Murine gammaherpesvirus (MHV-68) is well established as a small animal model for the study of gammaherpesviruses. The MHV-68 genome contains an open reading frame (ORF74) that has significant sequence homology with mammalian G-protein coupled receptors (GPCRs) and the GPCR from the related Kaposi's sarcoma-associated herpesvirus (KSHV). Here we show that the MHV-68 ORF74 is predicted to encode a GPCR since it has seven potential transmembrane helices and that it has other sequence motifs in common with GPCRS: Of interest is the observation that the sequence around a conserved arginine at the start of the second intracellular loop suggests that the ORF74 product may signal constitutively (agonist independent).
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