5-HTR3C Membrane Protein Introduction

Introduction of 5-HTR3C

5-hydroxytryptamine receptor 3C (5-HTR3C), also called the serotonin receptor 3C, is subunit C of the type 3 receptor for 5-hydroxytryptamine (serotonin), which is identified as a biogenic hormone that functions as a neurotransmitter, a mitogen and a hormone. This receptor in humans is encoded by the HTR3C gene. Notably, the HTR3C gene is absent from the rodent genome. In human, it is found in many tissues including adult brain, intestine, colon, lung, stomach and muscle, as well as fetal colon and kidney.

Basic Information of 5-HTR3C
Protein Name	5-hydroxytryptamine receptor 3C
Gene Name	HTR3C
Aliases	Serotonin receptor 3C, 5-HT3-C, 5-HT3C
Organism	Homo sapiens (Human)
UniProt ID	Q8WXA8
Transmembrane Times	4
Length (aa)	447
Sequence	MEGGWPARQSALLCLTVSLLLQGRGDAFTINCSGFDQHGVDPAVFQAVFDRKAFRPFTNYSIPTRVNISFTLSAILGVDAQLQLLTSFLWMDLVWDNPFINWNPKECVGINKLTVLAENLWLPDIFIVESMDVDQTPSGLTAYISSEGRIKYDKPMRVTSICNLDIFYFPFDQQNCTFTFSSFLYTVDSMLLGMDKEVWEITDTSRKVIQTQGEWELLGINKATPKMSMGNNLYDQIMFYVAIRRRPSLYIINLLVPSSFLVAIDALSFYLPAESENRAPFKITLLLGYNVFLLMMNDLLPASGTPLISVYFALCLSLMVVSLLETVFITYLLHVATTQPPPMPRWLHSLLLHCTSPGRCCPTAPQKGNKGLGLTLTHLPGPKEPGELAGKKLGPRETEPDGGSGWTKTQLMELWVQFSHAMDTLLFRLYLLFMASSILTVIVLWNT

Function of 5-HTR3C Membrane Protein

The 5-HTR3 receptor is known as the only ligand-gated ion channel (LGIC) within the family of 5-HTR receptors. The 5-HTR3C receptor is a ligand-gated ion channel, which causes fast, depolarizing responses upon activation. It consists of a huge N-terminal extracellular segment that contains a cysteine loop, four hydrophobic transmembrane regions, a large intracellular loop between the third and fourth transmembrane region, and an extracellular C terminus. The 5-HTR3C receptor is a cation-specific, but otherwise relatively nonselective, ion channel. The 5-HTR3C subunit in human does not act as a homomer. One study has shown that 5-HTR3C subunit alone is incapable of forming functional receptors. However, coexpression with 5-HTR3A leads to the formation of functional heteromeric complexes with different serotonin efficacies. The potency of agonists and antagonists observed for homopentameric 5-HTR3A receptors will not be altered by the co-expression of the 5-HTR3C and 5-HTR3A subunits.

Fig.1 Ligand binding sites in the 5-hydroxytryptamine3 receptor. (Thompson, 2013)

Application of 5-HTR3C Membrane Protein in Literature

Mukoyama N., et al. An Analysis of Behavioral and Genetic Risk Factors for Chemotherapy-Induced Nausea and Vomiting in Japanese Subjects. Biol Pharm Bull. 2016, 39(11):1852-1858. PubMed ID: 27803457

The findings of this study indicate that serotonin 5-HT3C receptor gene is associated with the frequency of CINV.
Kapeller J., et al. Serotonin receptor diversity in the human colon: Expression of serotonin type 3 receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E. J Comp Neurol. 2011, 519(3):420-32. PubMed ID: 21192076

Authors in this article provide a strong basis for future studies of the roles that specific 5-HT3 receptor subtypes play functions in the enteric and central nervous systems.
Walstab J., et al. RIC-3 exclusively enhances the surface expression of human homomeric 5-hydroxytryptamine type 3A (5-HT3A) receptors despite direct interactions with 5-HT3A, -C, -D, and -E subunits. J Biol Chem. 2010, 285(35):26956-65. PubMed ID: 20522555

Authors in this study suggest that RIC-3 (a chaperone) can interact with 5-HT3A, -C, -D, and -E subunits.
Holbrook J.D., et al. Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits: evolution, distribution and function. J Neurochem. 2009, 108(2):384-96. PubMed ID: 19012743

The results show that the expression or function of 5-HT(3A) receptor is modified by 5-HT(3C) and 5-HT(3E).

5-HTR3C Preparation Options

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Reference

Thompson A J. (2013). Recent developments in 5-HT3 receptor pharmacology. Trends in pharmacological sciences. 34(2): pp.100-109.

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