Trace amine-associated receptor

Trace amine-associated receptors, abbreviated TAAR and otherwise known as trace amine receptors, abbreviated TAR or TA, are a class of G protein-coupled receptors identified in 2001.^[1]^[2]^[3]

TAAR1 has gained considerable interest in academic and pharmaceutical industry research as endogenous receptors for trace amines, which are non-classical metabolic derivatives of phenylalanine and tryptophan and the psychostimulants amphetamine and methamphetamine.^[3]^[4]^[5]^[6]^[7]^[8]

In 2004 it was shown that in mammals TAAR1 is probably also a receptor for thyronamines, decarboxylated and deiodinated metabolites of the thyroid hormones,^[4] while the mouse mTAAR2 – mTAAR9 receptors are most probably olfactory receptors for volatile amines.^[9]^[10]

Animal TAAR complement 1
Receptor function and ligands 2
See also 3
External links 4
References 5

Animal TAAR complement

The following is a list of the TAARs contained in selected animal genomes:^[1]^[11]

Human — 6 genes (TAAR1, TAAR2, TAAR5, TAAR6, TAAR8, TAAR9), 2 pseudogenes (TAAR4P, TAAR7P), and one probable pseudogene (TAAR3)^[12]
Chimpanzee — 3 genes and 6 pseudogenes
Mouse — 15 genes and 1 pseudogene
Rat — 17 genes and 2 pseudogenes
Zebrafish — 112 genes and 4 pseudogenes
Frog — 3 genes and 0 pseudogenes
Medaka — 25 genes and 1 pseudogenes
Stickleback — 25 genes and 1 pseudogenes

Receptor function and ligands

HumanTAARs and their ligands
Group	Naming convention	Prior names	Known or putative function in humans^[13]	Known ligands	References
Group 1	TAAR1	TA1	• Neuromodulation of biogenic amines in the CNS • Chemotaxis of leukocytes • Chemoreceptor for volatile odorants^†	• Trace amines (e.g., phenethylamine, N-methylphenethylamine) • Classical monoamines (e.g., dopamine, serotonin, histamine) • Substituted amphetamines (e.g., amphetamine)	^[14]^[15]^[16]
Group 1	TAAR2^‡	GPR58	• Chemotaxis of leukocytes • Chemoreceptor for volatile odorants	phenethylamine, tyramine, 3-iodothyronamine	^[15]^[16]
Group 1	TAAR3	GPR57, GPR57P	Probably a pseudogene		^[12]^[15]
Group 1	~~TAAR4~~	–	Not present in humans		^[15]^[17]
Group 2	TAAR5	PNR	Chemoreceptor for volatile and foul odorants	trimethylamine, N,N-dimethylethylamine (agonists) 3-iodothyronamine (inverse agonist)	^[15]^[17]^[18]^[19]^[20]
Group 3	TAAR6	–	Chemoreceptor for volatile odorants		^[15]^[17]
Group 3	~~TAAR7~~	–	Not present in humans		^[15]^[17]
Group 3	TAAR8	TA5, TRAR5, TAR5, GPR102	Chemoreceptor for volatile odorants (Note: only known G_i/o-coupled TAAR)		^[15]^[17]^[21]
Group 3	TAAR9^‡	TA3, TRAR3, TAR3	Chemoreceptor for volatile odorants		^[15]^[17]

^†TAAR1 is not expressed in the human olfactory epithelium, but certain volatile odorants have been identified as agonists of hTAAR1;^[22] hence, it's not an olfactory receptor in spite of its capacity for odorant detection.^[22]

^‡TAAR2 is inactive in a subset of the human population, as there is a polymorphism with a premature stop codon in 10–15% of Asians.^[12]

^‡TAAR9 is a functional receptor in most of the population, but has a polymorphism with a premature stop codon in 10–30%, depending on the population subgroup.^[12]

External links

References

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TAAR ligands in humans

TAAR1

Agonists

Endogenous^†	Dopamine Histamine 3-Iodothyronamine 3-Methoxytyramine N-Methylphenethylamine N-Methyltyramine Norepinephrine m-Octopamine p-Octopamine Phenethylamine Phenylethanolamine Serotonin Synephrine Tryptamine m-Tyramine p-Tyramine

Synthetic^‡	Amphetamine DOB DOET 4-Hydroxyamphetamine Isoprenaline MDA MDMA 2-Methylphenethylamine 3-Methylphenethylamine 4-Methylphenethylamine β-Methylphenethylamine Methamphetamine 3-MMA Norfenfluramine Phentermine o-PIT Propylhexedrine RO5166017

Antagonists

EPPTB (RO5212773)

TAAR2

Agonists^‡	3-Iodothyronamine Phenethylamine Tyramine

Antagonists

TAAR5

Agonists^‡	Dimethylethylamine Trimethylamine

Antagonists^‡	3-Iodothyronamine

^†References for all endogenous human TAAR1 ligands are provided at List of trace amines

^‡References for synthetic TAAR1 agonists can be found at TAAR1 or in the associated compound articles. For TAAR2 and TAAR5 agonists and antagonists, see TAAR for references.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

Index of

Description	Pathways

Trace amine-associated receptor