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Gene and Protein Information  |
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| Adhesion G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 1321 | 4p15.2 | ADGRA3 | adhesion G protein-coupled receptor A3 | 13 |
| Mouse | 7 | 1310 | 5 B3 | Adgra3 | adhesion G protein-coupled receptor A3 | |
| Rat | 7 | 1455 | 14q11 | Adgra3 | adhesion G protein-coupled receptor A3 | |
| Previous and Unofficial Names |
| TEM5L | TEM5-like | PGR21 | GPR125 (G protein-coupled receptor 125) |
| Database Links |
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| Specialist databases | |
| GPCRdb | agra3_human (Hs), agra3_mouse (Mm) |
| Other databases | |
| Alphafold | Q8IWK6 (Hs), Q7TT36 (Mm) |
| CATH/Gene3D | 4.10.1240.10, 2.60.40.10, 3.80.10.10 |
| ChEMBL Target | CHEMBL4523887 (Hs) |
| Ensembl Gene | ENSG00000152990 (Hs), ENSMUSG00000029090 (Mm), ENSRNOG00000004279 (Rn) |
| Entrez Gene | 166647 (Hs), 70693 (Mm), 305408 (Rn) |
| Human Protein Atlas | ENSG00000152990 (Hs) |
| KEGG Gene | hsa:166647 (Hs), mmu:70693 (Mm), rno:305408 (Rn) |
| OMIM | 612303 (Hs) |
| Pharos | Q8IWK6 (Hs) |
| RefSeq Nucleotide | NM_145290 (Hs), NM_133911 (Mm) |
| RefSeq Protein | NP_660333 (Hs), NP_598672 (Mm) |
| UniProtKB | Q8IWK6 (Hs), Q7TT36 (Mm) |
| Wikipedia | ADGRA3 (Hs) |
| Agonist Comments | ||
| No ligands identified: orphan receptor. |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| G protein (identity unknown) | |
| Comments: Principal transduction via dishevelled [7]. | |
| References: | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| G protein (identity unknown) | |
| References: | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||
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| Biologically Significant Variants
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| General Comments |
| ADGRA3 (formerly GPR125) is an orphan receptor that belongs to Family III Adhesion-GPCRs along with ADGRA1 (GPR123) and ADGRA2 (GPR124) [1]. The gene is localized on human chromosome 4 and mouse chromosome 5. Phylogenetic analysis suggests that ADGRA1-3 share a common ancestor suggesting the evolution from an ancestral gene through gene duplication [1]. Deuterostome invertebrates like ciona, amphioxus, sea urchin and acorn worms contain a single copy that is very similar to ADGRA1-3 [6,8,10] indicating a gene duplication event at the emergence of vertebrates. As of now no direct function has been attributed to these receptors, however, GPR125 is useful as a potential stem and progenitor cell surface marker and therefore represents a novel target for purifying adult stem and progenitors from tissues, with the goal of developing autologous multipotent cell lines [11-12]. ADGRA3 is strongly expressed in the testis and the prostate and were predicted to have a role in development of spermatogonia and also a possible role role in germ cell development [5,11-12]. ADGRA3 in human is 1321 amino acids long and it is very similar to ADGRA2 in domain organisation. ADGRA3 has a GPCR proteolysis site (GPS), Ig-like domain and LRR repeats in the N terminus. A functional splice variant for ADGRA3 in human was found and it seems that the splice variant was found to be conserved in other species including mouse [2]. |
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. Bjarnadóttir TK, Geirardsdóttir K, Ingemansson M, Mirza MA, Fredriksson R, Schiöth HB. (2007) Identification of novel splice variants of Adhesion G protein-coupled receptors. Gene, 387 (1-2): 38-48. [PMID:17056209]
3. He Z, Kokkinaki M, Jiang J, Dobrinski I, Dym M. (2010) Isolation, characterization, and culture of human spermatogonia. Biol Reprod, 82 (2): 363-72. [PMID:19846602]
4. He Z, Kokkinaki M, Jiang J, Zeng W, Dobrinski I, Dym M. (2012) Isolation of human male germ-line stem cells using enzymatic digestion and magnetic-activated cell sorting. Methods Mol Biol, 825: 45-57. [PMID:22144235]
5. Izadyar F, Wong J, Maki C, Pacchiarotti J, Ramos T, Howerton K, Yuen C, Greilach S, Zhao HH, Chow M et al.. (2011) Identification and characterization of repopulating spermatogonial stem cells from the adult human testis. Hum Reprod, 26 (6): 1296-306. [PMID:21349855]
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. Li X, Roszko I, Sepich DS, Ni M, Hamm HE, Marlow FL, Solnica-Krezel L. (2013) Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development, 140 (14): 3028-39. [PMID:23821037]
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. Pickering C, Hägglund M, Szmydynger-Chodobska J, Marques F, Palha JA, Waller L, Chodobski A, Fredriksson R, Lagerström MC, Schiöth HB. (2008) The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury. BMC Neurosci, 9: 97. [PMID:18834514]
10. Raible F, Tessmar-Raible K, Arboleda E, Kaller T, Bork P, Arendt D, Arnone MI. (2006) Opsins and clusters of sensory G-protein-coupled receptors in the sea urchin genome. Dev Biol, 300 (1): 461-75. [PMID:17067569]
11. Seandel M, Falciatori I, Shmelkov SV, Kim J, James D, Rafii S. (2008) Niche players: spermatogonial progenitors marked by GPR125. Cell Cycle, 7 (2): 135-40. [PMID:18256534]
12. Seandel M, James D, Shmelkov SV, Falciatori I, Kim J, Chavala S, Scherr DS, Zhang F, Torres R, Gale NW et al.. (2007) Generation of functional multipotent adult stem cells from GPR125+ germline progenitors. Nature, 449 (7160): 346-50. [PMID:17882221]
13. Yamamoto Y, Irie K, Asada M, Mino A, Mandai K, Takai Y. (2004) Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein. Oncogene, 23 (22): 3889-97. [PMID:15021905]
