Trace amine-associated receptors (TAARs), sometimes referred to as trace amine receptors (TAs or TARs), are a class of

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

s that were discovered in 2001.

TAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...

, the first of six functional human TAARs, has gained considerable interest in academic and proprietary pharmaceutical research due to its role as the

endogenous Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell. In contrast, exogenous substances and processes are those that originate from outside of an organism. For example, es ...

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

for the

trace amine Trace amines are an endogenous group of trace amine-associated receptor 1 (TAAR1) agonists – and hence, monoaminergic neuromodulators – that are structurally and metabolically related to classical monoamine neurotransmitters. Compared to the ...

s phenylethylamine,

tyramine Tyramine ( ) (also spelled tyramin), also known under several other names, is a naturally occurring trace amine derived from the amino acid tyrosine. Tyramine acts as a catecholamine releasing agent. Notably, it is unable to cross the blood-b ...

, and

tryptamine Tryptamine is an indolamine metabolite of the essential amino acid, tryptophan. The chemical structure is defined by an indole ─ a fused benzene and pyrrole ring, and a 2-aminoethyl group at the second carbon (third aromatic atom, with the f ...

– metabolic derivatives of the amino acids

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amino a ...

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...

and

tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α- carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromatic ...

, respectively – ephedrine, as well as the synthetic psychostimulants,

amphetamine Amphetamine (contracted from alpha- methylphenethylamine) is a strong central nervous system (CNS) stimulant that is used in the treatment of attention deficit hyperactivity disorder (ADHD), narcolepsy, and obesity. It is also commonly used ...

methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...

and methylenedioxymethamphetamine (

MDMA 3,4-Methylenedioxymethamphetamine (MDMA), commonly seen in Tablet (pharmacy), tablet form (ecstasy) and crystal form (molly or mandy), is a potent empathogen–entactogen with stimulant properties primarily used for Recreational dru ...

, ecstasy). In 2004, it was shown that

mammalian Mammals () are a group of vertebrate animals constituting the class (biology), class Mammalia (), characterized by the presence of mammary glands which in Female#Mammalian female, females produce milk for feeding (nursing) their young, a ...

TAAR1 is also a receptor for

thyronamines Thyronamine refers both to a molecule, and to derivatives of that molecule: a family of decarboxylated and deiodinated metabolites of the thyroid hormones thyroxine (T4) and 3,5,3'-triiodothyronine (T3). Types The group includes: * Thyronamine ...

, decarboxylated and deiodinated relatives of

thyroid hormone File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4 rect 376 268 820 433 Thyroid-stimulating hormone rect 411 200 849 266 Thyrotropin-releasing hormone rect 297 168 502 200 Hypothalamus rect 66 216 386 25 ...

s. TAAR2–TAAR9 function as

olfactory receptor Olfactory receptors (ORs), also known as odorant receptors, are chemoreceptors expressed in the cell membranes of olfactory receptor neurons and are responsible for the detection of odorants (for example, compounds that have an odor) which give ri ...

s for volatile

amine In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituen ...

odorant An aroma compound, also known as an odorant, aroma, fragrance or flavoring, is a chemical compound that has a smell or odor. For an individual chemical or class of chemical compounds to impart a smell or fragrance, it must be sufficiently vol ...

s in

vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, ...

s.
Figure 2: Table of ligands, expression patterns, and species-specific behavioral responses for each TAAR
/ref>

Animal TAAR complement

The following is a list of the TAARs contained in selected animal

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

s: *

Human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...

– 6

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s (

TAAR2 Trace amine-associated receptor 2 (TAAR2), formerly known as G protein-coupled receptor 58 (GPR58), is a protein that in humans is encoded by the ''TAAR2'' gene. TAAR2 is coexpressed with Gα proteins; however, its signal transduction mechanism ...

, TAAR5,

TAAR6 Trace amine associated receptor 6, also known as TAAR6, is a protein which in humans is encoded by the ''TAAR6'' gene. Function TAAR6 belongs to the trace amine-associated receptor family. Trace amines are endogenous amine compounds that are c ...

TAAR8 Trace amine-associated receptor 8 is a protein that in humans is encoded by the ''TAAR8'' gene. In humans, TAAR8 is the only trace amine-associated receptor that is known to be Gi/o-coupled. In humans, molecular modelling and docking experiments ...

TAAR9 Trace amine-associated receptor 9 is a protein that in humans is encoded by the ''TAAR9'' gene. TAAR9 is a member of a large family of rhodopsin G protein–coupled receptors (GPCRs, or GPRs). GPCRs contain 7 transmembrane domains and transduce ...

) and 3 pseudogenes (

TAAR3 Putative trace amine-associated receptor 3 (TAAR3) is a human pseudogene with the gene symbol ''TAAR3P''. Retrieved 28 November 2019 In other species such as mice, TAAR3 is a functional protein-coding gene that encodes a trace amine-associated ...

, , ) *

Chimpanzee The chimpanzee (''Pan troglodytes''), also known as simply the chimp, is a species of great ape native to the forest and savannah of tropical Africa. It has four confirmed subspecies and a fifth proposed subspecies. When its close relative th ...

– 3 genes and 6 pseudogenes *

Mouse A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

– 15 genes and 1 pseudogene * Rat – 17 genes and 2 pseudogenes *

Zebrafish The zebrafish (''Danio rerio'') is a freshwater fish belonging to the minnow family ( Cyprinidae) of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (and thus often ...

– 112 genes and 4 pseudogenes *

Frog A frog is any member of a diverse and largely Carnivore, carnivorous group of short-bodied, tailless amphibians composing the order (biology), order Anura (ανοὐρά, literally ''without tail'' in Ancient Greek). The oldest fossil "proto-f ...

– 3 genes and 0 pseudogenes *

Medaka The Japanese rice fish (''Oryzias latipes''), also known as the medaka, is a member of genus ''Oryzias'' ( ricefish), the only genus in the subfamily Oryziinae. This small (up to about ) native of East Asia is a denizen of rice paddies, marshes, ...

– 25 genes and 1 pseudogenes * Stickleback – 25 genes and 1 pseudogenes

Human trace amine-associated receptors

Six human trace amine-associated receptors (hTAARs) –

hTAAR1 Trace amine-associated receptor 1 (TAAR1) is a trace amine-associated receptor (TAAR) protein that in humans is encoded by the ''TAAR1'' gene. TAAR1 is an intracellular amine-activated and G protein-coupled receptor (GPCR) that is primarily ex ...

, hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 – have been identified and partially characterized. The table below contains summary information from literature reviews, pharmacology databases, and supplementary primary research articles on the expression profiles, signal transduction mechanisms, ligands, and physiological functions of these receptors.

Disease links and clinical significance

Ulotaront / SEP 363856 is a TAAR1 agonist in phase 3 clinical trials for schizophrenia and earlier trials for Parkinson's Disease psychosis. The medicine has obtained Breakthrough designation from the US FDA.

References

External links

* {{G protein-coupled receptors G protein-coupled receptors Neuroscience

Animal TAAR complement

Human trace amine-associated receptors

Disease links and clinical significance

See also

References

External links