulation of insulin secretion	biological process	TAS
GO:0032148	activation of protein kinase B activity	biological process	IDA[17215105]
GO:0006112	energy reserve metabolic process	biological process	TAS
GO:0007596	blood coagulation	biological process	TAS
GO:0030818	negative regulation of cAMP biosynthetic process	biological process	IDA[16531006]; ISS
GO:0006928	cellular component movement	biological process	TAS[9624180]
GO:0071878	negative regulation of adrenergic receptor signaling pathway	biological process	ISS
GO:0002526	acute inflammatory response	biological process	IEA
GO:0050892	intestinal absorption	biological process	TAS[17655843]
GO:0043406	positive regulation of MAP kinase activity	biological process	IDA[19477270]
GO:1901020	negative regulation of calcium ion transmembrane transporter activity	biological process	ISS[1354394]
GO:0061179	negative regulation of insulin secretion involved in cellular response to glucose stimulus	biological process	IMP[19965390]
GO:0042593	glucose homeostasis	biological process	IMP[10952463]
GO:0042596	fear response	biological process	IEA
GO:0045955	negative regulation of calcium ion-dependent exocytosis	biological process	IC[19965390]
GO:0030335	positive regulation of cell migration	biological process	IMP[17655843]
GO:0032795	heterotrimeric G-protein binding	molecular function	IDA[10948191]
GO:0031696	alpha-2C adrenergic receptor binding	molecular function	IPI[16605244]
GO:0007265	Ras protein signal transduction	biological process	TAS[8226727]
GO:0031996	thioesterase binding	molecular function	IPI[19477270]
GO:0071881	adenylate cyclase-inhibiting adrenergic receptor signaling pathway	biological process	IDA[10948191]
GO:0032870	cellular response to hormone stimulus	biological process	IGI[10948198]
GO:0045202	synapse	cellular component	IEA
GO:0071882	phospholipase C-activating adrenergic receptor signaling pathway	biological process	IDA[10948191]
GO:0043268	positive regulation of potassium ion transport	biological process	ISS[1354394]
GO:0007194	negative regulation of adenylate cyclase activity	biological process	ISS[1354394]
GO:0046676	negative regulation of insulin secretion	biological process	IMP[10952463]
GO:0050955	thermoception	biological process	IEA
GO:0035625	epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway	biological process	IDA[17215105]
GO:0070473	negative regulation of uterine smooth muscle contraction	biological process	IEA
GO:0045741	positive regulation of epidermal growth factor-activated receptor activity	biological process	IDA[17655843]
GO:0032147	activation of protein kinase activity	biological process	IDA[15653687]
GO:0042803	protein homodimerization activity	molecular function	IDA[16605244]

ADRA2A related KEGG pathways (count: 1)

Gene mapped KEGG pathways
ID	Name	Brief Description	Full Description
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction

ADRA2A related BioCarta pathways (count: 0)

ADRA2A related Reactome pathways (count: 11)

ID	Name	Description
Gene mapped Reactome pathways
REACT_604	hemostasis	Two principal mechanisms limit blood loss after vascular inj...... Two principal mechanisms limit blood loss after vascular injury. Initially, platelets are activated, adhere to the site of the injury, and aggregate into a plug that limits blood loss. Proteins and small molecules released from activated platelets stimulate the plug formation process, and fibrinogen from the plasma forms bridges between activated platelets. These events allow the initiation of the clotting cascade, the second mechanism to limit blood loss. Negatively charged phospholipids exposed on cell surfaces at the site of injury and on activated platelets interact with tissue factor, setting off a cascade of reactions leading to generation of fibrin and the formation of an insoluble fibrin clot that strengthens the platelet plug. 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_15380	diabetes pathways
REACT_18339	inhibition of_insulin_secretion_by_adrenaline_noradrenaline	The catecholamines adrenaline (epinephrine) and noradrenalin...... The catecholamines adrenaline (epinephrine) and noradrenaline (norepinephrine) inhibit insulin secretion from pancreatic beta cells. Four effects are seen in the cells: 1. Inhibition of exocytosis of secretory granules, the major effect. 2. Opening of ATP-sensitive potassium channels (KATP channels) and repolarization of the cell. 3. Closing of L-type voltage-dependent calcium channels and inhibition of calcium influx. 4. Inhibition of adenylyl cyclase activity. The first event in adrenaline/noradrenaline signaling in beta cells is the binding of adrenaline or noradrenaline to alpha-2 adrenergic receptors, which are G-protein coupled receptors. Binding activates the alpha subunits in heterotrimeric Gi and Go complexes to exchange GDP for GTP, forming the active G alpha:GTP complex. Experiments using specific antibodies against the alpha subunits in mice show that Gi alpha-1, Gi alpha-2, and Go alpha-2 are responsible for adrenergic effects. The exact beta and gamma subunits of the heterotrimeric G-proteins are unknown. After activation by GTP, the heterotrimeric complex dissociates into the G alpha:GTP complex and the beta:gamma complex. The G alpha:GTP complex causes the inhibition of exocytosis by an unknown mechanism that involves protein acylation. This is responsible for most of the observed inhibition of insulin secretion. Additionally, the G alpha:GTP complex activates (opens) KATP channels, allowing the cell to repolarize. The beta:gamma complex inhibits (closes) voltage-dependent calcium channels, reducing the intracellular calcium concentration, and inhibits adenylyl cyclase, reducing the intracellular cAMP concentration. More...
REACT_19231	g alpha_i_signalling_events	The classical signalling mechanism for G alpha (i) is inhibi...... The classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased activity of cAMP-dependent protein kinases. 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_18325	regulation of_insulin_secretion	Pancreatic beta cells integrate signals from several metabol...... Pancreatic beta cells integrate signals from several metabolites and hormones to control the secretion of insulin. In general, glucose triggers insulin secretion while other factors can amplify or inhibit the amount of insulin secreted in response to glucose. Factors which increase insulin secretion include the incretin hormones Glucose-dependent insulinotropic polypeptide (GIP and glucagon-like peptide-1 (GLP-1), acetylcholine, and fatty acids. Factors which inhibit insulin secretion include adrenaline and noradrenaline. More...
REACT_16983	amine ligand_binding_receptors	The class A (rhodopsin-like) GPCRs that bind to classical bi...... The class A (rhodopsin-like) GPCRs that bind to classical biogenic amine ligands are annotated here. The amines involved (acetylcholine, adrenaline, noradrenaline, dopamine, serotonin and histamine) can all act as neurotransmitters in humans. The so-called 'trace amines', used when referring to p-tyramine, beta-phenylethylamine, tryptamine and octopamine, can also bind to recently-discovered GPCRs. 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...
REACT_20	formation of_platelet_plug	Hemostasis is a physiological response that culminates in th...... Hemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Acute vessel injury results in its constriction to reduce the loss of blood. Under normal conditions vascular endothelium supports vasodilation, inhibits platelet adhesion and activation, suppresses coagulation, enhances fibrin cleavage and is anti-inflammatory in character. Under acute vascular trauma vasoconstrictor mechanisms predominate and the endothelium becomes prothrombotic, procoagulatory and proinflammatory in nature. This is achieved by a reduction of endothelial dilating agents: adenosine, NO and prostacyclin; and the direct action of ADP, serotonin and thromboxane on vascular smooth muscle cells to elicit their contraction. The chief trigger for the change in endothelial function that leads to the formation of haemostatic thrombus is the loss of the endothelial cell barrier between blood and ECM components. Circulating platelets identify and discriminate areas of endothelial lesions; here, they adhere to the exposed sub endothelium. Their interaction with the various thrombogenic substrates and locally generated or released agonists results in platelet activation. This process is described as possessing two stages, firstly, adhesion - the initial tethering to a surface, and secondly aggregation - the platelet-platelet cohesion. More...
REACT_278	platelet aggregation_plug_formation	The tethering of platelets to the site of vascular injury is...... The tethering of platelets to the site of vascular injury is the first step in the formation of a platelet thrombus. Firm adhesion of these tethered platelets, as well as the additional recruitment of others onto their surface leads to the formation of large platelet aggregates. The formation of a thrombus is strictly dependent on the formation of interplatelet bonds. More...

ADRA2A related interactors from protein-protein interaction data in HPRD (count: 8)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
ADRA2A	YWHAZ	No	in vitro;in vivo	10224112
ADRA2A	PRKCD	No	in vitro	11732925
ADRA2A	GNAI2	No	in vivo	7887906
ADRA2A	ADRB1	No	in vivo	12529373
ADRA2A	GNAI1	No	in vitro	11732925
ADRA2A	EIF2B1	No	in vitro;in vivo	9235896
ADRA2A	GNAO1	No	in vitro;in vivo	11732925 , 7887906
ADRA2A	ADRBK1	No	in vitro;in vivo	7876239

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped Reactome pathways