RGS Domain

Domain Binding and Function

The RGS (Regulator of G protein Signaling) domain has been found in over 20 proteins in humans and is typically about 120 amino acids in length. RGS domains act allosterically by stabilizing the transition intermediate of the GTP binding pocket of the α subunit of heterotrimeric G proteins. This results in the acceleration of the intrinsic GTPase activity of that α subunit. The discovery of the RGS domain therefore answered the longstanding question of why the intrinsic rate of hydrolysis of many heterotrimeric G proteins was often slower than the apparent cycling time for a signaling process requiring that G protein. Heterotrimeric G proteins transmit signaling from seven transmembrane receptors, which, in turn, are activated by many important agonists such as hormones, neurotransmitters, light and odorants. Proteins that encode RGS domains also modulate such signaling events as they control the time of transmission of each of these agonists.

Structure Reference

1. Tesmer, J.J. et al. (1997) Cell 89(2), 251–261.

Examples of Domain Proteins

Binding Examples

RGS Domain proteins	Binding Partners
RGS-4	Gαi, Gαq
p115 RhoGEF	Gα12, Gα13
RGS-2	Gαq
GAIP	Gαi, Gαq