Regulators of G-protein signaling (RGS) proteins are known for the RGS domain that is composed of a conserved stretch of 120 amino acids, which binds directly to activated G-protein α subunits and acts as a GTPase-activating protein (GAP), leading to their deactivation and termination of downstream signals. In this study, a novel human RGS cDNA (RGS21), 1795 bp long and encoding a 152-amino acid polypeptide, was isolated by large-scale sequencing analysis of a human fetal brain cDNA library. Unlike other RGS family members, RGS21 gene has no additional domain/motif and may represent the smallest known member of RGS family. It may belong to the B/R4 subfamily, which suggests that it may serve exclusively as a negative regulator of αi/o family members and/or αq/11. PCR analysis showed that RGS21 mRNA was expressed ubiquitously in the 16 tissues examined, implying general physiological roles.
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