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, res ...
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 a ...
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 pro ...
activating proteins (GAPs) for
G alpha subunit
G alpha subunits are one of the three types of subunit of guanine nucleotide binding proteins, which are membrane-associated, heterotrimeric G proteins.
Background
G proteins and their receptors (GPCRs) form one of the most prevalent signalling ...
s 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
Gross domestic product (GDP) is a monetary measure of the market value of all the final goods and services produced and sold (not resold) in a specific time period by countries. Due to its complex and subjective nature this measure is ofte ...
-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 w ...
,
while some fail to detect an association.
RGS4 is also of interest as one of the three main RGS proteins (along with
RGS9 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 calle ...
) 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
Advocates for Informed Choice, doing business as, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex trai ...
with:
*
COPB2,
*
ERBB3,
and
*
GNAQ
Guanine nucleotide-binding protein G(q) subunit alpha is a protein that in humans is encoded by the ''GNAQ'' gene. Together with GNA11 (its paralogue), it functions as a Gq alpha subunit.
Function
Guanine nucleotide-binding proteins are a fam ...
.
References
Further reading
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{{PDB Gallery, geneid=5999
Proteins