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Regulators of G protein signaling (RGS) are protein
structural domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...
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 pro ...
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 act ...
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 p ...
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 fungus microorganisms). The species has been instrumental in winemaking, baking, and brewing since ancient times. It is believed to have been o ...
''). 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 Threonine ...
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
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 p ...
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 p ...
s (), PTB for phosphotyrosine-binding (),
RBD RBD is a Mexican Latin pop group that gained popularity from Televisa's telenovela ''Rebelde''. The group achieved international success from 2004 until their separation in 2009 and sold over 15 million records worldwide, making them one of ...
for
Ras Ras or RAS may refer to: Arts and media * RAS Records Real Authentic Sound, a reggae record label * Rundfunk Anstalt Südtirol, a south Tyrolese public broadcasting service * Rás 1, an Icelandic radio station * Rás 2, an Icelandic radio stati ...
-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 prote ...
,
AXIN2 Axin-2 also known as axin-like protein (Axil) or 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 r ...
*
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-s ...
,
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 of ...
,
GRK4 G protein-coupled receptor kinase 4 (GRK4) is an enzyme that in humans is encoded by the ''GRK4'' gene. 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 GRK ...
,
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 regu ...
, 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 co ...
,
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 p ...
,
RGS3 Regulator of G-protein signaling 3 is a protein that in humans is encoded by the ''RGS3'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''genera ...
,
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 that ...
,
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 RGS (regulator of G protein signaling) family have been shown to modulate the functioning of G proteins by activating the intrinsic GTPa ...
,
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 accel ...
,
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 10 is a protein that in humans is encoded by the ''RGS10'' gene. Function Regulator of G protein signaling (RGS) family members are regulatory molecules that act as GTPase activating proteins (GAPs) for G alpha ...
,
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 triphosphatas ...
, RGS13,
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. Function The protein encoded by this gene belongs to the 'regulator of G protein signaling' family. It inhibits signal transduction by increasing ...
,
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 and ...
,
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 RGS is the abbreviation of: * Burgos Airport, Spain, by IATA airport code * Congregation of Our Lady of Charity of the Good Shepherd * Raffles Girls' School (Secondary) * Rapid Global School, Uttar Pradesh, India * Redland Green School, Bristol * ...
* SNX13


See also

GTP-binding protein regulators: *
GEF Gef ( ), also referred to as the Talking Mongoose or the Dalby Spook, was the name given to an allegedly talking mongoose which was claimed to inhabit a farmhouse owned by the Irving family. The Irvings' farm was located at Cashen's Gap near ...
* GAP


References


Further reading

* * * * * * * *


External links



in
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