The alpha-2B adrenergic receptor (α_2B adrenoceptor), is a

G-protein coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large protein family, group of evoluti ...

. It is a subtype of the

adrenergic receptor The adrenergic receptors or adrenoceptors are a class of G protein-coupled receptors that are targets of many catecholamines like norepinephrine (noradrenaline) and epinephrine (adrenaline) produced by the body, but also many medications like b ...

family. The human

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

encoding this receptor has the symbol ADRA2B. ADRA2B

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

have been identified in several

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

Receptor

α₂-adrenergic receptors include 3 highly homologous subtypes: α_2A, α_2B, and α_2C. These receptors have a critical role in regulating

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

release from

sympathetic nerves The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

and from adrenergic neurons in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

Clinical significance

This gene encodes the α_2B subtype, which was observed to associate with eIF-2B, a guanine nucleotide exchange protein that functions in regulation of

translation Translation is the communication of the semantics, meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The English la ...

. A polymorphic variant of the α_2B subtype, which lacks 3

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

s from a glutamic acid repeat element, was identified to have decreased

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

-mediated phosphorylation and desensitization; this polymorphic form is also associated with reduced

basal metabolic rate Basal metabolic rate (BMR) is the rate of energy expenditure per unit time by endothermic animals at rest.. In other words it is the energy required by body organs to perform normal It is reported in energy units per unit time ranging from watt ( ...

obese Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classified as obese when ...

subjects and may therefore contribute to the pathogenesis of obesity. This gene contains no

introns An intron is any Nucleic acid sequence, nucleotide sequence within a gene that is not expressed or operative in the final RNA product. The word ''intron'' is derived from the term ''intragenic region'', i.e., a region inside a gene."The notion of ...

in either its coding or untranslated sequences. A deletion variant of the α_2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans. This variant also predisposed people who had it to focus more on negative aspects of a situation. * This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant

reboxetine Reboxetine, sold under the brand name Edronax among others, is a selective norepinephrine reuptake inhibitor (sNRI) medication marketed as an antidepressant by Pfizer for use in the treatment of major depressive disorder, although it has also be ...

, but was weakened in people without the variant. *

Evolution

The ''ADRA2B'' gene (sometimes referenced as ''A2AB'') is used in animals as a

nuclear DNA Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. ...

phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of

, and contributed to reveal that

placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguished ...

orders are distributed into four major clades:

Xenarthra Xenarthra (; from Ancient Greek ξένος, xénos, "foreign, alien" + ἄρθρον, árthron, "joint") is a superorder and major clade of placental mammals native to the Americas. There are 31 living species: the anteaters, tree sloths, and ...

Afrotheria Afrotheria ( from Latin ''Afro-'' "of Africa" + ''theria'' "wild beast") is a superorder of placental mammals, the living members of which belong to groups that are either currently living in Africa or of African origin: golden moles, elephan ...

Laurasiatheria Laurasiatheria (; "Laurasian beasts") is a superorder of Placentalia, placental mammals that groups together true insectivores (eulipotyphlans), bats (chiropterans), carnivorans, pangolins (Pholidota, pholidotes), even-toed ungulates (Artiodacty ...

, and

Euarchontoglires Euarchontoglires (from: '' Euarchonta'' ("true rulers") + '' Glires'' ("dormice")), synonymous with Supraprimates, is a clade and a superorder of placental mammals, the living members of which belong to one of the five following groups: rodents ...

. Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein–coupling. However, great variations are observed in the very long, third intracellular loop, with a polyglutamyl domain displaying pervasive length differences.

Ligands

; Agonists * (−)-Dibromophakellin ; Antagonists * Imiloxan *

Yohimbine Yohimbine, also known as quebrachine, is an indole alkaloid derived from the bark of the African tree '' Pausinystalia johimbe'' (yohimbe); also from the bark of the unrelated South American tree '' Aspidosperma quebracho-blanco''. Yohimbine is ...

Receptor

Clinical significance

Evolution

Ligands

See also

References

External links

Further reading