9.A.14.3.17

G-protein coupled receptor for 5-hydroxytryptamine (serotonin), 5-HTR2A of 471 aas and 7 TMSs (Cussac et al. 2008, Knauer et al. 2009). It also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD) (Wacker et al. 2017). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca²⁺ ions from intracellular stores. It affects neural activity, perception, cognition and mood (González-Maeso et al. 2008), and plays a role in the regulation of behavior, while acting as a receptor for human JC polyomavirus/JCPyV (Assetta et al. 2013). Additionally, 5-HT stimulates PLC/IP3 receptor signals via the 5-HT2A receptor, and the tmAC/PKA/CatSper channel signals via the 5-HT4 receptor. After sAC and PKA are activated by these stimulations, sperm hyperactivation is enhanced (Sakamoto et al. 2021). Lee et al. 2023 identified an activation switch" motif common to all aminergic receptors. This motif includes the middle subsegments of TMSs 3, 5, and 6 and integrates both the PIF motif and Trp.