TAAR1

Official Full Name

trace amine associated receptor 1

Organism

Homo sapiens

GeneID

134864

Background

The protein encoded by this gene is a G-protein coupled receptor activated by trace amines. The encoded protein responds little or not at all to dopamine, serotonin, epinephrine, or histamine, but responds well to beta-phenylethylamine, p-tyramine, octopamine, and tryptamine. While primarily functioning in neurologic systems, there is evidence that this gene is involved in blood cell and immunologic functions as well. This gene is thought to be intronless. [provided by RefSeq, Nov 2015]

Synonyms

TA1; TAR1; TRAR1;

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Price

Cat.No.	Product Name	Tag	Price

Cat.No.	Product Name	Price

Detailed Information

The TAAR1 gene encodes Trace Amine-Associated Receptor 1, a G protein-coupled receptor (GPCR) belonging to the class A rhodopsin-like family. TAAR1 is considered an intronless, single-exon gene, and its protein product features seven characteristic transmembrane α-helices, a topology typical of GPCRs. TAAR1 was the first member of the trace amine-associated receptor family to be successfully "deorphanized," with its endogenous ligands definitively identified. Unlike classical biogenic amine receptors, TAAR1 shows minimal or no response to major neurotransmitters such as dopamine, serotonin, norepinephrine, or histamine, and is instead selectively activated by a range of endogenous trace amines. These trace amines are low-abundance metabolic products of aromatic L-amino acid decarboxylase in the brain, whose physiological significance is increasingly recognized.

Biological Significance

TAAR1 functions as an intracellular GPCR that senses endogenous amine metabolites as well as exogenous psychoactive substances, acting as a regulatory "brake" in neural and psychophysiological homeostasis. Its ligand spectrum is broad, encompassing endogenous trace amines such as β-phenylethylamine, tyramine, octopamine, and tryptamine, as well as thyroid hormone metabolites like 3-iodothyronamine (T1AM). Importantly, TAAR1 is a direct molecular target for several drugs of abuse, including amphetamine and methamphetamine, which can bind and activate the receptor.

Figure 1. Illustration of signaling pathways underlying TAAR1 activation induced by its selective agonists. (Liu J, et al., 2024)

Upon activation, TAAR1 undergoes conformational changes and couples with different Gα protein subunits to initiate downstream signaling. The specificity of its signaling pathways is highly ligand-dependent. For example, cadaverine preferentially couples to Gi/Go proteins, inhibiting adenylyl cyclase activity; β-phenylethylamine and T1AM couple to Gs proteins, activating adenylyl cyclase and elevating intracellular cAMP; and certain ligands such as isopentylamine and cyclohexylamine can couple to Gq/G11 proteins, activating phospholipase C-β pathways. TAAR1 is broadly expressed in both central and peripheral nervous systems, particularly within monoaminergic neuronal pathways. Overall, TAAR1 activation modulates multiple neurotransmitter systems by reducing basal firing rates and desensitizing neurotransmitter receptors, serving as an endogenous "brake." This regulatory function is critical for maintaining the balance of dopaminergic, serotonergic, and glutamatergic signaling, and its dysregulation is closely associated with pathophysiology in schizophrenia, depression, and addiction.

Clinical Relevance

TAAR1 has emerged as a promising therapeutic target in neuropsychiatric disorders, particularly schizophrenia. Recognizing TAAR1 as a key modulator of multiple monoamine systems has led to the development of TAAR1 agonists as a novel strategy to circumvent the side effects associated with direct dopamine D2 receptor antagonism. Unlike conventional antipsychotics, TAAR1 agonists do not directly block D2 receptors but indirectly regulate mesolimbic dopaminergic activity through TAAR1 activation, theoretically alleviating positive symptoms while avoiding extrapyramidal side effects. Preclinical and clinical studies also indicate that TAAR1 agonists improve negative and cognitive symptoms of schizophrenia, areas where most existing drugs are limited. Selective TAAR1 agonists, such as Ulotaront, have advanced to late-stage clinical trials, showing significant efficacy and favorable tolerability, potentially representing the first non-D2 receptor-targeting antipsychotics in decades.

Beyond schizophrenia, TAAR1 is a promising target for depression and substance use disorders. In addiction studies, TAAR1 agonists reduce the rewarding effects and drug-seeking behaviors associated with amphetamines. Furthermore, TAAR1 expression in immune cells and peripheral organs suggests potential roles in immune regulation and metabolic control, opening new avenues for clinical applications. Although the complexity of ligand selectivity and signaling poses challenges for drug development, TAAR1, as an integrator of endogenous metabolic signals and neuropsychiatric function, offers unprecedented opportunities for next-generation central nervous system therapeutics.

References

Borowsky B, Adham N, Jones KA, et al. Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci U S A. 2001;98(16):8966-8971.
Revel FG, Moreau JL, Gainetdinov RR, et al. TAAR1 activation modulates monoaminergic neurotransmission, preventing hyperdopaminergic and hypoglutamatergic activity. Proc Natl Acad Sci U S A. 2011;108(20):8485-8490.
Dedic N, Jones PG, Hopkins SC, et al. SEP-363856, a novel psychotropic agent with a unique, non-D2 receptor mechanism of action. J Pharmacol Exp Ther. 2019;371(1):1-14.
Liu J, Wu R, Li JX. TAAR1 as an emerging target for the treatment of psychiatric disorders. Pharmacol Ther. 2024 Jan;253:108580.

Quick Inquiry

Interested in learning more?

Contact us today for a free consultation with the scientific team and discover how Creative Biogene can be a valuable resource and partner for your organization.

Request a quote today!

Inquiry