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Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
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Adhesion GPCRs are structurally identified on the basis of a large extracellular region, similar to the Class B GPCR, but which is linked to the 7TM region by a GPCR autoproteolysis-inducing (GAIN) domain [1] containing a GPCR proteolytic site. The N-terminus often shares structural homology with adhesive domains (e.g. cadherins, immunolobulin, lectins) facilitating inter- and matricellular interactions and leading to the term adhesion GPCR [13,47]. Several receptors have been suggested to function as mechanosensors [6,30,33,44]. The nomenclature of these receptors was revised in 2015 as recommended by NC-IUPHAR and the Adhesion GPCR Consortium [15].
ADGRA1
C
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ADGRA2
C
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ADGRA3
C
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ADGRB1
C
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ADGRB2
C
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ADGRB3
C
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CELSR1 / ADGRC1
C
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CELSR2 / ADGRC2
C
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CELSR3 / ADGRC3
C
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ADGRD1
C
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ADGRD2
C
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ADGRE1
C
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ADGRE2
C
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ADGRE3
C
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ADGRE4P
C
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ADGRE5
C
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ADGRF1
C
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ADGRF2
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ADGRF3
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ADGRF4
C
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ADGRF5
C
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ADGRG1
C
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ADGRG2
C
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ADGRG3
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ADGRG4
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ADGRG5
C
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ADGRG6
C
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ADGRG7
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ADGRL1
C
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ADGRL2
C
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ADGRL3
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ADGRL4
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ADGRV1
C
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* Key recommended reading is highlighted with an asterisk
* Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B et al.. (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol. Rev., 67 (2): 338-67. [PMID:25713288]
* Langenhan T, Aust G, Hamann J. (2013) Sticky signaling--adhesion class G protein-coupled receptors take the stage. Sci Signal, 6 (276): re3. [PMID:23695165]
* Liebscher I, Schöneberg T. (2016) Tethered Agonism: A Common Activation Mechanism of Adhesion GPCRs. Handb Exp Pharmacol, 234: 111-125. [PMID:27832486]
* Monk KR, Hamann J, Langenhan T, Nijmeijer S, Schöneberg T, Liebscher I. (2015) Adhesion G Protein-Coupled Receptors: From In Vitro Pharmacology to In Vivo Mechanisms. Mol. Pharmacol., 88 (3): 617-23. [PMID:25956432]
* Purcell RH, Hall RA. (2018) Adhesion G Protein-Coupled Receptors as Drug Targets. Annu. Rev. Pharmacol. Toxicol., 58: 429-449. [PMID:28968187]
Yona S, Lin HH, Siu WO, Gordon S, Stacey M. (2008) Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem. Sci., 33 (10): 491-500. [PMID:18789697]
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14. Gupte J, Swaminath G, Danao J, Tian H, Li Y, Wu X. (2012) Signaling property study of adhesion G-protein-coupled receptors. FEBS Lett., 586 (8): 1214-9. [PMID:22575658]
15. Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B et al.. (2015) International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors. Pharmacol. Rev., 67 (2): 338-67. [PMID:25713288]
16. Hamann J, Vogel B, van Schijndel GM, van Lier RA. (1996) The seven-span transmembrane receptor CD97 has a cellular ligand (CD55, DAF). J. Exp. Med., 184 (3): 1185-9. [PMID:9064337]
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18. Lee JW, Huang BX, Kwon H, Rashid MA, Kharebava G, Desai A, Patnaik S, Marugan J, Kim HY. (2016) Orphan GPR110 (ADGRF1) targeted by N-docosahexaenoylethanolamine in development of neurons and cognitive function. Nat Commun, 7: 13123. [PMID:27759003]
19. Leja J, Essaghir A, Essand M, Wester K, Oberg K, Tötterman TH, Lloyd R, Vasmatzis G, Demoulin JB, Giandomenico V. (2009) Novel markers for enterochromaffin cells and gastrointestinal neuroendocrine carcinomas. Mod. Pathol., 22 (2): 261-72. [PMID:18953328]
20. Lelianova VG, Davletov BA, Sterling A, Rahman MA, Grishin EV, Totty NF, Ushkaryov YA. (1997) Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors. J. Biol. Chem., 272 (34): 21504-8. [PMID:9261169]
21. Liebscher I, Schön J, Petersen SC, Fischer L, Auerbach N, Demberg LM, Mogha A, Cöster M, Simon KU, Rothemund S et al.. (2014) A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell Rep, 9 (6): 2018-26. [PMID:25533341]
22. Luo R, Jeong SJ, Jin Z, Strokes N, Li S, Piao X. (2011) G protein-coupled receptor 56 and collagen III, a receptor-ligand pair, regulates cortical development and lamination. Proc. Natl. Acad. Sci. U.S.A., 108 (31): 12925-30. [PMID:21768377]
23. Mogha A, Benesh AE, Patra C, Engel FB, Schöneberg T, Liebscher I, Monk KR. (2013) Gpr126 functions in Schwann cells to control differentiation and myelination via G-protein activation. J. Neurosci., 33 (46): 17976-85. [PMID:24227709]
24. Monk KR, Naylor SG, Glenn TD, Mercurio S, Perlin JR, Dominguez C, Moens CB, Talbot WS. (2009) A G protein-coupled receptor is essential for Schwann cells to initiate myelination. Science, 325 (5946): 1402-5. [PMID:19745155]
25. Müller A, Winkler J, Fiedler F, Sastradihardja T, Binder C, Schnabel R, Kungel J, Rothemund S, Hennig C, Schöneberg T et al.. (2015) Oriented Cell Division in the C. elegans Embryo Is Coordinated by G-Protein Signaling Dependent on the Adhesion GPCR LAT-1. PLoS Genet., 11 (10): e1005624. [PMID:26505631]
26. Ni YY, Chen Y, Lu SY, Sun BY, Wang F, Wu XL, Dang SY, Zhang GH, Zhang HX, Kuang Y et al.. (2014) Deletion of Gpr128 results in weight loss and increased intestinal contraction frequency. World J. Gastroenterol., 20 (2): 498-508. [PMID:24574718]
27. Park D, Tosello-Trampont AC, Elliott MR, Lu M, Haney LB, Ma Z, Klibanov AL, Mandell JW, Ravichandran KS. (2007) BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature, 450 (7168): 430-4. [PMID:17960134]
28. Patat O, Pagin A, Siegfried A, Mitchell V, Chassaing N, Faguer S, Monteil L, Gaston V, Bujan L, Courtade-Saïdi M et al.. (2016) Truncating Mutations in the Adhesion G Protein-Coupled Receptor G2 Gene ADGRG2 Cause an X-Linked Congenital Bilateral Absence of Vas Deferens. Am. J. Hum. Genet., 99 (2): 437-42. [PMID:27476656]
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31. Posokhova E, Shukla A, Seaman S, Volate S, Hilton MB, Wu B, Morris H, Swing DA, Zhou M, Zudaire E et al.. (2015) GPR124 functions as a WNT7-specific coactivator of canonical β-catenin signaling. Cell Rep, 10 (2): 123-30. [PMID:25558062]
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42. Wang S, Mandell JD, Kumar Y, Sun N, Morris MT, Arbelaez J, Nasello C, Dong S, Duhn C, Zhao X et al.. (2018) De Novo Sequence and Copy Number Variants Are Strongly Associated with Tourette Disorder and Implicate Cell Polarity in Pathogenesis. Cell Rep, 24 (13): 3441-3454.e12. [PMID:30257206]
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44. Wilde C, Fischer L, Lede V, Kirchberger J, Rothemund S, Schöneberg T, Liebscher I. (2016) The constitutive activity of the adhesion GPCR GPR114/ADGRG5 is mediated by its tethered agonist. FASEB J., 30 (2): 666-73. [PMID:26499266]
45. Willsey AJ, Fernandez TV, Yu D, King RA, Dietrich A, Xing J, Sanders SJ, Mandell JD, Huang AY, Richer P et al.. (2017) De Novo Coding Variants Are Strongly Associated with Tourette Disorder. Neuron, 94 (3): 486-499.e9. [PMID:28472652]
46. Xu L, Begum S, Hearn JD, Hynes RO. (2006) GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc. Natl. Acad. Sci. U.S.A., 103 (24): 9023-8. [PMID:16757564]
47. Yona S, Lin HH, Siu WO, Gordon S, Stacey M. (2008) Adhesion-GPCRs: emerging roles for novel receptors. Trends Biochem. Sci., 33 (10): 491-500. [PMID:18789697]
48. Zhou Y, Nathans J. (2014) Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev. Cell, 31 (2): 248-56. [PMID:25373781]
Demet Arac-Ozkan
Gabriela Aust
Tom I. Bonner
Heike Cappallo-Obermann
Caroline Formstone
Jörg Hamann
Breanne Harty
Henrike Heyne
Christiane Kirchhoff
Barbara Knapp
Arunkumar Krishnan
Tobias Langenhan
Diana Le Duc
Hsi-Hsien Lin
David C. Martinelli
Kelly Monk
Xianhua Piao
Simone Prömel
Helgi Schiöth
Torsten Schöneberg
Kathleen Singer
Martin Stacey
Yuri Ushkaryov
Uwe Wolfrum
Lei Xu |
Database page citation (select format):
Concise Guide to PHARMACOLOGY citation:
Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators. (2019) The Concise Guide to PHARMACOLOGY 2019/20: G protein-coupled receptors. Br J Pharmacol. 176 Issue S1: S21-S141.
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