Class A Orphans: Introduction

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The sequencing of the human genome has allowed NC-IUPHAR to catalog all of the human gene sequences potentially encoding GPCRs, excluding sensory receptors. In addition to established transmitter systems, the classification in the Guide to PHARMACOLOGY also includes ‘orphan’ GPCRs where the endogenous ligand(s) is not known. Considerable progress has been made in screening artificially expressed receptors to identify the cognate endogenous ligand. Where understanding of the physiology, pharmacology and pathology has begun to emerge, receptors have been officially classified and named (usually after the endogenous ligand following IUPHAR nomenclature conventions) and published in Pharmacological Reviews (Publications). Physiological functions have now been assigned to a number of receptors previously designated as orphans. These include the family of free fatty acid receptors (FFA1, FFA2 and FFA3, [84]); neuropeptide B and W as ligands of NPBW1 (GPR7) and NPBW2 (GPR8) [82]; the protein encoded by the APJ gene [27], now classified as the apelin receptor [77]; GPR30 as the estrogen G protein-coupled receptor (GPER: [67,78,80,87,94]); GPR54 as the kisspeptin receptor [35]; GHS-R1a as the ghrelin receptor [17]; the TA1 receptor activated by endogenous trace amine ligands, including tyramine and β-phenylethylamine [54] and GPR131 as the bile acid receptor (GPBA: [57]).

A recent update review published by NC-IUPHAR has extended the number of receptors where the criteria for deorphanisation has been met, particularly where replicated by independent groups (see Davenport et al., 2013 [16]; full details of the criteria for deorphanisation are also contained in this review). The following recommendations are made for new receptor names based on eleven pairings for class A GPCRs: Hydroxycarboxylic acid receptors, HCA1 (GPR81) with lactate; HCA2 (GPR109A) with 3-hydroxy-butyric acid; HCA3 (GPR109B) with 3-hydroxy octanoic acid [70]; lysophosphatidic acid receptors, LPA4 (GPR23) [42,69,85], LPA5 (GPR92) [36,41,46,97], LPA6 (p2y5) [75,100]; Free Fatty Acid receptors, FFA4 (GPR120) with Omega-3 fatty acids [10,23,25]; chemerin receptor (CMKLR1, ChemR23) with chemerin [49,60,101]; CXCR7 (CMKOR1, and recently renamed to ACKR3 by the NC-IUPHAR subcommittee for the chemokine receptors) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC) [4,9,79]; succinate receptor (SUCNR1) with succinate [22,83]; oxoglutarate receptor OXGR1 with 2-oxoglutarate [22,83]. Pairings have been highlighted for a further thirty receptors in Class A where further input is needed from the scientific community to validate these findings. Details of these pairings with cognate ligands reported by a single paper or where a formal pairing is yet to be agreed can be found in Davenport et al., 2013 [16]. Fifty-seven human Class A receptors (excluding pseudogenes) are still considered orphans; information is provided where there is a significant phenotype in genetically modified animals (see table below).

To reflect the dynamic nature of the field, where a single paper exists describing a new pairing, a list is maintained on the Guide to PHARMACOLOGY (Latest Pairings List). Occasionally reported pairings are retracted and these are also recorded here. Most, if not all, human orphan receptors have now been expressed in cell lines but despite intense effort particularly by the pharmaceutical industry, there is no public information about the cognate ligand for a significant number of them. It is possible that the remaining receptors may function without ligands by being constitutively active or by modulating the activity of other GPCRs for example by dimerization [20,43]. It is clear from knockout studies in mice and genetic deletions in man that these receptors may have a physiological or pathophysiological role and can still be exploited as drug targets in the absence of an identifiable ligand.

For a recent review on orphan GPCR deorphanizations please see Davenport et al., 2013 [16].

Gene name K/O mouse Y/NPhenotype Y/NPhenotype descriptionReference
BB3YesYesObesity, hypertension, impaired insulin metabolism[68,71]
BB3YesYesHyperphagia, reduced metabolic rate[2]
BB3YesYesOverexpression of melanin concentrating hormone receptors[53]
GPR1NoNo  
GPR3YesYesPremature ovarian aging, premature termination of meiotic arrest in oocytes[40,61]
GPR3YesYesLow basal intracellualar cAMP levels; increased stress levels [90]
GPR4YesYesMetabolic acidosis[86]
GPR4YesYesReduced tumour growth and pathological angiogenesis[98]
GPR6YesYesReduced striatal cAMP production[47]
GPR12YesYesDyslipidemia, higher body weight and fat mass [7]
GPR17YesYesEarly onset of oligodendrocyte myelination[12]
GPR17YesYesIncreased susceptibility to pulmonary inflammation [52]
GPR18Non/a  
GPR15Non/a  
GPR19YesNo  
GPR20YesNo  
GPR21YesYesResistance to diet-induced obesity, increase in glucose tolerance and insulin sensitivity, modest lean phenotype[19,73]
GPR21YesYesProtection from obesity-induced inflammation and insulin resistance, reduced macrophage infiltration into adipose tissue and liver [73]
GPR22YesYes Increased response to aortic banding including decreased fractional shortening and decompensated heart failure.[1]
GPR25Non/a  
GPR26YesYesIncreased anxiety and depression-like behaviours [102]
GPR27Non/a  
GPR27    
GPR31Non/a  
GPR32Non/a  
GPR33Non/a  
GPR34YesYesAltered immune response in hypersensitivity tests[45]
GPR35Non/a  
GPR37YesYesReduced striatal dopamine levels, enhanced amphetamine sensitivity, reduced motor activity and coordination and increased percentage of body fat in females.[26,56]
GPR37YesYesLower lever of endoplasmic reticulum-associated protein degradation (ERAD) and autophagic markers.[55]
GPR37L1YesYesHigh blood pressure and a high heart weight to body weight ratio [62]
GPR39YesYesAcceleration of gastric emptying, higher body weight and fat composition and increased cholesterol levels [63]
GPR39YesYesImpaired glucose tolerance, decreased insulin response to glucose [24,89]
GPR42Non/a  
GPR45Non/a  
GPR50YesYesLow body weight, partial resistance to diet induced obesity[28]
GPR50YesYesDecreased thermogenesis[5]
GPR52Non/a  
GPR55YesYesIncreased bone volume, impaired osteoclast function in male mice [3,96]
GPR61YesNo  
GPR62Non/a  
GPR63Non/a  
GPR65YesYesThermocytes and splenocytes are insensitive to pH-regulated cAMP production [37,72]
GPR68YesYesReduced osteoblast levels and decreased melanoma cell tumorigenesis [44]
GPR68YesYesUpregulated expression of Pyk2 and an increase in socdium-hydrogen antiporter activity[64]
GPR68YesYesEnhanced SPC-activation of ERK1/2[6]
GPR75Non/a  
GPR78Non/a  
GPR79Non/a  
GPR82YesYesLower body weight and fat content than wild type, higher insulin sensitivity and glucose tolerance and decreased serum triglycerides[18]
GPR83YesNo  
GPR84YesYesIncreased interleukin (Il-4, IL-5, IL-13) production by Th2 effector cells; increased IL-4 production from T cells treated with anti-CD3[91]
GPR85YesYesIncreased brain weight, enhanced neuronal survival in dendrate gyrus, and enhanced ability to discriminate spatial relationships[11,58]
GPR87YesNo  
GPR88YesYesHigher basal striatal phosphorylated DARPP-21-Thr-34 and lower basal dopamine[48]
GPR101Non/a  
GPR119YesYesLow body weight and low post-prandial levels of GLP-1 [38]
GPR132YesYesMildly cholestatic phenotype with altered hepatobiliary homeostasis and gall stone formation[30]
GPR132YesYesIncrease in IL-6 and MCP-1 production and a dramatic increase in nuclear localization of the p65 subunit of nuclear factor κB. Proinflammatory signaling and increased monocyte/endothelial interactions in the aortic wall[8]
GPR132YesYesReduced atherosclerotic plaque stability[74]
GPR132YesYesProgressive wasting syndrome in mice > 1 year. Secondary lymphoid organ enlargement associated with lymphocytic infiltration [39]
GPR135Non/a  
GPR139Non/a  
GPR141Non/a  
GPR142Non/a  
GPR146Non/a  
GPR148Non/a  
GPR149Non/a  
GPR150Non/a  
GPR151YesNo  
GPR152Non/a  
GPR153Non/a  
GPR160Non/a  
GPR161YesNo  
GPR162Non/a  
GPR171Non/a  
GPR173Non/a  
GPR174Non/a  
GPR176Non/a  
GPR182Non/a  
GPR183YesYesAbolished migration of bone-marrow-derived dendritic cells towards 7alpha, 25-dihydroxycholesterol[21]
GPR183YesYesReduction in the early antibody response to a T-dependent antigen[33,76]
GPR183YesYesFailure of B-cells to migrate to the outer follicle [33,76]
LGR4YesYesEmbryonic and perinatal lethality[59]
LGR4YesYesDelay in osteoblast differentiation and mineralization[51]
LGR4YesYesImpaired eye development [15]
LGR4YesYesReduced keratinocyte and epithelial cell proliferation[29,32,95]
LGR4YesYesRenal hypoplasia[31,65]
LGR5YesYesNeonatal lethality resulting from ankyloglossia, gastrointestinal distension, cyanosis and respiratory failure.[66]
LGR6Non/a  
MAS1YesYesElevated blood pressure and impaired endothelial function[99]
MAS1YesYesIncreased duration of long term potentiation in the dentate gyrus, increased anxiety and alterations in the onset of depotentiation[92]
MAS1YesYesErectile dysfunction [14]
MAS1YesYesIncreased sympathetic tone [93]
MAS1LNon/a  
MRGPRDYesYesDecreased sensitivity to mechanical, cold, and heat stimuli on a congenic C57BL/6 background 
MRGPREYesYesDeletion of MRGPRE increases MRGPRF expression in the spinal cord[13]
MRGPRFNon/a  
MRGPRGNon/a  
MRGPRX1Non/a  
MRGPRX2Non/a  
MRGPRX3Non/a  
MRGPRX4Non/a  
OPN3Non/a  
OPN4YesYesImpaired pupillary response at high irradiances[50]
OPN5Non/a  
OXGR1YesYesOtitis media with effusion resulting from histopathological changes in the middle ear epithelium[34]
P2RY8Non/a  
P2RY10Non/a  
SUCNR1 (GPR91)YesYesImpaired renin release from the kidney in response to high glucose levels [88]
SUCNR1 (GPR91)YesYesAbolished induction of hypertension by succinate [22]
SUCNR1 (GPR91)YesYesImpaired dendritic cell migration, decreased T- cell proliferation and diminished succinate-mediated immune responses[81]
TAAR2Non/a  
TAAR3Non/a  
TAAR4Non/a  
TAAR5Non/a  
TAAR6Non/a  
TAAR8Non/a  
TAAR9Non/a 

References

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1. Adams JW, Wang J, Davis JR, Liaw C, Gaidarov I, Gatlin J, Dalton ND, Gu Y, Ross J, Behan D, Chien K, Connolly D. (2008) Myocardial expression, signaling, and function of GPR22: a protective role for an orphan G protein-coupled receptor. Am. J. Physiol. Heart Circ. Physiol., 295 (2): H509-21. [PMID:18539757]

2. Aoki K, Sun YJ, Aoki S, Wada K, Wada E. (2002) Cloning, expression, and mapping of a gene that is upregulated in adipose tissue of mice deficient in bombesin receptor subtype-3. Biochem. Biophys. Res. Commun., 290 (4): 1282-8. [PMID:11812002]

3. Bab I, Smoum R, Bradshaw H, Mechoulam R. (2011) Skeletal lipidomics: regulation of bone metabolism by fatty acid amide family. Br. J. Pharmacol., 163 (7): 1441-6. [PMID:21557736]

4. Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F. (2005) The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J. Biol. Chem., 280 (42): 35760-6. [PMID:16107333]

5. Bechtold DA, Sidibe A, Saer BR, Li J, Hand LE, Ivanova EA, Darras VM, Dam J, Jockers R, Luckman SM et al.. (2012) A role for the melatonin-related receptor GPR50 in leptin signaling, adaptive thermogenesis, and torpor. Curr. Biol., 22 (1): 70-7. [PMID:22197240]

6. Bektas M, Barak LS, Jolly PS, Liu H, Lynch KR, Lacana E, Suhr KB, Milstien S, Spiegel S. (2003) The G protein-coupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Biochemistry, 42 (42): 12181-91. [PMID:14567679]

7. Bjursell M, Gerdin AK, Jönsson M, Surve VV, Svensson L, Huang XF, Törnell J, Bohlooly-Y M. (2006) G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice. Biochem. Biophys. Res. Commun., 348 (2): 359-66. [PMID:16887097]

8. Bolick DT, Whetzel AM, Skaflen M, Deem TL, Lee J, Hedrick CC. (2007) Absence of the G protein-coupled receptor G2A in mice promotes monocyte/endothelial interactions in aorta. Circ. Res., 100 (4): 572-80. [PMID:17255525]

9. Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ. (2006) A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J. Exp. Med., 203 (9): 2201-13. [PMID:16940167]

10. Cartoni C, Yasumatsu K, Ohkuri T, Shigemura N, Yoshida R, Godinot N, le Coutre J, Ninomiya Y, Damak S. (2010) Taste preference for fatty acids is mediated by GPR40 and GPR120. J. Neurosci., 30 (25): 8376-82. [PMID:20573884]

11. Chen Q, Kogan JH, Gross AK, Zhou Y, Walton NM, Shin R, Heusner CL, Miyake S, Tajinda K, Tamura K et al.. (2012) SREB2/GPR85, a schizophrenia risk factor, negatively regulates hippocampal adult neurogenesis and neurogenesis-dependent learning and memory. Eur. J. Neurosci., 36 (5): 2597-608. [PMID:22697179]

12. Chen Y, Wu H, Wang S, Koito H, Li J, Ye F, Hoang J, Escobar SS, Gow A, Arnett HA, Trapp BD, Karandikar NJ, Hsieh J, Lu QR. (2009) The oligodendrocyte-specific G protein-coupled receptor GPR17 is a cell-intrinsic timer of myelination. Nat. Neurosci., 12 (11): 1398-406. [PMID:19838178]

13. Cox PJ, Pitcher T, Trim SA, Bell CH, Qin W, Kinloch RA. (2008) The effect of deletion of the orphan G - protein coupled receptor (GPCR) gene MrgE on pain-like behaviours in mice. Mol Pain, 4: 2. [PMID:18197975]

14. da Costa Gonçalves AC, Leite R, Fraga-Silva RA, Pinheiro SV, Reis AB, Reis FM, Touyz RM, Webb RC, Alenina N, Bader M et al.. (2007) Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. Am. J. Physiol. Heart Circ. Physiol., 293 (4): H2588-96. [PMID:17616753]

15. Damond F, Benard A, Ruelle J, Alabi A, Kupfer B, Gomes P, Rodes B, Albert J, Böni J, Garson J et al.. (2008) Quality control assessment of human immunodeficiency virus type 2 (HIV-2) viral load quantification assays: results from an international collaboration on HIV-2 infection in 2006. J. Clin. Microbiol., 46 (6): 2088-91. [PMID:18434556]

16. Davenport AP, Alexander SP, Sharman JL, Pawson AJ, Benson HE, Monaghan AE, Liew WC, Mpamhanga CP, Bonner TI, Neubig RR et al.. (2013) International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. Pharmacol. Rev., 65 (3): 967-86. [PMID:23686350]

17. Davenport AP, Bonner TI, Foord SM, Harmar AJ, Neubig RR, Pin JP, Spedding M, Kojima M, Kangawa K. (2005) International Union of Pharmacology. LVI. Ghrelin receptor nomenclature, distribution, and function. Pharmacol. Rev., 57 (4): 541-6. [PMID:16382107]

18. Engel KM, Schröck K, Teupser D, Holdt LM, Tönjes A, Kern M, Dietrich K, Kovacs P, Krügel U, Scheidt HA et al.. (2011) Reduced food intake and body weight in mice deficient for the G protein-coupled receptor GPR82. PLoS ONE, 6 (12): e29400. [PMID:22216272]

19. Gardner J, Wu S, Ling L, Danao J, Li Y, Yeh WC, Tian H, Baribault H. (2012) G-protein-coupled receptor GPR21 knockout mice display improved glucose tolerance and increased insulin response. Biochem. Biophys. Res. Commun., 418 (1): 1-5. [PMID:22155242]

20. Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA et al.. (2012) Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat. Neurosci., 15 (7): 970-8. [PMID:22660477]

21. Hannedouche S, Zhang J, Yi T, Shen W, Nguyen D, Pereira JP, Guerini D, Baumgarten BU, Roggo S, Wen B et al.. (2011) Oxysterols direct immune cell migration via EBI2. Nature, 475 (7357): 524-7. [PMID:21796212]

22. He W, Miao FJ, Lin DC, Schwandner RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. (2004) Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature, 429 (6988): 188-93. [PMID:15141213]

23. Hirasawa A, Tsumaya K, Awaji T, Katsuma S, Adachi T, Yamada M, Sugimoto Y, Miyazaki S, Tsujimoto G. (2005) Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med, 11: 90-94. [PMID:15619630]

24. Holst B, Egerod KL, Jin C, Petersen PS, Østergaard MV, Hald J, Sprinkel AM, Størling J, Mandrup-Poulsen T, Holst JJ, Thams P, Orskov C, Wierup N, Sundler F, Madsen OD, Schwartz TW. (2009) G protein-coupled receptor 39 deficiency is associated with pancreatic islet dysfunction. Endocrinology, 150 (6): 2577-85. [PMID:19213833]

25. Ichimura A, Hirasawa A, Poulain-Godefroy O, Bonnefond A, Hara T, Yengo L, Kimura I, Leloire A, Liu N, Iida K et al.. (2012) Dysfunction of lipid sensor GPR120 leads to obesity in both mouse and human. Nature, 483 (7389): 350-4. [PMID:22343897]

26. Imai Y, Inoue H, Kataoka A, Hua-Qin W, Masuda M, Ikeda T, Tsukita K, Soda M, Kodama T, Fuwa T, Honda Y, Kaneko S, Matsumoto S, Wakamatsu K, Ito S, Miura M, Aosaki T, Itohara S, Takahashi R. (2007) Pael receptor is involved in dopamine metabolism in the nigrostriatal system. Neurosci. Res., 59 (4): 413-25. [PMID:17889953]

27. Ishida J, Hashimoto T, Hashimoto Y, Nishiwaki S, Iguchi T, Harada S, Sugaya T, Matsuzaki H, Yamamoto R, Shiota N et al.. (2004) Regulatory roles for APJ, a seven-transmembrane receptor related to angiotensin-type 1 receptor in blood pressure in vivo. J. Biol. Chem., 279 (25): 26274-9. [PMID:15087458]

28. Ivanova EA, Bechtold DA, Dupré SM, Brennand J, Barrett P, Luckman SM, Loudon AS. (2008) Altered metabolism in the melatonin-related receptor (GPR50) knockout mouse. Am. J. Physiol. Endocrinol. Metab., 294 (1): E176-82. [PMID:17957037]

29. Jin C, Yin F, Lin M, Li H, Wang Z, Weng J, Liu M, Da Dong X, Qu J, Tu L. (2008) GPR48 regulates epithelial cell proliferation and migration by activating EGFR during eyelid development. Invest. Ophthalmol. Vis. Sci., 49 (10): 4245-53. [PMID:18487371]

30. Johnson LE, Elias MS, Bolick DT, Skaflen MD, Green RM, Hedrick CC. (2008) The G protein-coupled receptor G2A: involvement in hepatic lipid metabolism and gallstone formation in mice. Hepatology, 48 (4): 1138-48. [PMID:18821587]

31. Kato S, Matsubara M, Matsuo T, Mohri Y, Kazama I, Hatano R, Umezawa A, Nishimori K. (2006) Leucine-rich repeat-containing G protein-coupled receptor-4 (LGR4, Gpr48) is essential for renal development in mice. Nephron Exp. Nephrol., 104 (2): e63-75. [PMID:16785743]

32. Kato S, Mohri Y, Matsuo T, Ogawa E, Umezawa A, Okuyama R, Nishimori K. (2007) Eye-open at birth phenotype with reduced keratinocyte motility in LGR4 null mice. FEBS Lett., 581 (24): 4685-90. [PMID:17850793]

33. Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. (2011) EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. J. Immunol., 187 (6): 3026-32. [PMID:21844396]

34. Kerschner JE, Hong W, Taylor SR, Kerschner JA, Khampang P, Wrege KC, North PE. (2013) A novel model of spontaneous otitis media with effusion (OME) in the Oxgr1 knock-out mouse. Int. J. Pediatr. Otorhinolaryngol., 77 (1): 79-84. [PMID:23200873]

35. Kirby HR, Maguire JJ, Colledge WH, Davenport AP. (2010) International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. Pharmacol. Rev., 62 (4): 565-78. [PMID:21079036]

36. Kotarsky K, Boketoft A, Bristulf J, Nilsson NE, Norberg A, Hansson S, Owman C, Sillard R, Leeb-Lundberg LM, Olde B. (2006) Lysophosphatidic acid binds to and activates GPR92, a G protein-coupled receptor highly expressed in gastrointestinal lymphocytes. J. Pharmacol. Exp. Ther., 318 (2): 619-28. [PMID:16651401]

37. Kottyan LC, Collier AR, Cao KH, Niese KA, Hedgebeth M, Radu CG, Witte ON, Khurana Hershey GK, Rothenberg ME, Zimmermann N. (2009) Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner. Blood, 114 (13): 2774-82. [PMID:19641187]

38. Lan H, Vassileva G, Corona A, Liu L, Baker H, Golovko A, Abbondanzo SJ, Hu W, Yang S, Ning Y et al.. (2009) GPR119 is required for physiological regulation of glucagon-like peptide-1 secretion but not for metabolic homeostasis. J. Endocrinol., 201 (2): 219-30. [PMID:19282326]

39. Le LQ, Kabarowski JH, Weng Z, Satterthwaite AB, Harvill ET, Jensen ER, Miller JF, Witte ON. (2001) Mice lacking the orphan G protein-coupled receptor G2A develop a late-onset autoimmune syndrome. Immunity, 14 (5): 561-71. [PMID:11371358]

40. Ledent C, Demeestere I, Blum D, Petermans J, Hämäläinen T, Smits G, Vassart G. (2005) Premature ovarian aging in mice deficient for Gpr3. Proc. Natl. Acad. Sci. U.S.A., 102 (25): 8922-6. [PMID:15956199]

41. Lee CW, Rivera R, Gardell S, Dubin AE, Chun J. (2006) GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J. Biol. Chem., 281 (33): 23589-97. [PMID:16774927]

42. Lee Z, Cheng CT, Zhang H, Subler MA, Wu J, Mukherjee A, Windle JJ, Chen CK, Fang X. (2008) Role of LPA4/p2y9/GPR23 in negative regulation of cell motility. Mol. Biol. Cell, 19 (12): 5435-45. [PMID:18843048]

43. Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, Jockers R. (2006) The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization. EMBO J., 25 (13): 3012-23. [PMID:16778767]

44. Li H, Wang D, Singh LS, Berk M, Tan H, Zhao Z, Steinmetz R, Kirmani K, Wei G, Xu Y. (2009) Abnormalities in osteoclastogenesis and decreased tumorigenesis in mice deficient for ovarian cancer G protein-coupled receptor 1. PLoS ONE, 4 (5): e5705. [PMID:19479052]

45. Liebscher I, Müller U, Teupser D, Engemaier E, Engel KM, Ritscher L, Thor D, Sangkuhl K, Ricken A, Wurm A et al.. (2011) Altered immune response in mice deficient for the G protein-coupled receptor GPR34. J. Biol. Chem., 286 (3): 2101-10. [PMID:21097509]

46. Lin ME, Rivera RR, Chun J. (2012) Targeted deletion of LPA5 identifies novel roles for lysophosphatidic acid signaling in development of neuropathic pain. J. Biol. Chem., 287 (21): 17608-17. [PMID:22461625]

47. Lobo MK, Cui Y, Ostlund SB, Balleine BW, Yang XW. (2007) Genetic control of instrumental conditioning by striatopallidal neuron-specific S1P receptor Gpr6. Nat. Neurosci., 10 (11): 1395-7. [PMID:17934457]

48. Logue SF, Grauer SM, Paulsen J, Graf R, Taylor N, Sung MA, Zhang L, Hughes Z, Pulito VL, Liu F, Rosenzweig-Lipson S, Brandon NJ, Marquis KL, Bates B, Pausch M. (2009) The orphan GPCR, GPR88, modulates function of the striatal dopamine system: a possible therapeutic target for psychiatric disorders?. Mol. Cell. Neurosci., 42 (4): 438-47. [PMID:19796684]

49. Luangsay S, Wittamer V, Bondue B, De Henau O, Rouger L, Brait M, Franssen JD, de Nadai P, Huaux F, Parmentier M. (2009) Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. J. Immunol., 183 (10): 6489-99. [PMID:19841182]

50. Lucas RJ, Hattar S, Takao M, Berson DM, Foster RG, Yau KW. (2003) Diminished pupillary light reflex at high irradiances in melanopsin-knockout mice. Science, 299 (5604): 245-7. [PMID:12522249]

51. Luo J, Zhou W, Zhou X, Li D, Weng J, Yi Z, Cho SG, Li C, Yi T, Wu X, Li XY, de Crombrugghe B, Höök M, Liu M. (2009) Regulation of bone formation and remodeling by G-protein-coupled receptor 48. Development, 136 (16): 2747-56. [PMID:19605502]

52. Maekawa A, Xing W, Austen KF, Kanaoka Y. (2010) GPR17 regulates immune pulmonary inflammation induced by house dust mites. J. Immunol., 185 (3): 1846-54. [PMID:20574000]

53. Maekawa F, Quah HM, Tanaka K, Ohki-Hamazaki H. (2004) Leptin resistance and enhancement of feeding facilitation by melanin-concentrating hormone in mice lacking bombesin receptor subtype-3. Diabetes, 53 (3): 570-6. [PMID:14988239]

54. Maguire JJ, Parker WA, Foord SM, Bonner TI, Neubig RR, Davenport AP. (2009) International Union of Pharmacology. LXXII. Recommendations for trace amine receptor nomenclature. Pharmacol. Rev., 61 (1): 1-8. [PMID:19325074]

55. Marazziti D, Di Pietro C, Golini E, Mandillo S, Matteoni R, Tocchini-Valentini GP. (2009) Induction of macroautophagy by overexpression of the Parkinson's disease-associated GPR37 receptor. FASEB J., 23 (6): 1978-87. [PMID:19218498]

56. Marazziti D, Golini E, Mandillo S, Magrelli A, Witke W, Matteoni R, Tocchini-Valentini GP. (2004) Altered dopamine signaling and MPTP resistance in mice lacking the Parkinson's disease-associated GPR37/parkin-associated endothelin-like receptor. Proc. Natl. Acad. Sci. U.S.A., 101 (27): 10189-94. [PMID:15218106]

57. Maruyama T, Miyamoto Y, Nakamura T, Tamai Y, Okada H, Sugiyama E, Nakamura T, Itadani H, Tanaka K. (2002) Identification of membrane-type receptor for bile acids (M-BAR). Biochem. Biophys. Res. Commun., 298 (5): 714-9. [PMID:12419312]

58. Matsumoto M, Straub RE, Marenco S, Nicodemus KK, Matsumoto S, Fujikawa A, Miyoshi S, Shobo M, Takahashi S, Yarimizu J, Yuri M, Hiramoto M, Morita S, Yokota H, Sasayama T, Terai K, Yoshino M, Miyake A, Callicott JH, Egan MF, Meyer-Lindenberg A, Kempf L, Honea R, Vakkalanka RK, Takasaki J, Kamohara M, Soga T, Hiyama H, Ishii H, Matsuo A, Nishimura S, Matsuoka N, Kobori M, Matsushime H, Katoh M, Furuichi K, Weinberger DR. (2008) The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia. Proc. Natl. Acad. Sci. U.S.A., 105 (16): 6133-8. [PMID:18413613]

59. Mazerbourg S, Bouley DM, Sudo S, Klein CA, Zhang JV, Kawamura K, Goodrich LV, Rayburn H, Tessier-Lavigne M, Hsueh AJ. (2004) Leucine-rich repeat-containing, G protein-coupled receptor 4 null mice exhibit intrauterine growth retardation associated with embryonic and perinatal lethality. Mol. Endocrinol., 18 (9): 2241-54. [PMID:15192078]

60. Meder W, Wendland M, Busmann A, Kutzleb C, Spodsberg N, John H, Richter R, Schleuder D, Meyer M, Forssmann WG. (2003) Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS Lett., 555 (3): 495-9. [PMID:14675762]

61. Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, Pendola FL, Knowles BB, Eppig JJ, Jaffe LA. (2004) The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science, 306 (5703): 1947-50. [PMID:15591206]

62. Min KD, Asakura M, Liao Y, Nakamaru K, Okazaki H, Takahashi T, Fujimoto K, Ito S, Takahashi A, Asanuma H, Yamazaki S, Minamino T, Sanada S, Seguchi O, Nakano A, Ando Y, Otsuka T, Furukawa H, Isomura T, Takashima S, Mochizuki N, Kitakaze M. (2010) Identification of genes related to heart failure using global gene expression profiling of human failing myocardium. Biochem. Biophys. Res. Commun., 393 (1): 55-60. [PMID:20100464]

63. Moechars D, Depoortere I, Moreaux B, de Smet B, Goris I, Hoskens L, Daneels G, Kass S, Ver Donck L, Peeters T, Coulie B. (2006) Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse. Gastroenterology, 131 (4): 1131-41. [PMID:17030183]

64. Mohebbi N, Benabbas C, Vidal S, Daryadel A, Bourgeois S, Velic A, Ludwig MG, Seuwen K, Wagner CA. (2012) The proton-activated G protein coupled receptor OGR1 acutely regulates the activity of epithelial proton transport proteins. Cell. Physiol. Biochem., 29 (3-4): 313-24. [PMID:22508039]

65. Mohri Y, Oyama K, Akamatsu A, Kato S, Nishimori K. (2011) Lgr4-deficient mice showed premature differentiation of ureteric bud with reduced expression of Wnt effector Lef1 and Gata3. Dev. Dyn., 240 (6): 1626-34. [PMID:21523854]

66. Morita H, Mazerbourg S, Bouley DM, Luo CW, Kawamura K, Kuwabara Y, Baribault H, Tian H, Hsueh AJ. (2004) Neonatal lethality of LGR5 null mice is associated with ankyloglossia and gastrointestinal distension. Mol. Cell. Biol., 24 (22): 9736-43. [PMID:15509778]

67. Mårtensson UE, Salehi SA, Windahl S, Gomez MF, Swärd K, Daszkiewicz-Nilsson J, Wendt A, Andersson N, Hellstrand P, Grände PO et al.. (2009) Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice. Endocrinology, 150 (2): 687-98. [PMID:18845638]

68. Nakamichi Y, Wada E, Aoki K, Ohara-Imaizumi M, Kikuta T, Nishiwaki C, Matsushima S, Watanabe T, Wada K, Nagamatsu S. (2004) Functions of pancreatic beta cells and adipocytes in bombesin receptor subtype-3-deficient mice. Biochem. Biophys. Res. Commun., 318 (3): 698-703. [PMID:15144894]

69. Noguchi K, Ishii S, Shimizu T. (2003) Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J. Biol. Chem., 278 (28): 25600-6. [PMID:12724320]

70. Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP. (2011) International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B). Pharmacol. Rev., 63 (2): 269-90. [PMID:21454438]

71. Ohki-Hamazaki H, Watase K, Yamamoto K, Ogura H, Yamano M, Yamada K, Maeno H, Imaki J, Kikuyama S, Wada E et al.. (1997) Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity. Nature, 390 (6656): 165-9. [PMID:9367152]

72. Onozawa Y, Fujita Y, Kuwabara H, Nagasaki M, Komai T, Oda T. (2012) Activation of T cell death-associated gene 8 regulates the cytokine production of T cells and macrophages in vitro. Eur. J. Pharmacol., 683 (1-3): 325-31. [PMID:22445881]

73. Osborn O, Oh da Y, McNelis J, Sanchez-Alavez M, Talukdar S, Lu M, Li P, Thiede L, Morinaga H, Kim JJ et al.. (2012) G protein-coupled receptor 21 deletion improves insulin sensitivity in diet-induced obese mice. J. Clin. Invest., 122 (7): 2444-53. [PMID:22653059]

74. Parks BW, Gambill GP, Lusis AJ, Kabarowski JH. (2005) Loss of G2A promotes macrophage accumulation in atherosclerotic lesions of low density lipoprotein receptor-deficient mice. J. Lipid Res., 46 (7): 1405-15. [PMID:15834123]

75. Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC. (2008) G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat. Genet., 40 (3): 329-34. [PMID:18297070]

76. Pereira JP, Kelly LM, Xu Y, Cyster JG. (2009) EBI2 mediates B cell segregation between the outer and centre follicle. Nature, 460 (7259): 1122-6. [PMID:19597478]

77. Pitkin SL, Maguire JJ, Bonner TI, Davenport AP. (2010) International Union of Basic and Clinical Pharmacology. LXXIV. Apelin receptor nomenclature, distribution, pharmacology, and function. Pharmacol. Rev., 62 (3): 331-42. [PMID:20605969]

78. Prossnitz ER, Barton M. (2011) The G-protein-coupled estrogen receptor GPER in health and disease. Nat Rev Endocrinol, 7 (12): 715-26. [PMID:21844907]

79. Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ. (2010) Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7. Proc. Natl. Acad. Sci. U.S.A., 107 (2): 628-32. [PMID:20018651]

80. Revankar CM, Cimino DF, Sklar LA, Arterburn JB, Prossnitz ER. (2005) A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science, 307 (5715): 1625-30. [PMID:15705806]

81. Rubic T, Lametschwandtner G, Jost S, Hinteregger S, Kund J, Carballido-Perrig N, Schwärzler C, Junt T, Voshol H, Meingassner JG et al.. (2008) Triggering the succinate receptor GPR91 on dendritic cells enhances immunity. Nat. Immunol., 9 (11): 1261-9. [PMID:18820681]

82. Singh G, Davenport AP. (2006) Neuropeptide B and W: neurotransmitters in an emerging G-protein-coupled receptor system. Br. J. Pharmacol., 148 (8): 1033-41. [PMID:16847439]

83. Southern C, Cook JM, Neetoo-Isseljee Z, Taylor DL, Kettleborough CA, Merritt A, Bassoni DL, Raab WJ, Quinn E, Wehrman TS et al.. (2013) Screening β-Arrestin Recruitment for the Identification of Natural Ligands for Orphan G-Protein-Coupled Receptors. J Biomol Screen, 18 (5): 599-609. [PMID:23396314]

84. Stoddart LA, Smith NJ, Milligan G. (2008) International Union of Pharmacology. LXXI. Free fatty acid receptors FFA1, -2, and -3: pharmacology and pathophysiological functions. Pharmacol. Rev., 60 (4): 405-17. [PMID:19047536]

85. Sumida H, Noguchi K, Kihara Y, Abe M, Yanagida K, Hamano F, Sato S, Tamaki K, Morishita Y, Kano MR et al.. (2010) LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. Blood, 116 (23): 5060-70. [PMID:20713964]

86. Sun X, Yang LV, Tiegs BC, Arend LJ, McGraw DW, Penn RB, Petrovic S. (2010) Deletion of the pH sensor GPR4 decreases renal acid excretion. J. Am. Soc. Nephrol., 21 (10): 1745-55. [PMID:20798260]

87. Thomas P, Pang Y, Filardo EJ, Dong J. (2005) Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology, 146 (2): 624-32. [PMID:15539556]

88. Toma I, Kang JJ, Sipos A, Vargas S, Bansal E, Hanner F, Meer E, Peti-Peterdi J. (2008) Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. J. Clin. Invest., 118 (7): 2526-34. [PMID:18535668]

89. Tremblay F, Perreault M, Klaman LD, Tobin JF, Smith E, Gimeno RE. (2007) Normal food intake and body weight in mice lacking the G protein-coupled receptor GPR39. Endocrinology, 148 (2): 501-6. [PMID:17095592]

90. Valverde O, Célérier E, Baranyi M, Vanderhaeghen P, Maldonado R, Sperlagh B, Vassart G, Ledent C. (2009) GPR3 receptor, a novel actor in the emotional-like responses. PLoS ONE, 4 (3): e4704. [PMID:19259266]

91. Venkataraman C, Kuo F. (2005) The G-protein coupled receptor, GPR84 regulates IL-4 production by T lymphocytes in response to CD3 crosslinking. Immunol. Lett., 101 (2): 144-53. [PMID:15993493]

92. Walther T, Balschun D, Voigt JP, Fink H, Zuschratter W, Birchmeier C, Ganten D, Bader M. (1998) Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene. J. Biol. Chem., 273 (19): 11867-73. [PMID:9565612]

93. Walther T, Wessel N, Kang N, Sander A, Tschöpe C, Malberg H, Bader M, Voss A. (2000) Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene. Braz. J. Med. Biol. Res., 33 (1): 1-9. [PMID:10625868]

94. Wang C, Dehghani B, Magrisso IJ, Rick EA, Bonhomme E, Cody DB, Elenich LA, Subramanian S, Murphy SJ, Kelly MJ et al.. (2008) GPR30 contributes to estrogen-induced thymic atrophy. Mol. Endocrinol., 22 (3): 636-48. [PMID:18063692]

95. Wang Z, Jin C, Li H, Li C, Hou Q, Liu M, Dong Xda E, Tu L. (2010) GPR48-Induced keratinocyte proliferation occurs through HB-EGF mediated EGFR transactivation. FEBS Lett., 584 (18): 4057-62. [PMID:20732323]

96. Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, Ross RA, Rogers MJ. (2009) The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo. Proc. Natl. Acad. Sci. U.S.A., 106 (38): 16511-6. [PMID:19805329]

97. Williams JR, Khandoga AL, Goyal P, Fells JI, Perygin DH, Siess W, Parrill AL, Tigyi G, Fujiwara Y. (2009) Unique ligand selectivity of the GPR92/LPA5 lysophosphatidate receptor indicates role in human platelet activation. J. Biol. Chem., 284 (25): 17304-19. [PMID:19366702]

98. Wyder L, Suply T, Ricoux B, Billy E, Schnell C, Baumgarten BU, Maira SM, Koelbing C, Ferretti M, Kinzel B et al.. (2011) Reduced pathological angiogenesis and tumor growth in mice lacking GPR4, a proton sensing receptor. Angiogenesis, 14 (4): 533-44. [PMID:22045552]

99. Xu P, Costa-Goncalves AC, Todiras M, Rabelo LA, Sampaio WO, Moura MM, Santos SS, Luft FC, Bader M, Gross V et al.. (2008) Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension, 51 (2): 574-80. [PMID:18180400]

100. Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F, Tajima Y, Taguchi R, Shimizu T, Ishii S. (2009) Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J. Biol. Chem., 284 (26): 17731-41. [PMID:19386608]

101. Zabel BA, Silverio AM, Butcher EC. (2005) Chemokine-like receptor 1 expression and chemerin-directed chemotaxis distinguish plasmacytoid from myeloid dendritic cells in human blood. J. Immunol., 174 (1): 244-51. [PMID:15611246]

102. Zhang LL, Wang JJ, Liu Y, Lu XB, Kuang Y, Wan YH, Chen Y, Yan HM, Fei J, Wang ZG. (2011) GPR26-deficient mice display increased anxiety- and depression-like behaviors accompanied by reduced phosphorylated cyclic AMP responsive element-binding protein level in central amygdala. Neuroscience, 196: 203-14. [PMID:21924326]

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