View source for Biology:Trace amine-associated receptor

{{Short description|Class of G protein-coupled receptors}}
'''Trace amine-associated receptors''' ('''TAARs'''), sometimes referred to as '''trace amine receptors''' ('''TA'''s or '''TAR'''s), are a class of [[Biology:G protein-coupled receptor|G protein-coupled receptor]]s that were discovered in 2001.<ref name="pmid11459929">{{cite journal | vauthors = Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C | display-authors = 6 | title = Trace amines: identification of a family of mammalian G protein-coupled receptors | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 16 | pages = 8966–8971 | date = July 2001 | pmid = 11459929 | pmc = 55357 | doi = 10.1073/pnas.151105198 | doi-access = free }}</ref><ref name="pmid11723224">{{cite journal | vauthors = Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK | display-authors = 6 | title = Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor | journal = Molecular Pharmacology | volume = 60 | issue = 6 | pages = 1181–1188 | date = December 2001 | pmid = 11723224 | doi = 10.1124/mol.60.6.1181 }}</ref> [[Biology:TAAR1|TAAR1]], the first of six functional human TAARs, has gained considerable interest in academic and proprietary pharmaceutical research due to its role as the endogenous [[Biology:Receptor (biochemistry)|receptor]] for the [[Biology:Trace amine|trace amine]]s [[Biology:Phenethylamine|phenethylamine]], [[Chemistry:Tyramine|tyramine]], and [[Chemistry:Tryptamine|tryptamine]]&nbsp;– [[Biology:Metabolite|metabolic derivatives]] of the amino acids [[Chemistry:Phenylalanine|phenylalanine]], [[Chemistry:Tyrosine|tyrosine]] and [[Chemistry:Tryptophan|tryptophan]], respectively&nbsp;–  ephedrine, as well as the synthetic psychostimulants, [[Chemistry:Amphetamine|amphetamine]], [[Chemistry:Methamphetamine|methamphetamine]] and methylenedioxymethamphetamine ([[Chemistry:MDMA|MDMA]], ecstasy).<!--<ref name="Grandy" />--><ref name="Miller" /><ref name="In-vivo TAAR1">{{cite journal | vauthors = Lam VM, Espinoza S, Gerasimov AS, Gainetdinov RR, Salahpour A | title = In-vivo pharmacology of Trace-Amine Associated Receptor 1 | journal = European Journal of Pharmacology | volume = 763 | issue = Pt B | pages = 136–142 | date = September 2015 | pmid = 26093041 | doi = 10.1016/j.ejphar.2015.06.026 }}</ref><ref name="pmid15146179">{{cite journal | vauthors = Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK | display-authors = 6 | title = 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone | journal = Nature Medicine | volume = 10 | issue = 6 | pages = 638–642 | date = June 2004 | pmid = 15146179 | doi = 10.1038/nm1051 | s2cid = 2389946 }}</ref><ref name="pmid15860375">{{cite journal | vauthors = Lindemann L, Hoener MC | title = A renaissance in trace amines inspired by a novel GPCR family | journal = Trends in Pharmacological Sciences | volume = 26 | issue = 5 | pages = 274–281 | date = May 2005 | pmid = 15860375 | doi = 10.1016/j.tips.2005.03.007 }}</ref><ref name="pmid16451074">{{cite journal | vauthors = Hart ME, Suchland KL, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS | title = Trace amine-associated receptor agonists: synthesis and evaluation of thyronamines and related analogues | journal = Journal of Medicinal Chemistry | volume = 49 | issue = 3 | pages = 1101–1112 | date = February 2006 | pmid = 16451074 | doi = 10.1021/jm0505718 }}</ref><ref name="pmid17888514">{{cite journal | vauthors = Grandy DK | title = Trace amine-associated receptor 1-Family archetype or iconoclast? | journal = Pharmacology & Therapeutics | volume = 116 | issue = 3 | pages = 355–390 | date = December 2007 | pmid = 17888514 | pmc = 2767338 | doi = 10.1016/j.pharmthera.2007.06.007 }}</ref> In 2004, it was shown that mammalian TAAR1 is also a receptor for thyronamines, [[Chemistry:Decarboxylation|decarboxylated]] and [[Chemistry:Iodine|deiodinated]] relatives of thyroid hormones.<ref name="pmid15146179"/> TAAR2–TAAR9 function as [[Biology:Olfactory receptor|olfactory receptor]]s for [[Chemistry:Volatility|volatile]] [[Chemistry:Amine|amine]] odorants in [[Biology:Vertebrate|vertebrate]]s.<ref name="TAAR 2015 review - olfactory TAARs">{{cite journal | vauthors = Liberles SD | title = Trace amine-associated receptors: ligands, neural circuits, and behaviors | journal = Current Opinion in Neurobiology | volume = 34 | pages = 1–7 | date = October 2015 | pmid = 25616211 | pmc = 4508243 | doi = 10.1016/j.conb.2015.01.001 | quote = Roles for another receptor are supported by TAAR5-independent trimethylamine anosmias in humans [32].&nbsp;... Several TAARs detect volatile and aversive amines, but the olfactory system is capable of discarding ligand-based or function-based constraints on TAAR evolution. Particular TAARs have mutated to recognize new ligands, with almost an entire teleost clade losing the canonical amine-recognition motif. Furthermore, while some TAARs detect aversive odors, TAAR-mediated behaviors can vary across species.&nbsp;... The ability of particular TAARs to mediate aversion and attraction behavior provides an exciting opportunity for mechanistic unraveling of odor valence encoding. }}<br />[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4508243/figure/F2/ 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 [[Biology:Genome|genome]]s:<ref name="pmid19237578">{{cite journal | vauthors = Hussain A, Saraiva LR, Korsching SI | title = Positive Darwinian selection and the birth of an olfactory receptor clade in teleosts | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 11 | pages = 4313–4318 | date = March 2009 | pmid = 19237578 | pmc = 2657432 | doi = 10.1073/pnas.0803229106 | bibcode = 2009PNAS..106.4313H | doi-access = free }}</ref><ref name="pmid19325074">{{cite journal | vauthors = Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP | title = International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature | journal = Pharmacological Reviews | volume = 61 | issue = 1 | pages = 1–8 | date = March 2009 | pmid = 19325074 | pmc = 2830119 | doi = 10.1124/pr.109.001107 }}</ref>

* [[Biology:Human|Human]] –  6 [[Biology:Gene|gene]]s ([[Biology:TAAR1|TAAR1]], [[Biology:TAAR2|TAAR2]], [[Biology:TAAR5|TAAR5]], [[Biology:TAAR6|TAAR6]], [[Biology:TAAR8|TAAR8]], [[Biology:TAAR9|TAAR9]]) and 3 [[Biology:Pseudogene|pseudogene]]s ([[Biology:TAAR3|TAAR3]], {{Gene|TAAR4P}}, {{Gene|TAAR7P}})<ref name="IUPHAR update" />
* [[Biology:Common chimpanzee|Chimpanzee]] – 3 genes and 6 pseudogenes
* [[Biology:Mouse|Mouse]] – 15 genes and 1 pseudogene
* [[Biology:Rat|Rat]] – 17 genes and 2 pseudogenes
* [[Biology:Zebrafish|Zebrafish]] – 112 genes and 4 pseudogenes
* [[Biology:Frog|Frog]] – 3 genes and 0 pseudogenes
* Medaka – 25 genes and 1 pseudogenes
* [[Biology:Stickleback|Stickleback]] – 25 genes and 1 pseudogenes

==Human trace amine-associated receptors==
Six human trace amine-associated receptors (hTAARs) – [[Biology:TAAR1|hTAAR1]], [[Biology:TAAR2|hTAAR2]], [[Biology:TAAR5|hTAAR5]], [[Biology:TAAR6|hTAAR6]], [[Biology:TAAR8|hTAAR8]], and [[Biology:TAAR9|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.
<div style="overflow-x:auto"><!--This div formatting creates a horizontal scrollbar for the table when the page is viewed on a low resolution display.-->
{| class="wikitable unsortable" style="width:100%;"
|+ The pharmacology and molecular biology of human trace amine-associated receptors
! scope="col" style="padding: 3px;" | TAAR<br />subtype
! scope="col" style="padding: 3px;" | Prior<br />names
! scope="col" style="padding: 3px;" | [[Biology:Signal transduction|Signal<br />transduction]]
! scope="col" style="padding: 3px;" | [[Biology:Gene expression|Expression<br />profile]]
! scope="col" style="padding: 3px;" | Known or putative function in humans{{#tag:ref|{{As of|December 2017|post=,}} the functions of hTAAR2, hTAAR5, hTAAR6, hTAAR8, and hTAAR9 in the [[Biology:Central nervous system|CNS]] and peripheral tissues outside the olfactory epithelium have not been determined.<ref name="Berry hTAAR pharmacology December 2017 review" />|group="note"}}
! scope="col" style="padding: 3px;" | Known [[Biology:Ligand (biochemistry)|ligands]]
! scope="col" style="padding: 2px;" | <small>Sources</small>

|- <!--hTAAR1-->

! scope="row" style="text-align:center;" | [[Biology:TAAR1|hTAAR1]]
| style="text-align:center;" | <small>TA<sub>1</sub></small><br /><small>TAR1</small>
| style="text-align:center;" | {{nowrap|[[Biology:Gs alpha subunit|G<sub>s</sub>]]}}, {{nowrap|[[Biology:Gq alpha subunit|G<sub>q</sub>]]}},<br />[[Biology:G protein-coupled inwardly-rectifying potassium channel|GIRKs]],<br />{{nowrap|β-arrestin 2}}
| {{nowrap|[[Biology:Central nervous system|CNS]]:&thinsp;[[Biology:Human brain|brain]]&thinsp;<small>(widespread)</small>,}} [[Biology:Spinal cord|spinal cord]]<br />Periphery:&thinsp;pancreatic {{nowrap|β-cells}}, [[Biology:Stomach|stomach]], [[Biology:Duodenum|duodenum]], [[Chemistry:Intestine|intestine]]s, leukocytes, <small>elsewhere</small>{{#tag:ref|hTAAR1 is the only TAAR subtype that is not expressed within the human olfactory epithelium.<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Liberles_2006">{{cite journal | vauthors = Liberles SD, Buck LB | title = A second class of chemosensory receptors in the olfactory epithelium | journal = Nature | volume = 442 | issue = 7103 | pages = 645–650 | date = August 2006 | pmid = 16878137 | doi = 10.1038/nature05066 | bibcode = 2006Natur.442..645L | s2cid = 2864195 }}</ref> Hence, unlike all other human trace amine-associated receptors, hTAAR1 does not function as an [[Biology:Olfactory receptor|olfactory receptor]] in humans.<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Liberles_2006" />|group="note"}}
| style="white-space:nowrap;" | {{bull}}[[Biology:Central nervous system|CNS]]:&thinsp;[[Biology:Neuromodulation|modulation]] of monoamine/glutamate [[Biology:Neurotransmission|neurotransmission]]<br />{{bull}}CNS:&thinsp;regulation of cognitive processes & mood states<br />{{bull}}Periphery:&thinsp;leukocyte [[Physics:Chemotaxis|chemotaxis]]<br />{{bull}}Periphery:&thinsp;regulation of [[Biology:Gastrointestinal hormone|GI hormone]] release & blood glucose<br />{{bull}}Regulation of satiety & body weight
| style="white-space:nowrap;" | {{bull}}Trace amines <small>(e.g., [[Chemistry:Tyramine|tyramine]], [[Biology:Phenethylamine|PEA]], NMPEA)</small><br />{{bull}}Monoamine neurotransmitters <small>(e.g., [[Biology:Dopamine|dopamine]])</small><br />{{bull}}[[Chemistry:Amphetamine|Amphetamine]] and [[Biology:TAAR1#Synthetic|some structural analogs]]
| style="text-align:center;"  | <ref name="Miller">{{cite journal | vauthors = Miller GM | title = The emerging role of trace amine-associated receptor 1 in the functional regulation of monoamine transporters and dopaminergic activity | journal = Journal of Neurochemistry | volume = 116 | issue = 2 | pages = 164–176 | date = January 2011 | pmid = 21073468 | pmc = 3005101 | doi = 10.1111/j.1471-4159.2010.07109.x }}</ref><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" /><ref name="pmid23315425" />

|- <!--hTAAR2-->

! scope="row" style="text-align:center;" | [[Biology:TAAR2|hTAAR2]]<br />{{#tag:ref|hTAAR2 is a non-functional receptor in 10–15% of Asians due to the occurrence of a [[Biology:Single-nucleotide polymorphism|single-nucleotide polymorphism]] involving a premature stop codon in the human ''TAAR2'' gene.<ref name="IUPHAR update" /><ref name="Berry hTAAR pharmacology December 2017 review" />|group="note"}}
| style="text-align:center;" | <small>GPR58</small>
| style="text-align:center;" | {{nowrap|G<sub>olf</sub>}},<small> other [[Biology:G protein|G protein]]&nbsp;coupling unknown</small>{{#tag:ref|hTAAR2 has been found to be coexpressed with [[Biology:G alpha subunit|G<sub>α</sub> proteins]], however its exact signal transduction mechanisms have not yet been established.<ref name="Berry hTAAR pharmacology December 2017 review" /><ref name="IUPHAR TAAR2" />|group="note"}}
| {{nowrap|CNS:&thinsp;brain&thinsp;<small>(restricted)</small>{{#tag:ref|hTAAR2 expression has been observed in the human [[Biology:Cerebellum|cerebellum]].<ref name="Human trace amines and hTAARs October 2016 review" />|group="note"}}}}&thinsp;<br />Periphery:&thinsp;olfactory epithelium, intestines, [[Biology:Heart|heart]], testes, leukocytes
| style="white-space:nowrap;" | {{bull}}Periphery:&thinsp;leukocyte [[Physics:Chemotaxis|chemotaxis]]<br />{{bull}}[[Biology:Olfaction|Olfaction]]:&thinsp;[[Biology:Chemoreceptor|chemoreceptor]] for [[Chemistry:Volatility|volatile]] odorants{{#tag:ref|In humans and other animals, TAARs that are expressed in the olfactory epithelium function as [[Biology:Olfactory receptor|olfactory receptor]]s that detect [[Chemistry:Volatility|volatile]] [[Chemistry:Amine|amine]] odorants, including certain [[Biology:Pheromone|pheromone]]s;<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="IUPHAR TAAR" /> these TAARs putatively function as a class of pheromone receptors involved in the olfactive detection of social cues.<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="IUPHAR TAAR" /><br /><br />A review of studies involving non-human animals indicated that TAARs in the olfactory epithelium can mediate [[Philosophy:Reward system|attractive]] or [[Philosophy:Aversives|aversive]] behavioral responses to an [[Biology:Agonist|agonist]].<ref name="TAAR 2015 review - olfactory TAARs" /> This review also noted that the behavioral response evoked by a TAAR can vary across species.<ref name="TAAR 2015 review - olfactory TAARs" /> For example, TAAR5 mediates attraction to [[Chemistry:Trimethylamine|trimethylamine]] in mice and aversion to trimethylamine in rats.<ref name="TAAR 2015 review - olfactory TAARs" /> In humans, hTAAR5 presumably mediates aversion to trimethylamine, which is known to act as an hTAAR5 agonist and to possess a foul, fishy odor that is aversive to humans;<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="hTAAR5 and trimethylamine aversion">{{cite journal | vauthors = Wallrabenstein I, Singer M, Panten J, Hatt H, Gisselmann G | title = Timberol® Inhibits TAAR5-Mediated Responses to Trimethylamine and Influences the Olfactory Threshold in Humans | journal = PLOS ONE | volume = 10 | issue = 12 | pages = e0144704 | date = 2015 | pmid = 26684881 | pmc = 4684214 | doi = 10.1371/journal.pone.0144704 | bibcode = 2015PLoSO..1044704W | quote = While mice produce gender-specific amounts of urinary TMA levels and were attracted by TMA, this odor is repellent to rats and aversive to humans [19], indicating that there must be species-specific functions.&nbsp;... Furthermore, a homozygous knockout of murine TAAR5 abolished the attraction behavior to TMA [19]. Thus, it is concluded that TAAR5 itself is sufficient to mediate a behavioral response at least in mice.&nbsp;... Whether the TAAR5 activation by TMA elicits specific behavioral output like avoidance behavior in humans still needs to be examined. | doi-access = free }}</ref> however, hTAAR5 is not the only olfactory receptor that is responsible for trimethylamine olfaction in humans.<ref name="TAAR 2015 review - olfactory TAARs" /><ref name="hTAAR5 and trimethylamine aversion" /> {{As of|December 2015|post=,}} hTAAR5-mediated trimethylamine aversion has not been examined in published research.<ref name="hTAAR5 and trimethylamine aversion" />|name="pheromone"|group="note"}}<br />
| style="white-space:nowrap;" |
| style="text-align:center;"  | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR">{{cite web|title=Trace amine receptor: Introduction|url=http://www.iuphar-db.org/DATABASE/FamilyIntroductionForward?familyId=64|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 February 2014 | quote = Importantly, three ligands identified activating mouse Taars are natural components of mouse urine, a major source of social cues in rodents. Mouse Taar4 recognizes β-phenylethylamine, a compound whose elevation in urine is correlated with increases in stress and stress responses in both rodents and humans. Both mouse Taar3 and Taar5 detect compounds (isoamylamine and trimethylamine, respectively) that are enriched in male versus female mouse urine. Isoamylamine in male urine is reported to act as a pheromone, accelerating puberty onset in female mice [34]. The authors suggest the Taar family has a chemosensory function that is distinct from odorant receptors with a role associated with the detection of social cues.&nbsp;... The evolutionary pattern of the TAAR gene family is characterized by lineage-specific phylogenetic clustering [26,30,35]. These characteristics are very similar to those observed in the olfactory GPCRs and vomeronasal (V1R, V2R) GPCR gene families.}}</ref><ref name="pmid23315425">{{cite journal | vauthors = Babusyte A, Kotthoff M, Fiedler J, Krautwurst D | title = Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2 | journal = Journal of Leukocyte Biology | volume = 93 | issue = 3 | pages = 387–394 | date = March 2013 | pmid = 23315425 | doi = 10.1189/jlb.0912433 | doi-access = free }}</ref><br /><ref name="IUPHAR TAAR2">{{cite web|title=TAAR2|url=http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=167|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 May 2018 | quote = '''Primary Transduction Mechanisms'''<br />Comments: TAAR2 is found to be coexpressed with Gα proteins. However, the transduction pathway of TAAR2 is yet to be determined.}}</ref><ref name="Human trace amines and hTAARs October 2016 review">{{cite journal | vauthors = Khan MZ, Nawaz W | title = The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system | journal = Biomedicine & Pharmacotherapy | volume = 83 | pages = 439–449 | date = October 2016 | pmid = 27424325 | doi = 10.1016/j.biopha.2016.07.002 }}</ref>

|- <!--TAAR3 pseudogene-->

! scope="row" style="text-align:center;" | [[Biology:TAAR3|TAAR3]]
| style="text-align:center;"             | <small>GPR57</small>
| style="text-align:center;"             | {{abbr|N/A|not applicable}}
| style="text-align:left;"               | {{abbr|N/A|not applicable}}
| style="white-space:nowrap;"            | ''[[Biology:Pseudogene|Pseudogene]] in humans''&nbsp;– {{abbr|N/A|not applicable}}
| style="white-space:nowrap;"            | {{abbr|N/A|not applicable}}
| style="text-align:center;"             | <ref name="IUPHAR update" /><ref name="Berry hTAAR pharmacology December 2017 review">{{cite journal | vauthors = Berry MD, Gainetdinov RR, Hoener MC, Shahid M | title = Pharmacology of human trace amine-associated receptors: Therapeutic opportunities and challenges | journal = Pharmacology & Therapeutics | volume = 180 | pages = 161–180 | date = December 2017 | pmid = 28723415 | doi = 10.1016/j.pharmthera.2017.07.002 | doi-access = free }}</ref><br /><ref name="IUPHAR TAAR" />

|- <!--TAAR4 pseudogene-->

! scope="row" style="text-align:center;" | TAAR4
| style="text-align:center;"             | <small>TA<sub>2</sub></small>
| style="text-align:center;"             | N/A
| style="text-align:left;"               | N/A
| style="white-space:nowrap;"            | ''Pseudogene in humans''&nbsp;– N/A
| style="white-space:nowrap;"            | N/A
| style="text-align:center;"             | <ref name="IUPHAR update" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" />

|- <!--hTAAR5-->

! scope="row" style="text-align:center;" | [[Biology:TAAR5|hTAAR5]]
| style="text-align:center;" | <small>PNR</small>
| style="text-align:center;" | {{nowrap|[[Biology:Gs alpha subunit|G<sub>s</sub>]]}}, {{nowrap|G<sub>olf</sub>}},<br />{{nowrap|[[Biology:Gq alpha subunit|G<sub>q</sub>]]}}, {{nowrap|G<sub>12/13</sub>}}
| CNS:&thinsp;brain&thinsp;<small>(restricted)</small>,<br />spinal cord<br />Periphery:&thinsp;olfactory epithelium, intestines, testes, leukocytes
| style="white-space:nowrap;" | {{bull}}Olfaction:&thinsp;chemoreceptor for volatile & foul odorants<ref name="pheromone" group="note" />
| style="white-space:nowrap;" | {{bull}}Agonists: [[Chemistry:Trimethylamine|trimethylamine]], ''N'',''N''-DMEA<br />{{bull}}Inverse agonists: 3-iodothyronamine
| style="text-align:center;"  | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" /><ref name="Molecular Pharm">{{cite book|last=Offermanns|first=Stefan|title=Encyclopedia of Molecular Pharmacology |url=https://archive.org/details/encyclopediamole12rose|url-access=limited| year=2008 | publisher=Springer | location=Berlin | isbn=978-3540389163 | pages=[https://archive.org/details/encyclopediamole12rose/page/n1211 1219]–1222 | edition=2nd | editor = Walter Rosenthal}}</ref><br /><ref name="pmid23393561">{{cite journal | vauthors = Wallrabenstein I, Kuklan J, Weber L, Zborala S, Werner M, Altmüller J, Becker C, Schmidt A, Hatt H, Hummel T, Gisselmann G | display-authors = 6 | title = Human trace amine-associated receptor TAAR5 can be activated by trimethylamine | journal = PLOS ONE | volume = 8 | issue = 2 | pages = e54950 | year = 2013 | pmid = 23393561 | pmc = 3564852 | doi = 10.1371/journal.pone.0054950 | bibcode = 2013PLoSO...854950W | doi-access = free }}</ref><ref name="hTAAR5 ligands">{{cite journal | vauthors = Zhang J, Pacifico R, Cawley D, Feinstein P, Bozza T | title = Ultrasensitive detection of amines by a trace amine-associated receptor | journal = The Journal of Neuroscience | volume = 33 | issue = 7 | pages = 3228–3239 | date = February 2013 | pmid = 23407976 | pmc = 3711460 | doi = 10.1523/JNEUROSCI.4299-12.2013 | quote = We show that [human TAAR5] responds to the tertiary amine N,N-dimethylethylamine and to a lesser extent to trimethylamine, a structurally related agonist for mouse and rat TAAR5 (Liberles and Buck, 2006; Staubert et al., 2010; Ferrero et al., 2012). }}</ref><br /><ref name="hTAAR5 inverse agonist">{{cite journal | vauthors = Dinter J, Mühlhaus J, Wienchol CL, Yi CX, Nürnberg D, Morin S, Grüters A, Köhrle J, Schöneberg T, Tschöp M, Krude H, Kleinau G, Biebermann H | display-authors = 6 | title = Inverse agonistic action of 3-iodothyronamine at the human trace amine-associated receptor 5 | journal = PLOS ONE | volume = 10 | issue = 2 | pages = e0117774 | year = 2015 | pmid = 25706283 | pmc = 4382497 | doi = 10.1371/journal.pone.0117774 | bibcode = 2015PLoSO..1017774D | doi-access = free }}</ref>

|- <!--hTAAR6-->

! scope="row" style="text-align:center;" | [[Biology:TAAR6|hTAAR6]]
| style="text-align:center;" | <small>TA<sub>4</sub></small><br /><small>TAR4</small>
| style="text-align:center;" | {{nowrap|G<sub>olf</sub>}},<small> other [[Biology:G protein|G protein]]&nbsp;coupling unknown</small>
| CNS:&thinsp;brain<br />Periphery:&thinsp;olfactory epithelium, intestines, testes, leukocytes, kidneys
| style="white-space:nowrap;" | {{bull}}Olfaction:&thinsp;chemoreceptor for volatile odorants<ref name="pheromone" group="note" />
| style="white-space:nowrap;" | {{bull}}Agonists:  [[Chemistry:Putrescine|putrescine]] and [[Chemistry:Cadaverine|cadaverine]]<ref name="pmid29324768">{{cite journal | vauthors = Izquierdo C, Gómez-Tamayo JC, Nebel JC, Pardo L, Gonzalez A | title = Identifying human diamine sensors for death related putrescine and cadaverine molecules | journal = PLOS Computational Biology | volume = 14 | issue = 1 | pages = e1005945 | date = January 2018 | pmid = 29324768 | pmc = 5783396 | doi = 10.1371/journal.pcbi.1005945 | bibcode = 2018PLSCB..14E5945I | doi-access = free }}</ref>
| style="text-align:center;"  | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" /><ref name="IUPHAR TAAR6">{{cite web|title=TAAR6|url=http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=171|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 May 2018 | quote = '''Tissue Distribution'''<br /> Kidney, amygdala, hippocampus; Species: Human; Technique: RT-PCR&nbsp;...<br />Human brain tissues (with the level of expression descending from hippocampus, substantia nigra, amygdala, frontal cortex to basal ganglia), human fetal liver. Not detected in the cerebellum or placenta.; Species: Human; Technique: RT-PCR}}</ref>

|- <!--TAAR7 pseudogene-->

! scope="row" style="text-align:center;" | TAAR7
| style="text-align:center;"             | –
| style="text-align:center;"             | N/A
| style="text-align:left;"               | N/A
| style="white-space:nowrap;"            | ''Pseudogene in humans''&nbsp;– N/A
| style="white-space:nowrap;"            | N/A
| style="text-align:center;"             | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" />

|- <!--hTAAR8-->

! scope="row" style="text-align:center;" | [[Biology:TAAR8|hTAAR8]]
| style="text-align:center;" | <small>TA<sub>5</sub></small><br /><span style="font-size:70%">GPR102</span>
| style="text-align:center;" | {{nowrap|G<sub>olf</sub>}}, G<sub>i/o</sub>
| CNS:&thinsp;brain<br />Periphery:&thinsp;olfactory epithelium, melanocytes,<ref>{{cite journal | vauthors = Vaganova AN, Kuvarzin SR, Sycheva AM, Gainetdinov RR | title = Deregulation of Trace Amine-Associated Receptors (TAAR) Expression and Signaling Mode in Melanoma | journal = Biomolecules | volume = 12 | issue = 1 | pages = 114 | date = January 2022 | pmid = 35053262 | doi = 10.3390/biom12010114 | pmc = 8774021 | doi-access = free }}</ref> stomach, intestines, heart, testes, leukocytes, kidneys, [[Medicine:Lung|lung]]s, [[Biology:Muscle|muscle]], [[Biology:Spleen|spleen]]
| style="white-space:nowrap;" | {{bull}}Olfaction:&thinsp;chemoreceptor for volatile odorants<ref name="pheromone" group="note" />
| style="white-space:nowrap;" | {{bull}}Agonists:  [[Chemistry:Putrescine|putrescine]] and [[Chemistry:Cadaverine|cadaverine]]<ref name="pmid29324768"/>

| style="text-align:center;"  | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" /><ref name="Gi/o">{{cite journal | vauthors = Mühlhaus J, Dinter J, Nürnberg D, Rehders M, Depke M, Golchert J, Homuth G, Yi CX, Morin S, Köhrle J, Brix K, Tschöp M, Kleinau G, Biebermann H | display-authors = 6 | title = Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and expression profile | journal = International Journal of Molecular Sciences | volume = 15 | issue = 11 | pages = 20638–20655 | date = November 2014 | pmid = 25391046 | pmc = 4264187 | doi = 10.3390/ijms151120638 | doi-access = free }}</ref>

|- <!--hTAAR9-->

! scope="row" style="text-align:center;" | [[Biology:TAAR9|hTAAR9]]<br />{{#tag:ref|hTAAR9 is a functional receptor in most individuals, but a loss-of-function mutation – specifically, a polymorphic premature stop codon – in the human ''TAAR9'' gene occurs in 10–30% of individuals.<ref name="IUPHAR update">{{cite journal | vauthors = Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR, Pin JP, Spedding M, Harmar AJ | display-authors = 6 | title = International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands | journal = Pharmacological Reviews | volume = 65 | issue = 3 | pages = 967–986 | date = July 2013 | pmid = 23686350 | pmc = 3698937 | doi = 10.1124/pr.112.007179 | quote = '''TAAR2 and TAAR9''' Two of the trace amine receptors are inactivated in a portion of the human population. There is a polymorphism in TAAR2 (rs8192646) producing a premature stop codon at amino acid 168 in 10–15% of Asians. TAAR9 (formerly TRAR3) appears to be functional in most individuals but has a polymorphic premature stop codon at amino acid 61 (rs2842899) with an allele frequency of 10–30% in different populations (Vanti et al., 2003). TAAR3 (formerly GPR57) and TAAR4 (current gene symbol, TAAR4P) are thought to be pseudogenes in man though functional in rodents (Lindemann et al., 2005). }}</ref><ref name="Berry hTAAR pharmacology December 2017 review" />|group="note"}}
| style="text-align:center;" | <small>TA<sub>3</sub></small><br /><small>TAR3</small>
| style="text-align:center;" | {{nowrap|G<sub>olf</sub>}},<small> other [[Biology:G protein|G protein]]&nbsp;coupling unknown</small>
| CNS:&thinsp;spinal cord<br />Periphery:&thinsp;olfactory epithelium, intestines, leukocytes, [[Medicine:Pituitary gland|pituitary gland]], [[Biology:Skeletal muscle|skeletal muscle]], spleen
| style="white-space:nowrap;" | {{bull}}Olfaction:&thinsp;chemoreceptor for volatile odorants<ref name="pheromone" group="note" />
| style="white-space:nowrap;" | {{bull}}Agonist: N-Methyl piperidine (CAS: [http://www.commonchemistry.org/ChemicalDetail.aspx?ref=626-67-5 626-67-5])  <ref name="pmid25616211">{{cite journal | vauthors = Liberles SD | title = Trace amine-associated receptors: ligands, neural circuits, and behaviors | journal = Current Opinion in Neurobiology | volume = 34 | pages = 1–7 | date = October 2015 | pmid = 25616211 | pmc = 4508243 | doi = 10.1016/j.conb.2015.01.001 }}</ref>
| style="text-align:center;"  | <ref name="TAAR 2015 review - olfactory TAARs" /><ref name="Berry hTAAR pharmacology December 2017 review" /><br /><ref name="IUPHAR TAAR" /><ref name="IUPHAR TAAR9">{{cite web|title=TAAR9|url=http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=173|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 May 2018 | quote = '''Tissue Distribution Comments'''&nbsp;... No expression of TAAR9 was detected by RT-PCR in the Grueneberg ganglion [2]. TAAR9 expression was not detected by Northern blot analysis in thalamus, amygdala, midbrain, hippocampus, putamen, caudate, frontal cortex, pons, prostate, stomach, heart, bladder, small intestine, colon or uterus [4].}}</ref>
|-
| colspan=7 style="background:#F8F9FA;" | 
;Notes
{{reflist|group=note|1}}
|}</div>

===Disease links and clinical significance===
[[Chemistry:Ulotaront|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.<ref>{{cite journal | vauthors = Heffernan ML, Herman LW, Brown S, Jones PG, Shao L, Hewitt MC, Campbell JE, Dedic N, Hopkins SC, Koblan KS, Xie L | display-authors = 6 | title = Ulotaront: A TAAR1 Agonist for the Treatment of Schizophrenia | journal = ACS Medicinal Chemistry Letters | volume = 13 | issue = 1 | pages = 92–98 | date = January 2022 | pmid = 35047111 | pmc = 8762745 | doi = 10.1021/acsmedchemlett.1c00527 }}</ref><ref>{{Cite web |title=Sunovion: creating therapies to help transform people's lives |url=https://www.sunovion.com/ |access-date=2022-06-04 |website=www.sunovion.com}}</ref><ref>{{Cite web |title=Sunovion and PsychoGenics Announce that SEP-363856 Has Received FDA Breakthrough Therapy Designation for the Treatment of People with Schizophrenia |url=https://news.sunovion.com/press-releases/press-releases-details/2019/Sunovion-and-PsychoGenics-Announce-that-SEP-363856-Has-Received-FDA-Breakthrough-Therapy-Designation-for-the-Treatment-of-People-with-Schizophrenia/default.aspx |access-date=2022-06-04 |website=news.sunovion.com |language=en-US}}</ref>{{expand section|with=coverage of relevant material from this review<ref name="Berry hTAAR pharmacology December 2017 review" />|date=March 2018}}

== See also ==
* [[Biology:Olfactory receptor|Olfactory receptor]]
* Odorant
* [[Biology:Pheromone|Pheromone]]
* Pheromone receptor
* Psychostimulant
* [[Chemistry:Thyronamine|Thyronamine]]
* [[Biology:Trace amine|Trace amine]]

== References ==
{{Reflist}}

== External links ==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1355 | title = Trace Amine Receptors | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology }}
{{TAAR ligands|state=expanded}}
{{G protein-coupled receptors}}

[[Category:G protein-coupled receptors]]
[[Category:Neuroscience]]

{{Sourceattribution|Trace amine-associated receptor}}