GPR64

{{Short description|Protein-coding gene in humans}}

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{{Infobox gene}}

G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ADGRG2 gene.{{cite journal | vauthors = 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 | title = International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors | journal = Pharmacological Reviews | volume = 67 | issue = 2 | pages = 338–367 | date = April 2015 | pmid = 25713288 | pmc = 4394687 | doi = 10.1124/pr.114.009647 }} GPR64 is a member of the adhesion GPCR family.{{cite book | author = Stacey M, Yona S | title = Adhesion-GPCRs: Structure to Function (Advances in Experimental Medicine and Biology) | publisher = Springer | location = Berlin | year = 2011 | isbn = 978-1-4419-7912-4 }}{{cite journal | vauthors = Langenhan T, Aust G, Hamann J | title = Sticky signaling--adhesion class G protein-coupled receptors take the stage | journal = Science Signaling | volume = 6 | issue = 276 | pages = re3 | date = May 2013 | pmid = 23695165 | doi = 10.1126/scisignal.2003825 | s2cid = 6958640 }}

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.{{cite journal | vauthors = Araç D, Boucard AA, Bolliger MF, Nguyen J, Soltis SM, Südhof TC, Brunger AT | title = A novel evolutionarily conserved domain of cell-adhesion GPCRs mediates autoproteolysis | journal = The EMBO Journal | volume = 31 | issue = 6 | pages = 1364–1378 | date = March 2012 | pmid = 22333914 | pmc = 3321182 | doi = 10.1038/emboj.2012.26 }}{{cite journal | vauthors = Azimzadeh P, Talamantez-Lyburn SC, Chang KT, Inoue A, Balenga N | title = Spatial regulation of GPR64/ADGRG2 signaling by β-arrestins and GPCR kinases | journal = Annals of the New York Academy of Sciences | volume = 1456 | issue = 1 | pages = 26–43 | date = November 2019 | pmid = 31502283 | pmc = 7236788 | doi = 10.1111/nyas.14227 | bibcode = 2019NYASA1456...26A }}

The adhesion GPCR, GPR64, is an orphan receptor characterized by a long N-terminus with that has been suggested to be highly glycosylated.{{cite journal | vauthors = Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, Theuring F, Gottwald U | title = Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility | journal = Molecular and Cellular Biology | volume = 24 | issue = 19 | pages = 8642–8648 | date = October 2004 | pmid = 15367682 | pmc = 516748 | doi = 10.1128/mcb.24.19.8642-8648.2004 }} 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{{cite journal | vauthors = Balenga N, Azimzadeh P, Hogue JA, Staats PN, Shi Y, Koh J, Dressman H, Olson JA | title = Orphan Adhesion GPCR GPR64/ADGRG2 Is Overexpressed in Parathyroid Tumors and Attenuates Calcium-Sensing Receptor-Mediated Signaling | journal = Journal of Bone and Mineral Research | volume = 32 | issue = 3 | pages = 654–666 | date = March 2017 | pmid = 27760455 | pmc = 7211037 | doi = 10.1002/jbmr.3023 }} and central nervous system.{{cite journal | vauthors = Haitina T, Olsson F, Stephansson O, Alsiö J, Roman E, Ebendal T, Schiöth HB, Fredriksson R | title = Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat | journal = BMC Neuroscience | volume = 9 | issue = 1 | pages = 43 | date = April 2008 | pmid = 18445277 | pmc = 2386866 | doi = 10.1186/1471-2202-9-43 | doi-access = free }} GPR64 is mainly expressed in human and mouse epididymis as well as human prostate and parathyroid.{{cite journal | vauthors = 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 | title = International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors | journal = Pharmacological Reviews | volume = 67 | issue = 2 | pages = 338–367 | date = April 2015 | pmid = 25713288 | pmc = 4394687 | doi = 10.1124/pr.114.009647 }} 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.{{cite journal | vauthors = Obermann H, Samalecos A, Osterhoff C, Schröder B, Heller R, Kirchhoff C | title = HE6, a two-subunit heptahelical receptor associated with apical membranes of efferent and epididymal duct epithelia | journal = Molecular Reproduction and Development | volume = 64 | issue = 1 | pages = 13–26 | date = January 2003 | pmid = 12420295 | doi = 10.1002/mrd.10220 | s2cid = 29953802 | doi-access = free }}{{cite journal | vauthors = Kirchhoff C, Osterhoff C, Samalecos A | title = HE6/GPR64 adhesion receptor co-localizes with apical and subapical F-actin scaffold in male excurrent duct epithelia | journal = Reproduction | volume = 136 | issue = 2 | pages = 235–245 | date = August 2008 | pmid = 18469038 | doi = 10.1530/REP-08-0078 | doi-access = free }}