Protein-coding gene in humans
| ADGRG2 |
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| Identifiers |
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| Aliases | ADGRG2, EDDM6, HE6, TM7LN2, GPR64, adhesion G protein-coupled receptor G2, CBAVDX |
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| External IDs | OMIM: 300572 MGI: 2446854 HomoloGene: 4208 GeneCards: ADGRG2 |
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| Gene location (Human) |
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 | | Chr. | X chromosome (human)[1] |
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| | Band | Xp22.13 | Start | 18,989,307 bp[1] |
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| End | 19,122,637 bp[1] |
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| Gene location (Mouse) |
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 | | Chr. | X chromosome (mouse)[2] |
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| | Band | X|X F4 | Start | 159,173,686 bp[2] |
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| End | 159,281,066 bp[2] |
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|
| RNA expression pattern |
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| Bgee | | Human | Mouse (ortholog) |
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| Top expressed in | - corpus epididymis
- caput epididymis
- parotid gland
- synovial joint
- synovial membrane
- spinal ganglia
- pancreatic ductal cell
- islet of Langerhans
- oocyte
- germinal epithelium
|
| | Top expressed in | - trigeminal ganglion
- epithelium of stomach
- epididymis
- vas deferens
- otolith organ
- utricle
- white adipose tissue
- substantia nigra
- condyle
- mammary gland
|
| | More reference expression data |
|
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| BioGPS |  | | More reference expression data |
|
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| Gene ontology |
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| Molecular function | - G protein-coupled receptor activity
- signal transducer activity
- transmembrane signaling receptor activity
| | Cellular component | - integral component of membrane
- cell surface
- integral component of plasma membrane
- extracellular exosome
- apical plasma membrane
- membrane
- cytosol
- plasma membrane
| | Biological process | - G protein-coupled receptor signaling pathway
- cell surface receptor signaling pathway
- spermatogenesis
- signal transduction
- adenylate cyclase-activating G protein-coupled receptor signaling pathway
| | Sources:Amigo / QuickGO |
|
| Orthologs |
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| Species | Human | Mouse |
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| Entrez | | |
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| Ensembl | | |
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| UniProt | | |
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| RefSeq (mRNA) | NM_001079858
NM_001079859
NM_001079860
NM_001184833
NM_001184834
|
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NM_001184835
NM_001184836
NM_001184837
NM_005756 |
| NM_001079847
NM_001079848
NM_001079857
NM_001290445
NM_001290446
|
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NM_178712 |
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| RefSeq (protein) | NP_001073327
NP_001073328
NP_001073329
NP_001171762
NP_001171763
|
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NP_001171764
NP_001171765
NP_001171766
NP_005747 |
| NP_001073316
NP_001073317
NP_001073326
NP_001277374
NP_001277375
|
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NP_848827 |
|
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| Location (UCSC) | Chr X: 18.99 – 19.12 Mb | Chr X: 159.17 – 159.28 Mb |
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| PubMed search | [3] | [4] |
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| Wikidata |
| View/Edit Human | View/Edit Mouse |
|
G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ADGRG2 gene.[5] GPR64 is a member of the adhesion GPCR family.[6][7] Adhesion GPCRs are characterized by an extended extracellular region often possessing N-terminal protein modules that is linked to a TM7 region via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain.[8][9]
The adhesion GPCR, GPR64, is an orphan receptor characterized by a long N-terminus with that has been suggested to be highly glycosylated.[10] GPR64's N-terminus has been reported to be cleaved at the GPS domain to allow for trafficking to the plasma membrane. After cleavage the N-terminus is believed to remain non-covalently associated with the 7TM. GPR64 expression has been mostly reported in the male reproductive organs, but more recently has been shown to be expressed in the parathyroid glands[11] and central nervous system.[12] GPR64 is mainly expressed in human and mouse epididymis as well as human prostate and parathyroid.[11][13] GPR64, together with F-actin scaffold, locates at the nonciliated principal cells of the proximal male excurrent duct epithelia, where reabsorption of testicular fluid and concentration of sperm takes place.[14][15]
Function
Targeting of Gpr64 in mice causes reduced fertility or infertility in males; but the reproductive capacity was unaffected in females.[16] Unchanged hormone expression in knockout males indicates that the receptor functions immediately in the male genital tract. Lack of Gpr64 expression causes sperm stasis and duct obstruction due to abnormal fluid reabsorption. In addition, expression of GPR64 has been found in fibroblast-like synovial cells obtained from osteoarthritis but not from rheumatoid arthritis.[17]
Clinical significance
GPR64 is significantly overexpressed in the Wnt signaling-dependent subgroup of medulloblastoma,[18] as well as in ewing sarcomas and carcinomas derived from prostate, kidney or lung.[19] Richter et al. demonstrated that GPR64 promotes tumor invasion and metastasis through placental growth factor and MMP1.[19] Upregulation and activation of GPR64 are associated with primary hyperparathyroidism and hypersecretion of parathyroid hormone.[11]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000173698 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031298 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Hamann, J; Aust, G; Araç, D; Engel, FB; Formstone, C; Fredriksson, R; Hall, RA; Harty, BL; Kirchhoff, C; Knapp, B; Krishnan, A; Liebscher, I; Lin, HH; Martinelli, DC; Monk, KR; Peeters, MC; Piao, X; Prömel, S; Schöneberg, T; Schwartz, TW; Singer, K; Stacey, M; Ushkaryov, YA; Vallon, M; Wolfrum, U; Wright, MW; Xu, L; Langenhan, T; Schiöth, HB (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
- ^ Stacey M, Yona S (2011). Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN 978-1-4419-7912-4.
- ^ Langenhan, T; Aust, G; Hamann, J (21 May 2013). "Sticky signaling--adhesion class G protein-coupled receptors take the stage". Science Signaling. 6 (276): re3. doi:10.1126/scisignal.2003825. PMID 23695165. S2CID 6958640.
- ^ Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT (March 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–78. doi:10.1038/emboj.2012.26. PMC 3321182. PMID 22333914.
- ^ Azimzadeh, Pedram; Talamantez-Lyburn, Sarah C.; Chang, Katarina T.; Inoue, Asuka; Balenga, Nariman (November 2019). "Spatial regulation of GPR64/ADGRG2 signaling by β-arrestins and GPCR kinases". Annals of the New York Academy of Sciences. 1456 (1): 26–43. Bibcode:2019NYASA1456...26A. doi:10.1111/nyas.14227. ISSN 1749-6632. PMC 7236788. PMID 31502283.
- ^ 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): 8642–8648. doi:10.1128/mcb.24.19.8642-8648.2004. PMC 516748. PMID 15367682.
- ^ a b c Balenga, Nariman; Azimzadeh, Pedram; Hogue, Joyce A.; Staats, Paul N.; Shi, Yuhong; Koh, James; Dressman, Holly; Olson, John A. (March 2017). "Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling". Journal of Bone and Mineral Research. 32 (3): 654–666. doi:10.1002/jbmr.3023. ISSN 1523-4681. PMC 7211037. PMID 27760455.
- ^ Haitina T, Olsson F, Stephansson O, Alsiö J, Roman E, Ebendal T, Schiöth HB, Fredriksson R (2008). "Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat". BMC Neurosci. 9 (1): 43. doi:10.1186/1471-2202-9-43. PMC 2386866. PMID 18445277.
- ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, Hall RA, Harty BL, Kirchhoff C, Knapp B, Krishnan A, Liebscher I, Lin HH, Martinelli DC, Monk KR, Peeters MC, Piao X, Prömel S, Schöneberg T, Schwartz TW, Singer K, Stacey M, Ushkaryov YA, Vallon M, Wolfrum U, Wright MW, Xu L, Langenhan T, Schiöth HB (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
- ^ Obermann H, Samalecos A, Osterhoff C, Schröder B, Heller R, Kirchhoff C (January 2003). "HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia". Molecular Reproduction and Development. 64 (1): 13–26. doi:10.1002/mrd.10220. PMID 12420295. S2CID 29953802.
- ^ Kirchhoff C, Osterhoff C, Samalecos A (August 2008). "HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia". Reproduction. 136 (2): 235–45. doi:10.1530/REP-08-0078. PMID 18469038.
- ^ Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, Theuring F, Gottwald U (October 2004). "Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility". Molecular and Cellular Biology. 24 (19): 8642–8. doi:10.1128/MCB.24.19.8642-8648.2004. PMC 516748. PMID 15367682.
- ^ Galligan CL, Baig E, Bykerk V, Keystone EC, Fish EN (September 2007). "Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity". Genes and Immunity. 8 (6): 480–91. doi:10.1038/sj.gene.6364400. PMID 17568789. S2CID 22240185.
- ^ Whittier KL, Boese EA, Gibson-Corley KN, Kirby PA, Darbro BW, Qian Q, Ingram WJ, Robertson T, Remke M, Taylor MD, O'Dorisio MS (10 October 2013). "G-protein coupled receptor expression patterns delineate medulloblastoma subgroups". Acta Neuropathologica Communications. 1 (1): 66. doi:10.1186/2051-5960-1-66. PMC 3893540. PMID 24252460.
- ^ a b Richter GH, Fasan A, Hauer K, Grunewald TG, Berns C, Rössler S, Naumann I, Staege MS, Fulda S, Esposito I, Burdach S (May 2013). "G-Protein coupled receptor 64 promotes invasiveness and metastasis in Ewing sarcomas through PGF and MMP1". The Journal of Pathology. 230 (1): 70–81. doi:10.1002/path.4170. PMID 23338946. S2CID 11129426.
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