Contents:
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Rank order lists
- Agonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Biologically Significant Variants
- General Comments
- References
- Contributors
- How to cite this page
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 | 1017 | Xp22.13 | ADGRG2 | adhesion G protein-coupled receptor G2 | 16 |
| Mouse | 7 | 1009 | X F4 | Adgrg2 | adhesion G protein-coupled receptor G2 | 15 |
| Rat | 7 | 1013 | Xq14 | Adgrg2 | adhesion G protein-coupled receptor G2 | 15 |
| Previous and Unofficial Names |
| GPR64 (G protein-coupled receptor 64) | HE6 (human epididymal 6) | TM7LN2 |
| Database Links |
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| Specialist databases | |
| GPCRdb | agrg2_human (Hs), agrg2_mouse (Mm), agrg2_rat (Rn) |
| Other databases | |
| Alphafold | Q8IZP9 (Hs), Q8CJ12 (Mm), Q8CJ11 (Rn) |
| ChEMBL Target | CHEMBL4523893 (Hs) |
| Ensembl Gene | ENSG00000173698 (Hs), ENSMUSG00000031298 (Mm), ENSRNOG00000032472 (Rn) |
| Entrez Gene | 10149 (Hs), 237175 (Mm), 266735 (Rn) |
| Human Protein Atlas | ENSG00000173698 (Hs) |
| KEGG Gene | hsa:10149 (Hs), mmu:237175 (Mm), rno:266735 (Rn) |
| OMIM | 300572 (Hs) |
| Pharos | Q8IZP9 (Hs) |
| RefSeq Nucleotide | NM_001079859 (Hs), NM_001079858 (Hs), NM_001079860 (Hs), NM_005756 (Hs), NM_001184833 (Hs), NM_001184834 (Hs), NM_001184835 (Hs), NM_001184836 (Hs), NM_178712 (Mm), NM_181366 (Rn) |
| RefSeq Protein | NP_001171762 (Hs), NP_001073328 (Hs), NP_005747 (Hs), NP_001171764 (Hs), NP_001073329 (Hs), NP_001171765 (Hs), NP_001073327 (Hs), NP_001171763 (Hs), NP_848827 (Mm), NP_852031 (Rn) |
| UniProtKB | Q8IZP9 (Hs), Q8CJ12 (Mm), Q8CJ11 (Rn) |
| Wikipedia | ADGRG2 (Hs) |
| Selected 3D Structures |
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| Endogenous agonists |
| Peptides derived from the Stachel sequence: TSFGVLLDLSRTSLPP [5] |
| Agonist Comments | ||
| Peptides derived from the Stachel sequence: TSFGVLLDLSRTSLPP [5]. |
| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| Comments: This pathway applies to the recombinant expression of human ADGRG2 protein in Xenopus melanophores [7]. There is a brief note in the literature that the receptor will activate G proteins Gs and Gq when overexpressed in Xenopus melanophores (C. Jayawickreme, pers. communication, cited in [7]) which couple to adenylate cyclase and phospholipase C, respectively (see below). | |
| References: 5,11 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| Gq/G11 family | Phospholipase C stimulation |
| Comments: This pathway also applies to the recombinant expression of human ADGRG2 protein in Xenopus melanophores [1] (see above). | |
| References: 5,22 | |
| Tissue Distribution
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| Tissue Distribution Comments | ||||||||
| ADGRG2 is also specific to certain cell types, namely the non-ciliated principal cells in the ductuli efferentes [12]. It is not expressed in the neighbouring ciliated cells. In the Ductuli efferentes and proximal epididymal duct, the mature receptor is a heterodimeric membrane protein of the apical epithelial membrane domain [15]. | ||||||||
| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Physiological Functions Comments | ||||||||
| KO mice show a downregulation of the following genes: Enpp2/autotaxin, the lipocalins 8 and 9, the beta-defensin Defb42, cystatins 8 and 12, as well as the membrane proteins ADAM (a disintegrin and metalloprotease) 28, claudin-10, EAAC1, and Me9 (Teddm1). In contrast, clusterin/ApoJ and osteopontin/Spp1 mRNAsare are upregulated in KO tissue [4]. | ||||||||
| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||||||||
| The human ADGRG2 gene was assigned to the X chromosome (Xp22.13) in a region which is syntenic to the mouse [15]. Three DNA variants (single nucleotide polymorphisms) of the human gene sequence have been reported [20] which are listed in the LOVD X-chromosome gene database. 10 transcripts exist in human [6,15-16]. The transcripts affect predominantly the open reading frame in the N-terminal part immediately following the signal peptide. Nine of the transcripts encode proteins which differ in length. |
| General Comments |
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ADGRG2 (adhesion G protein-coupled receptor G2, formerly GPR64) is an orphan receptor belonging to Family VIII Adhesion-GPCRs together with ADGRG1 and ADGRG3-7 [8]. The gene is localized on human chromosome X and mouse chromosome 8. The long extracellular ectosubunit of ADGRG2 is highly glycosylated [15], showing similarity to mucin-like cell-surface molecules. Gene product appears to be cleaved shortly before the first transmembrane domain to produce a large, highly glycoslylated (approximately 180 kDa) amino terminal domain and carboxly terminal domain containing seven transmemberane domains (40 kDa in human) [15]. The putative cysteine-rich cleavage site, GPS (GPCR proteolysis site), is found in several other class B GPCRs [9]. Full coding sequence human cDNA is publicly available, IMAGE:7447877 [13] in mammalian expression vector pCDNA3.1. |
References
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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. Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, Theuring F, Gottwald U. (2004) Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility. Mol Cell Biol, 24 (19): 8642-8. [PMID:15367682]
4. Davies B, Behnen M, Cappallo-Obermann H, Spiess AN, Theuring F, Kirchhoff C. (2007) Novel epididymis-specific mRNAs downregulated by HE6/Gpr64 receptor gene disruption. Mol Reprod Dev, 74 (5): 539-53. [PMID:17034053]
5. Demberg LM, Rothemund S, Schöneberg T, Liebscher I. (2015) Identification of the tethered peptide agonist of the adhesion G protein-coupled receptor GPR64/ADGRG2. Biochem Biophys Res Commun, 464 (3): 743-7. [PMID:26188515]
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12. Kirchhoff C, Osterhoff C, Samalecos A. (2008) HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia. Reproduction, 136 (2): 235-45. [PMID:18469038]
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14. Lin H, Xiao P, Bu RQ, Guo S, Yang Z, Yuan D, Zhu ZL, Zhang CX, He QT, Zhang C et al.. (2022) Structures of the ADGRG2-Gs complex in apo and ligand-bound forms. Nat Chem Biol, 18 (11): 1196-1203. [PMID:35982227]
15. Obermann H, Samalecos A, Osterhoff C, Schröder B, Heller R, Kirchhoff C. (2003) HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia. Mol Reprod Dev, 64 (1): 13-26. [PMID:12420295]
16. Osterhoff C, Ivell R, Kirchhoff C. (1997) Cloning of a human epididymis-specific mRNA, HE6, encoding a novel member of the seven transmembrane-domain receptor superfamily. DNA Cell Biol, 16 (4): 379-89. [PMID:9150425]
17. Pagin A, Bergougnoux A, Girodon E, Reboul MP, Willoquaux C, Kesteloot M, Raynal C, Bienvenu T, Humbert M, Lalau G et al.. (2020) Novel ADGRG2 truncating variants in patients with X-linked congenital absence of vas deferens. Andrology, 8 (3): 618-624. [PMID:31845523]
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