ADRA2A Membrane Protein Introduction

Introduction of ADRA2A

The alpha-2A adrenergic receptor (ADRA2A), which in humans is encoded by the ADRA2A gene, is an α₂adrenergic receptor. The gene ADRA2A encodes α2A subtype and it contains no introns in either its coding or untranslated sequences. α₂adrenergic receptors can be divided into 3 highly homologous subtypes: α_2A, α_2B, and α_2C, which are important in regulating neurotransmitter release from sympathetic nerves and adrenergic neurons in the central nervous system.

Basic Information of ADRA2A
Protein Name	Alpha-2A adrenergic receptor
Gene Name	ADRA2A
Aliases	Alpha-2 adrenergic receptor subtype C10, Alpha-2A adrenoreceptor, Alpha-2A adrenoceptor, Alpha-2AAR, ADRA2R, ADRAR
Organism	Homo sapiens (Human)
UniProt ID	P08913
Transmembrane Times	7
Length (aa)	450
Sequence	MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS LNPVIYTIFNHDFRRAFKKILCRGDRKRIV

Function of ADRA2A Membrane Protein

Several diseases are associated with ADRA2A, such as Horner's Syndrome and Gilles De La Tourette Syndrome. Among its related pathways are response to elevated platelet cytosolic Ca²⁺ and Monoamine GPCRs. Many post-synaptic α_2A receptors play important roles in brain function. α_2A receptors are localized on prefrontal cortical neurons in which they regulate higher cognitive function. α2 adrenoreceptors (α2-ARs) play a key role in the control of noradrenaline and dopamine release in the medial prefrontal cortex (mPFC). The ADRA2A rs553668 variant is also associated with type 2 diabetes. Adrenaline physiologically exerts its insulinostatic action via α2A-adrenoceptor-mediated attenuation of TRPM2 channels. α2A-adrenergic is also associated with osteoarthritis. Activation of α2A-adrenergic signal transduction in chondrocytes promotes degenerative remodeling of temporomandibular joint.

ADRA2A Membrane Protein Introduction Fig.1 Responses that can be mediated by α₂-adrenergic receptors. (Takahiko, 2000)

Application of ADRA2A Membrane Protein in Literature

1. Totomoch-Serra A., et al. The ADRA2A rs553668 variant is associated with type 2 diabetes and five variants were associated at nominal significance levels in a population-based case-control study from Mexico City. Gene. 2018. 669: 28-34. PubMed ID: 29800730

Authors in this group discovered that five variants of ADRA2A were associated at nominal significance levels in a population-based case-control study from Mexico City and the ADRA2A rs553668 variant is associated with type 2 diabetes.

2. Huang HC., et al. The Alpha-2A Adrenergic Receptor Gene - 1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder. Psychiatry Investig. 2018, 15(3): 306-312. PubMed ID: 29486545

The article reports that the ADRA2A gene - 1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents.

3. Ito K., et al. Endogenous α2A-Adrenoceptor-Operated Sympathoadrenergic Tones Attenuate Insulin Secretion via cAMP/TRPM2 Signaling. Diabetes. 2017, 66(3): 699-709. PubMed ID: 28028077

The article suggests that a physiological concentration of adrenaline attenuates insulin release via coupling of α2A-adrenoceptor to cAMP/TRPM2 signaling. The results provide a potential therapeutic tool to treat patients with type 2 diabetes.

4. Castelli MP., et al. α2A adrenergic receptors highly expressed in mesoprefrontal dopamine neurons. Neuroscience. 2016, 332: 130-9. PubMed ID: 27365174

Authors in this group investigated whether α2A-ARs might function as autoreceptors in the mesoprefrontal dopaminergic neurons, replacing the lack of D2 autoreceptors.

5. Adefurin A., et al. Alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction. Int J Cardiol. 2016, 215: 482-6. PubMed ID: 27131769

This article reveals that alpha2A adrenergic receptor genetic variation contributes to hyperglycemia after myocardial infarction. Three ADRA2A genetic variants in Caucasians are associated with blood glucose and stress-induced hyperglycemia after AMI.

ADRA2A Preparation Options

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Reference

Takahiko Kamibayashi. (2000). Clinical Uses of α²-Adrenergic Agonists. Anesthesiology. 93, 1345-1349.

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