Regulators of G protein signaling (RGS) are protein

structural domain In molecular biology, a protein domain is a region of a protein's Peptide, polypeptide chain that is self-stabilizing and that Protein folding, folds independently from the rest. Each domain forms a compact folded Protein tertiary structure, thre ...

s or the proteins that contain these domains, that function to activate the

GTPase GTPases are a large family of hydrolase enzymes that bind to the nucleotide guanosine triphosphate (GTP) and hydrolyze it to guanosine diphosphate (GDP). The GTP binding and hydrolysis takes place in the highly conserved P-loop "G domain", a ...

activity of heterotrimeric

G-protein G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their ...

α-subunits. RGS proteins are multi-functional, GTPase-accelerating proteins that promote GTP hydrolysis by the α-subunit of heterotrimeric G proteins, thereby inactivating the G protein and rapidly switching off

G protein-coupled receptor G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

signaling pathways. Upon activation by receptors, G proteins exchange GDP for GTP, are released from the receptor, and dissociate into a free, active GTP-bound α-subunit and βγ-dimer, both of which activate downstream effectors. The response is terminated upon GTP hydrolysis by the α-subunit (), which can then re-bind the βγ-dimer ( ) and the receptor. RGS proteins markedly reduce the lifespan of GTP-bound α-subunits by stabilising the G protein transition state. Whereas receptors stimulate GTP binding, RGS proteins stimulate GTP hydrolysis. RGS proteins have been conserved in evolution. The first to be identified was Sst2 ("SuperSensiTivity to

pheromone A pheromone () is a secreted or excreted chemical factor that triggers a social response in members of the same species. Pheromones are chemicals capable of acting like hormones outside the body of the secreting individual, to affect the behavio ...

") in yeast (''

Saccharomyces cerevisiae ''Saccharomyces cerevisiae'' () (brewer's yeast or baker's yeast) is a species of yeast (single-celled fungal microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have be ...

''). All RGS proteins contain an RGS-box (or RGS domain), which is required for activity. Some small RGS proteins such as RGS1 and RGS4 are little more than an RGS domain, while others also contain additional domains that confer further functionality. RGS domains in the

G protein-coupled receptor kinases G protein-coupled receptor kinases (GPCRKs, GRKs) are a family of protein kinases within the AGC (protein kinase A, protein kinase G, protein kinase C) group of kinases. Like all AGC kinases, GRKs use ATP to add phosphate to Serine and Threonin ...

are able to bind to Gq family α-subunits, but do not accelerate their GTP hydrolysis. Instead, GRKs appear to reduce Gq signaling by sequestering the active α-subunits away from effectors such as phospholipase C-β. Plants have RGS proteins but do not have canonical

s. Thus G proteins and GTPase accelerating proteins appear to have evolved before any known G protein activator. RGS domains can be found within the same protein in combination with a variety of other domains, including: DEP for membrane targeting (), PDZ for binding to

GPCR G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

s (), PTB for phosphotyrosine-binding (),

RBD RBD was a Mexican Latin pop group that gained popularity from Televisa's telenovela ''Rebelde'' (2004–2006). It was composed of Anahí, Dulce María, Maite Perroni, Alfonso Herrera, Christopher von Uckermann and Christian Chávez. The group ac ...

for Ras-binding (), GoLoco for guanine nucleotide inhibitor activity (), PX for phosphoinositide-binding (), PXA that is associated with PX (), PH for phosphatidylinositol-binding (), and GGL (G protein gamma subunit-like) for binding G protein beta subunits ( Those RGS proteins that contain GGL domains can interact with G protein beta subunits to form novel dimers that prevent G protein gamma subunit binding and G protein alpha subunit association, thereby preventing heterotrimer formation.

Examples

Human proteins containing this domain include: *

AXIN1 Axin-1 is a protein that in humans is encoded by the ''AXIN1'' gene. Function This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protei ...

AXIN2 Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the ''AXIN2'' gene. Function The Axin-related protein, Axin2, presumably plays an important role in the ...

GRK1 Rhodopsin kinase (, ''rod opsin kinase'', ''G-protein-coupled receptor kinase 1'', ''GPCR kinase 1'', ''GRK1'', ''opsin kinase'', ''opsin kinase (phosphorylating)'', ''rhodopsin kinase (phosphorylating)'', ''RK'', ''STK14'') is a serine/threonine- ...

GRK2 G-protein-coupled receptor kinase 2 (GRK2) is an enzyme that in humans is encoded by the ''ADRBK1'' gene. GRK2 was initially called Beta-adrenergic receptor kinase (βARK or βARK1), and is a member of the G protein-coupled receptor kinase subfam ...

GRK3 G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ''ADRBK2'' gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily o ...

GRK4 G protein-coupled receptor kinase 4 (GRK4) is an enzyme that is encoded by the ''GRK4'' gene in humans. This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most similar to G ...

GRK5 G protein-coupled receptor kinase 5 is a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinases, and is most highly similar to GRK4 and GRK6. The protein phosphorylates the activated forms of G protein-coupled re ...

GRK6 This gene encodes a member of the G protein-coupled receptor kinase subfamily of the Ser/Thr protein kinase family, and is most highly similar to GRK4 and GRK5. The protein phosphorylates the activated forms of G protein-coupled receptors to reg ...

, GRK7 *

RGS1 Regulator of G-protein signaling 1 is a protein that in humans is encoded by the ''RGS1'' gene. This gene encodes a member of the regulator of G-protein signaling family. This protein is located on the cytosolic side of the plasma membrane and c ...

RGS2 Regulator of G-protein signaling 2 is a protein that in humans is encoded by the ''RGS2'' gene. It is part of a larger family of RGS proteins that control signalling through G-protein coupled receptors (GPCR). Function RGS2 is thought to have ...

RGS3 Regulator of G-protein signaling 3 is a protein that in humans is encoded by the ''RGS3'' gene. This gene encodes a member of the regulator of G-protein signaling (RGS) family. This protein is a GTP-ase activating protein which inhibits G-prote ...

RGS4 Regulator of G protein signaling 4 also known as RGP4 is a protein that in humans is encoded by the ''RGS4'' gene. RGP4 regulates G protein signaling. Function Regulator of G protein signalling (RGS) family members are regulatory molecules th ...

RGS5 Regulator of G-protein signaling 5 is a protein that in humans is encoded by the ''RGS5'' gene. The regulator of G protein signaling (RGS) proteins are signal transduction molecules that have structural homology to SST2 of Saccharomyces cerevisia ...

RGS6 Regulator of G-protein signaling 6 is a protein that in humans is encoded by the ''RGS6'' gene. Members of the Regulator of G protein signaling (RGS) family have been shown to modulate the functioning of G proteins by activating the intrinsic GTP ...

RGS7 Regulator of G-protein signaling 7 is a protein that in humans is encoded by the ''RGS7'' gene. RGS7 is highly enriched in the brain where it acts as a universal inhibitor of Gi/o-coupled GPCR. RGS7 is a GTPase-activating protein (GAP). It accele ...

RGS8 Regulator of G-protein signaling 8 is a protein that in humans is encoded by the ''RGS8'' gene. This gene is a member of the regulator of G protein signaling (RGS) family and encodes a protein with a single RGS domain. Regulator of G protein si ...

RGS9 Regulator of G-protein signalling 9, also known as RGS9, is a human gene, which codes for a protein involved in regulation of signal transduction inside cells. Members of the RGS family, such as RGS9, are signaling proteins that suppress the acti ...

RGS10 Regulator of G-protein signaling 1 is a protein that in humans is encoded by the ''RGS1'' gene. This gene encodes a member of the regulator of G-protein signaling family. This protein is located on the cytosolic side of the plasma membrane and c ...

RGS11 Regulator of G-protein signaling 11 is a protein that in humans is encoded by the ''RGS11'' gene. The protein encoded by this gene belongs to the RGS (regulator of G protein signaling) family. Members of the RGS family act as GTPase-activating p ...

RGS12 Regulator of G-protein signaling 12 is a protein that in humans is encoded by the ''RGS12'' gene. This gene encodes a member of the 'regulator of G protein signaling' (RGS) gene family. The encoded protein may function as a guanosine triphospha ...

RGS13 Regulator of G-protein signaling 13 (RGS13) is a protein that in humans is encoded by the ''RGS13'' gene. RGS13 is a member of R4 subfamily of the Regulator of G protein signaling (RGS) protein family, whose members have only short peptide sequ ...

RGS14 Regulator of G-protein signaling 14 (RGS14) is a protein that in humans is encoded by the ''RGS14'' gene. Function RGS14 is a member of the regulator of G protein signalling family. This protein contains one RGS domain, two Raf-like Ras-bind ...

RGS16 Regulator of G-protein signaling 16 is a protein that in humans is encoded by the ''RGS16'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in ...

RGS17 Regulator of G-protein signaling 17 is a protein that in humans is encoded by the ''RGS17'' gene. Function This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved, 120 amino acid motif calle ...

RGS18 Regulator of G-protein signaling 18 is a protein that in humans is encoded by the ''RGS18'' gene. Function This gene encodes a member of the regulator of G-protein signaling family. This protein contains a conserved 120 amino acid motif called ...

RGS19 Regulator of G-protein signaling 19 is a protein that in humans is encoded by the ''RGS19'' gene. G proteins mediate a number of cellular processes. The protein encoded by this gene belongs to the RGS (regulators of G-protein signaling) family an ...

RGS20 Regulator of G-protein signaling 20 is a protein that in humans is encoded by the ''RGS20'' gene. Regulator of G protein signaling (RGS) proteins are regulatory and structural components of G protein-coupled receptor complexes. RGS proteins are G ...

, RGS21 * SNX13

References

External links

PROSITE PROSITE is a protein database. It consists of entries describing the protein families, domains and functional sites as well as amino acid patterns and profiles in them. These are manually curated by a team of the Swiss Institute of Bioinformati ...

{{Portal bar, Biology, border=no G proteins Protein domains Peripheral membrane proteins

Examples

See also

References

Further reading

External links