Trace amine-associated receptor 1

UniProt Q96RJ0 Organism Homo sapiens Gene TA1, TAAR1, TAR1, TRAR1

Also known as: TA1, TAAR1, TAR1, TRAR1

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. Also functions as a receptor for various drugs and psychoactive substances, such as amphetamine and methamphetamine. Unresponsive to classical biogenic amines, such as epinephrine and histamine and only partially activated by dopamine and serotonin. 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. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors. 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. CAD-binding is coupled to G(i)/G(o) G alpha proteins and mediates inhibition of adenylate cyclase activity. T1AM- or beta-PEA-binding is coupled to G(s) G alpha proteins and mediates activation of adenylate cyclase activity. 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. TMA-binding is coupled with all three G(i)/G(o)-, G(s)- or G(q)/G(11) G alpha protein subtypes. Amphetamine-binding is coupled with G(s)- or G(12)/G(13) G alpha protein subtypes.

Classification

Family (Pfam): PF00001 7tm_1
InterPro: GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, TAAR, TAAR1, TAAR_fam
Functional cluster: G Protein-Coupled Receptors

Experimental structures · PDB · 17

8JLN EM 3.24A
8JLO EM 3.52A
8JLP EM 3.23A
8JLQ EM 2.84A
8JLR EM 3.00A
8JSO EM 3.40A
8UHB EM 3.35A
8W87 EM 2.80A
8W88 EM 2.60A
8W89 EM 3.00A
8W8A EM 2.80A
8WC8 EM 2.90A
… and 5 more

A predicted model is available from AlphaFold.

Gene Ontology · 9

Drugs targeting this protein · 1

ULOTARONT agonist

Related proteins · sequence + function similarity

Trace amine-associated receptor 1 1.00
Trace amine-associated receptor 1 1.00
Trace amine-associated receptor 3 0.97
Trace amine-associated receptor 1 0.97
Trace amine-associated receptor 1 0.96
Trace amine-associated receptor 3 0.96
Trace amine-associated receptor 2 0.96
Trace amine-associated receptor 13c 0.95
Trace amine-associated receptor 2 0.95
Trace amine-associated receptor 2 0.95
Trace amine-associated receptor 4 0.95
Trace amine-associated receptor 4 0.95

Co-cited proteins · studied together in the literature

Trace amine-associated receptor 1 3 shared papers
Trace amine-associated receptor 1 4 shared papers
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 1 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 4 shared papers
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 4 shared papers
5-hydroxytryptamine receptor 1A 2 shared papers
Guanine nucleotide-binding protein G(i) subunit alpha-1 3 shared papers
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short 2 shared papers
Trace amine-associated receptor 4 1 shared papers
Trace amine-associated receptor 7a 1 shared papers
Trace amine-associated receptor 7e 1 shared papers
Trace amine-associated receptor 7g 1 shared papers

Literature · 11 cited papers

Molecular basis of human trace amine-associated receptor 1 activation. Nat. Commun. · 2024
Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. Cell · 2023
Recognition of methamphetamine and other amines by trace amine receptor TAAR1. Nature · 2023
Ligand recognition and G-protein coupling of trace amine receptor TAAR1. Nature · 2023
TAAR1 dependent and independent actions of the potential antipsychotic and dual TAAR1/5-HT1A receptor agonist SEP-383856. Neuropsychopharmacology · 2022
Amphetamines signal through intracellular TAAR1 receptors coupled to Galpha13 and GalphaS in discrete subcellular domains. Mol. Psychiatry · 2021
Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and analysis of human chromosome 6. Nature · 2003
Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol. Pharmacol. · 2001
Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc. Natl. Acad. Sci. U.S.A. · 2001

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