GPR156

Last updated
GPR156
Identifiers
Aliases GPR156 , GABABL, PGR28, G protein-coupled receptor 156
External IDs OMIM: 610464 MGI: 2653880 HomoloGene: 17683 GeneCards: GPR156
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001168271
NM_153002

NM_153394

RefSeq (protein)

NP_001161743
NP_694547

NP_700443

Location (UCSC) Chr 3: 120.16 – 120.29 Mb Chr 16: 37.74 – 37.83 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

GPR156 (G protein-coupled receptor 156), is a human gene which encodes a G protein-coupled receptor belonging to metabotropic glutamate receptor subfamily. [5] By sequence homology, this gene was proposed as being a possible GABAB receptor subunit, however when expressed in cells alone or with other GABAB subunits, no response to GABAB ligands could be detected. In vitro studies on GPR156 constitutive activity revealed a high level of basal activation and coupling with members of the Gi/Go heterotrimeric G protein family. [6] In 2021, an article was reported that GPR156 modulates hair cell orientation in the cochlea. [7] Also, it was proposed that GPR156 is related to congenital hearing loss. [8] In 2024, molecular structures of GPR156 were characterized by using cryogenic electron microscopy. [9] GPR156 in complex with any of the Gi/o heterotrimer regulates the hair cell orientation [10] .

Contents

Structure

Among class C GPCR family members, GPR156 is unique because it lacks a large extracellular domain. Structural analyses revealed that the asymmetric binding of G-protein to GPR156 triggers conformational change of its cytoplasmic face without altering dimer interface. [9] Structural and functional analyses suggest that abundant endogenous phospholipids, receptor dimerization, and the G-protein binding-induced conformational change of the cytoplasmic face are the primary reasons for constitutive activation of GPR156. [9] Phosphatidylglycerol further stimulates the activity of GPR156, which suggests the environmental changes of the phospholipid composition may regulate the GPR156 activity. [9]

G-bound GPR156 G-bound GPR156.png
G-bound GPR156
G-free GPR156 G-free GPR156.png
G-free GPR156

Related Research Articles

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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 proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.

<span class="mw-page-title-main">G protein</span> Type of proteins

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 activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.

<span class="mw-page-title-main">Signal transduction</span> Cascade of intracellular and molecular events for transmission/amplification of signals

Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events. Most commonly, protein phosphorylation is catalyzed by protein kinases, ultimately resulting in a cellular response. Proteins responsible for detecting stimuli are generally termed receptors, although in some cases the term sensor is used. The changes elicited by ligand binding in a receptor give rise to a biochemical cascade, which is a chain of biochemical events known as a signaling pathway.

<span class="mw-page-title-main">Receptor (biochemistry)</span> Protein molecule receiving signals for a cell

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 receptor and produce physiological responses such as change in the electrical activity of a cell. For example, GABA, an inhibitory neurotransmitter, inhibits electrical activity of neurons by binding to GABAA receptors. There are three main ways the action of the receptor can be classified: relay of signal, amplification, or integration. Relaying sends the signal onward, amplification increases the effect of a single ligand, and integration allows the signal to be incorporated into another biochemical pathway.

Steroid hormone receptors are found in the nucleus, cytosol, and also on the plasma membrane of target cells. They are generally intracellular receptors and initiate signal transduction for steroid hormones which lead to changes in gene expression over a time period of hours to days. The best studied steroid hormone receptors are members of the nuclear receptor subfamily 3 (NR3) that include receptors for estrogen and 3-ketosteroids. In addition to nuclear receptors, several G protein-coupled receptors and ion channels act as cell surface receptors for certain steroid hormones.

GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABAB-mediated IPSP is –100 mV, which is much more hyperpolarized than the GABAA IPSP. GABAB receptors are found in the central nervous system and the autonomic division of the peripheral nervous system.

<span class="mw-page-title-main">Phosphatidylinositol 4,5-bisphosphate</span> Chemical compound

Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)P2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)P2 is enriched at the plasma membrane where it is a substrate for a number of important signaling proteins. PIP2 also forms lipid clusters that sort proteins.

<span class="mw-page-title-main">Smoothened</span> Protein-coding gene in the species Homo sapiens

Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA).

<span class="mw-page-title-main">Arrestin</span> Family of proteins

Arrestins are a small family of proteins important for regulating signal transduction at G protein-coupled receptors. Arrestins were first discovered as a part of a conserved two-step mechanism for regulating the activity of G protein-coupled receptors (GPCRs) in the visual rhodopsin system by Hermann Kühn, Scott Hall, and Ursula Wilden and in the β-adrenergic system by Martin J. Lohse and co-workers.

<span class="mw-page-title-main">Follicle-stimulating hormone receptor</span> Protein-coding gene in the species Homo sapiens

The follicle-stimulating hormone receptor or FSH receptor (FSHR) is a transmembrane receptor that interacts with the follicle-stimulating hormone (FSH) and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning of FSH. FSHRs are found in the ovary, testis, and uterus.

<span class="mw-page-title-main">Luteinizing hormone/choriogonadotropin receptor</span> Transmembrane receptor found in humans

The luteinizing hormone/choriogonadotropin receptor (LHCGR), also lutropin/choriogonadotropin receptor (LCGR) or luteinizing hormone receptor (LHR), is a transmembrane receptor found predominantly in the ovary and testis, but also many extragonadal organs such as the uterus and breasts. The receptor interacts with both luteinizing hormone (LH) and chorionic gonadotropins and represents a G protein-coupled receptor (GPCR). Its activation is necessary for the hormonal functioning during reproduction.

<span class="mw-page-title-main">ACVR1</span> Protein-coding gene

Activin A receptor, type I (ACVR1) is a protein which in humans is encoded by the ACVR1 gene; also known as ALK-2. ACVR1 has been linked to the 2q23-24 region of the genome. This protein is important in the bone morphogenic protein (BMP) pathway which is responsible for the development and repair of the skeletal system. While knock-out models with this gene are in progress, the ACVR1 gene has been connected to fibrodysplasia ossificans progressiva, an extremely rare progressive genetic disease characterized by heterotopic ossification of muscles, tendons and ligaments. It is a bone morphogenetic protein receptor, type 1.

Gq protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gq/11 (Gq/G11) family or Gq/11/14/15 family to include closely related family members. G alpha subunits may be referred to as Gq alpha, Gαq, or Gqα. Gq proteins couple to G protein-coupled receptors to activate beta-type phospholipase C (PLC-β) enzymes. PLC-β in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 acts as a second messenger to release stored calcium into the cytoplasm, while DAG acts as a second messenger that activates protein kinase C (PKC).

Gi protein alpha subunit is a family of heterotrimeric G protein alpha subunits. This family is also commonly called the Gi/o family or Gi/o/z/t family to include closely related family members. G alpha subunits may be referred to as Gi alpha, Gαi, or Giα.

<span class="mw-page-title-main">Coagulation factor II receptor</span> Mammalian protein found in humans

Proteinase-activated receptor 1 (PAR1) also known as protease-activated receptor 1 or coagulation factor II (thrombin) receptor is a protein that in humans is encoded by the F2R gene. PAR1 is a G protein-coupled receptor and one of four protease-activated receptors involved in the regulation of thrombotic response. Highly expressed in platelets and endothelial cells, PAR1 plays a key role in mediating the interplay between coagulation and inflammation, which is important in the pathogenesis of inflammatory and fibrotic lung diseases. It is also involved both in disruption and maintenance of endothelial barrier integrity, through interaction with either thrombin or activated protein C, respectively.

<span class="mw-page-title-main">GABBR2</span> Protein-coding gene in the species Homo sapiens

Gamma-aminobutyric acid (GABA) B receptor, 2 (GABAB2) is a G-protein coupled receptor subunit encoded by the GABBR2 gene in humans.

<span class="mw-page-title-main">GPR3</span> Protein

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<span class="mw-page-title-main">TAS2R10</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 10 is a protein that in humans is encoded by the TAS2R10 gene. The protein is responsible for bitter taste recognition in mammals. It serves as a defense mechanism to prevent consumption of toxic substances which often have a characteristic bitter taste.

<span class="mw-page-title-main">Dedicator of cytokinesis protein 2</span> Protein found in humans

Dedicator of cytokinesis protein 2 (Dock2) is a protein encoded in the human by the DOCK2 gene. Dock2 is a large protein involved in intracellular signalling networks. It is a member of the DOCK-A subfamily of the DOCK family of guanine nucleotide exchange factors (GEFs) which function as activators of small G-proteins. Dock2 specifically activates isoforms of the small G protein Rac.

<span class="mw-page-title-main">Cell surface receptor</span> Class of ligand activated receptors localized in surface of plama cell membrane

Cell surface receptors are receptors that are embedded in the plasma membrane of cells. They act in cell signaling by receiving extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000175697 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000046961 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: GPR156 G protein-coupled receptor 156".
  6. Watkins LR, Orlandi C (2021-03-30). "In vitro profiling of orphan G protein coupled receptor (GPCR) constitutive activity". British Journal of Pharmacology. 178 (15): 2963–2975. doi: 10.1111/bph.15468 . ISSN   1476-5381. PMID   33784795. S2CID   232430996.
  7. Kindt KS, Akturk A, Jarysta A, Day M, Beirl A, Flonard M, Tarchini B (2021-05-17). "EMX2-GPR156-Gαi reverses hair cell orientation in mechanosensory epithelia". Nature Communications. 12 (1): 2861. Bibcode:2021NatCo..12.2861K. doi:10.1038/s41467-021-22997-1. ISSN   2041-1723. PMC   8129141 . PMID   34001891.
  8. Ramzan M, Bozan N, Seyhan S, Zafeer MF, Ayral A, Duman D, Bademci G, Tekin M (2023-10-09). "Novel GPR156 variants confirm its role in moderate sensorineural hearing loss". Scientific Reports. 13 (1): 17010. Bibcode:2023NatSR..1317010R. doi:10.1038/s41598-023-44259-4. ISSN   2045-2322. PMC   10562426 . PMID   37814107.
  9. 1 2 3 4 Shin J, Park J, Jeong J, Lam JH, Qiu X, Wu D, Kim K, Lee J, Robinson CV, Hyun J, Katritch V, Kim KP, Cho Y (2024-02-08). "Constitutive activation mechanism of a class C GPCR". Nature Structural & Molecular Biology: 1–10. doi:10.1038/s41594-024-01224-7. ISSN   1545-9985. PMID   38332368.
  10. Jarysta A, Tadenev AL, Day M, Krawchuk B, Low BE, Wiles MV, Tarchini B (2023-07-18). "Inhibitory G proteins play multiple roles to polarize sensory hair cell morphogenesis". eLife. 12. doi: 10.7554/eLife.88186.1 .

Further reading