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GPR64
G protein-coupled receptor 64 also known as HE6 is a protein encoded by the ''ADGRG2'' gene. GPR64 is a member of the adhesion GPCR family.
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.
The adhesion GPCR, GPR64, is an orphan receptor characterized by a long N-terminus with that has been suggested to be highly glycosylated.〔Davies B, Baumann C, Kirchhoff C, Ivell R, Nubbemeyer R, Habenicht UF, Theuring F, Gottwald U. Targeted deletion of the epididymal receptor HE6 results in fluid dysregulation and male infertility" ''Mol Cell Biol'' 2004; 24: 8642 8648〕 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 central nervous system.〔Haitina T, Olsson F, Stephansson O, Alsiö J, Roman E, Ebendal T, Schiöth HB, Fredriksson R. Expression profile of the entire family of Adhesion G protein-coupled receptors in mouse and rat. BMC Neurosci. 2008;9:43–43. 〕 GPR64 is mainly expressed in human and mouse epididymis as well as human prostate and parathyroid. 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.
== Function ==
Targeting of ''Gpr64'' in mice causes reduced fertility or infertility in males; but the reproductive capacity was unaffected in females. 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.
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