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Gpr62 is one of the orphan GPCRs that is expressed in the rat and human brain. In this study, we found that Gpr62 is also expressed in male germ cells in mice, and its expression increases along with sperm differentiation. GPR62 lacks the BBXXB and DRY motifs, which are conserved across many GPCRs, and it was able to induce cAMP signaling in the absence of a ligand. These structural and functional features are conserved among mammals, and the mutant analysis of GPR62 has revealed that lacking of these motifs is involved in the constitutive activity. We also found that GPR62 can homooligomerize, but it is not sufficient for its constitutive activity. We further investigated its physiological function by using Gpr62 knockout (Gpr62\u2212\/\u2212) mice. Gpr62\u2212\/\u2212 mice were born normally and did not show any abnormality in growth and behavior. In addition, both male and female Gp62\u2212\/\u2212 mice were fertile, and the differentiation and motility of spermatozoa were normal. We also found that Gpr61, the gene most similar to Gpr62 in the GPCR family shows a constitutive activity and an expression pattern similar to those of Gpr62. Our results suggest that GPR62 constitutively activates the cAMP pathway in male germ cells but is dispensable for male fertility, which is probably due to its functional redundancy with GPR61.<\/jats:p>","DOI":"10.1530\/rep-17-0333","type":"journal-article","created":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T20:45:17Z","timestamp":1505421917000},"page":"755-764","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":19,"title":["GPR62 constitutively activates cAMP signaling but is dispensable for male fertility in mice"],"prefix":"10.1093","volume":"154","author":[{"given":"Tomoyuki","family":"Muroi","sequence":"first","affiliation":[{"name":"Department of Agriculture , Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri","family":"Matsushima","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ryota","family":"Kanamori","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hikari","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Applied Biological Chemistry , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wataru","family":"Fujii","sequence":"additional","affiliation":[{"name":"Department of Animal Resource Sciences , Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiro","family":"Yogo","sequence":"additional","affiliation":[{"name":"Department of Agriculture , Graduate School of Integrated Science and Technology, Shizuoka University, Shizuoka, Japan"},{"name":"Department of Applied Biological Chemistry , Faculty of Agriculture, Shizuoka University, Shizuoka, Japan"},{"name":"College of Agriculture , Academic Institute, Shizuoka University, Shizuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2017,12,1]]},"reference":[{"key":"2026041107024378600_bib1","doi-asserted-by":"crossref","first-page":"10445","DOI":"10.1074\/jbc.273.17.10445","article-title":"Functional microdomains in G-protein-coupled receptors. 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