Alpha-2A adrenergic receptor
Also known as: ADRA2A, ADRA2R, ADRAR
Function
Alpha-2 adrenergic receptors are G protein-coupled receptors for catecholamines that activate the G(i/o) protein pathway, thereby promoting adenylyl cyclase inhibition, ERK1/2 stimulation, and voltage-gated calcium channels suppression. Control a variety of physiological processes, such as regulation of blood pressure, lipolysis and insulin release. ADRA2A and ADRA2C mediates the presynaptic feedback inhibition of neurotransmitter release from noradrenergic nerve terminals in sympathetic and central nervous systems. ADRA2A inhibits transmitter release at high stimulation frequencies, whereas ADRA2C modulates neurotransmission at lower levels of nerve activity (By similarity). The rank order of potency for agonists of ADRA2A is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Classification
- Family (Pfam)
- PF00001 7tm_1
- InterPro
- ADR_fam, ADRA2A_rcpt, GPCR_Rhodpsn, GPCR_Rhodpsn_7TM
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 19
- 1HLL NMR
- 1HO9 NMR
- 1HOD NMR
- 1HOF NMR
- 6K42 EM 4.10A
- 6KUX X-ray 2.70A
- 6KUY X-ray 3.20A
- 7EJ0 EM 3.20A
- 7EJ8 EM 3.00A
- 7EJA EM 3.60A
- 7EJK EM 3.40A
- 7W6P EM 3.47A
- … and 7 more
A predicted model is available from AlphaFold.
Gene Ontology · 60
- GO:0043679 axon terminus
- GO:0016323 basolateral plasma membrane
- GO:0005737 cytoplasm
- GO:0098691 dopaminergic synapse
- GO:0098982 GABA-ergic synapse
- GO:0098978 glutamatergic synapse
- GO:0043025 neuronal cell body
- GO:0005886 plasma membrane
- GO:0098839 postsynaptic density membrane
- GO:0048787 presynaptic active zone membrane
- GO:0043235 receptor complex
- GO:0031692 alpha-1B adrenergic receptor binding
- GO:0031696 alpha-2C adrenergic receptor binding
- GO:0004938 alpha2-adrenergic receptor activity
- GO:0051379 epinephrine binding
- GO:0032795 heterotrimeric G-protein binding
- GO:0051380 norepinephrine binding
- GO:0042803 protein homodimerization activity
- GO:0019901 protein kinase binding
- GO:0031996 thioesterase binding
- GO:0030036 actin cytoskeleton organization
- GO:0071880 adenylate cyclase-activating adrenergic receptor signaling pathway
- GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
- GO:0071881 adenylate cyclase-inhibiting adrenergic receptor signaling pathway
- GO:0007193 adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
- GO:0071875 adrenergic receptor signaling pathway
- GO:0032870 cellular response to hormone stimulus
- GO:0006260 DNA replication
- GO:0007173 epidermal growth factor receptor signaling pathway
- GO:0007565 female pregnancy
- GO:0007186 G protein-coupled receptor signaling pathway
- GO:0042593 glucose homeostasis
- GO:0050892 intestinal absorption
- GO:0051926 negative regulation of calcium ion transport
- GO:0045955 negative regulation of calcium ion-dependent exocytosis
- GO:0032811 negative regulation of epinephrine secretion
- GO:0046676 negative regulation of insulin secretion
- GO:0061179 negative regulation of insulin secretion involved in cellular response to glucose stimulus
- GO:0050995 negative regulation of lipid catabolic process
- GO:0010700 negative regulation of norepinephrine secretion
- GO:0070473 negative regulation of uterine smooth muscle contraction
- GO:0071882 phospholipase C-activating adrenergic receptor signaling pathway
- GO:0030168 platelet activation
- GO:0030335 positive regulation of cell migration
- GO:0008284 positive regulation of cell population proliferation
- GO:0001819 positive regulation of cytokine production
- GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway
- GO:0043410 positive regulation of MAPK cascade
- GO:0051044 positive regulation of membrane protein ectodomain proteolysis
- GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
- GO:0043268 positive regulation of potassium ion transport
- GO:0090303 positive regulation of wound healing
- GO:0099171 presynaptic modulation of chemical synaptic transmission
- GO:0007265 Ras protein signal transduction
- GO:0019229 regulation of vasoconstriction
- GO:0097305 response to alcohol
- GO:0043278 response to morphine
- GO:0007266 Rho protein signal transduction
- GO:0050955 thermoception
- GO:0042311 vasodilation
Disease associations
- lipodystrophy, familial partial, type 8 MONDO:0958022
Drugs targeting this protein · 39
- IDAZOXAN antagonist
- LABETALOL HYDROCHLORIDE antagonist
- TIZANIDINE HYDROCHLORIDE agonist
- APRACLONIDINE HYDROCHLORIDE agonist
- BRIMONIDINE TARTRATE agonist
- TETRAHYDROZOLINE HYDROCHLORIDE agonist
- METHYLDOPATE HYDROCHLORIDE agonist
- GUANFACINE HYDROCHLORIDE agonist
- GUANABENZ ACETATE agonist
- HYDROXYAMPHETAMINE HYDROBROMIDE agonist
- PHENOXYBENZAMINE HYDROCHLORIDE antagonist
- OXYMETAZOLINE HYDROCHLORIDE agonist
- DIPIVEFRIN HYDROCHLORIDE agonist
- PHENTOLAMINE MESYLATE antagonist
- FIPAMEZOLE antagonist
- XYLOMETAZOLINE HYDROCHLORIDE agonist
- EPINEPHRINE BITARTRATE agonist
- CLONIDINE agonist
- NOREPINEPHRINE BITARTRATE agonist
- EPHEDRINE SULFATE agonist
- MOXISYLYTE antagonist
- TOLAZOLINE HYDROCHLORIDE antagonist
- CLONIDINE HYDROCHLORIDE agonist
- NAPHAZOLINE HYDROCHLORIDE agonist
- LOFEXIDINE HYDROCHLORIDE agonist
- AVIPTADIL antagonist
- DROXIDOPA agonist
- DEXMEDETOMIDINE HYDROCHLORIDE agonist
- FADOLMIDINE HYDROCHLORIDE agonist
- ESMIRTAZAPINE MALEATE antagonist
- EPHEDRINE HYDROCHLORIDE agonist
- ERGOLOID MESYLATES antagonist
- ERGOTAMINE TARTRATE agonist
- CELIPROLOL antagonist
- MEPHENTERMINE SULFATE agonist
- METHYLDOPA agonist
- MIRTAZAPINE antagonist
- LEVONORDEFRIN agonist
- EPINEPHRINE agonist
Related proteins · sequence + function similarity
- Alpha-2A adrenergic receptor 1.00
- Alpha-2A adrenergic receptor 0.99
- Alpha-2A adrenergic receptor 0.99
- Alpha-2A adrenergic receptor 0.99
- Alpha-2A adrenergic receptor 0.99
- Alpha-2C adrenergic receptor 0.94
- Alpha-2C adrenergic receptor 0.94
- Alpha-2C adrenergic receptor 0.93
- Alpha-2B adrenergic receptor 0.92
- Alpha-2B adrenergic receptor 0.92
- Alpha-2B adrenergic receptor 0.92
- Alpha-2B adrenergic receptor 0.91
Co-cited proteins · studied together in the literature
- Alpha-2C adrenergic receptor 1 shared papers
- Alpha-2A adrenergic receptor 1 shared papers
- Ras-related protein Rab-26 1 shared papers
- Alpha-2B adrenergic receptor 1 shared papers
Literature · 14 cited papers
- Structural insights into ligand recognition, activation, and signaling of the alpha2A adrenergic receptor. Sci. Adv. · 2022
- Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy. JCI Insight · 2016
- Rab26 modulates the cell surface transport of alpha2-adrenergic receptors from the Golgi. J. Biol. Chem. · 2012
- Complex haplotypes derived from noncoding polymorphisms of the intronless alpha-2A-adrenergic gene diversify receptor expression. Proc. Natl. Acad. Sci. U.S.A. · 2006
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The DNA sequence and comparative analysis of human chromosome 10. Nature · 2004
- NMR structure of the second intracellular loop of the alpha 2A adrenergic receptor: evidence for a novel cytoplasmic helix. Biochemistry · 2002
- An Asn to Lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling. J. Biol. Chem. · 2000
- Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science · 1987
- Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation. J. Biol. Chem. · 1989
- Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs. J. Biol. Chem. · 1990
- Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR. FEBS Lett. · 1991
- … and 2 more in the literature graph