GPR32
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G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human
receptor (biochemistry) In biochemistry and pharmacology, receptors are chemical structures, composed of protein, that receive and transduce signals that may be integrated into biological systems. These signals are typically chemical messengers which bind to a recept ...
belonging to the rhodopsin-like subfamily of
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.


Gene

The ''GPR32'' was initially identified and defined by
molecular cloning Molecular cloning is a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their DNA replication, replication within Host (biology), host organisms. The use of the word ''cloning'' re ...
in 1998 as coding for an
orphan receptor In biochemistry, an orphan receptor is a protein that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to ...
, i.e. a protein with an amino acid sequence similar to known receptors but having no known
ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...
(s) to which it responds and no known function. The projected amino acid sequence of GPR32, however, shared 35-39% amino acid identity with certain members of the chemotactic factor receptor family, i.e. 39% identity with
Formyl peptide receptor 1 Formyl peptide receptor 1 (FPR1, FPR1 receptor, fMet-Leu-Phe receptor 1, FMLP receptor 1, or N-formylmethionyl-leucyl-phenylalanine receptor 1) is a cell surface receptor protein that in humans is encoded by the ''formyl peptide receptor 1'' (''F ...
, which is a receptor for N-Formylmethionine-leucyl-phenylalanine and related N-formyl peptide chemotactic factors, and 35% identity with Formyl peptide receptor 2, which likewise is also a receptor for N-formyl peptides but also a receptor for certain lipoxins which are arachidonic acid metabolites belonging to a set of
specialized proresolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...
that act to resolve or inhibit inflammatory reactions. GPR32 mapped to chromosomal 19, region q13.3. There are no mouse or other
ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...
s of GPR32.


Receptor

The GPR32 protein is a G protein coupled receptor although the specific G protein subtypes which it activates has not yet been reported. GPR32 is expressed in human blood neutrophils, certain types of blood
lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic ad ...
s (i.e. activated CD8+ cells,
CD4+ T cell The T helper cells (Th cells), also known as CD4+ cells or CD4-positive cells, are a type of T cell that play an important role in the adaptive immune system. They aid the activity of other immune cells by releasing cytokines. They are considere ...
s, and
T helper 17 cell T helper 17 cells (Th17) are a subset of pro-inflammatory T helper cells defined by their production of interleukin 17 (IL-17). They are related to T regulatory cells and the signals that cause Th17s to differentiate actually inhibit Treg differ ...
s), tissue
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...
, small airway epithelial cells, and adipose tissue. When expressed in
Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have found wide ...
s, GPR32 inhibits the
Cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
signaling pathway under both baseline and forskolin-stimulated conditions indicating that it is a member of the class of orphan G protein coupled receptors that possesses constitutive signaling activity. At least 6 members of the D series of resolvins (RvDs) viz., RvD1, RvD2m AT-RVD1, RvD3, AT-RvD3, and RvD5, activate their target cells through this receptor; these results have led to naming GPR32 the RVD1 receptor (see resolvin mechanisms of action). RvDs are members of the
specialized proresolving mediators Specialized pro-resolving mediators (SPM, also termed specialized proresolving mediators) are a large and growing class of cell signaling molecules formed in cells by the metabolism of polyunsaturated fatty acids (PUFA) by one or a combination of ...
(SPM) class of
polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...
metabolites. RVDs are metabolites of the
omega-3 fatty acid Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...
,
docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is a primary structural component of the human brain, cerebral cortex, skin, and retina. In physiological literature, it is given the name 22:6(n-3). It can be synthesized from alpha-lin ...
(DHA), and, along with other SRMs contribute to the inhibition and resolution of a diverse range of
inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...
and inflammation-related responses as well as to the healing of these inflammatory lesions in animals and humans. The metabolism of DHA to RVD's and the activation of GPR32 by these RVD's are proposed to be one mechanism by which omega-3 fatty acids may ameliorate inflammation as well as various inflammation-based and other diseases.


References


Further reading

* G protein-coupled receptors {{transmembranereceptor-stub