GPR158
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Probable G-protein coupled receptor 158 (GPR158), also known as the metabotropic glycine receptor (mGlyR), is a
protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''GPR158''
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 DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.


Function

This protein is an
orphan An orphan is a child whose parents have died, are unknown, or have permanently abandoned them. It can also refer to a child who has lost only one parent, as the Hebrew language, Hebrew translation, for example, is "fatherless". In some languages ...
class C GPCR The class C G-protein-coupled receptors () are a class of G-protein coupled receptors that include the metabotropic glutamate receptors () and several additional receptors. Structurally they are composed of four elements; an N-terminal signal s ...
. It is highly expressed in the brain, where it binds to
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 ...
, an inhibitor of Gi/o-coupled
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 ...
signaling, localizing it to the
plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
. It is expressed at lower levels in other organs and shows an unusual subcellular localization pattern, being found at both the plasma membrane and in the
nucleus Nucleus (: nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucleu ...
.


Clinical significance


Role in mood regulation

GPR158 in the
medial prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, BA ...
(mPFC) has been shown to regulate stress-induced depression in a mouse model of depression and has been found to be
upregulated In biochemistry, in the biological context of organisms' regulation of gene expression and production of gene products, downregulation is the process by which a cell decreases the production and quantities of its cellular components, such as RNA ...
in
post-mortem An autopsy (also referred to as post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough examination of a corpse by dissection to determine the cause, mode, and manner of death ...
tissue samples from humans with
major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...
(MDD).


Role in prostate cancer

The ''GPR158'' gene is an androgen-regulated gene that stimulates cell proliferation in
prostate cancer Prostate cancer is the neoplasm, uncontrolled growth of cells in the prostate, a gland in the male reproductive system below the bladder. Abnormal growth of the prostate tissue is usually detected through Screening (medicine), screening tests, ...
cell lines, and it is linked to neuroendocrine differentiation.


References

G protein-coupled receptors {{transmembranereceptor-stub