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CHRNA3 Membrane Protein Introduction

Introduction of CHRNA3

CHRNA3, also known as neuronal acetylcholine receptor subunit alpha-3 (NACHRA3), is a subunit in neuronal acetylcholine receptor (nAChRs) and is encoded by the CHRNA3 gene. nAChRs are ligand-gated ion channels activated by acetylcholine and nicotine, mediating synaptic transmission in brain and diverse functions in the periphery. nAChR is thought to be composed of different permutations of nine α subunits (α2–α10) and three β subunits (β2–β4) in humans. Some of these subunits form homopentameric receptors when expressed in heterologous expression systems (α7, α8 or α9), whereas other subunits assemble into heteropentameric structures with various combinations of α and β subunits. They form a dynamic structure which is able to adopt several conformational states responsible for different functional characteristics.

Basic Information of CHRNA3
Protein Name Neuronal acetylcholine receptor subunit alpha-3
Gene Name CHRNA3
Aliases NACHRA3
Organism Homo sapiens (Human)
UniProt ID P32297
Transmembrane Times 4
Length (aa) 505
Sequence MGSGPLSLPLALSPPRLLLLLLLSLLPVARASEAEHRLFERLFEDYNEIIRPVANVSDPVIIHFEVSMSQLVKVDEVNQIMETNLWLKQIWNDYKLKWNPSDYGGAEFMRVPAQKIWKPDIVLYNNAVGDFQVDDKTKALLKYTGEVTWIPPAIFKSSCKIDVTYFPFDYQNCTMKFGSWSYDKAKIDLVLIGSSMNLKDYWESGEWAIIKAPGYKHDIKYNCCEEIYPDITYSLYIRRLPLFYTINLIIPCLLISFLTVLVFYLPSDCGEKVTLCISVLLSLTVFLLVITETIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVLNVHYRTPTTHTMPSWVKTVFLNLLPRVMFMTRPTSNEGNAQKPRPLYGAELSNLNCFSRAESKGCKEGYPCQDGMCGYCHHRRIKISNFSANLTRSSSSESVDAVLSLSALSPEIKEAIQSVKYIAENMKAQNEAKEIQDDWKYVAMVIDRIFLWVFTLVCILGTAGLFLQPLMAREDA

Function of CHRNA3 Membrane Protein

nAChRs assembled with different subunits may mediate different physiological functions. The α3-containing nAChRs subtype plays a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages. In addition, several single nucleotide polymorphisms (SNPs) in NACHRA3 is identified to be associated with chronic obstructive pulmonary disease based on a Norwegian population. Moreover, both the CHRNA3 and CHRNA5 genes are expressed in areas of the human brain associated with addiction, such as the nucleus accumbens, amygdala and entorhinal cortex. The α3 and α5 subunits are obligate accessory subunits which cannot form functional nAChRs by themselves or in combination with only one other type of subunit. Moreover, the α3, α5 and β4 gene clusters are involved in the ethanol-induced stimulation and nicotine effects and play an important role in this process.

Fig.1 Schematic representation of an individual nAChR subunit protein. (Scofield. 2010)

Application of CHRNA3 Membrane Protein Literature

  1. Criado M. Acetylcholine nicotinic receptor subtypes in chromaffin cells. Journal of Physiology. 2018, 470(1):13-20. PubMed ID:28791474

    This article reports that the α3, β4 and α5 subunits are clustered in genomes of different species, with the transcription factor Sp1 playing a coordinating role in the transcriptional regulation of these three subunits.

  2. Kamens H.M., et al. The α3 subunit gene of the nicotinic acetylcholine receptor is a candidate gene for ethanol stimulation. Genes Brain Behav. 2009, 8(6):600-609. PubMed ID: 18826434

    This article describes that Chrna3 is a candidate gene for the acute locomotor stimulant response to ethanol that deserves further examination.

  3. Joshi P.K., et al. Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan. Nature Communications. 2016, 7:11174. PubMed ID: 27029810

    This article suggests that common variants near the apolipoprotein E and CHRNA5 genes are associated with lifespan and a locus near CHRNA3/5 differentially affecting paternal lifespan.

  4. Shmulewitz D., et al. CHRNA5/A3/B4 variant rs3743078 and nicotine-related phenotypes: indirect effects through nicotine craving. Journal of Studies on Alcohol & Drugs. 2016, 77(2):227-37. PubMed ID: 26997181

    This article suggests that CHRNA3, allele G of rs3743078 is associated with increased craving, CPD, and FTND scores and participants with several copies of the G allele smoke more cigarettes.

  5. Yang C., et.al. Role of α3-containing nicotinic acetylcholine receptors subtypes in vascular inflammation. British Journal of Pharmacology. 2016, 173(22):3235-3247. PubMed ID: 27572927

    This article indicates that α3-nAChRs play a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages and the mechanisms involve the modulations of multiple cell signaling pathways.

CHRNA3 Preparation Options

Membrane protein research has made significant progress over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a range of membrane protein preparation services for worldwide customers in reconstitution forms and multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-CHRNA3 antibody development services.


In the past years, Creative Biolabs has successfully produced many functional membrane proteins for our global customers. We are very honored to accelerate the development of our clients’ programs through our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

  1. Scofield M D. (2010). Elucidating the transcriptional network underlying expression of a neuronal nicotinic receptor gene: a dissertation. University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 497.

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