TAAR2

Protein-coding gene in the species Homo sapiens

TAAR2

Identifiers
Aliases| TAAR2, GPR58, taR-2, trace amine associated receptor 2, trace amine associated receptor 2 (gene/pseudogene)
External IDs| OMIM: 604849; MGI: 2685071; HomoloGene: 110760; GeneCards: TAAR2; OMA:TAAR2 - orthologs
| Gene location (Human)

Chr.| Chromosome 6 (human)[1]

Band| 6q23.2| Start| 132,617,022 bp[1]
End| 132,624,275 bp[1]
| Gene location (Mouse)

Chr.| Chromosome 10 (mouse)[2]

Band| 10|10 A4| Start| 23,814,470 bp[2]
End| 23,817,481 bp[2]
| RNA expression pattern

Bgee| | Human| Mouse (ortholog)

|

| Top expressed in

* testicle

* tibialis anterior muscle

* gonad

* deltoid muscle

* lower lobe of lung

* left testis

* right testis

| Top expressed in

* embryo

* morula

* nose

* nasal septum

* ganglion

* Grüneberg ganglion

* stomach

More reference expression data
BioGPS| |

More reference expression data
| Gene ontology

Molecular function|

* signal transducer activity
* G protein-coupled receptor activity
* trace-amine receptor activity

Cellular component|

* plasma membrane
* membrane
* integral component of membrane

Biological process|

* signal transduction
* G protein-coupled receptor signaling pathway

Sources:Amigo / QuickGO
| Orthologs

Species| Human| Mouse
Entrez| |

9287

209512

Ensembl| |

ENSG00000146378

ENSMUSG00000059763

UniProt| |

Q9P1P5

Q5QD17

RefSeq (mRNA)| |

NM_001033080
NM_014626

NM_001007266

RefSeq (protein)| |

NP_001028252
NP_055441

NP_001007267

Location (UCSC)| Chr 6: 132.62 – 132.62 Mb| Chr 10: 23.81 – 23.82 Mb
PubMed search| [3]| [4]
Wikidata
| View/Edit Human| View/Edit Mouse

|

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.[5][6][7][8] TAAR2 is co-expressed with Gα proteins;[8] however, as of February 2017,[update] its signal transduction mechanisms have not been determined.[8]

## Tissue distribution

[edit]

Human TAAR2 (hTAAR2) is expressed in the cerebellum, olfactory sensory neurons in the olfactory epithelium, and leukocytes (i.e., white blood cells), among other tissues.[9][10] hTAAR1 and hTAAR2 are both required for white blood cell activation by trace amines in granulocytes.[11]

Using brain histochemistry staining of mice with LacZ insertion into TAAR2 gene histochemical reaction was found in the glomerular layer of the olfactory bulb, but intensive staining was found in the deeper layer as well. The histochemical reaction was observed in the fibers of the olfactory nerve, in the glomeruli of the glomerular layer, several short axon (SA) cells (outer plexiform layer or granular layer) and neuronal projections that were visualized throughout the depth of the olfactory bulb. Furthermore, LacZ staining was observed in the limbic areas of the brain receiving olfactory input, i.e., piriform cortex molecular area, hippocampus (CA1 field, pyramidal layer), hypothalamic lateral zone (zone incerta) and lateral habenula. In addition, a histochemical reaction was found in the midbrain raphe nuclei and primary somatosensory area of the cortex (layer 5). Real-time quantitative PCR with reverse transcription confirmed TAAR2 gene expression in the mouse brain areas such as the frontal cortex, hypothalamus, and brainstem.[12][13]

## Involvement in the functioning of monoamine systems

[edit]

TAAR2 knockout mice have significantly higher level of dopamine in the striatum tissue than wild-type littermates and lower level of norepinephrine in hippocampus. Also, they have lower levels of MAO-B expression in midbrain and striatum. A significantly higher number of the dopamine neurons was detected in TAAR2-KO mice in the substantia nigra pars compacta. TAAR2 knockout mice have significantly higher level of horizontal activity and lower immobilization time in forced swim test.[12]

## Involvement in adult neurogenesis

[edit]

It has been found that TAAR2 knockout mice have an increased number of neuroblast-like and proliferating cells in both subventricular and subgranular zones of the dentate gyrus in comparison to wild type animals. Furthermore, TAAR2 knockout mice have an increased the brain-derived neurotrophic factor (BDNF) level in the striatum.[12]

A single nucleotide polymorphism nonsense mutation of the TAAR2 gene is associated with schizophrenia.[8][9] TAAR2 is a probable pseudogene in 10–15% of Asians as a result of a polymorphism that produces a premature stop codon at amino acid 168.[8]

## Involvement in immune cell migration and function

[edit]

TCells, B Cells and Peripheral Mononuclear cells express TAAR2 mRNA. Migration toward TAAR1 ligands required both TAAR1 and TAAR2 expression based on siRNA experiments.[11] In T cells, the same stimuli triggered cytokine secretion while in B cells Immunoglobulin secretion is triggered.[11]

## Possible Ligands

[edit]

3‐Iodothyronamine (T1AM) was identified as a non-selective ligand for TAAR2.[10] Additional TAAR1 ligands, tyramine and phenethylamine trigger TAAR2 dependant actions, though direct binding has not been demonstrated.[11]

## See also

[edit]

* Trace amine
* Trace amine-associated receptor

## References

[edit]

1. ^ a b c GRCh38: Ensembl release 89: ENSG00000146378 - Ensembl, May 2017
2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000059763 - Ensembl, May 2017
3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. ^ Lee DK, Lynch KR, Nguyen T, Im DS, Cheng R, Saldivia VR, et al. (February 2000). "Cloning and characterization of additional members of the G protein-coupled receptor family". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1490 (3): 311–23\. doi:10.1016/s0167-4781(99)00241-9. PMID 10684976.
6. ^ Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC (March 2005). "Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors". Genomics. 85 (3): 372–85\. doi:10.1016/j.ygeno.2004.11.010. PMID 15718104.
7. ^ "Entrez Gene: TAAR2 trace amine associated receptor 2".
8. ^ a b c d e Davenport AP, Alexander S, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga C, Battey J, Benya RV, Jensen RT, Karnik S, Kostenis E, Spindel E, Storjohann L, Tirupula K, Bonner TI, Neubig R, Pin JP, Spedding M, Harmar A (25 June 2015). "TAAR2". IUPHAR/BPS Guide to PHARMACOLOGY. International Union of Basic and Clinical Pharmacology. Retrieved 22 February 2017.
9. ^ a b Khan MZ, Nawaz W (October 2016). "The emerging roles of human trace amines and human trace amine-associated receptors (hTAARs) in central nervous system". Biomedicine & Pharmacotherapy. 83: 439–449\. doi:10.1016/j.biopha.2016.07.002. PMID 27424325.
10. ^ a b Cichero E, Tonelli M (May 2017). "New insights into the structure of the trace amine-associated receptor 2: Homology modelling studies exploring the binding mode of 3-iodothyronamine". Chemical Biology & Drug Design. 89 (5): 790–796\. doi:10.1111/cbdd.12903. PMID 27863038. S2CID 21073152.
11. ^ a b c d Babusyte A, Kotthoff M, Fiedler J, Krautwurst D (March 2013). "Biogenic amines activate blood leukocytes via trace amine-associated receptors TAAR1 and TAAR2". Journal of Leukocyte Biology. 93 (3): 387–94\. doi:10.1189/jlb.0912433. PMID 23315425. S2CID 206996784.
12. ^ a b c Efimova EV, Kuvarzin SR, Mor MS, Katolikova NV, Shemiakova T, Razenkova V, et al. (2022). "Trace Amine-Associated Receptor 2 Is Expressed in the Limbic Brain Areas and Is Involved in Dopamine Regulation and Adult Neurogenesis". Frontiers in Behavioral Neuroscience. 16: 847410. doi:10.3389/fnbeh.2022.847410. ISSN 1662-5153. PMC 9011332. PMID 35431833.
13. ^ Kuvarzin S, Efimova E, Mor M, Katolikova N, Smirnova D, Kozlova A, Gainetdinov R (17 November 2020). "Trace amine-associated receptor 2: brain expression and it's [sic] role in neurochemistry and behaviour". European Neuropsychopharmacology. 40: S41 – S42. doi:10.1016/j.euroneuro.2020.09.059. S2CID 226986365.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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Trace amine-associated receptor modulators

TAAR1Tooltip Trace amine-associated receptor 1|

| Agonists|

| Endogenous|

* Monoamine neurotransmitters
* Dopamine
* Histamine
* Epinephrine (adrenaline)
* Norepinephrine (noradrenaline)
* Serotonin
* Trace amines
* 3-Iodothyronamine
* 3-Methoxytyramine
* N-Methylphenethylamine
* N-Methyltyramine
* m-Octopamine
* p-Octopamine
* β-Phenethylamine
* Phenylethanolamine
* Synephrine
* Tryptamine
* m-Tyramine
* p-Tyramine
* Others
* Cyclohexylamine
* Isoamylamine
* Trimethylamine

|

Exogenous|

* 2C-B
* 2C-B-Fly
* 2C-E
* 2C-H
* 2C-P
* 2C-T-7
* A-77636
* 2-Aminoindane
* Amphetamine
* AP163
* Apomorphine
* Asenapine
* Bromocriptine
* Cathinone
* Chlorpromazine
* Clonidine
* Cyproheptadine
* Dihydroergotamine
* Dimethyltryptamine
* DOB
* DOET
* DOI
* DOM
* N,N-Dimethylphenethylamine
* Ergometrine
* Fenoldopam
* Fenoterol
* 4-Fluoroamphetamine
* Guanabenz
* Guanfacine
* Halostachine
* Higenamine
* Hordenine
* 4-Hydroxyamphetamine (norpholedrine)
* Idazoxan
* 5-Iodo-2-aminoindane
* Isoprenaline
* Isopropyloctopamine
* Lisuride
* LK00764
* LSD
* MDA (tenamfetamine)
* MDAI
* MDMA (midomafetamine)
* Mescaline
* Metergoline
* N-Methyl-2-AI
* 2-Methylphenethylamine
* 3-Methylphenethylamine
* 4-Methylphenethylamine
* β-Methylphenethylamine
* Methamphetamine
* MMA
* MPTP
* Naphazoline
* Nomifensine
* Norfenfluramine
* Oxymetazoline
* Phentermine
* Phentolamine
* o-PIT
* Psilocin
* Ralmitaront (RG-7906, RO6889450)
* RG-7351
* RG-7410
* RO5073012
* RO5166017
* RO5203648
* RO5256390
* RO5263397
* S18616
* Selegiline (L-deprenyl)
* Solriamfetol
* Tolazoline
* Ulotaront (SEP-363856)

Antagonists|

* Compound 22
* EPPTB (RO-5212773)
* RTI-7470-44

Inverse agonists|

* EPPTB (RO-5212773)

TAAR5Tooltip Trace amine-associated receptor 5|

| Agonists|

* N,N-Dimethylethylamine
* Trimethylamine

|

Inverse agonists|

* 3-Iodothyronamine

Notes: (1) TAAR1 activity of ligands varies significantly between species. Some agents that are TAAR1 ligands in some species are not in other species. This navbox includes all TAAR1 ligands regardless of species. (2) See the individual pages for references, as well as the List of trace amines, TAAR, and TAAR1 pages. See also: Receptor/signaling modulators

* v
* t
* e

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
* GHB receptor
* Histamine
* H1
* H2
* H3
* H4
* Melatonin (1A
* 1B
* 1C)
* TAAR (1
* 2
* 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)
* Hydroxycarboxylic acids
* 1
* 2
* 3
* Lysophosphatidic acid (1
* 2
* 3
* 4
* 5
* 6)
* Lysophospholipid (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8)
* 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 (1
* 2))
* 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)
* 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|

| Taste, bitter|

* 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
* Vomeronasal receptor type 1

|

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
* 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|

* ADGRB
* Brain-specific angiogenesis inhibitor
* 1
* 2
* 3
* ADGRC
* Cadherin
* 1
* 2
* 3
* ADGRE
* EMR
* 1
* 2
* 3
* CD97
* ADGRG
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* ADGRL
* Latrophilin
* 1
* 2
* 3
* ELTD1

|

Orphan|

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

Other|

* Calcitonin
* CALCRL
* Corticotropin-releasing hormone (1
* 2)
* Glucagon (GR
* GIPR
* GLP1R
* GLP2R)
* Growth-hormone-releasing hormone
* PACAPR1
* GPR
* Methuselah-like proteins
* Parathyroid hormone (1
* 2)
* Secretin
* Vasoactive intestinal peptide (1
* 2)

Class C: Metabotropic glutamate / pheromone

| Taste, sweet|

* TAS1R
* 1
* 2
* 3
* Vomeronasal receptor, type 2

|

Other|

* Calcium-sensing receptor
* GABAB (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

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* v
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[TAAR1]: Trace amine-associated receptor 1
*[TAAR5]: Trace amine-associated receptor 5