GPR64

ADGRG2
Identifiers
AliasesADGRG2, EDDM6, HE6, TM7LN2, GPR64, adhesion G protein-coupled receptor G2, CBAVDX
External IDsOMIM: 300572; MGI: 2446854; HomoloGene: 4208; GeneCards: ADGRG2; OMA:ADGRG2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr X: 18.99 – 19.12 MbChr X: 159.17 – 159.28 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000173698Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031298Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, et al. (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–367. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
  6. ^ Stacey M, Yona S (2011). Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology). Berlin: Springer. ISBN 978-1-4419-7912-4.
  7. ^ Langenhan T, Aust G, Hamann J (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.
  8. ^ Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, et al. (March 2012). "A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis". The EMBO Journal. 31 (6): 1364–1378. doi:10.1038/emboj.2012.26. PMC 3321182. PMID 22333914.
  9. ^ Azimzadeh P, Talamantez-Lyburn SC, Chang KT, Inoue A, Balenga N (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. PMC 7236788. PMID 31502283.
  10. ^ Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, et al. (October 2004). "Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility". Molecular and Cellular Biology. 24 (19): 8642–8648. doi:10.1128/mcb.24.19.8642-8648.2004. PMC 516748. PMID 15367682.
  11. ^ a b Balenga N, Azimzadeh P, Hogue JA, Staats PN, Shi Y, Koh J, et al. (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. PMC 7211037. PMID 27760455.
  12. ^ Haitina T, Olsson F, Stephansson O, Alsiö J, Roman E, Ebendal T, et al. (April 2008). "Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat". BMC Neuroscience. 9 (1): 43. doi:10.1186/1471-2202-9-43. PMC 2386866. PMID 18445277.
  13. ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, et al. (April 2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–367. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
  14. ^ 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.
  15. ^ 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): 235–245. doi:10.1530/REP-08-0078. PMID 18469038.