Recombinant Human Trace amine-associated receptor 1 (TAAR1) Protein

Function

Intracellular G protein-coupled receptor for trace amines, which recognizes endogenous amine-containing metabolites such as beta-phenylethylamine (beta-PEA), 3-iodothyronamine (T1AM), isoamylamine (IAA), cadaverine (CAD), cyclohexylamine (CHA), p-tyramine (p-TYR), trimethylamine (TMA), octopamine and tryptamine (PubMed:11459929, PubMed:11723224, PubMed:15718104, PubMed:31399635, PubMed:36100653, PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38168118). Also functions as a receptor for various drugs and psychoactive substances, such as amphetamine and methamphetamine (PubMed:31399635, PubMed:37935376, PubMed:37935377). Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin (PubMed:11459929, PubMed:11723224). Expressed in both the central and peripheral nervous system: TAAR1 activation regulates the activity of several neurotransmitter signaling pathways by (1) decreasing the basal firing rates of the neurons involved and by (2) lowering the sensitivity of receptors to neurotransmitters (PubMed:37935376, PubMed:37935377, PubMed:37963465, PubMed:38168118). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors (PubMed:31399635, PubMed:37935376, PubMed:37963465). TAAR1 is coupled with different G(i)/G(o)-, G(s)- or G(q)/G(11) classes of G alpha proteins depending on the ligand (PubMed:31399635, PubMed:37935376, PubMed:37963465). CAD-binding is coupled to G(i)/G(o) G alpha proteins and mediates inhibition of adenylate cyclase activity (PubMed:37935376, PubMed:37963465). T1AM- or beta-PEA-binding is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity (PubMed:37935376, PubMed:37963465). CHA- or IAA-binding is coupled to G(q)/G(11) G alpha proteins and activates phospholipase C-beta, releasing diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers (PubMed:37935376, PubMed:37963465). TMA-binding is coupled with all three G(i)/G(o)-, G(s)- or G(q)/G(11) G alpha protein subtypes (PubMed:37935376, PubMed:37963465). Amphetamine-binding is coupled with G(s)- or G(12)/G(13) G alpha protein subtypes (PubMed:31399635)

Subcellular Location

Endomembrane system; Endoplasmic reticulum membrane (Multi-pass membrane protein); Cell membrane (Multi-pass membrane protein)

Tissue Specificity

Expressed at low level in both the central and peripheral nervous system (PubMed:11459929). Moderately expressed in stomach (PubMed:11459929). Low levels in amygdala, kidney, and lung, and small intestine (PubMed:11459929). Trace amounts in cerebellum, dorsal root ganglia, hippocampus, hypothalamus, liver, medulla, pancreas, pituitary, pontine reticular formation, prostate, skeletal muscle and spleen (PubMed:11459929)

• Borowsky B. et al. Trace amines: identification of a family of mammalian G protein-coupled receptors. — Proc. Natl. Acad. Sci. U.S.A. (2001)
• Bunzow J.R. et al. Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. — Mol. Pharmacol. (2001)
• Kopatz S.A. et al. cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org). (NOV-)
• Mungall A.J. et al. The DNA sequence and analysis of human chromosome 6. — Nature (2003)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lindemann L. et al. Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. — Genomics (2005)
• Underhill S.M. et al. Amphetamines signal through intracellular TAAR1 receptors coupled to Galpha13 and GalphaS in discrete subcellular domains. — Mol. Psychiatry (2021)
• Saarinen M. et al. TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT1A receptor agonist SEP-383856. — Neuropsychopharmacology (2022)