ADGRD1 | Adhesion Class GPCRs | IUPHAR/BPS Guide to PHARMACOLOGY

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ADGRD1

Target not currently curated in GtoImmuPdb

Target id: 202

Nomenclature: ADGRD1

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 7 874 12q24.33 ADGRD1 adhesion G protein-coupled receptor D1
Mouse 7 903 5 G1.3 Adgrd1 adhesion G protein-coupled receptor D1
Rat - - 12q14 Adgrd1 adhesion G protein-coupled receptor D1
Previous and Unofficial Names
GPR133 (G protein-coupled receptor 133)
Database Links
Specialist databases
GPCRDB agrd1_human (Hs), agrd1_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  The study verified the Gs protein-coupling by Gαs knockdown with siRNA, overexpression of Gαs, coexpression of the chimeric Gqs4 protein that routes ADGRD1 activity to the phospholipase C/inositol phosphate pathway, and missense mutation within the transmembrane domain that abolished receptor activity without changing cell surface expression.
References:  2
Secondary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  2
Tissue Distribution
Expressed in the CNS in pitutary and putamen, no expression in pons, hippocampus, thalamus, medulla, midbrain, hypothalamus, amygdala and frontal cortex
Species:  Human
Technique:  Northern blot
References:  16
Expressed during embryonic development in the thymus primordium and the adrenal glands
Species:  Mouse
Technique:  in situ hybridisation
References:  4
Expressed in intestinal follicle-associated epithelium, not expressed in microfold cells
Species:  Mouse
Technique:  Microarray analysis
References:  11
Gastric antrum
Species:  Mouse
Technique:  RT-PCR
References:  6
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Alpha screen cAMP assay
Species:  Human
Tissue:  COS-7 and HEK293 cells
Response measured:  Increased cAMP production
References:  2,7
Alpha screen cAMP assay
Species:  Mouse
Tissue:  COS-7 cells
Response measured:  Increased cAMP production
References:  2
CRE-SEAP reporter assay
Species:  Mouse
Tissue:  COS-7 cells
Response measured:  Elevated basal activities
References:  2
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Influences lipoprotein fractions
Nucleotide accession: 
Protein accession: 
References:  12
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Variants influencing human height
Nucleotide accession: 
Protein accession: 
References:  9
Type:  Single nucleotide polymorphism
Species:  Mouse
Description:  Controls body weight
Nucleotide accession: 
Protein accession: 
References:  3
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Role for ADGRD1 in affecting the length of the electrocardiographic RR interval and heart rate. The RR interval was associated with common variants (rs885389) within ADGRD1
Nucleotide accession: 
Protein accession: 
References:  13
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Two variants in ADGRD1 (rs1569019 [G/T] and rs1976930 [A/G]) were found to be associated with height in the three cohorts individually
Nucleotide accession: 
Protein accession: 
References:  15
General Comments
ADGRD1 (formerly GPR133) [16] is an orphan receptor belonging to Family V Adhesion-GPCRs together with ADGRD2 (formerly GPR144) [5]. The gene is localized on human chromosome 12 and mouse chromosome 5. ADGRD1 and ADGRD2 are the Adhesion-GPCRs most closely related to the Secretin class of GPCRs [14]. A search for homologs in the invertebrates like ciona and amphioxus revealed that ADGRD1 and ADGRD2 are well conserved in pre-vertebrate genomes [8,14]. Interestingly, no known domains or motifs apart from the GPCR proteolysis site (GPS) were found in the rather short N terminus of ADGRD1, while the structurally related ADGRD2 was found to contain a pentraxin (PTX) domain. As of now, the function of ADGRD1 is unknown, however, recent studies revealed a stongly association with body height [9-10,15]. Moreover, ADGRD1 is one of the few Adhesion-GPCRs that are experimentally proven to bind to G protein (GαS subunit) and also to activate adenylate cyclase pathway [2]. The last 12 exons out of 26 were identified as a GPCR in gene predictions [1]. An additional 4 exons were predicted and confirmed as PGR25 [17]. The complete human coding sequence is identified by the cDNA AY532280. Note that the ADGRD1 of [16] refers to a different receptor which is now called OR5212, i.e. a nominal olfactory receptor.

The mouse cDNA, AK153762 from neonatal thymus, contains an extra coding exon compared to the human brain cDNA AY532280 . It is located between human exons 3 and 4.

The rat gene exists, but there are gaps in the genomic sequence.

There are two known amino acid-changing SNPs in the human gene:
V508N (14% sub-saharan africa, 3% african-american)
S523L (1.7% european)

The full coding sequence human cDNA is publicly available (see I.M.A.G.E), as IMAGE:8327775 and IMAGE:8327777. A splice variant, which represents about 50% of brain cDNA, splices out the 180 base exon 5 and is available as IMAGE:8317337.

References

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1. Bjarnadóttir TK, Fredriksson R, Höglund PJ, Gloriam DE, Lagerström MC, Schiöth HB. (2004) The human and mouse repertoire of the adhesion family of G-protein-coupled receptors. Genomics, 84 (1): 23-33. [PMID:15203201]

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

3. Chan YF, Jones FC, McConnell E, Bryk J, Bünger L, Tautz D. (2012) Parallel selection mapping using artificially selected mice reveals body weight control loci. Curr. Biol., 22 (9): 794-800. [PMID:22445301]

4. Diez-Roux G, Banfi S, Sultan M, Geffers L, Anand S, Rozado D, Magen A, Canidio E, Pagani M, Peluso I et al.. (2011) A high-resolution anatomical atlas of the transcriptome in the mouse embryo. PLoS Biol., 9 (1): e1000582. [PMID:21267068]

5. 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]

6. Gromova P, Ralea S, Lefort A, Libert F, Rubin BP, Erneux C, Vanderwinden JM. (2009) Kit K641E oncogene up-regulates Sprouty homolog 4 and trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumours. J. Cell. Mol. Med., 13 (8A): 1536-48. [PMID:19453770]

7. 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]

8. 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]

9. Kim JJ, Park YM, Baik KH, Choi HY, Yang GS, Koh I, Hwang JA, Lee J, Lee YS, Rhee H et al.. (2012) Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height. Hum. Genet., 131 (3): 471-8. [PMID:21959382]

10. Kim YK, Moon S, Hwang MY, Kim DJ, Oh JH, Kim YJ, Han BG, Lee JY, Kim BJ. (2013) Gene-based copy number variation study reveals a microdeletion at 12q24 that influences height in the Korean population. Genomics, 101 (2): 134-8. [PMID:23147675]

11. Kobayashi A, Donaldson DS, Kanaya T, Fukuda S, Baillie JK, Freeman TC, Ohno H, Williams IR, Mabbott NA. (2012) Identification of novel genes selectively expressed in the follicle-associated epithelium from the meta-analysis of transcriptomics data from multiple mouse cell and tissue populations. DNA Res., 19 (5): 407-22. [PMID:22991451]

12. Kraja AT, Borecki IB, Tsai MY, Ordovas JM, Hopkins PN, Lai CQ, Frazier-Wood AC, Straka RJ, Hixson JE, Province MA et al.. (2013) Genetic analysis of 16 NMR-lipoprotein fractions in humans, the GOLDN study. Lipids, 48 (2): 155-65. [PMID:23192668]

13. Marroni F, Pfeufer A, Aulchenko YS, Franklin CS, Isaacs A, Pichler I, Wild SH, Oostra BA, Wright AF, Campbell H, Witteman JC, Kääb S, Hicks AA, Gyllensten U, Rudan I, Meitinger T, Pattaro C, van Duijn CM, Wilson JF, Pramstaller PP, EUROSPAN Consortium. (2009) A genome-wide association scan of RR and QT interval duration in 3 European genetically isolated populations: the EUROSPAN project. Circ Cardiovasc Genet, 2 (4): 322-8. [PMID:20031603]

14. 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]

15. Tönjes A, Koriath M, Schleinitz D, Dietrich K, Böttcher Y, Rayner NW, Almgren P, Enigk B, Richter O, Rohm S, Fischer-Rosinsky A, Pfeiffer A, Hoffmann K, Krohn K, Aust G, Spranger J, Groop L, Blüher M, Kovacs P, Stumvoll M. (2009) Genetic variation in GPR133 is associated with height: genome wide association study in the self-contained population of Sorbs. Hum. Mol. Genet., 18 (23): 4662-8. [PMID:19729412]

16. Vanti WB, Nguyen T, Cheng R, Lynch KR, George SR, O'Dowd BF. (2003) Novel human G-protein-coupled receptors. Biochem. Biophys. Res. Commun., 305 (1): 67-71. [PMID:12732197]

17. Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, Brown A, Rodriguez SS, Weller JR, Wright AC et al.. (2003) The G protein-coupled receptor repertoires of human and mouse. Proc. Natl. Acad. Sci. U.S.A., 100 (8): 4903-8. [PMID:12679517]

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