· S.P.H.Alexanderetal.TheConciseGuidetoPHARMACOLOGY2015/16:Gprotein-coupledreceptors.BritishJournalofPharmacology(2015)172,5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY

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The Concise Guide to PHARMACOLOGY 2015/16

Citation for published version:Alexander, SP, Davenport, AP, Kelly, E, Marrion, N, Peters, JA, Benson, HE, Faccenda, E, Pawson, AJ,Sharman, JL, Southan, C, Davies, JA & Collaborators, C 2015, 'The Concise Guide to PHARMACOLOGY2015/16: G protein-coupled receptors', British Journal of Pharmacology, vol. 172, no. 24, pp. 5744-5869.https://doi.org/10.1111/bph.13348

Digital Object Identifier (DOI):10.1111/bph.13348

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S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2015/16: G protein-coupled receptors. British Journal of Pharmacology (2015) 172, 5744–5869

THE CONCISE GUIDE TO PHARMACOLOGY 2015/16:G protein-coupled receptors

Stephen PH Alexander1, Anthony P Davenport2, Eamonn Kelly3, Neil Marrion3, John A Peters4,Helen E Benson5, Elena Faccenda5, Adam J Pawson5, Joanna L Sharman5, Christopher Southan5,Jamie A Davies5 and CGTP Collaborators

1School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK,2Clinical Pharmacology Unit, University of Cambridge, Cambridge, CB2 0QQ, UK,3School of Physiology and Pharmacology, University of Bristol, Bristol, BS8 1TD, UK,4Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK,5Centre for Integrative Physiology, University of Edinburgh, Edinburgh, EH8 9XD, UK

Abstract

The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebaseof drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13348/full. G protein-coupled receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: ligand-gated ion channels, voltage-gatedion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the bestavailable pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets.It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presentedin the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classificationand nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable,point-in-time record that will survive database updates.

Conflict of interest

The authors state that there are no conflicts of interest to declare.

c 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Overview: G protein-coupled receptors (GPCRs) are the largestclass of membrane proteins in the human genome. The term"7TM receptor" is commonly used interchangeably with "GPCR",although there are some receptors with seven transmembranedomains that do not signal through G proteins. GPCRs sharea common architecture, each consisting of a single polypeptidewith an extracellular N-terminus, an intracellular C-terminus andseven hydrophobic transmembrane domains (TM1-TM7) linkedby three extracellular loops (ECL1-ECL3) and three intracellular

loops (ICL1-ICL3). About 800 GPCRs have been identified inman, of which about half have sensory functions, mediating ol-faction ( 400), taste (33), light perception (10) and pheromonesignalling (5) [1309]. The remaining 350 non-sensory GPCRsmediate intersignalling by ligands that range in size from smallmolecules to peptide to large proteins; they are the targets forthe majority of drugs in clinical usage [1451, 1560], althoughonly a minority of these receptors are exploited therapeutically.The first classification scheme to be proposed for GPCRs [984] di-

vided them, on the basic of sequence homology, into six classes.These classes and their prototypemembers were as follows: ClassA (rhodopsin-like), Class B (secretin receptor family), Class C(metabotropic glutamate), Class D (fungal mating pheromonereceptors), Class E (cyclic AMP receptors) and Class F (friz-zled/smoothened). Of these, classes D and E are not found invertebrates. An alternative classification scheme "GRAFS" [1666]divides vertebrate GPCRs into five classes, overlapping with theA-F nomenclature, viz:

Searchable database: http://www.guidetopharmacology.org/index.jsp G-Protein-coupled receptors 5744

Full Contents of ConciseGuide: http://onlinelibrary.wiley.com/doi/10.1111/bph.13348/full

http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=694http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=694http://www.guidetopharmacology.orghttp://onlinelibrary.wiley.com/doi /10.1111/bph.13348/fullhttp://onlinelibrary.wiley.com/doi /10.1111/bph.13348/fullhttp://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/17139284?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/24016212?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/8081729?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/15862553?dopt=AbstractPlushttp://www.guidetopharmacology.org/index.jsphttp://www.guidetopharmacology.org/index.jsp


Glutamate family (class C), which includes metabotropic glutamate receptors, a calcium-sensing receptor and GABAB receptors, as well as three taste type 1 receptors [class C list] and a family ofpheromone receptors (V2 receptors) that are abundant in rodents but absent in man [1309].

Rhodopsin family (class A), which includes receptors for a wide variety of small molecules, neurotransmitters, peptides and hormones, together with olfactory receptors, visual pigments, taste type 2receptors and five pheromone receptors (V1 receptors). [Class A list]

Adhesion family GPCRs are phylogenetically related to class B receptors, from which they differ by possessing large extracellular N-termini that are autoproteolytically cleaved from their 7TM domainsat a conserved "GPCR proteolysis site" (GPS) which lies within a much larger ( 320 residue) "GPCR autoproteolysis-inducing" (GAIN) domain, an evolutionary ancient mofif also found in polycystic kidneydisease 1 (PKD1)-like proteins, which has been suggested to be both required and sufficient for autoproteolysis [1538]. [Adhesion family list].

Frizzled family (class F) consists of 10 Frizzled proteins (FZD(1-10)) and Smoothened (SMO). [Frizzled family list]. The FZDs are activated by secreted lipoglycoproteins of the WNT family, whereasSMO is indirectly activated by the Hedgehog (HH) family of proteins acting on the transmembrane protein Patched (PTCH).

Secretin family (class B), encoded by 15 genes in humans. The ligands for receptors in this family are polypeptide hormones of 27-141 amino-acid residues; nine of the mammalian receptors respondto ligands that are structurally related to one another (glucagon, glucagon-like peptides (GLP-1, GLP-2), glucose-dependent insulinotropic polypeptide (GIP), secretin, vasoactive intestinal peptide (VIP),pituitary adenylate cyclase-activating polypeptide (PACAP) and growth-hormone-releasing hormone (GHRH) [703].

GPCR families

Family Class A Class B (Secretin) Class C (Glutamate) Adhesion Frizzled

Receptors with known ligands 197a 15 12 0 11

Orphans 87 (54)a - 8 (1)a 26 (6)a 0

Sensory (olfaction) 390b,c - - - -

Sensory (vision) 10d opsins - - - -

Sensory (taste) 30c taste 2 - 3c taste 1 - -

Sensory (pheromone) 5c vomeronasal 1 - - - -

Total 719 15 22 33 11

aNumbers in brackets refer to orphan receptors for which an endogenous ligand has been proposed in at least one publication, see [396]; b[1443]; c[1309]; d[1866].

Much of our current understanding of the structure and function of GPCRs is the result of pioneering work on the visual pigment rhodopsin and on the β2 adrenoceptor, the latter culminating in theaward of the 2012 Nobel Prize in chemistry to Robert Lefkowitz and Brian Kobilka [975, 1073].

Family structure

5746 Orphan and other 7TM receptors

5746 Class A Orphans

5756 Class C Orphans

5756 Taste 1 receptors

5757 Taste 2 receptors

5758 Other 7TM proteins

5759 5-Hydroxytryptamine receptors

5764 Acetylcholine receptors (muscarinic)

5766 Adenosine receptors

5768 Adhesion Class GPCRs5770 Adrenoceptors

5774 Angiotensin receptors

5775 Apelin receptor

5777 Bile acid receptor

5778 Bombesin receptors

5780 Bradykinin receptors

5781 Calcitonin receptors

5783 Calcium-sensing receptors

5784 Cannabinoid receptors

5785 Chemerin receptor

5785 Chemokine receptors

5791 Cholecystokinin receptors

5792 Class Frizzled GPCRs5793 Complement peptide receptors

5795 Corticotropin-releasing factor receptors

5796 Dopamine receptors

5798 Endothelin receptors

5799 G protein-coupled estrogen receptor

5800 Formylpeptide receptors

5801 Free fatty acid receptors

5803 GABAB receptors

5805 Galanin receptors

5806 Ghrelin receptor

5807 Glucagon receptor family

5809 Glycoprotein hormone receptors

5810 Gonadotrophin-releasing hormone receptors

5811 GPR18, GPR55 and GPR119

5812 Histamine receptors

5814 Hydroxycarboxylic acid receptors

5815 Kisspeptin receptor

5816 Leukotriene receptors

5818 Lysophospholipid (LPA) receptors

5819 Lysophospholipid (S1P) receptors

5820 Melanin-concentrating hormone receptors

5821 Melanocortin receptors

Searchable database: http://www.guidetopharmacology.org/index.jsp G-Protein-coupled receptors 5745


http://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Chttp://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Ahttp://www.ncbi.nlm.nih.gov/pubmed/23850273?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Adhesionhttp://www.guidetopharmacology.org/GRAC/GPCRListForward?class=Frizzledhttp://www.ncbi.nlm.nih.gov/pubmed/11790261?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/19129093?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/15034552?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/15774036?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23650120?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23650015?dopt=AbstractPlushttp://www.guidetopharmacology.org/index.jsphttp://www.guidetopharmacology.org/index.jsp


5822 Melatonin receptors

5823 Metabotropic glutamate receptors

5826 Motilin receptor

5827 Neuromedin U receptors

5828 Neuropeptide FF/neuropeptide AF receptors

5829 Neuropeptide S receptor

5829 Neuropeptide W/neuropeptide B receptors

5830 Neuropeptide Y receptors

5832 Neurotensin receptors

5833 Opioid receptors

5835 Orexin receptors

5836 Oxoglutarate receptor

5836 P2Y receptors

5838 Parathyroid hormone receptors

5839 Platelet-activating factor receptor

5840 Prokineticin receptors

5841 Prolactin-releasing peptide receptor

5842 Prostanoid receptors

5844 Proteinase-activated receptors

5846 QRFP receptor

5846 Relaxin family peptide receptors

5848 Somatostatin receptors

5850 Succinate receptor

5850 Tachykinin receptors

5852 Thyrotropin-releasing hormone receptors

5852 Trace amine receptor

5854 Urotensin receptor

5854 Vasopressin and oxytocin receptors

5856 VIP and PACAP receptors

Orphan and other 7TM receptorsG protein-coupled receptors! Orphan and other 7TM receptorsClass A OrphansG protein-coupled receptors! Orphan and other 7TM receptors! Class A OrphansOverview: Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [530], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potentiallink to a disease, or disorder. These GPCRs have recently been reviewed in detail [396]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putativeGPCRs with as-yet unidentified endogenous ligands.

Table 1: Class A orphan GPCRs with putative endogenous ligands

GPR1 GPR3 GPR4 GPR6 GPR12 GPR15 GPR17 GPR20

GPR22 GPR26 GPR31 GPR34 GPR35 GPR37 GPR39 GPR50

GPR63 GRP65 GPR68 GPR75 GPR84 GPR87 GPR88 GPR132

GPR149 GPR161 GPR183 LGR4 LGR5 LGR6 MAS1 MRGPRD

MRGPRX1 MRGPRX2 P2RY10 TAAR2

In addition the orphan receptors GPR18, GPR55 and GPR119 which are reported to respond to endogenous agents analogous to the endogenous cannabinoid ligands have been grouped together(GPR18, GPR55 and GPR119).

Nomenclature GPR1 GPR3 GPR4 GPR6

HGNC, UniProt GPR1, P46091 GPR3, P46089 GPR4, P46093 GPR6, P46095

Endogenous ligand – – Protons –

Endogenous agonists chemerin (RARRES2, Q99969)(pKd 8.3) [95]

– – –

Agonists – diphenyleneiodonium chloride(pEC50 6) [2091]

– –

Searchable database: http://www.guidetopharmacology.org/index.jsp Class A Orphans 5746


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=115http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=16http://www.ncbi.nlm.nih.gov/pubmed/15914470?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/23686350?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/#82http://www.guidetopharmacology.org/GRAC/#83http://www.guidetopharmacology.org/GRAC/#84http://www.guidetopharmacology.org/GRAC/#85http://www.guidetopharmacology.org/GRAC/#86http://www.guidetopharmacology.org/GRAC/#87http://www.guidetopharmacology.org/GRAC/#88http://www.guidetopharmacology.org/GRAC/#91http://www.guidetopharmacology.org/GRAC/#93http://www.guidetopharmacology.org/GRAC/#96http://www.guidetopharmacology.org/GRAC/#98http://www.guidetopharmacology.org/GRAC/#101http://www.guidetopharmacology.org/GRAC/#102http://www.guidetopharmacology.org/GRAC/#103http://www.guidetopharmacology.org/GRAC/#105http://www.guidetopharmacology.org/GRAC/#107http://www.guidetopharmacology.org/GRAC/#112http://www.guidetopharmacology.org/GRAC/#113http://www.guidetopharmacology.org/GRAC/#114http://www.guidetopharmacology.org/GRAC/#115http://www.guidetopharmacology.org/GRAC/#120http://www.guidetopharmacology.org/GRAC/#122http://www.guidetopharmacology.org/GRAC/#123http://www.guidetopharmacology.org/GRAC/#128http://www.guidetopharmacology.org/GRAC/#135http://www.guidetopharmacology.org/GRAC/#141http://www.guidetopharmacology.org/GRAC/#81http://www.guidetopharmacology.org/GRAC/#147http://www.guidetopharmacology.org/GRAC/#148http://www.guidetopharmacology.org/GRAC/#149http://www.guidetopharmacology.org/GRAC/#150http://www.guidetopharmacology.org/GRAC/#152http://www.guidetopharmacology.org/GRAC/#156http://www.guidetopharmacology.org/GRAC/#157http://www.guidetopharmacology.org/GRAC/#165http://www.guidetopharmacology.org/GRAC/#167http://www.guidetopharmacology.org/GRAC/#89http://www.guidetopharmacology.org/GRAC/#109http://www.guidetopharmacology.org/GRAC/#126http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=114http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=82http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=83http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=84http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=85http://www.genenames.org/data/hgnc_data.php?hgnc_id=4463http://www.uniprot.org/uniprot/P46091http://www.genenames.org/data/hgnc_data.php?hgnc_id=4484http://www.uniprot.org/uniprot/P46089http://www.genenames.org/data/hgnc_data.php?hgnc_id=4497http://www.uniprot.org/uniprot/P46093http://www.genenames.org/data/hgnc_data.php?hgnc_id=4515http://www.uniprot.org/uniprot/P46095http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2945http://www.genenames.org/data/hgnc_data.php?hgnc_id=9868http://www.uniprot.org/uniprot/Q99969http://www.ncbi.nlm.nih.gov/pubmed/18165312?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=7802http://www.ncbi.nlm.nih.gov/pubmed/24633425?dopt=AbstractPlushttp://www.guidetopharmacology.org/index.jsphttp://www.guidetopharmacology.org/index.jsp


(continued)


Comments Reported to act as a co-receptorfor HIV [1724]. See review [396]for discussion of pairing withchemerin.

sphingosine 1-phosphate wasreported to be an endogenous agonist[1921], but this finding was notreplicated in subsequent studies[2093]. Reported to activate adenylylcyclase constitutively through Gs[466]. Gene disruption results inpremature ovarian ageing [1063],reduced β-amyloid deposition [1868]and hypersensitivity to thermal pain[1615] in mice. First small moleculeinverse agonist [860] and agonistsidentified [2091].

An initial report suggesting activationby lysophosphatidylcholine andsphingosylphosphorylcholine [2131]has been retracted [2148]. GPR4,GPR65, GPR68 and GPR132 are nowthought to function as proton-sensingreceptors detecting acidic pH [396,1704]. Gene disruption is associatedwith increased perinatal mortality andimpaired vascular proliferation [2085].Negative allosteric modulators ofGPR4 have been reported [1889].

An initial report thatsphingosine 1-phosphate (S1P) was ahigh-affinity ligand (EC50 value of39nM) [815, 1921] was not repeatedby arrestin PathHunter[TM] assays[1785, 2093]. Reported to activateadenylyl cyclase constitutively throughGs and to be located intracellularly[1453]. GPR6-deficient mice showedreduced striatal cyclic AMP productionin vitro and selected alterations ininstrumental conditioning in vivo.[1134].


HGNC, UniProt GPR12, P47775 GPR15, P49685 GPR17, Q13304 GPR19, Q15760

Endogenousagonists

– – UDP-glucose (pEC50 5.9–9.5)[130, 344], LTC4 (pEC50 7.8–9.5)[344], UDP-galactose (pEC506–8.9) [130, 344],uridine diphosphate (pEC506–8.8) [130, 344], LTD4 (pEC508.1–8.4) [344]

–

Comments Reports thatsphingosine 1-phosphate is aligand of GPR12 [814, 1921] havenot been replicated inarrestin-based assays [1785,2093]. Gene disruption results indyslipidemia and obesity [154].

Reported to act as a co-receptorfor HIV [462]. In aninfection-induced colitis model,Gpr15 knockout mice were moreprone to tissue damage andinflammatory cytokine expression[945].

Reported to be a dual leukotrieneand uridine diphosphate receptor[344]. Another group insteadproposed that GPR17 functions asa negative regulator of the CysLT1receptor response to leukotrieneD4 (LTD4). For further discussion,see [396]. Reported to antagonizeCysLT1 receptor signalling in vivoand in vitro [1175]. See reviews[250] and [396].

–



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Nomenclature GPR20 GPR21 GPR22 GPR25 GPR26

HGNC, UniProt GPR20, Q99678 GPR21, Q99679 GPR22, Q99680 GPR25, O00155 GPR26, Q8NDV2

Comments Reported to inhibit adenylylcyclase constitutively throughGi/o [708]. GPR20 deficient miceexhibit hyperactivity characterisedby increased total distancetravelled in an open field test[207].

Gpr21 knockout mice wereresistant to diet-induced obesity,exhibiting an increase in glucosetolerance and insulin sensitivity, aswell as a modest lean phenotype[1448].

Gene disruption results inincreased severity of functionaldecompensation following aorticbanding [10]. Identified as asusceptibility locus forosteoarthritis [494, 929, 1935].

– Has been reported to activateadenylyl cyclase constitutivelythrough Gs [880]. Gpr26knockout mice show increasedlevels of anxiety anddepression-like behaviours [2117].


HGNC, UniProt GPR27, Q9NS67 GPR31, O00270 GPR32, O75388 GPR33, Q49SQ1 GPR34, Q9UPC5

Rank order ofpotency

– – resolvin D1 > LXA4 – –Endogenousagonists

– 12S-HETE (Selective) (pEC50 9.6)[665] – Mouse

resolvin D1 (pEC50 11.1) [1006],LXA4 (pEC50 9.7) [1006]

– lysophosphatidylserine(Selective) (pEC50 6.6–6.9) [960,1817]

Labelled ligands – – [3H]resolvin D1 (Agonist) (pKd9.7) [1006]

– –

Comments Knockdown of Gpr27 reducesendogenous mouse insulinpromotor activity andglucose-stimulated insulinsecretion [1012].

See [396] for discussion ofpairing.

resolvin D1 has beendemonstrated to activate GPR32in two publications [316, 1006].The pairing was not replicated ina recent study based on arrestinrecruitment [1785]. GPR32 is apseudogene in mice and rats.See reviews [250] and [396].

GPR33 is a pseudogene in mostindividuals, containing apremature stop codon within thecoding sequence of the secondintracellular loop [1621].

Lysophosphatidylserine has beenreported to be a ligand of GPR34in several publications, but thepairing was not replicated in arecent study based on arrestinrecruitment [1785]. Fails torespond to a variety oflipid-derived agents [2093].Gene disruption results in anenhanced immune response[1102]. Characterization ofagonists at this receptor isdiscussed in [819] and [396].



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Nomenclature GPR35 GPR37 GPR37L1 GPR39 GPR42

HGNC, UniProt GPR35, Q9HC97 GPR37, O15354 GPR37L1, O60883 GPR39, O43194 GPR42, O15529

Endogenous agonists 2-oleoyl-LPA (pEC50 7.3–7.5)[1436], kynurenic acid (pEC503.9–4.4) [1785, 1980]

– – Zn2+ [775] –

Agonists – neuropeptide head activator(pEC50 8–8.5) [1578]

– compound 1 [PMID: 24900608](pEC50 4.9–7.2) [166]

–

Comments Several studies have shown thatkynurenic acid is an agonist ofGPR35 but it remainscontroversial whether theproposed endogenous ligandreaches sufficient tissueconcentrations to activate thereceptor [1015]. 2-oleoyl-LPA hasalso been proposed as anendogenous ligand [1436] butthese results were not replicatedin an arrestin assay [1785]. Thephosphodiesterase inhibitorzaprinast [1863] has becomewidely used as a surrogate agonistto investigate GPR35pharmacology and signalling[1863]. GPR35 is also activated bythe pharmaceutical adjunctpamoic acid [2124]. See reviews[396] and [429].

Reported to associate andregulate the dopaminetransporter [1207] and to be asubstrate for parkin [1205]. Genedisruption results in altered striatalsignalling [1206]. The peptidesprosaptide and prosaposin areproposed as endogenous ligandsfor GPR37 and GPR37L1 [1264].

The peptides prosaptide andprosaposin are proposed asendogenous ligands for GPR37and GPR37L1 [1264].

Zn2+ has been reported to be apotent and efficacious agonist ofhuman, mouse and rat GPR39[2089]. obestatin (GHRL,Q9UBU3), a fragment from theghrelin precursor, was reportedinitially as an endogenous ligand,but subsequent studies failed toreproduce these findings. GPR39has been reported to bedown-regulated in adipose tissuein obesity-related diabetes [273].Gene disruption results in obesityand altered adipocyte metabolism[1497]. Reviewed in [396].

–


HGNC, UniProt GPR45, Q9Y5Y3 GPR50, Q13585 GPR52, Q9Y2T5 GPR61, Q9BZJ8

Comments – GPR50 is structurally related to MT1and MT2 melatonin receptors, withwhich it heterodimerisesconstitutively and specifically[1089]. Gpr50 knockout micedisplay abnormal thermoregulationand are much more likely thanwild-type mice to enterfasting-induced torpor [111].

First small moleculeagonist reported [1703].

GPR61 deficient mice exhibit obesityassociated with hyperphagia [1363].Although no endogenous ligandshave been identified,5-(nonyloxy)tryptamine has beenreported to be a low affinity inverseagonist [1852].



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HGNC, UniProt GPR62, Q9BZJ7 GPR63, Q9BZJ6 GPR65, Q8IYL9 GPR68, Q15743 GPR75, O95800

Endogenousligand

– – Protons Protons –

Comments – sphingosine 1-phosphate anddioleoylphosphatidic acid have beenreported to be low affinity agonistsfor GPR63 [1394] but this findingwas not replicated in anarrestin-based assay [2093].

GPR4, GPR65, GPR68 and GPR132are now thought to function asproton-sensing receptors detectingacidic pH [396, 1704]. Reported toactivate adenylyl cyclase; genedisruption leads to reducedeosinophilia in models of allergicairway disease [1000].

GPR68 was previously identified as areceptor forsphingosylphosphorylcholine (SPC)[2068], but the original publicationhas been retracted [2067]. GPR4,GPR65, GPR68 and GPR132 are nowthought to function asproton-sensing receptors detectingacidic pH [396, 1704]. A family of3,5-disubstituted isoxazoles wereidentified as agonists of GPR68[1617].

CCL5 (CCL5, P13501) was reportedto be an agonist of GPR75 [816],but the pairing could not berepeated in an arrestin assay [1785].


HGNC, UniProt GPR78, Q96P69 GPR79, – GPR82, Q96P67 GPR83, Q9NYM4 GPR84, Q9NQS5

Agonists – – – Zn2+ (pEC50 5) [1351] – Mouse decanoic acid (pEC50 5–5.4)[1785, 1981], undecanoic acid(pEC50 5.1) [1981], lauric acid(pEC50 5) [1981]

Comments GPR78 has been reported to beconstitutively active, coupled toelevated cAMP production [880].

– Mice with Gpr82 knockout have alower body weight and body fatcontent associated with reducedfood intake, decreased serumtriglyceride levels, as well as higherinsulin sensitivity and glucosetolerance [479].

One isoform has been implicatedin the induction of CD4(+)CD25(+) regulatory T cells (Tregs)during inflammatory immuneresponses [696]. The extracellularN-terminal domain is reported asan intramolecular inverse agonist[1352].

Medium chain free fatty acids withcarbon chain lengths of 9-14activate GPR84 [1828, 1981]. Asurrogate ligand for GPR84,6-n-octylaminouracil has also beenproposed [1828]. See review [396]for discussion of classification.Mutational analysis and molecularmodelling of GPR84 has beenreported [1397].



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HGNC, UniProt GPR85, P60893 GPR87, Q9BY21 GPR88, Q9GZN0 GPR101, Q96P66

Endogenousagonists

– LPA (pEC50 7.4) [1344,1836]

– –

Agonists – – compound 2 [PMID: 24793972](pEC50 6.2) [868]

–

Comments Proposed to regulatehippocampal neurogenesis inthe adult, as well asneurogenesis-dependentlearning and memory [303].

– Gene disruption results in alteredstriatal signalling [1137]. Smallmolecule agonists have beenreported [147].

Mutations in GPR101 havebeen linked to gigantism andacromegaly [1906].


HGNC, UniProt GPR132, Q9UNW8 GPR135, Q8IZ08 GPR139, Q6DWJ6 GPR141, Q7Z602 GPR142, Q7Z601

Endogenousligand

Protons – – – –

Agonists – – compound 1a [PMID: 24900311](pEC50 7.4) [1721]

– –

Comments GPR4, GPR65, GPR68 andGPR132 are now thought tofunction as proton-sensingreceptors detecting acidic pH[396, 1704]. Reported to respondto lysophosphatidylcholine [891],but later retracted [2038].

– Peptide agonists have beenreported [828].

– Small molecule agonists havebeen reported [1890, 2106].



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HGNC, UniProt GPR146, Q96CH1 GPR148, Q8TDV2 GPR149, Q86SP6 GPR150, Q8NGU9 GPR151, Q8TDV0

Comments Yosten et al. demonstratedinhibition of proinsulin C-peptide(INS, P01308)-inducedstimulation of cFos expressionfolllowing knockdown of GPR146in KATO III cells, suggestingproinsulin C-peptide as anendogenous ligand of thereceptor [2103].

– Gpr149 knockout mice displayedincreased fertility and enhancedovulation, with increased levels ofFSH receptor and cyclin D2 mRNAlevels [463].

– GPR151 responded to galaninwith an EC50 value of 2 �M,suggesting that the endogenousligand shares structural featureswith galanin (GAL, P22466) [813].


HGNC, UniProt GPR152, Q8TDT2 GPR153, Q6NV75 GPR160, Q9UJ42 GPR161, Q8N6U8 GPR162, Q16538

Comments – – – A C-terminal truncation (deletion) mutation in Gpr161 causescongenital cataracts and neural tube defects in the vacuolated lens(vl) mouse mutant [1226]. The mutated receptor is associated withcataract, spina bifida and white belly spot phenotypes in mice [994].Gene disruption is associated with a failure of asymmetric embryonicdevelopment in zebrafish [1085].

–


HGNC, UniProt GPR171, O14626 GPR173, Q9NS66 GPR174, Q9BXC1 GPR176, Q14439 GPR182, O15218

Endogenousagonists

– – lysophosphatidylserine (pEC507.1) [825]

– –

Comments GPR171 has been shown to beactivated by the endogenouspeptide BigLEN {Mouse}. Thisreceptor-peptide interaction isbelieved to be involved inregulating feeding andmetabolism responses [621].

– See [819] which discussescharacterization of agonists at thisreceptor.

– Rat GPR182 was first proposed asthe adrenomedullin receptor[904]. However, it was laterreported that rat and humanGPR182 did not respond toadrenomedullin [927] andGPR182 is not currentlyconsidered to be a genuineadrenomedullin receptor [722].



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Nomenclature GPR183 LGR4 LGR5 LGR6 MAS1

HGNC, UniProt GPR183, P32249 LGR4, Q9BXB1 LGR5, O75473 LGR6, Q9HBX8 MAS1, P04201

Endogenousagonists

7α,25-dihydroxycholesterol(Selective) (pEC50 8.1–9.8)[694, 1125],7α,27-dihydroxycholesterol(Selective) (pEC50 8.9) [1125],7β, 25-dihydroxycholesterol(Selective) (pEC50 8.7) [1125],7β, 27-dihydroxycholesterol(Selective) (pEC50 7.3) [1125]

R-spondin-2 (RSPO2, Q6UXX9)(pEC50 12.5) [266], R-spondin-1(RSPO1, Q2MKA7) (pEC50 10.7)[266], R-spondin-3 (RSPO3,Q9BXY4) (pEC50 10.7) [266],R-spondin-4 (RSPO4, Q2I0M5)(pEC50 10.1) [266]

R-spondin-2 (RSPO2, Q6UXX9)(pEC50 12) [266], R-spondin-1(RSPO1, Q2MKA7) (pEC50 11.1)[266], R-spondin-3 (RSPO3,Q9BXY4) (pEC50 11) [266],R-spondin-4 (RSPO4, Q2I0M5)(pEC50 9.4) [266]

R-spondin-1 (RSPO1,Q2MKA7) [266, 2140],R-spondin-2 (RSPO2,Q6UXX9) [266, 2140],R-spondin-3 (RSPO3,Q9BXY4) [266, 2140],R-spondin-4 (RSPO4,Q2I0M5) [266, 2140]

–

Agonists – – – – angiotensin-(1-7) (AGT,P01019) (pKi 7.3) [612]– Mouse

Comments Two independent publicationshave shown that7α,25-dihydroxycholesterol isan agonist of GPR183 and havedemonstrated by massspectrometry that this oxysterolis present endogenously intissues [694, 1125].Gpr183-deficient mice show areduction in the early antibodyresponse to a T-dependentantigen. GPR183-deficient Bcells fail to migrate to the outerfollicle and instead stay in thefollicle centre [923, 1488].

LGR4 does not couple toheterotrimeric G proteins orrecruit arrestins whenstimulated by the R-spondins,indicating a unique mechanismof action. R-spondins bind toLGR4, which specificallyassociates with Frizzled and LDLreceptor-related proteins (LRPs)that are activated by theextracellular Wnt molecules andthen trigger canonical Wntsignalling to increase geneexpression [266, 1612, 2140].Gene disruption leads tomultiple developmentaldisorders [869, 1154, 1781,2005].

The four R-spondins can bind toLGR4, LGR5, and LGR6, whichspecifically associate withFrizzled and LDLreceptor-related proteins (LRPs),proteins that are activated byextracellular Wnt molecules andwhich then trigger canonicalWnt signalling to increase geneexpression [266, 2140].

– –



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Nomenclature MAS1L MRGPRD MRGPRE MRGPRF MRGPRG

HGNC, UniProt MAS1L, P35410 MRGPRD, Q8TDS7 MRGPRE, Q86SM8 MRGPRF, Q96AM1 MRGPRG, Q86SM5

Endogenousagonists

– β-alanine (pEC50 4.8) [1729, 1785] – – –

Comments – An endogenous peptide with a high degree ofsequence similarity to angiotensin-(1-7) (AGT,P01019), alamandine (AGT), was shown topromote NO release in MRGPRD-transfectedcells. The binding of alamandine to MRGPRDto was shown to be blocked byD-Pro7-angiotensin-(1-7), β-alanine andPD123319 [1045]. Genetic ablation ofMRGPRD+ neurons of adult mice decreasedbehavioural sensitivity to mechanical stimulibut not to thermal stimuli [278]. See reviews[396] and [1779].

See reviews [396] and[1779].

MRGPRF has been reported torespond to stimulation byangiotensin metabolites [589].See reviews [396] and [1779].

See reviews [396] and[1779].

Nomenclature MRGPRX1 MRGPRX2 MRGPRX3 MRGPRX4

HGNC, UniProt MRGPRX1, Q96LB2 MRGPRX2, Q96LB1 MRGPRX3, Q96LB0 MRGPRX4, Q96LA9

Endogenousagonists

bovine adrenal medulla peptide 8-22 (PENK,P01210) (Selective) (pEC50 5.3–7.8) [299, 1080,1785]

PAMP-20 (ADM, P35318) (Selective) [899] – –

Agonists – cortistatin-14 {Mouse, Rat} (pEC50 6.9–7.6) [899,1594, 1785]

– –

Selective agonists – PAMP-12 (human) (pEC50 7.2–7.7) [899] – –

Comments Reported to mediate the sensation of itch [1131,1739]. Reports thatbovine adrenal medulla peptide 8-22 (PENK,P01210) was the most potent of a series ofproenkephalin A-derived peptides as an agonist ofMRGPRX1 in assays of calcium mobilisation andradioligand binding [1080] were replicated in anindependent study using an arrestin recruitmentassay [1785]. See reviews [396] and [1779].

A diverse range of substances has been reported tobe agonists of MRGPRX2, with cortistatin 14 thehighest potency agonist in assays of calciummobilisation [1594], also confirmed in anindependent study using an arrestin recruitmentassay [1785]. See reviews [396] and [1779].

– See reviews [396] and[1779].



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Nomenclature OPN3 OPN4 OPN5 P2RY8

HGNC, UniProt OPN3, Q9H1Y3 OPN4, Q9UHM6 OPN5, Q6U736 P2RY8, Q86VZ1

Comments – – Evidence indicates OPN5 triggers a UV-sensitive Gi-mediatedsignalling pathway in mammalian tissues [982].

–

Nomenclature P2RY10 TAAR2 TAAR3 TAAR4P

HGNC, UniProt P2RY10, O00398 TAAR2, Q9P1P5 TAAR3, Q9P1P4 TAAR4P, –

Rank order ofpotency

– β-phenylethylamine> tryptamine[185]

– –

Endogenousagonists

sphingosine 1-phosphate (Selective)(pEC50 7.3) [1344], LPA (Selective)(pEC50 6.9) [1344]

– – –

Comments – Probable pseudogene in 10-15% ofAsians due to a polymorphism(rs8192646) producing a prematurestop codon at amino acid 168 [396].

TAAR3 is thought to be a pseudogenein man though functional in rodents[396].

Pseudogene in man but functional inrodents [396].

Nomenclature TAAR5 TAAR6 TAAR8 TAAR9

HGNC, UniProt TAAR5, O14804 TAAR6, Q96RI8 TAAR8, Q969N4 TAAR9, Q96RI9

Comments Trimethylamine is reported as an agonist [1974]and 3-iodothyronamine an inverse agonist [426].

– – TAAR9 appears to be functional in most individualsbut has a polymorphic premature stop codon atamino acid 61 (rs2842899) with an allele frequencyof 10-30% in different populations [1944].



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Class C OrphansG protein-coupled receptors! Orphan and other 7TM receptors! Class C Orphans

Nomenclature GPR156 GPR158 GPR179 GPRC5A GPRC5B GPRC5C GPRC5D

HGNC, UniProt GPR156, Q8NFN8 GPR158, Q5T848 GPR179, Q6PRD1 GPRC5A, Q8NFJ5 GPRC5B, Q9NZH0 GPRC5C, Q9NQ84 GPRC5D, Q9NZD1

Taste 1 receptorsG protein-coupled receptors! Orphan and other 7TM receptors! Taste 1 receptorsOverview: Whilst the taste of acid and salty foods appear to besensed by regulation of ion channel activity, bitter, sweet and umamitastes are sensed by specialised GPCR. Two classes of taste GPCRhave been identified, T1R and T2R, which are similar in sequenceand structure to Class C and Class A GPCR, respectively. Activation

of taste receptors appears to involve gustducin- (Gαt3) and Gα14-mediated signalling, although the precise mechanisms remain ob-scure. Gene disruption studies suggest the involvement of PLCβ2[2122], TRPM5 [2122] and IP3 [764] receptors in post-receptor sig-nalling of taste receptors. Although predominantly associated with

the oral cavity, taste receptors are also located elsewhere, includ-ing further down the gastrointestinal system, in the lungs and in thebrain.

Sweet/Umami

T1R3 acts as an obligate partner in T1R1/T1R3 and T1R2/T1R3 heterodimers, which sense umami or sweet, respectively. T1R1/T1R3 heterodimers respond to L-glutamic acid and may be positively allostericallymodulated by 5’-nucleoside monophosphates, such as 5’-GMP [1096]. T1R2/T1R3 heterodimers respond to sugars, such as sucrose, and artificial sweeteners, such as saccharin [1376].

Nomenclature TAS1R1 TAS1R2 TAS1R3

HGNC, UniProt TAS1R1, Q7RTX1 TAS1R2, Q8TE23 TAS1R3, Q7RTX0

Searchable database: http://www.guidetopharmacology.org/index.jsp Taste 1 receptors 5756


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=18http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=209http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=210http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=211http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=258http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=259http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=260http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=261http://www.genenames.org/data/hgnc_data.php?hgnc_id=20844http://www.uniprot.org/uniprot/Q8NFN8http://www.genenames.org/data/hgnc_data.php?hgnc_id=23689http://www.uniprot.org/uniprot/Q5T848http://www.genenames.org/data/hgnc_data.php?hgnc_id=31371http://www.uniprot.org/uniprot/Q6PRD1http://www.genenames.org/data/hgnc_data.php?hgnc_id=9836http://www.uniprot.org/uniprot/Q8NFJ5http://www.genenames.org/data/hgnc_data.php?hgnc_id=13308http://www.uniprot.org/uniprot/Q9NZH0http://www.genenames.org/data/hgnc_data.php?hgnc_id=13309http://www.uniprot.org/uniprot/Q9NQ84http://www.genenames.org/data/hgnc_data.php?hgnc_id=13310http://www.uniprot.org/uniprot/Q9NZD1http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=116http://www.ncbi.nlm.nih.gov/pubmed/12581520?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/12581520?dopt=AbstractPlushttp://www.ncbi.nlm.nih.gov/pubmed/17925404?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1369http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5123http://www.ncbi.nlm.nih.gov/pubmed/12013525?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5411http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5432http://www.ncbi.nlm.nih.gov/pubmed/11509186?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=656http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=657http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=658http://www.genenames.org/data/hgnc_data.php?hgnc_id=14448http://www.uniprot.org/uniprot/Q7RTX1http://www.genenames.org/data/hgnc_data.php?hgnc_id=14905http://www.uniprot.org/uniprot/Q8TE23http://www.genenames.org/data/hgnc_data.php?hgnc_id=15661http://www.uniprot.org/uniprot/Q7RTX0http://www.guidetopharmacology.org/index.jsphttp://www.guidetopharmacology.org/index.jsp


Taste 2 receptorsG protein-coupled receptors! Orphan and other 7TM receptors! Taste 2 receptorsBitter

The composition and stoichiometry of bitter taste receptors is not yet established. Bitter receptors appear to separate into two groups, with very restricted ligand specificity or much broader responsiveness. Forexample, T2R5 responded to cycloheximide, but not 10 other bitter compounds [287], while T2R14 responded to at least eight different bitter tastants, including (-)-α-thujone and picrotoxinin [119].

Specialist database BitterDB contains additional information on bitter compounds and receptors [2023].

Nomenclature TAS2R1 TAS2R3 TAS2R4 TAS2R5 TAS2R7 TAS2R8

HGNC, UniProt TAS2R1, Q9NYW7 TAS2R3, Q9NYW6 TAS2R4, Q9NYW5 TAS2R5, Q9NYW4 TAS2R7, Q9NYW3 TAS2R8, Q9NYW2


HGNC, UniProt TAS2R9, Q9NYW1 TAS2R10, Q9NYW0 TAS2R13, Q9NYV9 TAS2R14, Q9NYV8 TAS2R16, Q9NYV7 TAS2R19, P59542


HGNC, UniProt TAS2R20, P59543 TAS2R30, P59541 TAS2R31, P59538 TAS2R38, P59533 TAS2R39, P59534 TAS2R40, P59535

Nomenclature TAS2R41 TAS2R42 TAS2R43 TAS2R45 TAS2R46 TAS2R50 TAS2R60

HGNC, UniProt TAS2R41, P59536 TAS2R42, Q7RTR8 TAS2R43, P59537 TAS2R45, P59539 TAS2R46, P59540 TAS2R50, P59544 TAS2R60, P59551

Searchable database: http://www.guidetopharmacology.org/index.jsp Taste 2 receptors 5757


http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=117http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5433http://www.ncbi.nlm.nih.gov/pubmed/10761935?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=5344http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=2291http://www.ncbi.nlm.nih.gov/pubmed/15178431?dopt=AbstractPlushttp://bitterdb.agri.huji.ac.il/dbbitter.phphttp://www.ncbi.nlm.nih.gov/pubmed/21940398?dopt=AbstractPlushttp://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=659http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=660http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=661http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=662http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=663http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=664http://www.genenames.org/data/hgnc_data.php?hgnc_id=14909http://www.uniprot.org/uniprot/Q9NYW7http://www.genenames.org/data/hgnc_data.php?hgnc_id=14910http://www.uniprot.org/uniprot/Q9NYW6http://www.genenames.org/data/hgnc_data.php?hgnc_id=14911http://www.uniprot.org/uniprot/Q9NYW5http://www.genenames.org/data/hgnc_data.php?hgnc_id=14912http://www.uniprot.org/uniprot/Q9NYW4http://www.genenames.org/data/hgnc_data.php?hgnc_id=14913http://www.uniprot.org/uniprot/Q9NYW3http://www.genenames.org/data/hgnc_data.php?hgnc_id=14915http://www.uniprot.org/uniprot/Q9NYW2http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=665http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=666http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=667http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=668http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=669http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=670http://www.genenames.org/data/hgnc_data.php?hgnc_id=14917http://www.uniprot.org/uniprot/Q9NYW1http://www.genenames.org/data/hgnc_data.php?hgnc_id=14918http://www.uniprot.org/uniprot/Q9NYW0http://www.genenames.org/data/hgnc_data.php?hgnc_id=14919http://www.uniprot.org/uniprot/Q9NYV9http://www.genenames.org/data/hgnc_data.php?hgnc_id=14920http://www.uniprot.org/uniprot/Q9NYV8http://www.genenames.org/data/hgnc_data.php?hgnc_id=14921http://www.uniprot.org/uniprot/Q9NYV7http://www.genenames.org/data/hgnc_data.php?hgnc_id=19108http://www.uniprot.org/uniprot/P59542http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=671http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=673http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=674http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=682http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=675http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=676http://www.genenames.org/data/hgnc_data.php?hgnc_id=19109http://www.uniprot.org/uniprot/P59543http://www.genenames.org/data/hgnc_data.php?hgnc_id=19112http://www.uniprot.org/uniprot/P59541http://www.genenames.org/data/hgnc_data.php?hgnc_id=19113http://www.uniprot.org/uniprot/P59538http://www.genenames.org/data/hgnc_data.php?hgnc_id=9584http://www.uniprot.org/uniprot/P59533http://www.genenames.org/data/hgnc_data.php?hgnc_id=18886http://www.uniprot.org/uniprot/P59534http://www.genenames.org/data/hgnc_data.php?hgnc_id=18885http://www.uniprot.org/uniprot/P59535http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=680http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=672http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=678http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2828http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=679http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=677http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=681http://www.genenames.org/data/hgnc_data.php?hgnc_id=18883http://www.uniprot.org/uniprot/P59536http://www.genenames.org/data/hgnc_data.php?hgnc_id=18888http://www.uniprot.org/uniprot/Q7RTR8http://www.genenames.org/data/hgnc_data.php?hgnc_id=18875http://www.uniprot.org/uniprot/P59537http://www.genenames.org/data/hgnc_data.php?hgnc_id=18876http://www.uniprot.org/uniprot/P59539http://www.genenames.org/data/hgnc_data.php?hgnc_id=18877http://www.uniprot.org/uniprot/P59540http://www.genenames.org/data/hgnc_data.php?hgnc_id=18882http://www.uniprot.org/uniprot/P59544http://www.genenames.org/data/hgnc_data.php?hgnc_id=20639http://www.uniprot.org/uniprot/P59551http://www.guidetopharmacology.org/index.jsphttp://www.guidetopharmacology.org/index.jsp


Other 7TM proteinsG protein-coupled receptors! Orphan and other 7TM receptors! Other 7TM proteinsNomenclature GPR107 GPR137 OR51E1 TPRA1 GPR143 GPR157

HGNC, UniProt GPR107, Q5VW38 GPR137, Q96N19 OR51E1, Q8TCB6 TPRA1, Q86W33 GPR143, P51810 GPR157, Q5UAW9

Endogenousagonists

– – – – levodopa [1141] –

Comments GPR107 is a member ofthe LUSTR family ofproteins found in bothplants and animals,having similar topologyto Gprotein-coupledreceptors [461]

– OR51E1 is a puta

Documents

· S.P.H.Alexanderetal.TheConciseGuidetoPHARMACOLOGY2015/16:Gprotein-coupledreceptors.BritishJournalofPharmacology(2015)172,5744–5869 THE CONCISE GUIDE TO PHARMACOLOGY