RGD Reference Report - RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity. - Rat Genome Database

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RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity.

Authors: Kimple, RJ  De Vries, L  Tronchere, H  Behe, CI  Morris, RA  Gist Farquhar, M  Siderovski, DP 
Citation: Kimple RJ, etal., J Biol Chem. 2001 Aug 3;276(31):29275-81. Epub 2001 May 31.
RGD ID: 7207387
Pubmed: PMID:11387333   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M103208200   (Journal Full-text)

The regulators of G-protein signaling (RGS) proteins accelerate the intrinsic guanosine triphosphatase activity of heterotrimeric G-protein alpha subunits and are thus recognized as key modulators of G-protein-coupled receptor signaling. RGS12 and RGS14 contain not only the hallmark RGS box responsible for GTPase-accelerating activity but also a single G alpha(i/o)-Loco (GoLoco) motif predicted to represent a second G alpha interaction site. Here, we describe functional characterization of the GoLoco motif regions of RGS12 and RGS14. Both regions interact exclusively with G alpha(i1), G alpha(i2), and G alpha(i3) in their GDP-bound forms. In GTP gamma S binding assays, both regions exhibit guanine nucleotide dissociation inhibitor (GDI) activity, inhibiting the rate of exchange of GDP for GTP by G alpha(i1). Both regions also stabilize G alpha(i1) in its GDP-bound form, inhibiting the increase in intrinsic tryptophan fluorescence stimulated by AlF(4)(-). Our results indicate that both RGS12 and RGS14 harbor two distinctly different G alpha interaction sites: a previously recognized N-terminal RGS box possessing G alpha(i/o) GAP activity and a C-terminal GoLoco region exhibiting G alpha(i) GDI activity. The presence of two, independent G alpha interaction sites suggests that RGS12 and RGS14 participate in a complex coordination of G-protein signaling beyond simple G alpha GAP activity.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane located_inIDA 7207387PMID:11387333UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Gnai1  (G protein subunit alpha i1)
Gnai2  (G protein subunit alpha i2)
Gnai3  (G protein subunit alpha i3)
Rgs12  (regulator of G-protein signaling 12)
Rgs14  (regulator of G-protein signaling 14)


Additional Information