ADGRD2 | Adhesion Class GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

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ADGRD2

Target not currently curated in GtoImmuPdb

Target id: 204

Nomenclature: ADGRD2

Family: Adhesion Class GPCRs

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

Gene and Protein Information
Adhesion G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 - 9q34.11 ADGRD2 adhesion G protein-coupled receptor D2
Mouse 7 - 2 B Adgrd2-ps adhesion G protein-coupled receptor D2
Previous and Unofficial Names
GPR144 (G protein-coupled receptor 144) | adhesion G protein-coupled receptor D2, pseudogene | adhesion G protein-coupled receptor D2
Database Links
Specialist databases
GPCRDB agrd2_human (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
Pharos
UniProtKB
Wikipedia
Primary Transduction Mechanisms
Transducer Effector/Response
G protein (identity unknown)
Comments:  Predicted to transduce signal through G proteins based on sequence signatures [3]. However, studies on several different adhesion GPCRs have provided evidence that these receptors are in fact authentic G protein-coupled receptors. Adhesion GPCRs with experimentally verified G-protein coupling includes ADGRG1 [5], ADGRD1 [2] and ADGRG6 [7]. Recent reviews [9] and adhesion GPCR consortium meeting report [1] addressed the issues to unravel the signal transduction of adhesion GPCRs and provided further preliminary evidences [4] for other adhesion GPCRs to transduce signal through G proteins.
References: 
Secondary Transduction Mechanisms
Transducer Effector/Response
G protein (identity unknown)
References: 
General Comments
ADGRD2 (formerly GPR144) is an orphan receptor belonging to Family V Adhesion-GPCRs together with ADGRD1 (formerly GPR133) [3]. ADGRD1 and ADGRD2 are the Adhesion-GPCRs most closely related to the Secretin class of GPCRs [8]. A search for homologs in the invertebrates like ciona and amphioxus revealed that ADGRD1 and ADGRD2 are well conserved in pre-vertebrate genomes [6,8]. Unlike the close paralog ADGRD1, which only contains a GPCR proteolysis site (GPS) motif in its rather short N terminus, ADGRD2 was found to contain a pentraxin (PTX) domain along with the GPS motif. The PTX domain has previously been found in one other Adhesion-GPCR (ADGRG4, previously GPR112). ADGRG4 is, together with CELSR1-3 and VLGR1 (now known as ADGRV1), one the largest Adhesion-GPCRs. The PTX domain in ADGRD2 is only 33% similar to the PTX domain in ADGRG4. ADGRG4 belongs to a different phylogenetic cluster as ADGRD2 and these receptors are not particularly similar, sharing about 36–40% amino acid identity in the TM regions. The PTX domains are found in a number of other proteins and consist of up to five non-covalently bound identical subunits that are arranged in a flat pentameric disk.

References

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1. Araç D, Aust G, Calebiro D, Engel FB, Formstone C, Goffinet A, Hamann J, Kittel RJ, Liebscher I, Lin HH et al.. (2012) Dissecting signaling and functions of adhesion G protein-coupled receptors. Ann. N. Y. Acad. Sci., 1276: 1-25. [PMID:23215895]

2. Bohnekamp J, Schöneberg T. (2011) Cell adhesion receptor GPR133 couples to Gs protein. J. Biol. Chem., 286 (49): 41912-6. [PMID:22025619]

3. Fredriksson R, Gloriam DE, Höglund PJ, Lagerström MC, Schiöth HB. (2003) There exist at least 30 human G-protein-coupled receptors with long Ser/Thr-rich N-termini. Biochem. Biophys. Res. Commun., 301 (3): 725-34. [PMID:12565841]

4. 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]

5. Iguchi T, Sakata K, Yoshizaki K, Tago K, Mizuno N, Itoh H. (2008) Orphan G protein-coupled receptor GPR56 regulates neural progenitor cell migration via a G alpha 12/13 and Rho pathway. J. Biol. Chem., 283 (21): 14469-78. [PMID:18378689]

6. Kamesh N, Aradhyam GK, Manoj N. (2008) The repertoire of G protein-coupled receptors in the sea squirt Ciona intestinalis. BMC Evol. Biol., 8: 129. [PMID:18452600]

7. 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]

8. Nordström KJ, Fredriksson R, Schiöth HB. (2008) The amphioxus (Branchiostoma floridae) genome contains a highly diversified set of G protein-coupled receptors. BMC Evol. Biol., 8: 9. [PMID:18199322]

9. Paavola KJ, Hall RA. (2012) Adhesion G protein-coupled receptors: signaling, pharmacology, and mechanisms of activation. Mol. Pharmacol., 82 (5): 777-83. [PMID:22821233]

Contributors

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