Regulator of G protein signaling 4 also known as RGP4 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''RGS4''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. RGP4 regulates
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 ...
signaling.
Function
Regulator of G protein signalling (RGS) family members are regulatory molecules that act as
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 ...
activating proteins (GAPs) for
G alpha subunits of
heterotrimeric G protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a heterotrimeric complex. The biggest non-structu ...
s.
RGS proteins are able to deactivate G protein subunits of the
Gi alpha,
Go alpha and
Gq alpha subtypes. They drive G proteins into their inactive
GDP-bound forms. Regulator of G protein signaling 4 belongs to this family. All RGS proteins share a conserved 120-amino acid sequence termed the RGS domain which conveys GAP activity.
Regulator of G protein signaling 4 protein is 37% identical to
RGS1 and 97% identical to rat Rgs4. This protein negatively regulates signaling upstream or at the level of the heterotrimeric G protein and is localized in the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
.
Clinical significance
A number of studies associate the RGS4 gene with
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...
,
while some fail to detect an association.
RGS4 is also of interest as one of the three main RGS proteins (along with
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 ...
and
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 called ...
) involved in terminating signalling by the
mu opioid receptor,
and may be important in the development of tolerance to opioid drugs.
Inhibitors
* cyclic peptides
*
CCG-4986
Interactions
RGS4 has been shown to
interact with:
*
COPB2,
*
ERBB3
Receptor tyrosine-protein kinase erbB-3, also known as HER3 (human epidermal growth factor receptor 3), is a membrane bound protein that in humans is encoded by the ''ERBB3'' gene.
ErbB3 is a member of the epidermal growth factor receptor (EGF ...
,
and
*
GNAQ.
References
Further reading
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{{PDB Gallery, geneid=5999
Proteins