2538:, including proteases, which can function only at such low pH, and so the peptide bonds joining the residues of the GPCR together may be cleaved. Whether or not a given receptor is trafficked to a lysosome, detained in endosomes, or trafficked back to the plasma membrane depends on a variety of factors, including receptor type and magnitude of the signal. GPCR regulation is additionally mediated by gene transcription factors. These factors can increase or decrease gene transcription and thus increase or decrease the generation of new receptors (up- or down-regulation) that travel to the cell membrane.
2272:(GRKs) are protein kinases that phosphorylate only active GPCRs. G-protein-coupled receptor kinases (GRKs) are key modulators of G-protein-coupled receptor (GPCR) signaling. They constitute a family of seven mammalian serine-threonine protein kinases that phosphorylate agonist-bound receptor. GRKs-mediated receptor phosphorylation rapidly initiates profound impairment of receptor signaling and desensitization. Activity of GRKs and subcellular targeting is tightly regulated by interaction with receptor domains, G protein subunits, lipids, anchoring proteins and calcium-sensitive proteins.
2282:: The receptor is, along with the part of the membrane it is embedded in, brought to the inside of the cell, where it is dephosphorylated within the acidic vesicular environment and then brought back. This mechanism is used to regulate long-term exposure, for example, to a hormone, by allowing resensitisation to follow desensitisation. Alternatively, the receptor may undergo lysozomal degradation, or remain internalised, where it is thought to participate in the initiation of signalling events, the nature of which depending on the internalised vesicle's subcellular localisation.
2053:
2045:
1511:
245:
38:
440:
drugs currently on the market, mainly due to their involvement in signaling pathways related to many diseases i.e. mental, metabolic including endocrinological disorders, immunological including viral infections, cardiovascular, inflammatory, senses disorders, and cancer. The long ago discovered association between GPCRs and many endogenous and exogenous substances, resulting in e.g. analgesia, is another dynamically developing field of the pharmaceutical research.
2189:(CaM) binds Ca, undergoes a change in conformation, and activates CaM kinase II, which has unique ability to increase its binding affinity to CaM by autophosphorylation, making CaM unavailable for the activation of other enzymes. The kinase then phosphorylates target enzymes, regulating their activities. The two signal pathways are connected together by Ca-CaM, which is also a regulatory subunit of adenylyl cyclase and phosphodiesterase in the cAMP signal pathway.
474:
much more spacious than in the rhodopsin structure and was open to the exterior. In the other receptors crystallized shortly afterwards the binding side was even more easily accessible to the ligand. New structures complemented with biochemical investigations uncovered mechanisms of action of molecular switches which modulate the structure of the receptor leading to activation states for agonists or to complete or partial inactivation states for inverse agonists.
1326:
510:
2037:
938:
1103:
1543:
1416:
2922:
985:(mGluRs), the N-terminal tail. The class C GPCRs are distinguished by their large N-terminal tail, which also contains a ligand-binding domain. Upon glutamate-binding to an mGluR, the N-terminal tail undergoes a conformational change that leads to its interaction with the residues of the extracellular loops and TM domains. The eventual effect of all three types of
1980:-adrenoceptor has been demonstrated to activate the ERK2 pathway after arrestin-mediated uncoupling of G-protein-mediated signaling. Therefore, it seems likely that some mechanisms previously believed related purely to receptor desensitisation are actually examples of receptors switching their signaling pathway, rather than simply being switched off.
2121:
contains two catalytic subunits and two regulatory subunits. When there is no cAMP,the complex is inactive. When cAMP binds to the regulatory subunits, their conformation is altered, causing the dissociation of the regulatory subunits, which activates protein kinase A and allows further biological effects.
2352:
in their ability to deactivate G-proteins, while which RGS is involved in a given signaling pathway seems more determined by the tissue and GPCR involved than anything else. In addition, RGS proteins have the additional function of increasing the rate of GTP-GDP exchange at GPCRs, (i.e., as a sort of
2112:
Stimulative regulative G-protein is a G-protein linked to stimulative hormone receptor (Rs), and its α subunit upon activation could stimulate the activity of an enzyme or other intracellular metabolism. On the contrary, inhibitory regulative G-protein is linked to an inhibitory hormone receptor, and
1485:
capability, the inactive form of the α-subunit (Gα-GDP) is eventually regenerated, thus allowing reassociation with a Gβγ dimer to form the "resting" G-protein, which can again bind to a GPCR and await activation. The rate of GTP hydrolysis is often accelerated due to the actions of another family of
893:
GPCR structure proved highly similar to the bovine rhodopsin. The structures of activated or agonist-bound GPCRs have also been determined. These structures indicate how ligand binding at the extracellular side of a receptor leads to conformational changes in the cytoplasmic side of the receptor. The
461:
studies of the two-dimensional crystals. The crystal structure of rhodopsin, that came up three years later, was not a surprise apart from the presence of an additional cytoplasmic helix H8 and a precise location of a loop covering retinal binding site. However, it provided a scaffold which was hoped
1106:
Cartoon depicting the basic concept of GPCR conformational activation. Ligand binding disrupts an ionic lock between the E/DRY motif of TM-3 and acidic residues of TM-6. As a result, the GPCR reorganizes to allow activation of G-alpha proteins. The "side perspective" is a view from above and to the
473:
AR) with a diffusible ligand brought surprising results because it revealed quite a different shape of the receptor extracellular side than that of rhodopsin. This area is important because it is responsible for the ligand binding and is targeted by many drugs. Moreover, the ligand binding site was
439:
GPCRs are an important drug target and approximately 34% of all Food and Drug
Administration (FDA) approved drugs target 108 members of this family. The global sales volume for these drugs is estimated to be 180 billion US dollars as of 2018. It is estimated that GPCRs are targets for about 50% of
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Receptor desensitization is mediated through a combination phosphorylation, β-arr binding, and endocytosis as described above. Downregulation occurs when endocytosed receptor is embedded in an endosome that is trafficked to merge with an organelle called a lysosome. Because lysosomal membranes are
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activates the G-protein by facilitating the exchange of a molecule of GDP for GTP at the G-protein's α-subunit. The cell maintains a 10:1 ratio of cytosolic GTP:GDP so exchange for GTP is ensured. At this point, the subunits of the G-protein dissociate from the receptor, as well as each other, to
2120:
Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating specific committed enzymes in the metabolic pathway. It can also regulate specific gene expression, cellular secretion, and membrane permeability. The protein enzyme
2592:
R2 subunit alone, meanwhile, leads to surface expression of the subunit, although with no functional activity (i.e., the receptor does not bind agonist and cannot initiate a response following exposure to agonist). Expression of the two subunits together leads to plasma membrane expression of
2414:
the affinity for β-arrestin may be increased in a ligand occupation and GRK-independent manner through phosphorylation of different ser/thr sites (but also of IL-3 and the C-terminal tail) by PKC and PKA. These phosphorylations are often sufficient to impair G-protein coupling on their own as
448:
With the determination of the first structure of the complex between a G-protein coupled receptor (GPCR) and a G-protein trimer (Gαβγ) in 2011 a new chapter of GPCR research was opened for structural investigations of global switches with more than one protein being investigated. The previous
989:-induced activation is a change in the relative orientations of the TM helices (likened to a twisting motion) leading to a wider intracellular surface and "revelation" of residues of the intracellular helices and TM domains crucial to signal transduction function (i.e., G-protein coupling).
1918:
Although they are classically thought of working only together, GPCRs may signal through G-protein-independent mechanisms, and heterotrimeric G-proteins may play functional roles independent of GPCRs. GPCRs may signal independently through many proteins already mentioned for their roles in
679:
An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions.
2028:. There may even be specific proteins of these classes whose primary function is as part of GPCR-independent pathways, termed activators of G-protein signalling (AGS). Both the ubiquity of these interactions and the importance of Gα vs. Gβγ subunits to these processes are still unclear.
1999:
Although it is a relatively immature area of research, it appears that heterotrimeric G-proteins may also take part in non-GPCR signaling. There is evidence for roles as signal transducers in nearly all other types of receptor-mediated signaling, including
1393:
subunits interact with other intracellular proteins to continue the signal transduction cascade while the freed GPCR is able to rebind to another heterotrimeric G protein to form a new complex that is ready to initiate another round of signal transduction.
1401:
between active and inactive biophysical states. The binding of ligands to the receptor may shift the equilibrium toward the active receptor states. Three types of ligands exist: Agonists are ligands that shift the equilibrium in favour of active states;
2116:
Adenylyl cyclase is a 12-transmembrane glycoprotein that catalyzes the conversion of ATP to cAMP with the help of cofactor Mg or Mn. The cAMP produced is a second messenger in cellular metabolism and is an allosteric activator of protein kinase A.
2418:
PKC/PKA may, instead, phosphorylate GRKs, which can also lead to GPCR phosphorylation and β-arrestin binding in an occupation-independent manner. These latter two mechanisms allow for desensitization of one GPCR due to the activities of others, or
1107:
side of the GPCR as it is set in the plasma membrane (the membrane lipids have been omitted for clarity). The incorrectly labelled "intracellular perspective" shows an extracellular view looking down at the plasma membrane from outside the cell.
513:
Classification Scheme of GPCRs in 2006. Since this time, more genes have been found. Class A (Rhodopsin-like), Class B (Secretin-like), Class C (Glutamate
Receptor-like), Others (Adhesion (33), Frizzled (11), Taste type-2 (25), unclassified
2307:-adrenoreceptors acts as an adaptor for binding with clathrin, and with the beta-subunit of AP2 (clathrin adaptor molecules); thus, the arrestin here acts as a scaffold assembling the components needed for clathrin-mediated endocytosis of β
838:
Used in the endocrine system for peptide and amino-acid derivative hormones that bind to GCPRs on the cell membrane of a target cell. This activates cAMP, which in turn activates several kinases, allowing for a cellular response, such as
1675:
that may imbue them with differences ranging from subtle to distinct with regard to signaling properties, but in general they appear reasonably grouped into four classes. Because the signal transducing properties of the various possible
5669:
Nordström KJ, Sällman Almén M, Edstam MM, Fredriksson R, Schiöth HB (September 2011). "Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families".
3229:
1554:, it may activate it. Some evidence suggests that receptors and G proteins are actually pre-coupled. For example, binding of G proteins to receptors affects the receptor's affinity for ligands. Activated G proteins are bound to
1406:
are ligands that shift the equilibrium in favour of inactive states; and neutral antagonists are ligands that do not affect the equilibrium. It is not yet known how exactly the active and inactive states differ from each other.
1838:(PKC). Since many isoforms of PKC are also activated by increases in intracellular Ca, both these pathways can also converge on each other to signal through the same secondary effector. Elevated intracellular Ca also binds and
408:. The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (
319:, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (
1683:
While most GPCRs are capable of activating more than one Gα-subtype, they also show a preference for one subtype over another. When the subtype activated depends on the ligand that is bound to the GPCR, this is called
1622:
form of most GPCRs (see above or below), the majority of signaling is ultimately dependent upon G-protein activation. However, the possibility for interaction does allow for G-protein-independent signaling to occur.
1708:(e.g., phosphorylation) that alter the G-protein preference. Regardless of these various nuances, the GPCR's preferred coupling partner is usually defined according to the G-protein most obviously activated by the
1040:(internalization). As the phosphorylation of these Ser and Thr residues often occurs as a result of GPCR activation, the β-arr-mediated G-protein-decoupling and internalization of GPCRs are important mechanisms of
3193:
Bjarnadóttir TK, Gloriam DE, Hellstrand SH, Kristiansson H, Fredriksson R, Schiöth HB (September 2006). "Comprehensive repertoire and phylogenetic analysis of the G protein-coupled receptors in human and mouse".
1963:
mitogen-activated protein kinase, a key signal transduction mediator downstream of receptor activation in many pathways, has been shown to be activated in response to cAMP-mediated receptor activation in the
3615:
Qiu JD, Huang JH, Liang RP, Lu XQ (July 2009). "Prediction of G-protein-coupled receptor classes based on the concept of Chou's pseudo amino acid composition: an approach from discrete wavelet transform".
3651:
Gu Q, Ding YS, Zhang TL (May 2010). "Prediction of G-protein-coupled receptor classes in low homology using Chou's pseudo amino acid composition with approximate entropy and hydrophobicity patterns".
1502:) that become activated/inactivated upon interaction with Gα-GTP also have GAP activity. Thus, even at this early stage in the process, GPCR-initiated signaling has the capacity for self-termination.
2109:
Stimulative hormone receptor (Rs) is a receptor that can bind with stimulative signal molecules, while inhibitory hormone receptor (Ri) is a receptor that can bind with inhibitory signal molecules.
1044:. In addition, internalized "mega-complexes" consisting of a single GPCR, β-arr(in the tail conformation), and heterotrimeric G protein exist and may account for protein signaling from endosomes.
1111:
The G protein-coupled receptor is activated by an external signal in the form of a ligand or other signal mediator. This creates a conformational change in the receptor, causing activation of a
3237:
2525:
around the neck of an incoming vesicle, and their phosphorylation by c-SRC provides the energy necessary for the conformational change allowing the final "pinching off" from the membrane.
2628:
domain, and comparison of the family-specific motifs, have shown that the superfamily of GPCRs have a common origin. Characteristic motifs indicate that three of the five GRAFS families,
894:
biggest change is an outward movement of the cytoplasmic part of the 5th and 6th transmembrane helix (TM5 and TM6). The structure of activated beta-2 adrenergic receptor in complex with G
1991:(immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.
1341:). The receptor is colored red, Gα green, Gβ cyan, and Gγ yellow. The C-terminus of Gα is located in a cavity created by an outward movement of the cytoplasmic parts of TM5 and 6.
4029:
Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, et al. (November 2007). "Crystal structure of the human beta2 adrenergic G-protein-coupled receptor".
2521:, ERK-1/2) at which point signaling is initiated due to their close proximity to one another. Another target of c-SRC are the dynamin molecules involved in endocytosis. Dynamins
683:
Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the
2303:
cells to compensate for exposure to bright light. In many cases, arrestin's binding to the receptor is a prerequisite for translocation. For example, beta-arrestin bound to β
5787:
5615:
White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, et al. (December 1998). "Heterodimerization is required for the formation of a functional GABA(B) receptor".
818:
nervous systems are regulated by GPCR pathways, responsible for control of many automatic functions of the body such as blood pressure, heart rate, and digestive processes
2340:, accelerate the hydrolysis rate to ≈30 times/sec. This 1500-fold increase in rate allows for the cell to respond to external signals with high speed, as well as spatial
2241:, these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and the more receptors are phosphorylated. In
457:
AR) in 2007. The way in which the seven transmembrane helices of a GPCR are arranged into a bundle was suspected based on the low-resolution model of frog rhodopsin from
2328:(≈0.02 times/sec) and, thus, it would take around 50 seconds for any single G-protein to deactivate if other factors did not come into play. Indeed, there are around 30
3372:
Foord SM, Bonner TI, Neubig RR, Rosser EM, Pin JP, Davenport AP, et al. (June 2005). "International Union of
Pharmacology. XLVI. G protein-coupled receptor list".
1572:. Adenylate cyclase activity is activated when it binds to a subunit of the activated G protein. Activation of adenylate cyclase ends when the G protein returns to the
5164:"A novel protein-protein interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved in bradykinin-induced inhibition of cell proliferation"
536:. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B, and C) with no detectable shared
212:
9075:
4422:
Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, et al. (June 2003). "Cloning of adiponectin receptors that mediate antidiabetic metabolic effects".
2295:
molecules that prevent it from binding (and activating) G proteins, in effect switching it off for a short period of time. This mechanism is used, for example, with
1888:
5298:
Santulli G, Trimarco B, Iaccarino G (March 2013). "G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms".
5378:"The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification"
6329:
3976:
Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, et al. (August 2000). "Crystal structure of rhodopsin: A G protein-coupled receptor".
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prevent G-protein coupling and may recruit other proteins, leading to the creation of signaling complexes involved in extracellular-signal regulated kinase (
2849:
1579:
Adenylate cyclases (of which 9 membrane-bound and one cytosolic forms are known in humans) may also be activated or inhibited in other ways (e.g., Ca2+/
543:
The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are predicted to encode
2534:
rich in proton pumps, their interiors have low pH (≈4.8 vs. the pH≈7.2 cytosol), which acts to denature the GPCRs. In addition, lysosomes contain many
2124:
These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates protein kinase A.
8541:
2431:
Once β-arrestin is bound to a GPCR, it undergoes a conformational change allowing it to serve as a scaffolding protein for an adaptor complex termed
490:
6033:
4568:
Luttrell LM, Lefkowitz RJ (February 2002). "The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals".
7479:
4525:
Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (June 1990). "beta-Arrestin: a protein that regulates beta-adrenergic receptor function".
2725:
1000:
The structure of the N- and C-terminal tails of GPCRs may also serve important functions beyond ligand-binding. For example, The C-terminus of M
7681:
7676:
7671:
7666:
5419:"The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits"
1988:
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molecules, three intracellular loops interacting with G proteins, an N-terminal extracellular region and a C-terminal intracellular region) of
156:
144:
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muscarinic receptors is sufficient, and the six-amino-acid polybasic (KKKRRK) domain in the C-terminus is necessary for its preassembly with G
5341:
Penela P, Ribas C, Mayor F (November 2003). "Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases".
3876:
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM (February 2013). "Molecular signatures of G-protein-coupled receptors".
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may also initiate activation of multiple different G-proteins, as it may be capable of stabilizing more than one conformation of the GPCR's
2021:
3786:"G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei--serpentine gateways to neuroendocrine homeostasis"
961:(TM-1 to TM-7) connected by three intracellular (IL-1 to IL-3) and three extracellular loops (EL-1 to EL-3), and finally an intracellular
8411:
5825:
2197:
GPCRs become desensitized when exposed to their ligand for a long period of time. There are two recognized forms of desensitization: 1)
8801:
8796:
2938:
King N, Hittinger CT, Carroll SB (July 2003). "Evolution of key cell signaling and adhesion protein families predates animal origins".
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2182:
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a
Protein Structure Initiative:Biology Network Center aimed at determining the 3D structures of representative GPCR family proteins
2260:
class. cAMP-dependent PKA mediated phosphorylation can cause heterologous desensitisation in receptors other than those activated.
1781:
1115:. Further effect depends on the type of G protein. G proteins are subsequently inactivated by GTPase activating proteins, known as
973:-binding domain that is often covered by EL-2. Ligands may also bind elsewhere, however, as is the case for bulkier ligands (e.g.,
577:
According to the classical A-F system, GPCRs can be grouped into six classes based on sequence homology and functional similarity:
5780:
1349:
through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a
8816:
8498:
8493:
8488:
7454:
2518:
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Sharma N, Akhade AS, Qadri A (April 2013). "Sphingosine-1-phosphate suppresses TLR-induced CXCL8 secretion from human T cells".
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to be a universal template for homology modeling and drug design for other GPCRs – a notion that proved to be too optimistic.
2822:. G Protein-Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis. Vol. 114. Academic Press. pp. 89–107.
1688:(also known as agonist-directed trafficking, or conformation-specific agonism). However, the binding of any single particular
1309:
However, in contrast to other types of receptors that have been studied, wherein ligands bind externally to the membrane, the
921:. In addition, ADIPOR1 and ADIPOR2 are oriented oppositely to GPCRs in the membrane (i.e. GPCRs usually have an extracellular
8483:
7429:
5956:
2159:
1807:
2552:
G-protein-coupled receptor oligomerisation is a widespread phenomenon. One of the best-studied examples is the metabotropic
2348:
that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are
232:
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5971:"GPCR-I-TASSER: A Hybrid Approach to G Protein-Coupled Receptor Structure Modeling and the Application to the Human Genome"
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do not appear to radically differ from one another, these classes are defined according to the isoform of their α-subunit.
2926:
1583:
binding), which can modify the activity of these enzymes in an additive or synergistic fashion along with the G proteins.
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8470:
7119:
2635:
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997:
may also bind to a number of different sites, but the eventual effect must be prevention of this TM helix reorientation.
659:
3261:"Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands"
3230:"keyword:"G-protein coupled receptor [KW-0297]" AND organism:"Homo sapiens (Human) [9606]" in UniProtKB"
1362:
8375:
7344:
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2205:, wherein the activated GPCR causes downregulation of a different GPCR. The key reaction of this downregulation is the
2017:
1939:
was necessary for full efficacy chemotaxis of activated T cells. In addition, further scaffolding proteins involved in
1693:
1430:
1094:) domain primarily formed by a combination of IL-2 and IL-3 along with adjacent residues of the associated TM helices.
1091:
1051:
of one or more sites of the C-terminal tail or the intracellular loops. Palmitoylation is the covalent modification of
489:
for their work that was "crucial for understanding how G protein-coupled receptors function". There have been at least
393:
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receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as
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9019:
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2178:(PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
1959:
In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The
1924:
1903:
695:
GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
615:
494:
3141:"The top prescription drugs of 2012 globally: biologics dominate, but small molecule CNS drugs hold on to top spots"
969:
resembling a barrel, with the seven transmembrane helices forming a cavity within the plasma membrane that serves a
8826:
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6837:
6832:
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1987:
has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine-phosphorylated
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of α, β, and γ subunits (known as Gα, Gβ, and Gγ, respectively) that is rendered inactive when reversibly bound to
1116:
982:
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awarded for some aspect of G protein–mediated signaling. As of 2012, two of the top ten global best-selling drugs (
3448:"The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi"
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signaling and GPCRs. Integrins are shown elevating Ca and phosphorylating FAK, which is weakening GPCR signaling.
1338:
651:
605:
5263:
Tan CM, Brady AE, Nickols HH, Wang Q, Limbird LE (2004). "Membrane trafficking of G protein-coupled receptors".
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domain, even over the course of a single interaction. In addition, a conformation that preferably activates one
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in the membrane of the smooth endoplasmic reticulum and mitochondria to open Ca channels. DAG helps activate
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Cartoon depicting the heterotrimeric G-protein activation/deactivation cycle in the context of GPCR signaling
1288:
1184:
684:
458:
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of the first GPCR, rhodopsin, in 2000 and the crystal structure of the first GPCR with a diffusible ligand (β
3565:
3030:
Wettschureck N, Offermanns S (October 2005). "Mammalian G proteins and their cell type specific functions".
1462:, which are now free to modulate the activity of other intracellular proteins. The extent to which they may
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3566:"GPCR-CA: A cellular automaton image approach for predicting G-protein-coupled receptor functional classes"
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When a ligand binds to the GPCR it causes a conformational change in the GPCR, which allows it to act as a
5460:"The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis"
1078:
GPCRs respond to extracellular signals mediated by a huge diversity of agonists, ranging from proteins to
1075:
pathways) are also targeted to lipid rafts, this has the effect of facilitating rapid receptor signaling.
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6409:
6389:
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4615:"Distinct conformations of GPCR-β-arrestin complexes mediate desensitization, signaling, and endocytosis"
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its α subunit upon activation could inhibit the activity of an enzyme or other intracellular metabolism.
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GPCRs include one or more receptors for the following ligands: sensory signal mediators (e.g., light and
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classification system based on GPCR fingerprints. Identification of the superfamily members across the
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2229:) are activated by the signal chain coming from the G protein (that was activated by the receptor) via
2198:
2013:
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1041:
966:
945:. Click the image for higher resolution to see details regarding the locations of important structures.
886:
811:
563:
216:
43:
4080:
Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, et al. (November 2007).
2756:"High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor"
2754:
Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, et al. (November 2007).
803:. GPCRs are also involved in immune-modulation, e. g. regulating interleukin induction or suppressing
9256:
7423:
7418:
7413:
7183:
7069:
6897:
6879:
6860:
6853:
6372:
6307:
6088:
4082:"GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function"
3998:
2337:
2181:
The effects of Ca are also remarkable: it cooperates with DAG in activating PKC and can activate the
2005:
1947:-containing proteins) may also act as signal transducers. Most often the effector is a member of the
1587:
1565:
is an example of a cellular protein that can be regulated by a G protein, in this case the G protein
1491:
849:
708:
168:
5074:"Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation"
5072:
Smith JS, Nicholson LT, Suwanpradid J, Glenn RA, Knape NM, Alagesan P, et al. (November 2018).
1745:, or AC. While there are ten different AC gene products in mammals, each with subtle differences in
1071:. As many of the downstream transducer and effector molecules of GPCRs (including those involved in
676:) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B.
173:
8978:
8847:
8807:
8453:
7377:
7339:
7198:
6987:
6911:
6865:
6355:
6232:
6201:
5816:
2659:
2630:
1968:
1940:
1434:
1350:
1152:
595:
585:
478:
4251:
Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, Leslie AG, et al. (January 2011).
3692:) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes"
2396:(β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both
1086:, but all transduce this signal via a mechanism of G-protein coupling. This is made possible by a
7711:
7706:
7701:
7696:
7691:
7651:
7646:
7563:
7558:
7553:
7543:
7409:
7293:
7261:
7256:
7218:
7213:
7124:
6848:
6098:
6046:
5963:, a database of 3D structural models of all human G-protein coupled receptors, built by the GPCR-
2443:
buds inwardly as a result of interactions between the molecules of clathrin, in a process called
2052:
2044:
1788:
1615:
1148:
1021:
770:
5205:"G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels"
2439:. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the
373:
There are two principal signal transduction pathways involving the G protein-coupled receptors:
7364:
7359:
7276:
7271:
6870:
6471:
6466:
6219:
6077:
4729:
Thomsen AR, Plouffe B, Cahill TJ, Shukla AK, Tarrasch JT, Dosey AM, et al. (August 2016).
3993:
3784:
Hazell GG, Hindmarch CC, Pope GR, Roper JA, Lightman SL, Murphy D, et al. (January 2012).
2613:
2163:
2081:
1984:
1900:
1896:
1892:
1811:
1757:
1685:
1661:
1555:
1446:
1370:
796:
430:
405:
5276:
5162:
Duchene J, Schanstra JP, Pecher C, Pizard A, Susini C, Esteve JP, et al. (October 2002).
917:). However, these 7TMH (7-transmembrane helices) receptors and channels do not associate with
9241:
8909:
7747:
7731:
7726:
7721:
7687:
7642:
7539:
7402:
7397:
7349:
7252:
7247:
7034:
6918:
6761:
6756:
6751:
6740:
6735:
6730:
6725:
6476:
6461:
6338:
6050:
5822:
5709:
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003).
4778:
Nguyen AH, Thomsen AR, Cahill TJ, Huang R, Huang LY, Marcink T, et al. (December 2019).
4672:
Kumari P, Srivastava A, Banerjee R, Ghosh E, Gupta P, Ranjan R, et al. (November 2016).
3505:
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003).
3068:
Hauser AS, Chavali S, Masuho I, Jahn LJ, Martemyanov KA, Gloriam DE, Babu MM (January 2018).
2709:
2585:
1851:
1823:
1599:
1573:
1442:
1374:
1354:
1310:
970:
548:
401:
343:
292:
4613:
Cahill TJ, Thomsen AR, Tarrasch JT, Plouffe B, Nguyen AH, Yang F, et al. (March 2017).
2683:
split is based on presumed function rather than signature, as the classical Class B (7tm_2,
8959:
8617:
7929:
7752:
7737:
7314:
7267:
6944:
6923:
6708:
6703:
6698:
6693:
6688:
6281:
6151:
5722:
5624:
5471:
5216:
4932:
4685:
4626:
4534:
4431:
4378:
4321:
4264:
4253:"The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor"
4207:
4150:
4137:
Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, et al. (January 2011).
4093:
4038:
3985:
3885:
3518:
3459:
2947:
2767:
2671:. Insect GPCRs appear to be in their own group and Taste2 is identified as descending from
2369:
2139:
2069:
2025:
1880:
1677:
1667:). Each sub-class of G-protein consists of multiple proteins, each the product of multiple
1595:
1459:
954:
902:
740:
625:
526:
385:
199:
7603:
7598:
7593:
5123:"Social senses: G-protein-coupled receptor signaling pathways in Dictyostelium discoideum"
4980:"Activation of G protein-coupled receptors entails cysteine modulation of agonist binding"
2485:
At any point in this process, the β-arrestins may also recruit other proteins—such as the
981:), which instead interact with the extracellular loops, or, as illustrated by the class C
885:), was solved. In 2007, the first structure of a human GPCR was solved This human
101:
8:
8782:
7717:
7608:
7392:
7355:
6820:
6449:
6381:
6209:
6093:
6073:
5203:
Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG (November 2000).
4365:
Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, et al. (July 2011).
4194:
Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, et al. (January 2011).
3927:
Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC (January 2014).
2609:
2320:
As mentioned above, G-proteins may terminate their own activation due to their intrinsic
1776:, and vice versa. The level of cytosolic cAMP may then determine the activity of various
1398:
1346:
994:
906:
853:
567:
17:
5726:
5628:
5475:
5220:
4936:
4689:
4630:
4538:
4435:
4382:
4325:
4268:
4211:
4154:
4097:
4042:
3989:
3889:
3522:
3463:
3005:
2951:
2771:
1606:
molecules. Currently, GPCRs are considered to utilize two primary types of transducers:
9001:
8512:
8336:
7448:
7443:
7438:
7372:
6747:
6720:
6457:
6103:
5995:
5970:
5891:
5866:
5865:
Munk C, Isberg V, Mordalski S, Harpsøe K, Rataj K, Hauser AS, et al. (July 2016).
5648:
5597:
5543:
5518:
5458:
Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS (March 1999).
5323:
5237:
5204:
5098:
5073:
5049:
5022:
4955:
4920:
4901:
4853:
4828:
4804:
4779:
4755:
4730:
4706:
4673:
4649:
4614:
4502:
4477:
4455:
4399:
4366:
4342:
4309:
4285:
4252:
4228:
4195:
4171:
4138:
4119:
4062:
3953:
3928:
3909:
3858:
3810:
3785:
3766:
3718:
3687:
3593:
3482:
3447:
3397:
3165:
3140:
3094:
3069:
2971:
2906:
2881:
2827:
2788:
2755:
2535:
2341:
2009:
1792:
1591:
1495:
1302:
GPCRs that act as receptors for stimuli that have not yet been identified are known as
804:
792:
704:
570:. The very large rhodopsin A group has been further subdivided into 19 subgroups (
544:
327:, although a spontaneous auto-activation of an empty receptor has also been observed.
316:
23:
Class of cell surface receptors coupled to G-protein-associated intracellular signaling
5745:
5710:
5584:
5567:
5354:
5228:
5139:
5122:
5023:"Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma"
4995:
3541:
3506:
3310:
Attwood TK, Findlay JB (February 1994). "Fingerprinting G-protein-coupled receptors".
3287:
3277:
3260:
2142:
signal pathway, the extracellular signal molecule binds with the G-protein receptor (G
311:
seven times in the form of six loops (three extracellular loops interacting with
8867:
8811:
8457:
8187:
8182:
7637:
7334:
6683:
6237:
6119:
6000:
5896:
5750:
5687:
5640:
5589:
5548:
5499:
5494:
5459:
5440:
5399:
5358:
5315:
5280:
5242:
5185:
5144:
5103:
5054:
4960:
4893:
4858:
4809:
4760:
4711:
4654:
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4507:
4447:
4404:
4347:
4290:
4233:
4176:
4111:
4054:
4011:
3958:
3901:
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3815:
3758:
3723:
3668:
3633:
3585:
3546:
3487:
3389:
3354:
3327:
3292:
3211:
3170:
3099:
3047:
3009:
2963:
2911:
2841:
2831:
2793:
2471:
2463:
2408:. Because only the liganded receptor is desensitized by this mechanism, it is called
2230:
2103:
2094:(Ri); stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi);
1854:. Once bound to GTP, Rho can then go on to activate various proteins responsible for
1834:
where it may activate any membrane localized forms of a second ser/thr kinase called
1636:
1562:
1510:
1499:
1334:
1072:
673:
555:
537:
533:
450:
207:
149:
5601:
5327:
4905:
4459:
3862:
3770:
3415:
3401:
2687:
76:
7662:
7584:
7434:
6042:
5990:
5982:
5886:
5878:
5740:
5730:
5679:
5652:
5632:
5579:
5538:
5530:
5489:
5479:
5430:
5389:
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5307:
5272:
5232:
5224:
5175:
5134:
5093:
5085:
5044:
5034:
4991:
4950:
4940:
4885:
4848:
4840:
4799:
4791:
4750:
4742:
4701:
4693:
4644:
4634:
4585:
4577:
4542:
4497:
4489:
4439:
4394:
4386:
4337:
4329:
4280:
4272:
4223:
4215:
4166:
4158:
4123:
4101:
4066:
4046:
4003:
3948:
3940:
3913:
3893:
3842:
3805:
3797:
3750:
3713:
3703:
3660:
3625:
3577:
3536:
3526:
3477:
3467:
3381:
3319:
3282:
3272:
3203:
3160:
3152:
3089:
3081:
3039:
3001:
2975:
2955:
2901:
2893:
2823:
2816:"Chapter Three - Obestatin Receptor in Energy Homeostasis and Obesity Pathogenesis"
2783:
2775:
2510:
2423:. GRKs may also have GAP domains and so may contribute to inactivation through non-
2345:
2254:
2226:
2175:
2099:
2095:
2091:
1835:
1784:
1746:
1742:
1566:
869:
754:
486:
423:
416:
409:
359:
339:
195:
5842:. University of Edinburgh / International Union of Basic and Clinical Pharmacology
4889:
3597:
1883:–signalling, which can also be important, in particular in the case of activated G
161:
137:
89:
9055:
8842:
8651:
7940:
7622:
7589:
7329:
6626:
6611:
6606:
6601:
6591:
6586:
6581:
6576:
6571:
5960:
5953:
5829:
5774:
Reference for molecular and mathematical models for the initial receptor response
4007:
3833:
Dorsam RT, Gutkind JS (February 2007). "G-protein-coupled receptors and cancer".
3472:
2731:
2714:
2448:
2440:
2377:
2365:
2329:
2206:
2147:
2133:
1831:
1803:
1632:
1403:
1303:
1296:
1079:
1017:
990:
562:. Despite the lack of sequence homology between classes, all GPCRs have a common
559:
113:
47:
4731:"GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling"
3801:
3207:
8928:
7788:
7616:
6843:
6636:
6631:
6621:
6597:
6567:
6562:
5715:
Proceedings of the
National Academy of Sciences of the United States of America
5464:
Proceedings of the
National Academy of Sciences of the United States of America
4925:
Proceedings of the
National Academy of Sciences of the United States of America
4746:
4619:
Proceedings of the
National Academy of Sciences of the United States of America
4308:
Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, et al. (April 2011).
3944:
3664:
3511:
Proceedings of the
National Academy of Sciences of the United States of America
3085:
3043:
2897:
2880:
Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A, Filipek S (2012).
2553:
2522:
2214:
2167:
1887:-coupled GPCRs. The primary effectors of Gβγ are various ion channels, such as
1839:
1672:
1619:
1467:
1450:
1438:
1252:
1204:
1192:
1176:
1160:
1048:
865:
669:
300:
288:
244:
5986:
5311:
5089:
4795:
3323:
1024:
of the intracellular surface for the binding of scaffolding proteins called β-
868:
to stabilize the receptor structure. Some seven-transmembrane helix proteins (
518:
The exact size of the GPCR superfamily is unknown, but at least 831 different
9230:
8983:
8632:
8627:
8622:
7548:
7484:
6552:
6167:
4478:"Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers"
4196:"Structure and function of an irreversible agonist-β(2) adrenoceptor complex"
3708:
3629:
2882:"Action of molecular switches in GPCRs--theoretical and experimental studies"
2648:
2547:
2506:
2325:
2151:
1944:
1931:. Such signaling has been shown to be physiologically relevant, for example,
1713:
1631:
There are three main G-protein-mediated signaling pathways, mediated by four
1475:
1272:
1232:
857:
780:
482:
308:
37:
5912:
5735:
5683:
4945:
4639:
4546:
4333:
4106:
4081:
3531:
2959:
2779:
1700:
of Gα may activate another if the preferred is less available. Furthermore,
8905:
7303:
7297:
6907:
6892:
6715:
6482:
6004:
5900:
5754:
5691:
5593:
5552:
5534:
5503:
5484:
5444:
5435:
5418:
5362:
5319:
5284:
5246:
5189:
5180:
5163:
5107:
5058:
4964:
4897:
4862:
4813:
4780:"Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex"
4764:
4715:
4658:
4599:
4511:
4451:
4408:
4351:
4294:
4237:
4180:
4115:
4058:
4015:
3962:
3905:
3854:
3819:
3762:
3727:
3672:
3637:
3589:
3550:
3491:
3393:
3296:
3215:
3174:
3103:
3051:
2992:
Gilman AG (1987). "G proteins: transducers of receptor-generated signals".
2967:
2915:
2845:
2797:
2502:
2444:
2432:
2171:
1855:
1847:
1717:
1530:. Integrin signaling will phosphorylate FAK, which can then decrease GPCR G
1329:
Crystal structure of activated beta-2 adrenergic receptor in complex with G
1264:
1248:
1224:
1172:
1156:
1064:
821:
Cell density sensing: A novel GPCR role in regulating cell density sensing.
800:
784:
601:
591:
498:
5644:
5403:
5148:
5039:
4581:
4554:
4139:"Structure of a nanobody-stabilized active state of the β(2) adrenoceptor"
3358:
3331:
3013:
2814:
Zhang, Jian V.; Li, Lei; Huang, Qingsheng; Ren, Pei-Gen (1 January 2013).
2560:. This so-called constitutive receptor is formed by heterodimerization of
2249:, this phosphorylation results in the switching of the coupling from the G
1994:
1445:(GDP) (or, alternatively, no guanine nucleotide) but active when bound to
743:
bind odorants (olfactory receptors) and pheromones (vomeronasal receptors)
346:
that bind and activate these receptors include light-sensitive compounds,
16:"GPCR" redirects here. For the Great Proletarian Cultural Revolution, see
4844:
4493:
3192:
3119:"The Nobel Prize in Chemistry 2012 Robert J. Lefkowitz, Brian K. Kobilka"
2654:
2479:
2467:
2460:
2452:
2349:
1815:
1561:
Further signal transduction depends on the type of G protein. The enzyme
1200:
1188:
1180:
1060:
1037:
958:
875:
In 2000, the first crystal structure of a mammalian GPCR, that of bovine
6041:
5394:
5377:
4697:
4443:
4390:
4276:
4219:
4162:
4050:
3897:
3754:
2086:
The cAMP signal transduction contains five main characters: stimulative
1325:
9207:
9123:
8350:
6276:
6187:
5668:
5568:"A trafficking checkpoint controls GABA(B) receptor heterodimerization"
2625:
2490:
2397:
2389:
2353:
co-GEF) further contributing to the time resolution of GPCR signaling.
2234:
2186:
2016:), as well as modulation of various other "accessory" proteins such as
1965:
1928:
1843:
1738:
1709:
1607:
1603:
1580:
1471:
1284:
1268:
1256:
1240:
1236:
1144:
1140:
1068:
1056:
1029:
962:
950:
942:
926:
922:
828:
639:
552:
125:
6337:
5882:
5762:
4674:"Functional competence of a partially engaged GPCR-β-arrestin complex"
4590:
3581:
3385:
3345:
Kolakowski LF (1994). "GCRDb: a G-protein-coupled receptor database".
3156:
881:
872:) that resemble GPCRs may contain ion channels, within their protein.
509:
8916:
8837:
6359:
5860:
Data, diagrams and web tools for G protein-coupled receptors (GPCRs).
5855:
5519:"G-protein-coupled receptor phosphorylation: where, when and by whom"
3601:
3446:
Krishnan A, Almén MS, Fredriksson R, Schiöth HB (2012). Xue C (ed.).
2427:
mechanisms as well. A combination of these mechanisms may also occur.
2385:
2296:
2210:
2001:
1760:(ATP) to cAMP, and all are directly stimulated by G-proteins of the G
1754:
1551:
1424:
1220:
1216:
1212:
1208:
1132:
1128:
1112:
1013:
918:
876:
788:
774:
766:
758:
733:
732:
The gustatory sense (taste): GPCRs in taste cells mediate release of
712:
655:
397:
351:
331:
320:
304:
50:
4921:"Some G protein heterotrimers physically dissociate in living cells"
4367:"Crystal structure of the β2 adrenergic receptor-Gs protein complex"
3846:
2584:
R2 in heterologous systems leads to retention of the subunit in the
2220:
901:
GPCRs exhibit a similar structure to some other proteins with seven
9141:
9119:
6183:
5964:
5867:"GPCRdb: the G protein-coupled receptor database - an introduction"
2728:, a technique for control of cell signaling through synthetic GPCRs
2719:
2668:
2642:
2475:
2436:
2393:
2286:
2060:
There are two principal signal transduction pathways involving the
1973:
despite the absence of the associated G protein α- and β-subunits.
1932:
1920:
1750:
1701:
1611:
1586:
The signaling pathways activated through a GPCR are limited by the
1523:
1522:
GPCRs downstream signals have been shown to possibly interact with
1515:
1397:
It is believed that a receptor molecule exists in a conformational
1292:
1228:
1196:
1136:
1052:
1025:
949:
In terms of structure, GPCRs are characterized by an extracellular
937:
861:
762:
665:
635:
296:
108:
5636:
2036:
1764:
class. In contrast, however, interaction with Gα subunits of the G
1313:
of GPCRs typically bind within the transmembrane domain. However,
1102:
898:
confirmed that the Gα binds to a cavity created by this movement.
8212:
7922:
7917:
7912:
7907:
7902:
7897:
7892:
7887:
7882:
7877:
7872:
7867:
7862:
7857:
7852:
7847:
7842:
7837:
7533:
7528:
7523:
7518:
3686:
Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL (December 2019).
3116:
2921:
2879:
2612:
mediated by the superfamily of GPCRs dates back to the origin of
2601:
R1 causes masking of a retention signal of functional receptors.
2456:
2087:
1697:
1689:
1542:
1482:
1463:
1455:
1317:
are activated by cleavage of part of their extracellular domain.
1087:
1083:
986:
978:
974:
914:
910:
723:
716:
367:
363:
355:
324:
120:
5417:
Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG (July 2000).
4079:
3926:
2753:
2604:
1768:
type inhibits AC from generating cAMP. Thus, a GPCR coupled to G
9094:
9089:
9084:
9079:
9069:
9064:
9059:
9050:
8995:
8990:
8952:
8947:
8942:
8904:
8787:
8763:
8758:
8753:
8748:
8743:
8738:
8733:
8728:
8723:
8718:
8713:
8708:
8703:
8698:
8693:
8688:
8683:
8605:
8600:
8595:
8590:
8527:
8522:
8517:
8425:
8370:
8365:
8360:
8331:
8312:
8307:
8302:
8297:
8292:
8287:
8282:
8277:
8272:
8267:
8262:
8257:
8252:
8247:
8242:
8237:
8232:
8227:
8222:
8217:
8207:
8202:
8197:
8192:
8172:
7832:
7827:
7822:
7817:
7812:
7807:
7802:
7513:
7508:
7503:
7498:
7463:
7154:
6977:
6971:
6541:
6536:
6526:
6521:
5711:"The G protein-coupled receptor repertoires of human and mouse"
4876:
Brass LF (September 2003). "Thrombin and platelet activation".
3507:"The G protein-coupled receptor repertoires of human and mouse"
3445:
2569:
2561:
2424:
2381:
2321:
2300:
2155:
1594:
of the GPCR itself but ultimately determined by the particular
1164:
1009:
747:
529:
312:
249:
227:
5376:
Krueger KM, Daaka Y, Pitcher JA, Lefkowitz RJ (January 1997).
5071:
4979:
4250:
2501:(MAPK) signaling through, for example, phosphorylation of the
1654:
1647:
1640:
860:. These extracellular loops also contain two highly conserved
9190:
8881:
8876:
8678:
8673:
8668:
8663:
8639:
8585:
8580:
8575:
8420:
8415:
8405:
8400:
8341:
8167:
8162:
8157:
8152:
8147:
8142:
8137:
8132:
8127:
8122:
8117:
8112:
8107:
8102:
8097:
8092:
8087:
8082:
8077:
8072:
8067:
8062:
8057:
8052:
8047:
8042:
8037:
8032:
8027:
8022:
8017:
8012:
8007:
8002:
7997:
7992:
7987:
7982:
7977:
7972:
7493:
7458:
7308:
7148:
7143:
7138:
7133:
7128:
7114:
7108:
7103:
7098:
7093:
7088:
7083:
7078:
7073:
7063:
7058:
7053:
7048:
7043:
7038:
7006:
6966:
6961:
6884:
6796:
6791:
6786:
6781:
6776:
6771:
6531:
6516:
6511:
6506:
6501:
6496:
6491:
6486:
4671:
4028:
3875:
2925:
Text was copied from this source, which is available under a
2621:
2617:
2514:
2400:
hinder G-protein coupling as well as initiate the process of
1960:
1936:
1827:
1668:
1415:
1244:
1168:
832:
750:
700:
647:
522:
519:
370:. G protein-coupled receptors are involved in many diseases.
335:
5375:
5161:
4612:
4310:"Structure of an agonist-bound human A2A adenosine receptor"
3975:
736:
in response to bitter-, umami- and sweet-tasting substances.
9185:
9180:
9175:
9170:
9165:
9160:
9155:
9150:
9145:
8563:
8556:
8551:
8546:
8355:
8345:
7967:
7962:
7957:
7952:
7612:
7488:
6982:
6286:
5935:
2684:
2275:
Phosphorylation of the receptor can have two consequences:
1948:
1907:
1527:
646:
More recently, an alternative classification system called
347:
189:
132:
96:
83:
71:
9117:
5864:
4919:
Digby GJ, Lober RM, Sethi PR, Lambert NA (November 2006).
4728:
1906:, as well as some isoforms of AC and PLC, along with some
1449:(GTP). Upon receptor activation, the GEF domain, in turn,
1410:
8380:
5297:
2466:. At this point, the adapter molecules and clathrin have
4777:
4421:
3783:
2392:
tail. Upon GRK phosphorylation, the GPCR's affinity for
2315:
1353:
complex. Binding of an agonist to the GPCR results in a
5708:
4524:
4364:
4193:
4136:
3504:
3371:
3067:
2820:
Progress in
Molecular Biology and Translational Science
2201:, in which the activated GPCR is downregulated; and 2)
1995:
GPCR-independent signaling by heterotrimeric G-proteins
1806:(PLCβ), which catalyzes the cleavage of membrane-bound
1433:
domain may be bound to an also inactive α-subunit of a
1008:
proteins. In particular, the C-terminus often contains
303:
and activate cellular responses. They are coupled with
5565:
5457:
5416:
4918:
3029:
2324:
capability. However, this reaction proceeds at a slow
2127:
3117:
Royal Swedish Academy of Sciences (10 October 2012).
941:
Two-dimensional schematic of a generic GPCR set in a
5202:
5120:
2937:
2031:
5836:"IUPHAR/BPS Guide to PHARMACOLOGY Database (GPCRs)"
5300:
High Blood Pressure & Cardiovascular Prevention
5262:
3685:
3132:
3110:
3025:
3023:
932:
532:) have been predicted to code for them from genome
5968:
5614:
1913:
1889:G-protein-regulated inwardly rectifying K channels
1830:release from the ER, while DAG diffuses along the
1357:in the receptor that is transmitted to the bound G
1059:, and has the effect of targeting the receptor to
4977:
4829:"The year in G protein-coupled receptor research"
4567:
3740:
2875:
2873:
2871:
2869:
2867:
2221:Phosphorylation by cAMP-dependent protein kinases
1067:-rich microdomains of the plasma membrane called
856:. The extracellular parts of the receptor can be
746:Behavioral and mood regulation: Receptors in the
9228:
5969:Zhang J, Yang J, Jang R, Zhang Y (August 2015).
5566:Margeta-Mitrovic M, Jan YN, Jan LY (July 2000).
5340:
5121:Kim JY, Haastert PV, Devreotes PN (April 1996).
4475:
4471:
4469:
3020:
2593:functional receptor. It has been shown that GABA
2451:due to the actions of two other proteins called
2435:, which in turn recruits another protein called
1626:
852:that possess seven membrane-spanning domains or
810:Autonomic nervous system transmission: Both the
501:) act by targeting G protein-coupled receptors.
396:(GEF). The GPCR can then activate an associated
5664:
5662:
5258:
5256:
4476:Qin K, Dong C, Wu G, Lambert NA (August 2011).
4307:
3614:
3441:
3439:
3437:
3188:
3186:
3184:
2813:
2749:
2747:
2726:Receptor activated solely by a synthetic ligand
2291:: The phosphorylated receptor can be linked to
1635:of G-proteins distinguished from each other by
1047:A final common structural theme among GPCRs is
4073:
4022:
3929:"Insights into the structure of class B GPCRs"
3309:
2864:
2722:, a class of drug candidates targeted at GPCRs
2056:The effect of Ri and Gi in cAMP signal pathway
2048:The effect of Rs and Gs in cAMP signal pathway
2040:Activation effects of cAMP on protein kinase A
1772:counteracts the actions of a GPCR coupled to G
1550:If a receptor in an active state encounters a
1385:dimer and from the receptor. The dissociated G
330:G protein-coupled receptors are found only in
6323:
6027:
4466:
3869:
3832:
3063:
3061:
2987:
2985:
2605:Origin and diversification of the superfamily
1935:signaling mediated by the chemokine receptor
1879:The above descriptions ignore the effects of
824:Homeostasis modulation (e.g., water balance).
248:The seven-transmembrane α-helix structure of
5659:
5559:
5510:
5451:
5410:
5334:
5291:
5265:Annual Review of Pharmacology and Toxicology
5253:
5196:
4912:
4869:
4826:
4820:
4771:
4722:
4665:
4606:
4561:
4415:
4358:
4301:
4244:
4187:
4130:
3969:
3920:
3777:
3696:ACS Pharmacology & Translational Science
3644:
3608:
3563:
3434:
3258:
3181:
2744:
2620:, and have been classified according to the
2185:pathway, in which calcium-modulated protein
1377:which in turn triggers the dissociation of G
1361:subunit of the heterotrimeric G protein via
449:breakthroughs involved determination of the
6354:
5608:
5369:
5020:
4518:
3650:
2931:
2927:Attribution 2.5 Generic (CC BY 2.5) licence
2809:
2807:
2690:) is used to identify both in the studies.
2541:
2528:
2474:back to the plasma membrane or targeted to
1055:(Cys) residues via addition of hydrophobic
465:Seven years later, the crystallization of β
443:
362:, and vary in size from small molecules to
265:seven-(pass)-transmembrane domain receptors
8452:
6330:
6316:
6034:
6020:
3344:
3058:
2982:
2263:
2022:guanine-nucleotide dissociation inhibitors
36:
5994:
5890:
5815:at the U.S. National Library of Medicine
5744:
5734:
5583:
5542:
5493:
5483:
5434:
5393:
5277:10.1146/annurev.pharmtox.44.101802.121558
5236:
5179:
5138:
5097:
5048:
5038:
4954:
4944:
4852:
4803:
4784:Nature Structural & Molecular Biology
4754:
4705:
4648:
4638:
4589:
4501:
4398:
4341:
4284:
4227:
4170:
4105:
3997:
3952:
3809:
3717:
3707:
3540:
3530:
3481:
3471:
3286:
3276:
3164:
3093:
2905:
2787:
2667:GPCR receptor family before the split of
1866:also couple to other sub-classes, often G
1514:Proposed downstream interactions between
323:-like family). They are all activated by
6228:Serine/threonine-specific protein kinase
5909:"G Protein-Coupled Receptors on the NET"
4984:Journal of Molecular Structure: Theochem
3138:
2804:
2447:. Once the pit has been pinched off the
2051:
2043:
2035:
1787:(PKA) family. Thus cAMP is considered a
1541:
1509:
1414:
1324:
1320:
1101:
936:
508:
289:group of evolutionarily related proteins
243:
3070:"Pharmacogenomics of GPCR Drug Targets"
1494:, or GAP. In fact, many of the primary
1490:, or RGS proteins, which are a type of
1411:G-protein activation/deactivation cycle
807:-induced immune responses from T cells.
9229:
7480:Luteinizing hormone/choriogonadotropin
2991:
2225:Cyclic AMP-dependent protein kinases (
2192:
2075:
1976:In mammalian cells, the much-studied β
1919:G-protein-dependent signaling such as
1486:allosteric modulating proteins called
1028:(β-arr). Once bound, β-arrestins both
715:, for example, uses the conversion of
690:
9116:
8903:
8484:Brain-specific angiogenesis inhibitor
8451:
6353:
6311:
6015:
5516:
4875:
4827:Millar RP, Newton CL (January 2010).
3564:Xiao X, Wang P, Chou KC (July 2009).
3422:from the original on 21 February 2008
2336:that, when bound to Gα through their
2316:Mechanisms of GPCR signal termination
2160:phosphatidylinositol 4,5-bisphosphate
1808:phosphatidylinositol 4,5-bisphosphate
843:
739:The sense of smell: Receptors of the
6292:Lipoprotein receptor-related protein
5793:from the original on 18 October 2012
2852:from the original on 17 January 2023
2700:G protein-coupled receptors database
2616:. Mammalian-like GPCRs are found in
2146:) on the cell surface and activates
1546:G-protein-coupled receptor mechanism
799:and engage target cell types in the
547:, while the remaining receptors are
5781:"The Nobel Prize in Chemistry 2012"
5423:The Journal of Biological Chemistry
5382:The Journal of Biological Chemistry
5168:The Journal of Biological Chemistry
3259:Joost P, Methner A (October 2002).
3006:10.1146/annurev.bi.56.070187.003151
2653:cAMP receptors before the split of
2162:(PIP2) into two second messengers:
2128:Phosphatidylinositol signal pathway
1862:(ROCK). Most GPCRs that couple to G
1429:When the receptor is inactive, the
909:and adiponectin receptors 1 and 2 (
13:
5702:
4978:Rubenstein LA, Lanzara RG (1998).
3933:Trends in Pharmacological Sciences
3570:Journal of Computational Chemistry
2828:10.1016/B978-0-12-386933-3.00003-0
2270:G protein-coupled receptor kinases
2164:inositol 1,4,5-trisphosphate (IP3)
1810:(PIP2) into the second messengers
965:. The GPCR arranges itself into a
394:guanine nucleotide exchange factor
14:
9278:
5806:
3278:10.1186/gb-2002-3-11-research0063
2509:, or recruit the proteins of the
2032:Details of cAMP and PIP2 pathways
1602:, as well as the availability of
1488:regulators of G-protein signaling
1466:, however, is limited due to the
1122:
1036:) pathway activation or receptor
929:, whereas ADIPORs are inverted).
616:Fungal mating pheromone receptors
504:
8833:Growth-hormone-releasing hormone
5021:Teoh CM, Tam JK, Tran T (2012).
5002:from the original on 16 May 2011
2920:
2576:subunits. Expression of the GABA
2499:mitogen-activated protein kinase
1874:
983:metabotropic glutamate receptors
933:Structure–function relationships
8793:Corticotropin-releasing hormone
6136:Metabotropic glutamate receptor
5871:British Journal of Pharmacology
5672:Molecular Biology and Evolution
5523:British Journal of Pharmacology
5155:
5114:
5065:
5014:
4971:
3826:
3790:Frontiers in Neuroendocrinology
3734:
3679:
3557:
3498:
3408:
3365:
3338:
3303:
3252:
3222:
1914:G-protein-independent signaling
1723:
7455:Gonadotropin-releasing hormone
6259:Tumor necrosis factor receptor
1812:inositol (1,4,5) trisphosphate
1749:distribution or function, all
1739:cyclic-adenosine monophosphate
1478:added to the C-termini of Gγ.
1281:gonadotropin-releasing hormone
1:
8873:Vasoactive intestinal peptide
7743:Thyrotropin-releasing hormone
6297:Progestin and adipoQ receptor
5585:10.1016/S0896-6273(00)00012-X
5355:10.1016/S0898-6568(03)00099-8
5229:10.1016/S0006-3495(00)76495-2
5140:10.1016/S1074-5521(96)90103-9
4996:10.1016/S0166-1280(98)90217-2
4890:10.1378/chest.124.3_suppl.18S
2994:Annual Review of Biochemistry
2737:
2470:, and the receptor is either
2406:clathrin-mediated endocytosis
2356:In addition, the GPCR may be
1822:found in the membrane of the
1627:G-protein-dependent signaling
1470:of Gα and the presence of an
1289:thyrotropin-releasing hormone
1185:vasoactive intestinal peptide
1151:), hepatocyte growth factor (
1090:-nucleotide exchange factor (
685:pseudo amino acid composition
459:cryogenic electron microscopy
404:bound to the G protein for a
184:Available protein structures:
4008:10.1126/science.289.5480.739
3743:Journal of Leukocyte Biology
3473:10.1371/journal.pone.0029817
2705:List of MeSH codes (D12.776)
2487:non-receptor tyrosine kinase
2421:heterologous desensitization
2203:heterologous desensitization
2090:receptor (Rs) or inhibitory
1614:. Because β-arr's have high
1537:
1505:
1315:protease-activated receptors
1277:follicle-stimulating hormone
1097:
46:in complex with the partial
7:
9237:G protein-coupled receptors
7658:Prolactin-releasing peptide
6343:G protein-coupled receptors
6272:-Acetylglucosamine receptor
6254:Asialoglycoprotein receptor
6084:Protease-activated receptor
5813:G-protein-coupled+receptors
3802:10.1016/j.yfrne.2011.07.002
3688:"Cannabinoid Receptor 2 (CB
3653:Protein and Peptide Letters
3208:10.1016/j.ygeno.2006.04.001
2886:Current Medicinal Chemistry
2693:
2360:itself. This can occur as:
1954:
1598:stabilized by a particular
1437:. These "G-proteins" are a
1267:); peptide hormones (e.g.,
525:(or about 4% of the entire
257:G protein-coupled receptors
10:
9283:
9247:Integral membrane proteins
6264:Immunoglobulin superfamily
6059:G protein-coupled receptor
4747:10.1016/j.cell.2016.07.004
3945:10.1016/j.tips.2013.11.001
3665:10.2174/092986610791112693
3086:10.1016/j.cell.2017.11.033
3044:10.1152/physrev.00003.2005
2898:10.2174/092986712799320556
2818:. In Tao, Ya-Xiong (ed.).
2545:
2410:homologous desensitization
2253:class of G-protein to the
2199:homologous desensitization
2170:(DAG). IP3 binds with the
2150:, which is located on the
2131:
2079:
2062:G protein-linked receptors
1842:activates proteins called
1780:as well as members of the
1729:The effector of both the G
1458:and a tightly interacting
1422:
1347:transduction of the signal
1261:platelet-activating factor
1016:(Thr) residues that, when
850:integral membrane proteins
281:G protein-linked receptors
44:beta-2 adrenergic receptor
15:
9200:
9134:
9130:
9112:
8969:
8927:
8923:
8899:
8773:
8650:
8469:
8465:
8447:
8322:
7939:
7787:
7780:
7286:
7174:
7167:
6932:
6819:
6810:
6646:
6551:
6448:
6380:
6371:
6367:
6349:
6246:
6218:
6200:
6176:
6160:
6144:
6128:
6112:
6089:Neurotransmitter receptor
6066:
6057:
5987:10.1016/j.str.2015.06.007
5932:"PSI GPCR Network Center"
5925:a classification of GPCRs
5312:10.1007/s40292-013-0001-8
5090:10.1126/scisignal.aaq1075
4796:10.1038/s41594-019-0330-y
3145:ACS Chemical Neuroscience
3139:Lindsley CW (June 2013).
2388:residues of IL-3 and the
2344:due to limited amount of
2209:of the intracellular (or
2006:receptor tyrosine kinases
1908:phosphoinositide-3-kinase
1904:voltage-gated Ca channels
1741:(cAMP)-generating enzyme
1492:GTPase-activating protein
1481:Because Gα also has slow
709:electromagnetic radiation
226:
206:
188:
183:
179:
167:
155:
143:
131:
119:
107:
95:
82:
70:
62:
57:
35:
30:
8979:Calcium-sensing receptor
8848:Methuselah-like proteins
6233:Receptor tyrosine kinase
6202:Ligand-gated ion channel
5817:Medical Subject Headings
5763:"GPCR Reference Library"
3709:10.1021/acsptsci.9b00049
3630:10.1016/j.ab.2009.04.009
3347:Receptors & Channels
2663:family evolved from the
2588:. Expression of the GABA
2542:Receptor oligomerization
2529:GPCR cellular regulation
2402:receptor internalization
2368:, wherein the change in
1941:subcellular localization
1846:, which in turn tosolic
1435:heterotrimeric G-protein
1351:heterotrimeric G protein
1131:stimulatory molecules);
596:Secretin receptor family
491:seven other Nobel Prizes
479:Nobel Prize in Chemistry
444:History and significance
307:. They pass through the
7125:Sphingosine-1-phosphate
7013:Hydroxycarboxylic acids
6099:Biogenic amine receptor
5959:1 February 2016 at the
5736:10.1073/pnas.0230374100
5517:Tobin AB (March 2008).
5127:Chemistry & Biology
4946:10.1073/pnas.0607116103
4833:Molecular Endocrinology
4640:10.1073/pnas.1701529114
4570:Journal of Cell Science
4547:10.1126/science.2163110
4482:Nature Chemical Biology
4334:10.1126/science.1202793
4107:10.1126/science.1150609
3618:Analytical Biochemistry
3532:10.1073/pnas.0230374100
3374:Pharmacological Reviews
3324:10.1093/protein/7.2.195
2960:10.1126/science.1083853
2780:10.1126/science.1150577
2376:(GRKs), which go on to
2374:GPCR-Regulating Kinases
2264:Phosphorylation by GRKs
2068:signal pathway and the
1704:pathways may result in
1363:protein domain dynamics
1147:, γ-aminobutyric acid (
827:Involved in growth and
753:bind several different
711:into cellular signals.
469:-adrenergic receptor (β
9006:Metabotropic glutamate
6220:Enzyme-linked receptor
6078:Prostaglandin receptor
6051:cell surface receptors
5535:10.1038/sj.bjp.0707662
5485:10.1073/pnas.96.7.3712
5436:10.1074/jbc.M002581200
5181:10.1074/jbc.M202744200
3835:Nature Reviews. Cancer
2372:allows recruitment of
2082:cAMP-dependent pathway
2057:
2049:
2041:
1985:bradykinin receptor B2
1758:adenosine triphosphate
1706:receptor modifications
1686:functional selectivity
1547:
1519:
1447:guanosine triphosphate
1420:
1342:
1108:
946:
797:inflammatory mediators
707:reaction to translate
699:The visual sense: The
606:Metabotropic glutamate
515:
293:cell surface receptors
273:heptahelical receptors
253:
9267:Protein superfamilies
7035:Lysophosphatidic acid
6339:Cell surface receptor
5684:10.1093/molbev/msr061
4678:Nature Communications
4582:10.1242/jcs.115.3.455
3032:Physiological Reviews
2710:Metabotropic receptor
2586:endoplasmic reticulum
2213:) receptor domain by
2100:protein kinase A
2055:
2047:
2039:
1983:In kidney cells, the
1824:endoplasmic reticulum
1798:The effector of the G
1785:protein kinase A
1545:
1513:
1474:moiety that has been
1443:Guanosine diphosphate
1418:
1355:conformational change
1328:
1321:Conformational change
1105:
940:
903:transmembrane domains
854:transmembrane helices
801:inflammatory response
558:or are classified as
512:
247:
8960:Vomeronasal receptor
7930:Vomeronasal receptor
6282:Transferrin receptor
5828:3 April 2015 at the
5529:(Suppl 1): S167–76.
4884:(3 Suppl): 18S–25S.
4845:10.1210/me.2009-0473
4494:10.1038/nchembio.642
3271:(11): RESEARCH0063.
3240:on 15 September 2020
2493:—which may activate
2140:phosphatidylinositol
2070:phosphatidylinositol
2026:protein phosphatases
1791:and PKA a secondary
953:, followed by seven
907:microbial rhodopsins
891:-adrenergic receptor
741:olfactory epithelium
626:Cyclic AMP receptors
386:phosphatidylinositol
277:serpentine receptors
9262:Signal transduction
8853:Parathyroid hormone
6813:signaling molecules
6210:Purinergic receptor
6094:Purinergic receptor
6074:Eicosanoid receptor
5727:2003PNAS..100.4903V
5629:1998Natur.396..679W
5476:1999PNAS...96.3712L
5395:10.1074/jbc.272.1.5
5343:Cellular Signalling
5221:2000BpJ....79.2547C
5209:Biophysical Journal
5040:10.1155/2012/341282
4937:2006PNAS..10317789D
4698:10.1038/ncomms13416
4690:2016NatCo...713416K
4631:2017PNAS..114.2562C
4539:1990Sci...248.1547L
4444:10.1038/nature01705
4436:2003Natur.423..762Y
4391:10.1038/nature10361
4383:2011Natur.477..549R
4326:2011Sci...332..322X
4277:10.1038/nature09746
4269:2011Natur.469..241W
4220:10.1038/nature09665
4212:2011Natur.469..236R
4163:10.1038/nature09648
4155:2011Natur.469..175R
4098:2007Sci...318.1266R
4051:10.1038/nature06325
4043:2007Natur.450..383R
3990:2000Sci...289..739P
3898:10.1038/nature11896
3890:2013Natur.494..185V
3755:10.1189/jlb.0712328
3523:2003PNAS..100.4903V
3464:2012PLoSO...729817K
3312:Protein Engineering
2952:2003Sci...301..361K
2772:2007Sci...318.1258C
2646:, evolved from the
2610:Signal transduction
2580:R1 without the GABA
2536:degradative enzymes
2364:a direct result of
2193:Receptor regulation
2076:cAMP signal pathway
1858:regulation such as
1818:(DAG). IP3 acts on
864:residues that form
793:histamine receptors
691:Physiological roles
568:signal transduction
545:olfactory receptors
317:amino acid residues
18:Cultural Revolution
9002:Glutamate receptor
8387:Protease-activated
6152:Pheromone receptor
6104:Olfactory receptor
5027:Journal of Allergy
3080:(1–2): 41–54.e19.
2597:R2 binding to GABA
2322:GTP→GDP hydrolysis
2239:feedback mechanism
2058:
2050:
2042:
2010:cytokine receptors
1753:the conversion of
1712:ligand under most
1592:tertiary structure
1548:
1520:
1500:adenylate cyclases
1483:GTP→GDP hydrolysis
1421:
1381:subunit from the G
1369:subunit exchanges
1343:
1109:
967:tertiary structure
947:
844:Receptor structure
705:photoisomerization
516:
400:by exchanging the
381:signal pathway and
254:
9252:Molecular biology
9224:
9223:
9220:
9219:
9216:
9215:
9108:
9107:
9104:
9103:
8895:
8894:
8891:
8890:
8443:
8442:
8439:
8438:
8435:
8434:
7776:
7775:
7163:
7162:
6806:
6805:
6305:
6304:
6238:Guanylate cyclase
6196:
6195:
6120:Secretin receptor
6043:Membrane proteins
5883:10.1111/bph.13509
5084:(555): eaaq1075.
5078:Science Signaling
4790:(12): 1123–1131.
4625:(10): 2562–2567.
4533:(4962): 1547–50.
4092:(5854): 1266–73.
3582:10.1002/jcc.21163
3386:10.1124/pr.57.2.5
3157:10.1021/cn400107y
2766:(5854): 1258–65.
2366:ligand occupation
2311:-adrenoreceptors.
2231:adenylate cyclase
2104:phosphodiesterase
1910:(PI3K) isoforms.
1804:phospholipase C-β
1743:adenylate cyclase
1673:splice variations
1637:sequence homology
1563:adenylate cyclase
1526:signals, such as
1365:. The activated G
1183:, members of the
1073:negative feedback
831:of some types of
755:neurotransmitters
729:for this purpose.
566:and mechanism of
540:between classes.
538:sequence homology
534:sequence analysis
451:crystal structure
360:neurotransmitters
340:choanoflagellates
263:), also known as
242:
241:
238:
237:
233:structure summary
9274:
9257:Protein families
9132:
9131:
9114:
9113:
8925:
8924:
8901:
8900:
8467:
8466:
8449:
8448:
7785:
7784:
7172:
7171:
7070:Lysophospholipid
6817:
6816:
6378:
6377:
6373:Neurotransmitter
6369:
6368:
6351:
6350:
6332:
6325:
6318:
6309:
6308:
6064:
6063:
6036:
6029:
6022:
6013:
6012:
6008:
5998:
5981:(8): 1538–1549.
5950:
5945:
5943:
5934:. Archived from
5927:
5922:
5920:
5911:. Archived from
5904:
5894:
5877:(14): 2195–207.
5862:
5851:
5849:
5847:
5802:
5800:
5798:
5792:
5785:
5776:
5771:
5769:
5758:
5748:
5738:
5696:
5695:
5666:
5657:
5656:
5623:(6712): 679–82.
5612:
5606:
5605:
5587:
5563:
5557:
5556:
5546:
5514:
5508:
5507:
5497:
5487:
5455:
5449:
5448:
5438:
5414:
5408:
5407:
5397:
5373:
5367:
5366:
5338:
5332:
5331:
5295:
5289:
5288:
5260:
5251:
5250:
5240:
5200:
5194:
5193:
5183:
5174:(43): 40375–83.
5159:
5153:
5152:
5142:
5118:
5112:
5111:
5101:
5069:
5063:
5062:
5052:
5042:
5018:
5012:
5011:
5009:
5007:
4975:
4969:
4968:
4958:
4948:
4931:(47): 17789–94.
4916:
4910:
4909:
4873:
4867:
4866:
4856:
4824:
4818:
4817:
4807:
4775:
4769:
4768:
4758:
4726:
4720:
4719:
4709:
4669:
4663:
4662:
4652:
4642:
4610:
4604:
4603:
4593:
4576:(Pt 3): 455–65.
4565:
4559:
4558:
4522:
4516:
4515:
4505:
4473:
4464:
4463:
4419:
4413:
4412:
4402:
4377:(7366): 549–55.
4362:
4356:
4355:
4345:
4305:
4299:
4298:
4288:
4248:
4242:
4241:
4231:
4206:(7329): 236–40.
4191:
4185:
4184:
4174:
4149:(7329): 175–80.
4134:
4128:
4127:
4109:
4077:
4071:
4070:
4026:
4020:
4019:
4001:
3999:10.1.1.1012.2275
3984:(5480): 739–45.
3973:
3967:
3966:
3956:
3924:
3918:
3917:
3884:(7436): 185–94.
3873:
3867:
3866:
3830:
3824:
3823:
3813:
3781:
3775:
3774:
3738:
3732:
3731:
3721:
3711:
3683:
3677:
3676:
3648:
3642:
3641:
3612:
3606:
3605:
3604:on 9 April 2017.
3600:. Archived from
3561:
3555:
3554:
3544:
3534:
3502:
3496:
3495:
3485:
3475:
3443:
3432:
3431:
3429:
3427:
3412:
3406:
3405:
3369:
3363:
3362:
3342:
3336:
3335:
3307:
3301:
3300:
3290:
3280:
3256:
3250:
3249:
3247:
3245:
3236:. Archived from
3226:
3220:
3219:
3190:
3179:
3178:
3168:
3136:
3130:
3129:
3127:
3125:
3114:
3108:
3107:
3097:
3065:
3056:
3055:
3027:
3018:
3017:
2989:
2980:
2979:
2935:
2929:
2924:
2919:
2909:
2877:
2862:
2861:
2859:
2857:
2811:
2802:
2801:
2791:
2751:
2675:. Note that the
2614:multicellularity
2513:directly (i.e.,
2346:second messenger
2227:protein kinase A
2176:protein kinase C
2102:(PKA); and cAMP
2096:adenylyl cyclase
2092:hormone receptor
2072:signal pathway.
1943:of GPCRs (e.g.,
1836:protein kinase C
1789:second messenger
1782:ser/thr-specific
1737:pathways is the
1588:primary sequence
1498:proteins (e.g.,
1404:inverse agonists
1304:orphan receptors
1297:endocannabinoids
991:Inverse agonists
884:
870:channelrhodopsin
560:orphan receptors
487:Robert Lefkowitz
287:), form a large
181:
180:
40:
28:
27:
9282:
9281:
9277:
9276:
9275:
9273:
9272:
9271:
9227:
9226:
9225:
9212:
9196:
9126:
9100:
8987:
8965:
8919:
8887:
8769:
8646:
8461:
8431:
8318:
7935:
7772:
7378:Cholecystokinin
7282:
7159:
6988:Free fatty acid
6928:
6812:
6811:Metabolites and
6802:
6642:
6547:
6444:
6363:
6345:
6336:
6306:
6301:
6247:Other/ungrouped
6242:
6214:
6192:
6172:
6156:
6140:
6124:
6108:
6053:
6040:
5961:Wayback Machine
5941:
5939:
5938:on 25 July 2013
5930:
5918:
5916:
5915:on 23 July 2011
5907:
5854:
5845:
5843:
5840:IUPHAR Database
5834:
5830:Wayback Machine
5809:
5796:
5794:
5790:
5783:
5779:
5767:
5765:
5761:
5705:
5703:Further reading
5700:
5699:
5667:
5660:
5613:
5609:
5564:
5560:
5515:
5511:
5456:
5452:
5429:(30): 23120–6.
5415:
5411:
5374:
5370:
5339:
5335:
5296:
5292:
5261:
5254:
5201:
5197:
5160:
5156:
5119:
5115:
5070:
5066:
5019:
5015:
5005:
5003:
4976:
4972:
4917:
4913:
4874:
4870:
4825:
4821:
4776:
4772:
4727:
4723:
4670:
4666:
4611:
4607:
4566:
4562:
4523:
4519:
4474:
4467:
4430:(6941): 762–9.
4420:
4416:
4363:
4359:
4320:(6027): 322–7.
4306:
4302:
4263:(7329): 241–4.
4249:
4245:
4192:
4188:
4135:
4131:
4078:
4074:
4037:(7168): 383–7.
4027:
4023:
3974:
3970:
3925:
3921:
3874:
3870:
3847:10.1038/nrc2069
3831:
3827:
3782:
3778:
3739:
3735:
3691:
3684:
3680:
3649:
3645:
3613:
3609:
3562:
3558:
3503:
3499:
3444:
3435:
3425:
3423:
3414:
3413:
3409:
3370:
3366:
3343:
3339:
3308:
3304:
3257:
3253:
3243:
3241:
3234:www.uniprot.org
3228:
3227:
3223:
3191:
3182:
3137:
3133:
3123:
3121:
3115:
3111:
3066:
3059:
3038:(4): 1159–204.
3028:
3021:
2990:
2983:
2946:(5631): 361–3.
2936:
2932:
2892:(8): 1090–109.
2878:
2865:
2855:
2853:
2838:
2812:
2805:
2752:
2745:
2740:
2732:TOG superfamily
2715:Orphan receptor
2696:
2607:
2600:
2596:
2591:
2583:
2579:
2573:
2565:
2557:
2550:
2544:
2531:
2459:, it is now an
2449:plasma membrane
2318:
2310:
2306:
2266:
2258:
2252:
2246:
2223:
2215:protein kinases
2207:phosphorylation
2195:
2152:plasma membrane
2148:phospholipase C
2145:
2136:
2134:IP3/DAG pathway
2130:
2084:
2078:
2034:
1997:
1979:
1957:
1916:
1886:
1877:
1869:
1865:
1832:plasma membrane
1826:(ER) to elicit
1801:
1775:
1771:
1767:
1763:
1736:
1732:
1726:
1678:βγ combinations
1665:
1658:
1651:
1644:
1629:
1570:
1540:
1533:
1508:
1454:yield a Gα-GTP
1427:
1413:
1392:
1388:
1384:
1380:
1368:
1360:
1332:
1323:
1193:biogenic amines
1125:
1100:
1080:biogenic amines
1042:desensitization
1020:, increase the
1007:
1003:
935:
897:
890:
880:
866:disulfide bonds
846:
816:parasympathetic
693:
507:
481:was awarded to
472:
468:
456:
446:
434:
427:
420:
413:
388:signal pathway.
145:OPM superfamily
53:
48:inverse agonist
24:
21:
12:
11:
5:
9280:
9270:
9269:
9264:
9259:
9254:
9249:
9244:
9239:
9222:
9221:
9218:
9217:
9214:
9213:
9211:
9210:
9204:
9202:
9198:
9197:
9195:
9194:
9188:
9183:
9178:
9173:
9168:
9163:
9158:
9153:
9148:
9138:
9136:
9128:
9127:
9110:
9109:
9106:
9105:
9102:
9101:
9099:
9098:
9092:
9087:
9082:
9073:
9067:
9062:
9053:
9048:
9042:
9037:
9032:
9027:
9022:
9017:
9012:
8999:
8993:
8985:
8981:
8975:
8973:
8967:
8966:
8964:
8963:
8957:
8956:
8955:
8950:
8945:
8934:
8932:
8921:
8920:
8897:
8896:
8893:
8892:
8889:
8888:
8886:
8885:
8879:
8870:
8865:
8859:
8850:
8845:
8840:
8835:
8830:
8824:
8819:
8814:
8805:
8799:
8790:
8785:
8779:
8777:
8771:
8770:
8768:
8767:
8761:
8756:
8751:
8746:
8741:
8736:
8731:
8726:
8721:
8716:
8711:
8706:
8701:
8696:
8691:
8686:
8681:
8676:
8671:
8666:
8656:
8654:
8648:
8647:
8645:
8644:
8643:
8642:
8637:
8636:
8635:
8630:
8625:
8610:
8609:
8608:
8603:
8598:
8593:
8588:
8583:
8578:
8568:
8567:
8566:
8561:
8560:
8559:
8554:
8549:
8534:
8533:
8532:
8531:
8530:
8525:
8520:
8505:
8504:
8503:
8502:
8501:
8496:
8491:
8475:
8473:
8463:
8462:
8445:
8444:
8441:
8440:
8437:
8436:
8433:
8432:
8430:
8429:
8423:
8418:
8409:
8403:
8398:
8393:
8384:
8378:
8373:
8368:
8363:
8358:
8353:
8348:
8339:
8334:
8332:Adrenomedullin
8328:
8326:
8320:
8319:
8317:
8316:
8310:
8305:
8300:
8295:
8290:
8285:
8280:
8275:
8270:
8265:
8260:
8255:
8250:
8245:
8240:
8235:
8230:
8225:
8220:
8215:
8210:
8205:
8200:
8195:
8190:
8185:
8180:
8175:
8170:
8165:
8160:
8155:
8150:
8145:
8140:
8135:
8130:
8125:
8120:
8115:
8110:
8105:
8100:
8095:
8090:
8085:
8080:
8075:
8070:
8065:
8060:
8055:
8050:
8045:
8040:
8035:
8030:
8025:
8020:
8015:
8010:
8005:
8000:
7995:
7990:
7985:
7980:
7975:
7970:
7965:
7960:
7955:
7945:
7943:
7937:
7936:
7934:
7933:
7927:
7926:
7925:
7920:
7915:
7910:
7905:
7900:
7895:
7890:
7885:
7880:
7875:
7870:
7865:
7860:
7855:
7850:
7845:
7840:
7835:
7830:
7825:
7820:
7815:
7810:
7805:
7794:
7792:
7782:
7778:
7777:
7774:
7773:
7771:
7770:
7764:
7759:
7750:
7745:
7740:
7735:
7729:
7724:
7715:
7709:
7704:
7699:
7694:
7685:
7679:
7674:
7669:
7660:
7655:
7649:
7640:
7635:
7629:
7620:
7606:
7601:
7596:
7587:
7582:
7576:
7567:
7561:
7556:
7551:
7546:
7537:
7531:
7526:
7521:
7516:
7511:
7506:
7501:
7496:
7491:
7482:
7477:
7472:
7467:
7461:
7452:
7446:
7441:
7432:
7427:
7421:
7416:
7410:Formyl peptide
7407:
7406:
7405:
7400:
7390:
7384:
7375:
7370:
7369:
7368:
7362:
7353:
7347:
7342:
7332:
7327:
7321:
7312:
7306:
7300:
7290:
7288:
7284:
7283:
7281:
7280:
7274:
7265:
7259:
7250:
7241:
7235:
7230:
7225:
7216:
7211:
7205:
7196:
7190:
7180:
7178:
7169:
7165:
7164:
7161:
7160:
7158:
7157:
7152:
7146:
7141:
7136:
7131:
7122:
7117:
7112:
7106:
7101:
7096:
7091:
7086:
7081:
7076:
7067:
7061:
7056:
7051:
7046:
7041:
7032:
7031:
7030:
7025:
7020:
7010:
7004:
6999:
6994:
6985:
6980:
6975:
6969:
6964:
6951:
6942:
6936:
6934:
6930:
6929:
6927:
6926:
6921:
6916:
6915:
6914:
6905:
6900:
6895:
6882:
6868:
6863:
6858:
6857:
6856:
6851:
6841:
6835:
6825:
6823:
6814:
6808:
6807:
6804:
6803:
6801:
6800:
6794:
6789:
6784:
6779:
6774:
6765:
6759:
6754:
6745:
6744:
6743:
6738:
6733:
6728:
6718:
6713:
6712:
6711:
6706:
6701:
6696:
6691:
6681:
6675:
6670:
6665:
6660:
6650:
6648:
6644:
6643:
6641:
6640:
6634:
6629:
6624:
6615:
6609:
6604:
6595:
6589:
6584:
6579:
6574:
6557:
6555:
6549:
6548:
6546:
6545:
6539:
6534:
6529:
6524:
6519:
6514:
6509:
6504:
6499:
6494:
6489:
6480:
6474:
6469:
6464:
6454:
6452:
6446:
6445:
6443:
6442:
6437:
6432:
6427:
6421:
6416:
6407:
6401:
6396:
6386:
6384:
6375:
6365:
6364:
6347:
6346:
6335:
6334:
6327:
6320:
6312:
6303:
6302:
6300:
6299:
6294:
6289:
6284:
6279:
6274:
6266:
6261:
6256:
6250:
6248:
6244:
6243:
6241:
6240:
6235:
6230:
6224:
6222:
6216:
6215:
6213:
6212:
6206:
6204:
6198:
6197:
6194:
6193:
6191:
6190:
6180:
6178:
6174:
6173:
6171:
6170:
6164:
6162:
6158:
6157:
6155:
6154:
6148:
6146:
6142:
6141:
6139:
6138:
6132:
6130:
6126:
6125:
6123:
6122:
6116:
6114:
6110:
6109:
6107:
6106:
6101:
6096:
6091:
6086:
6081:
6070:
6068:
6061:
6055:
6054:
6039:
6038:
6031:
6024:
6016:
6010:
6009:
5951:
5928:
5905:
5852:
5832:
5823:GPCR Cell Line
5820:
5808:
5807:External links
5805:
5804:
5803:
5777:
5759:
5704:
5701:
5698:
5697:
5678:(9): 2471–80.
5658:
5607:
5558:
5509:
5450:
5409:
5368:
5349:(11): 973–81.
5333:
5290:
5271:(1): 559–609.
5252:
5215:(5): 2547–56.
5195:
5154:
5113:
5064:
5013:
4970:
4911:
4868:
4819:
4770:
4741:(4): 907–919.
4721:
4664:
4605:
4560:
4517:
4465:
4414:
4357:
4300:
4243:
4186:
4129:
4072:
4021:
3968:
3919:
3868:
3825:
3776:
3733:
3702:(6): 414–428.
3689:
3678:
3643:
3607:
3576:(9): 1414–23.
3556:
3497:
3433:
3407:
3364:
3337:
3318:(2): 195–203.
3302:
3265:Genome Biology
3251:
3221:
3180:
3131:
3109:
3057:
3019:
2981:
2930:
2863:
2836:
2803:
2742:
2741:
2739:
2736:
2735:
2734:
2729:
2723:
2717:
2712:
2707:
2702:
2695:
2692:
2606:
2603:
2598:
2594:
2589:
2581:
2577:
2571:
2563:
2555:
2546:Main article:
2543:
2540:
2530:
2527:
2429:
2428:
2416:
2412:
2317:
2314:
2313:
2312:
2308:
2304:
2283:
2265:
2262:
2256:
2250:
2247:-adrenoceptors
2244:
2222:
2219:
2194:
2191:
2168:diacylglycerol
2143:
2132:Main article:
2129:
2126:
2080:Main article:
2077:
2074:
2033:
2030:
1996:
1993:
1977:
1956:
1953:
1915:
1912:
1884:
1876:
1873:
1872:
1871:
1867:
1863:
1840:allosterically
1816:diacylglycerol
1799:
1796:
1773:
1769:
1765:
1761:
1734:
1730:
1725:
1722:
1663:
1656:
1649:
1642:
1628:
1625:
1620:phosphorylated
1576:-bound state.
1568:
1539:
1536:
1531:
1507:
1504:
1468:palmitoylation
1451:allosterically
1412:
1409:
1390:
1386:
1382:
1378:
1366:
1358:
1330:
1322:
1319:
1253:prostaglandins
1205:norepinephrine
1161:neuropeptide Y
1124:
1123:Ligand binding
1121:
1099:
1096:
1049:palmitoylation
1018:phosphorylated
1005:
1001:
934:
931:
925:, cytoplasmic
895:
888:
845:
842:
841:
840:
839:transcription.
836:
825:
822:
819:
808:
779:Regulation of
777:
744:
737:
730:
692:
689:
644:
643:
629:
619:
609:
599:
589:
586:Rhodopsin-like
527:protein-coding
506:
505:Classification
503:
470:
466:
454:
445:
442:
432:
425:
418:
411:
390:
389:
382:
240:
239:
236:
235:
230:
224:
223:
210:
204:
203:
193:
186:
185:
177:
176:
171:
165:
164:
159:
153:
152:
147:
141:
140:
135:
129:
128:
123:
117:
116:
111:
105:
104:
99:
93:
92:
87:
80:
79:
74:
68:
67:
64:
60:
59:
55:
54:
41:
33:
32:
22:
9:
6:
4:
3:
2:
9279:
9268:
9265:
9263:
9260:
9258:
9255:
9253:
9250:
9248:
9245:
9243:
9240:
9238:
9235:
9234:
9232:
9209:
9206:
9205:
9203:
9199:
9192:
9189:
9187:
9184:
9182:
9179:
9177:
9174:
9172:
9169:
9167:
9164:
9162:
9159:
9157:
9154:
9152:
9149:
9147:
9143:
9140:
9139:
9137:
9133:
9129:
9125:
9121:
9115:
9111:
9096:
9093:
9091:
9088:
9086:
9083:
9081:
9077:
9074:
9071:
9068:
9066:
9063:
9061:
9057:
9054:
9052:
9049:
9046:
9043:
9041:
9038:
9036:
9033:
9031:
9028:
9026:
9023:
9021:
9018:
9016:
9013:
9011:
9007:
9003:
9000:
8997:
8994:
8992:
8988:
8982:
8980:
8977:
8976:
8974:
8972:
8968:
8961:
8958:
8954:
8951:
8949:
8946:
8944:
8941:
8940:
8939:
8936:
8935:
8933:
8930:
8926:
8922:
8918:
8914:
8911:
8907:
8902:
8898:
8883:
8880:
8878:
8874:
8871:
8869:
8866:
8863:
8860:
8858:
8854:
8851:
8849:
8846:
8844:
8841:
8839:
8836:
8834:
8831:
8828:
8825:
8823:
8820:
8818:
8815:
8813:
8809:
8806:
8803:
8800:
8798:
8794:
8791:
8789:
8786:
8784:
8781:
8780:
8778:
8776:
8772:
8765:
8762:
8760:
8757:
8755:
8752:
8750:
8747:
8745:
8742:
8740:
8737:
8735:
8732:
8730:
8727:
8725:
8722:
8720:
8717:
8715:
8712:
8710:
8707:
8705:
8702:
8700:
8697:
8695:
8692:
8690:
8687:
8685:
8682:
8680:
8677:
8675:
8672:
8670:
8667:
8665:
8661:
8658:
8657:
8655:
8653:
8649:
8641:
8638:
8634:
8631:
8629:
8626:
8624:
8621:
8620:
8619:
8616:
8615:
8614:
8611:
8607:
8604:
8602:
8599:
8597:
8594:
8592:
8589:
8587:
8584:
8582:
8579:
8577:
8574:
8573:
8572:
8569:
8565:
8562:
8558:
8555:
8553:
8550:
8548:
8545:
8544:
8543:
8540:
8539:
8538:
8535:
8529:
8526:
8524:
8521:
8519:
8516:
8515:
8514:
8511:
8510:
8509:
8506:
8500:
8497:
8495:
8492:
8490:
8487:
8486:
8485:
8482:
8481:
8480:
8477:
8476:
8474:
8472:
8468:
8464:
8459:
8455:
8450:
8446:
8427:
8424:
8422:
8419:
8417:
8413:
8410:
8407:
8404:
8402:
8399:
8397:
8394:
8392:
8388:
8385:
8382:
8379:
8377:
8374:
8372:
8369:
8367:
8364:
8362:
8359:
8357:
8354:
8352:
8349:
8347:
8343:
8340:
8338:
8335:
8333:
8330:
8329:
8327:
8325:
8321:
8314:
8311:
8309:
8306:
8304:
8301:
8299:
8296:
8294:
8291:
8289:
8286:
8284:
8281:
8279:
8276:
8274:
8271:
8269:
8266:
8264:
8261:
8259:
8256:
8254:
8251:
8249:
8246:
8244:
8241:
8239:
8236:
8234:
8231:
8229:
8226:
8224:
8221:
8219:
8216:
8214:
8211:
8209:
8206:
8204:
8201:
8199:
8196:
8194:
8191:
8189:
8186:
8184:
8181:
8179:
8176:
8174:
8171:
8169:
8166:
8164:
8161:
8159:
8156:
8154:
8151:
8149:
8146:
8144:
8141:
8139:
8136:
8134:
8131:
8129:
8126:
8124:
8121:
8119:
8116:
8114:
8111:
8109:
8106:
8104:
8101:
8099:
8096:
8094:
8091:
8089:
8086:
8084:
8081:
8079:
8076:
8074:
8071:
8069:
8066:
8064:
8061:
8059:
8056:
8054:
8051:
8049:
8046:
8044:
8041:
8039:
8036:
8034:
8031:
8029:
8026:
8024:
8021:
8019:
8016:
8014:
8011:
8009:
8006:
8004:
8001:
7999:
7996:
7994:
7991:
7989:
7986:
7984:
7981:
7979:
7976:
7974:
7971:
7969:
7966:
7964:
7961:
7959:
7956:
7954:
7950:
7947:
7946:
7944:
7942:
7938:
7931:
7928:
7924:
7921:
7919:
7916:
7914:
7911:
7909:
7906:
7904:
7901:
7899:
7896:
7894:
7891:
7889:
7886:
7884:
7881:
7879:
7876:
7874:
7871:
7869:
7866:
7864:
7861:
7859:
7856:
7854:
7851:
7849:
7846:
7844:
7841:
7839:
7836:
7834:
7831:
7829:
7826:
7824:
7821:
7819:
7816:
7814:
7811:
7809:
7806:
7804:
7801:
7800:
7799:
7796:
7795:
7793:
7790:
7786:
7783:
7781:Miscellaneous
7779:
7768:
7765:
7763:
7760:
7758:
7754:
7751:
7749:
7746:
7744:
7741:
7739:
7736:
7733:
7730:
7728:
7725:
7723:
7719:
7716:
7713:
7710:
7708:
7705:
7703:
7700:
7698:
7695:
7693:
7689:
7686:
7683:
7680:
7678:
7675:
7673:
7670:
7668:
7664:
7661:
7659:
7656:
7653:
7650:
7648:
7644:
7641:
7639:
7636:
7633:
7630:
7628:
7624:
7621:
7618:
7614:
7610:
7607:
7605:
7602:
7600:
7597:
7595:
7591:
7588:
7586:
7583:
7580:
7577:
7575:
7571:
7568:
7565:
7562:
7560:
7557:
7555:
7552:
7550:
7547:
7545:
7541:
7538:
7535:
7532:
7530:
7527:
7525:
7522:
7520:
7517:
7515:
7512:
7510:
7507:
7505:
7502:
7500:
7497:
7495:
7492:
7490:
7486:
7483:
7481:
7478:
7476:
7473:
7471:
7468:
7465:
7462:
7460:
7456:
7453:
7450:
7447:
7445:
7442:
7440:
7436:
7433:
7431:
7428:
7425:
7422:
7420:
7417:
7415:
7411:
7408:
7404:
7401:
7399:
7396:
7395:
7394:
7391:
7388:
7385:
7383:
7379:
7376:
7374:
7371:
7366:
7363:
7361:
7357:
7354:
7351:
7348:
7346:
7343:
7341:
7338:
7337:
7336:
7333:
7331:
7328:
7325:
7322:
7320:
7316:
7313:
7310:
7307:
7305:
7301:
7299:
7295:
7294:Anaphylatoxin
7292:
7291:
7289:
7285:
7278:
7275:
7273:
7269:
7266:
7263:
7260:
7258:
7254:
7251:
7249:
7245:
7242:
7239:
7236:
7234:
7231:
7229:
7226:
7224:
7220:
7217:
7215:
7212:
7209:
7206:
7204:
7200:
7197:
7194:
7191:
7189:
7185:
7182:
7181:
7179:
7177:
7173:
7170:
7166:
7156:
7153:
7150:
7147:
7145:
7142:
7140:
7137:
7135:
7132:
7130:
7126:
7123:
7121:
7118:
7116:
7113:
7110:
7107:
7105:
7102:
7100:
7097:
7095:
7092:
7090:
7087:
7085:
7082:
7080:
7077:
7075:
7071:
7068:
7065:
7062:
7060:
7057:
7055:
7052:
7050:
7047:
7045:
7042:
7040:
7036:
7033:
7029:
7026:
7024:
7021:
7019:
7016:
7015:
7014:
7011:
7008:
7005:
7003:
7000:
6998:
6995:
6993:
6989:
6986:
6984:
6981:
6979:
6976:
6973:
6970:
6968:
6965:
6963:
6959:
6955:
6952:
6950:
6946:
6943:
6941:
6938:
6937:
6935:
6931:
6925:
6922:
6920:
6917:
6913:
6909:
6906:
6904:
6901:
6899:
6896:
6894:
6890:
6886:
6883:
6881:
6877:
6874:
6873:
6872:
6871:Prostaglandin
6869:
6867:
6864:
6862:
6859:
6855:
6852:
6850:
6847:
6846:
6845:
6842:
6839:
6836:
6834:
6830:
6827:
6826:
6824:
6822:
6818:
6815:
6809:
6798:
6795:
6793:
6790:
6788:
6785:
6783:
6780:
6778:
6775:
6773:
6769:
6766:
6763:
6760:
6758:
6755:
6753:
6749:
6746:
6742:
6739:
6737:
6734:
6732:
6729:
6727:
6724:
6723:
6722:
6719:
6717:
6714:
6710:
6707:
6705:
6702:
6700:
6697:
6695:
6692:
6690:
6687:
6686:
6685:
6682:
6679:
6676:
6674:
6671:
6669:
6666:
6664:
6661:
6659:
6655:
6654:Acetylcholine
6652:
6651:
6649:
6645:
6638:
6635:
6633:
6630:
6628:
6625:
6623:
6619:
6616:
6613:
6610:
6608:
6605:
6603:
6599:
6596:
6593:
6590:
6588:
6585:
6583:
6580:
6578:
6575:
6573:
6569:
6566:
6564:
6559:
6558:
6556:
6554:
6550:
6543:
6540:
6538:
6535:
6533:
6530:
6528:
6525:
6523:
6520:
6518:
6515:
6513:
6510:
6508:
6505:
6503:
6500:
6498:
6495:
6493:
6490:
6488:
6484:
6481:
6478:
6475:
6473:
6470:
6468:
6465:
6463:
6459:
6456:
6455:
6453:
6451:
6447:
6441:
6438:
6436:
6433:
6431:
6428:
6425:
6422:
6420:
6417:
6415:
6411:
6408:
6405:
6402:
6400:
6397:
6395:
6391:
6388:
6387:
6385:
6383:
6379:
6376:
6374:
6370:
6366:
6361:
6357:
6352:
6348:
6344:
6340:
6333:
6328:
6326:
6321:
6319:
6314:
6313:
6310:
6298:
6295:
6293:
6290:
6288:
6285:
6283:
6280:
6278:
6275:
6273:
6271:
6267:
6265:
6262:
6260:
6257:
6255:
6252:
6251:
6249:
6245:
6239:
6236:
6234:
6231:
6229:
6226:
6225:
6223:
6221:
6217:
6211:
6208:
6207:
6205:
6203:
6199:
6189:
6185:
6182:
6181:
6179:
6175:
6169:
6168:cAMP receptor
6166:
6165:
6163:
6159:
6153:
6150:
6149:
6147:
6143:
6137:
6134:
6133:
6131:
6127:
6121:
6118:
6117:
6115:
6111:
6105:
6102:
6100:
6097:
6095:
6092:
6090:
6087:
6085:
6082:
6079:
6075:
6072:
6071:
6069:
6065:
6062:
6060:
6056:
6052:
6048:
6044:
6037:
6032:
6030:
6025:
6023:
6018:
6017:
6014:
6006:
6002:
5997:
5992:
5988:
5984:
5980:
5976:
5972:
5966:
5962:
5958:
5955:
5952:
5949:
5937:
5933:
5929:
5926:
5914:
5910:
5906:
5902:
5898:
5893:
5888:
5884:
5880:
5876:
5872:
5868:
5861:
5857:
5853:
5841:
5837:
5833:
5831:
5827:
5824:
5821:
5818:
5814:
5811:
5810:
5789:
5782:
5778:
5775:
5764:
5760:
5756:
5752:
5747:
5742:
5737:
5732:
5728:
5724:
5721:(8): 4903–8.
5720:
5716:
5712:
5707:
5706:
5693:
5689:
5685:
5681:
5677:
5673:
5665:
5663:
5654:
5650:
5646:
5642:
5638:
5637:10.1038/25354
5634:
5630:
5626:
5622:
5618:
5611:
5603:
5599:
5595:
5591:
5586:
5581:
5578:(1): 97–106.
5577:
5573:
5569:
5562:
5554:
5550:
5545:
5540:
5536:
5532:
5528:
5524:
5520:
5513:
5505:
5501:
5496:
5491:
5486:
5481:
5477:
5473:
5470:(7): 3712–7.
5469:
5465:
5461:
5454:
5446:
5442:
5437:
5432:
5428:
5424:
5420:
5413:
5405:
5401:
5396:
5391:
5387:
5383:
5379:
5372:
5364:
5360:
5356:
5352:
5348:
5344:
5337:
5329:
5325:
5321:
5317:
5313:
5309:
5305:
5301:
5294:
5286:
5282:
5278:
5274:
5270:
5266:
5259:
5257:
5248:
5244:
5239:
5234:
5230:
5226:
5222:
5218:
5214:
5210:
5206:
5199:
5191:
5187:
5182:
5177:
5173:
5169:
5165:
5158:
5150:
5146:
5141:
5136:
5133:(4): 239–43.
5132:
5128:
5124:
5117:
5109:
5105:
5100:
5095:
5091:
5087:
5083:
5079:
5075:
5068:
5060:
5056:
5051:
5046:
5041:
5036:
5032:
5028:
5024:
5017:
5001:
4997:
4993:
4989:
4985:
4981:
4974:
4966:
4962:
4957:
4952:
4947:
4942:
4938:
4934:
4930:
4926:
4922:
4915:
4907:
4903:
4899:
4895:
4891:
4887:
4883:
4879:
4872:
4864:
4860:
4855:
4850:
4846:
4842:
4839:(1): 261–74.
4838:
4834:
4830:
4823:
4815:
4811:
4806:
4801:
4797:
4793:
4789:
4785:
4781:
4774:
4766:
4762:
4757:
4752:
4748:
4744:
4740:
4736:
4732:
4725:
4717:
4713:
4708:
4703:
4699:
4695:
4691:
4687:
4683:
4679:
4675:
4668:
4660:
4656:
4651:
4646:
4641:
4636:
4632:
4628:
4624:
4620:
4616:
4609:
4601:
4597:
4592:
4587:
4583:
4579:
4575:
4571:
4564:
4556:
4552:
4548:
4544:
4540:
4536:
4532:
4528:
4521:
4513:
4509:
4504:
4499:
4495:
4491:
4488:(10): 740–7.
4487:
4483:
4479:
4472:
4470:
4461:
4457:
4453:
4449:
4445:
4441:
4437:
4433:
4429:
4425:
4418:
4410:
4406:
4401:
4396:
4392:
4388:
4384:
4380:
4376:
4372:
4368:
4361:
4353:
4349:
4344:
4339:
4335:
4331:
4327:
4323:
4319:
4315:
4311:
4304:
4296:
4292:
4287:
4282:
4278:
4274:
4270:
4266:
4262:
4258:
4254:
4247:
4239:
4235:
4230:
4225:
4221:
4217:
4213:
4209:
4205:
4201:
4197:
4190:
4182:
4178:
4173:
4168:
4164:
4160:
4156:
4152:
4148:
4144:
4140:
4133:
4125:
4121:
4117:
4113:
4108:
4103:
4099:
4095:
4091:
4087:
4083:
4076:
4068:
4064:
4060:
4056:
4052:
4048:
4044:
4040:
4036:
4032:
4025:
4017:
4013:
4009:
4005:
4000:
3995:
3991:
3987:
3983:
3979:
3972:
3964:
3960:
3955:
3950:
3946:
3942:
3938:
3934:
3930:
3923:
3915:
3911:
3907:
3903:
3899:
3895:
3891:
3887:
3883:
3879:
3872:
3864:
3860:
3856:
3852:
3848:
3844:
3840:
3836:
3829:
3821:
3817:
3812:
3807:
3803:
3799:
3795:
3791:
3787:
3780:
3772:
3768:
3764:
3760:
3756:
3752:
3748:
3744:
3737:
3729:
3725:
3720:
3715:
3710:
3705:
3701:
3697:
3693:
3682:
3674:
3670:
3666:
3662:
3659:(5): 559–67.
3658:
3654:
3647:
3639:
3635:
3631:
3627:
3623:
3619:
3611:
3603:
3599:
3595:
3591:
3587:
3583:
3579:
3575:
3571:
3567:
3560:
3552:
3548:
3543:
3538:
3533:
3528:
3524:
3520:
3517:(8): 4903–8.
3516:
3512:
3508:
3501:
3493:
3489:
3484:
3479:
3474:
3469:
3465:
3461:
3458:(1): e29817.
3457:
3453:
3449:
3442:
3440:
3438:
3421:
3417:
3411:
3403:
3399:
3395:
3391:
3387:
3383:
3380:(2): 279–88.
3379:
3375:
3368:
3360:
3356:
3352:
3348:
3341:
3333:
3329:
3325:
3321:
3317:
3313:
3306:
3298:
3294:
3289:
3284:
3279:
3274:
3270:
3266:
3262:
3255:
3239:
3235:
3231:
3225:
3217:
3213:
3209:
3205:
3202:(3): 263–73.
3201:
3197:
3189:
3187:
3185:
3176:
3172:
3167:
3162:
3158:
3154:
3150:
3146:
3142:
3135:
3120:
3113:
3105:
3101:
3096:
3091:
3087:
3083:
3079:
3075:
3071:
3064:
3062:
3053:
3049:
3045:
3041:
3037:
3033:
3026:
3024:
3015:
3011:
3007:
3003:
3000:(1): 615–49.
2999:
2995:
2988:
2986:
2977:
2973:
2969:
2965:
2961:
2957:
2953:
2949:
2945:
2941:
2934:
2928:
2923:
2917:
2913:
2908:
2903:
2899:
2895:
2891:
2887:
2883:
2876:
2874:
2872:
2870:
2868:
2851:
2847:
2843:
2839:
2837:9780123869333
2833:
2829:
2825:
2821:
2817:
2810:
2808:
2799:
2795:
2790:
2785:
2781:
2777:
2773:
2769:
2765:
2761:
2757:
2750:
2748:
2743:
2733:
2730:
2727:
2724:
2721:
2718:
2716:
2713:
2711:
2708:
2706:
2703:
2701:
2698:
2697:
2691:
2689:
2686:
2682:
2678:
2674:
2670:
2666:
2662:
2661:
2657:. Later, the
2656:
2652:
2650:
2649:Dictyostelium
2645:
2644:
2639:
2638:
2633:
2632:
2627:
2623:
2619:
2615:
2611:
2602:
2587:
2575:
2567:
2559:
2549:
2548:GPCR oligomer
2539:
2537:
2526:
2524:
2520:
2516:
2512:
2508:
2504:
2500:
2496:
2492:
2488:
2483:
2481:
2477:
2473:
2469:
2465:
2462:
2458:
2454:
2450:
2446:
2442:
2438:
2434:
2426:
2422:
2417:
2413:
2411:
2407:
2403:
2399:
2395:
2391:
2387:
2383:
2379:
2378:phosphorylate
2375:
2371:
2367:
2363:
2362:
2361:
2359:
2354:
2351:
2347:
2343:
2339:
2335:
2331:
2327:
2323:
2302:
2298:
2294:
2290:
2288:
2284:
2281:
2280:Translocation
2278:
2277:
2276:
2273:
2271:
2261:
2259:
2248:
2240:
2237:(cAMP). In a
2236:
2232:
2228:
2218:
2216:
2212:
2208:
2204:
2200:
2190:
2188:
2184:
2179:
2177:
2173:
2169:
2165:
2161:
2157:
2153:
2149:
2141:
2135:
2125:
2122:
2118:
2114:
2110:
2107:
2105:
2101:
2097:
2093:
2089:
2083:
2073:
2071:
2067:
2063:
2054:
2046:
2038:
2029:
2027:
2023:
2019:
2015:
2011:
2007:
2003:
1992:
1990:
1986:
1981:
1974:
1972:
1971:
1970:D. discoideum
1967:
1962:
1952:
1950:
1946:
1942:
1938:
1934:
1930:
1926:
1922:
1911:
1909:
1905:
1902:
1898:
1894:
1890:
1882:
1875:Gβγ signaling
1861:
1857:
1853:
1849:
1845:
1841:
1837:
1833:
1829:
1825:
1821:
1820:IP3 receptors
1817:
1813:
1809:
1805:
1797:
1794:
1790:
1786:
1783:
1779:
1759:
1756:
1752:
1748:
1744:
1740:
1728:
1727:
1721:
1719:
1715:
1714:physiological
1711:
1707:
1703:
1699:
1695:
1691:
1687:
1681:
1679:
1674:
1670:
1666:
1659:
1652:
1645:
1638:
1634:
1624:
1621:
1617:
1613:
1609:
1605:
1601:
1597:
1593:
1589:
1584:
1582:
1577:
1575:
1571:
1564:
1559:
1557:
1553:
1544:
1535:
1529:
1525:
1517:
1512:
1503:
1501:
1497:
1493:
1489:
1484:
1479:
1477:
1473:
1469:
1465:
1461:
1457:
1452:
1448:
1444:
1440:
1436:
1432:
1426:
1417:
1408:
1405:
1400:
1395:
1376:
1372:
1364:
1356:
1352:
1348:
1340:
1336:
1327:
1318:
1316:
1312:
1307:
1305:
1300:
1298:
1294:
1290:
1286:
1282:
1278:
1274:
1273:anaphylatoxin
1270:
1266:
1262:
1258:
1254:
1250:
1247:mediators of
1246:
1242:
1238:
1234:
1233:acetylcholine
1230:
1226:
1222:
1218:
1214:
1210:
1206:
1202:
1198:
1194:
1190:
1186:
1182:
1178:
1174:
1170:
1166:
1162:
1158:
1157:melanocortins
1154:
1150:
1146:
1142:
1138:
1134:
1130:
1120:
1118:
1114:
1104:
1095:
1093:
1089:
1085:
1081:
1076:
1074:
1070:
1066:
1062:
1058:
1054:
1050:
1045:
1043:
1039:
1035:
1031:
1027:
1023:
1019:
1015:
1011:
998:
996:
992:
988:
984:
980:
976:
972:
968:
964:
960:
956:
955:transmembrane
952:
944:
939:
930:
928:
924:
920:
916:
912:
908:
904:
899:
892:
883:
878:
873:
871:
867:
863:
859:
855:
851:
837:
834:
830:
826:
823:
820:
817:
813:
809:
806:
802:
798:
794:
790:
786:
783:activity and
782:
781:immune system
778:
776:
772:
768:
764:
760:
756:
752:
749:
745:
742:
738:
735:
731:
728:
726:
721:
719:
714:
710:
706:
702:
698:
697:
696:
688:
686:
681:
677:
675:
671:
667:
663:
662:
657:
653:
649:
641:
637:
633:
630:
627:
623:
620:
617:
613:
610:
607:
603:
600:
597:
593:
590:
587:
583:
580:
579:
578:
575:
573:
569:
565:
561:
557:
554:
550:
546:
541:
539:
535:
531:
528:
524:
521:
511:
502:
500:
496:
495:Advair Diskus
492:
488:
484:
483:Brian Kobilka
480:
475:
463:
460:
452:
441:
437:
435:
428:
421:
414:
407:
403:
399:
395:
387:
383:
380:
376:
375:
374:
371:
369:
365:
361:
357:
353:
349:
345:
341:
337:
333:
328:
326:
322:
318:
314:
310:
309:cell membrane
306:
302:
298:
294:
290:
286:
282:
278:
274:
270:
269:7TM receptors
266:
262:
258:
251:
246:
234:
231:
229:
225:
222:
218:
214:
211:
209:
205:
201:
197:
194:
191:
187:
182:
178:
175:
172:
170:
166:
163:
160:
158:
154:
151:
148:
146:
142:
139:
136:
134:
130:
127:
124:
122:
118:
115:
112:
110:
106:
103:
100:
98:
94:
91:
88:
85:
81:
78:
75:
73:
69:
65:
61:
56:
52:
49:
45:
39:
34:
29:
26:
19:
9242:Biochemistry
8970:
8937:
8910:Metabotropic
8774:
8659:
8612:
8570:
8536:
8507:
8478:
8323:
7948:
7797:
7748:Urotensin-II
7688:Somatostatin
7643:Prokineticin
7540:Melanocortin
7243:
7176:Neuropeptide
7115:Oxoglutarate
6957:
6919:Prostacyclin
6888:
6875:
6828:
6716:GHB receptor
6617:
6560:
6342:
6269:
6058:
5978:
5974:
5947:
5940:. Retrieved
5936:the original
5924:
5917:. Retrieved
5913:the original
5874:
5870:
5859:
5844:. Retrieved
5839:
5795:. Retrieved
5773:
5766:. Retrieved
5718:
5714:
5675:
5671:
5620:
5616:
5610:
5575:
5571:
5561:
5526:
5522:
5512:
5467:
5463:
5453:
5426:
5422:
5412:
5385:
5381:
5371:
5346:
5342:
5336:
5303:
5299:
5293:
5268:
5264:
5212:
5208:
5198:
5171:
5167:
5157:
5130:
5126:
5116:
5081:
5077:
5067:
5030:
5026:
5016:
5004:. Retrieved
4987:
4983:
4973:
4928:
4924:
4914:
4881:
4877:
4871:
4836:
4832:
4822:
4787:
4783:
4773:
4738:
4734:
4724:
4681:
4677:
4667:
4622:
4618:
4608:
4573:
4569:
4563:
4530:
4526:
4520:
4485:
4481:
4427:
4423:
4417:
4374:
4370:
4360:
4317:
4313:
4303:
4260:
4256:
4246:
4203:
4199:
4189:
4146:
4142:
4132:
4089:
4085:
4075:
4034:
4030:
4024:
3981:
3977:
3971:
3939:(1): 12–22.
3936:
3932:
3922:
3881:
3877:
3871:
3841:(2): 79–94.
3838:
3834:
3828:
3796:(1): 45–66.
3793:
3789:
3779:
3749:(4): 521–8.
3746:
3742:
3736:
3699:
3695:
3681:
3656:
3652:
3646:
3624:(1): 68–73.
3621:
3617:
3610:
3602:the original
3573:
3569:
3559:
3514:
3510:
3500:
3455:
3451:
3424:. Retrieved
3410:
3377:
3373:
3367:
3350:
3346:
3340:
3315:
3311:
3305:
3268:
3264:
3254:
3242:. Retrieved
3238:the original
3233:
3224:
3199:
3195:
3151:(6): 905–7.
3148:
3144:
3134:
3122:. Retrieved
3112:
3077:
3073:
3035:
3031:
2997:
2993:
2943:
2939:
2933:
2889:
2885:
2854:. Retrieved
2819:
2763:
2759:
2680:
2676:
2672:
2664:
2658:
2655:opisthokonts
2647:
2641:
2636:
2629:
2608:
2551:
2532:
2503:small GTPase
2484:
2445:opsonization
2430:
2370:conformation
2358:desensitized
2355:
2334:RGS proteins
2319:
2292:
2285:
2279:
2274:
2267:
2238:
2224:
2196:
2180:
2172:IP3 receptor
2137:
2123:
2119:
2115:
2111:
2108:
2085:
2059:
1998:
1982:
1975:
1969:
1958:
1917:
1878:
1856:cytoskeleton
1848:small GTPase
1778:ion channels
1724:Gα signaling
1720:conditions.
1718:experimental
1682:
1630:
1618:only to the
1596:conformation
1585:
1578:
1560:
1549:
1521:
1480:
1428:
1396:
1373:in place of
1344:
1308:
1301:
1265:leukotrienes
1249:inflammation
1225:metabotropic
1187:family, and
1173:somatostatin
1126:
1117:RGS proteins
1110:
1077:
1065:sphingolipid
1046:
999:
948:
900:
874:
858:glycosylated
847:
785:inflammation
757:, including
724:
717:
694:
682:
678:
660:
645:
576:
542:
517:
476:
464:
447:
438:
391:
372:
334:, including
329:
299:outside the
295:that detect
284:
280:
276:
272:
268:
264:
260:
256:
255:
25:
8618:Latrophilin
7753:Vasopressin
7738:Thyrotropin
7315:Angiotensin
7268:Neurotensin
6945:Cannabinoid
6924:Thromboxane
6277:Neuropilins
5919:10 November
5306:(1): 5–12.
3426:10 December
2511:ERK cascade
2497:, or other
2480:degradation
2468:dissociated
2453:amphiphysin
2350:promiscuous
2211:cytoplasmic
2158:hydrolyzes
2024:(GDIs) and
1844:calmodulins
1802:pathway is
1633:sub-classes
1612:β-arrestins
1399:equilibrium
1257:prostanoids
1201:epinephrine
1189:vasopressin
1181:tachykinins
1069:lipid rafts
1061:cholesterol
1057:acyl groups
1038:endocytosis
995:antagonists
812:sympathetic
608:/pheromone)
157:OPM protein
58:Identifiers
9231:Categories
9208:Smoothened
9201:Smoothened
9124:Smoothened
8783:Calcitonin
7718:Tachykinin
7615:, but not
7609:Nociceptin
7475:Kisspeptin
7393:Endothelin
7356:Bradykinin
7244:Neuromedin
6821:Eicosanoid
6450:Purinergic
6382:Adrenergic
6188:smoothened
5954:GPCR-HGmod
5846:6 February
5797:10 October
5388:(1): 5–8.
5033:: 341282.
5006:14 January
4591:10161/7805
3416:"InterPro"
3353:(1): 1–7.
3124:10 October
2856:24 October
2738:References
2651:discoideum
2626:eukaryotic
2523:polymerize
2472:trafficked
2398:sterically
2394:β-arrestin
2390:C-terminal
2342:resolution
2338:GAP domain
2235:cyclic AMP
2187:calmodulin
2183:CaM kinase
1966:slime mold
1945:PDZ-domain
1933:β-arrestin
1860:Rho-kinase
1814:(IP3) and
1710:endogenous
1608:G-proteins
1604:transducer
1581:calmodulin
1534:activity.
1476:covalently
1472:isoprenoid
1423:See also:
1285:neurokinin
1269:calcitonin
1241:chemokines
1237:muscarinic
1167:peptides,
1145:endothelin
1141:bradykinin
1030:sterically
963:C-terminus
951:N-terminus
943:lipid raft
927:C-terminus
923:N-terminus
919:G proteins
905:, such as
848:GPCRs are
829:metastasis
687:approach.
640:Smoothened
553:endogenous
352:pheromones
332:eukaryotes
305:G proteins
196:structures
42:The human
9118:Class F:
8917:pheromone
8913:glutamate
8337:Olfactory
7373:Chemokine
7155:Succinate
6940:Bile acid
6748:Melatonin
6721:Histamine
6561:(all but
6553:Serotonin
6458:Adenosine
6360:Rhodopsin
6047:receptors
5975:Structure
5967:pipeline
5768:11 August
4990:: 57–71.
4684:: 13416.
3994:CiteSeerX
2720:Pepducins
2673:Rhodopsin
2669:nematodes
2631:Rhodopsin
2476:lysosomes
2461:endocytic
2386:threonine
2297:rhodopsin
2014:JAK/STATs
2002:integrins
1891:(GIRKs),
1755:cytosolic
1552:G protein
1538:Signaling
1506:Crosstalk
1460:Gβγ dimer
1425:G protein
1239:effect);
1227:effect);
1221:glutamate
1217:melatonin
1213:serotonin
1209:histamine
1133:adenosine
1129:olfactory
1113:G protein
1098:Mechanism
1026:arrestins
1014:threonine
1012:(Ser) or
977:or large
959:α-helices
877:rhodopsin
789:chemokine
775:glutamate
767:histamine
759:serotonin
748:mammalian
734:gustducin
725:all-trans
713:Rhodopsin
656:Rhodopsin
652:Glutamate
564:structure
556:compounds
551:by known
477:The 2012
398:G protein
366:to large
321:rhodopsin
297:molecules
291:that are
252:rhodopsin
126:PDOC00210
114:IPR000276
51:carazolol
9142:Frizzled
9135:Frizzled
9120:Frizzled
8962:, type 2
8868:Secretin
8808:Glucagon
8513:Cadherin
8471:Adhesion
8458:Secretin
7791:, bitter
7638:Oxytocin
7335:Bombesin
6983:Estrogen
6684:Dopamine
6184:Frizzled
6005:26190572
5965:I-TASSER
5957:Archived
5901:27155948
5856:"GPCRdb"
5826:Archived
5788:Archived
5755:12679517
5692:21402729
5602:15430860
5594:10939334
5553:18193069
5504:10097102
5445:10770944
5363:14499340
5328:45674941
5320:23532739
5285:14744258
5247:11053129
5190:12177051
5108:30401786
5059:23056062
5000:Archived
4965:17095603
4906:22279536
4898:12970120
4863:20019124
4814:31740855
4765:27499021
4716:27827372
4659:28223524
4600:11861753
4512:21873996
4460:52860797
4452:12802337
4409:21772288
4352:21393508
4295:21228877
4238:21228876
4181:21228869
4116:17962519
4059:17952055
4016:10926528
3963:24359917
3906:23407534
3863:10996598
3855:17251915
3820:21802439
3771:21897008
3763:23345392
3728:32259074
3673:19594431
3638:19364489
3590:19037861
3551:12679517
3492:22238661
3452:PLOS ONE
3420:Archived
3402:34541683
3394:15914470
3297:12429062
3216:16753280
3196:Genomics
3175:24024784
3104:29249361
3052:16183910
2968:12869759
2916:22300046
2850:Archived
2846:23317783
2798:17962520
2694:See also
2681:Adhesion
2677:Secretin
2665:Adhesion
2660:Secretin
2643:Frizzled
2637:Adhesion
2558:receptor
2489:(nRTK),
2441:membrane
2437:clathrin
2404:through
2380:various
2330:isoforms
2293:arrestin
2287:Arrestin
2008:(RTKs),
1955:Examples
1951:family.
1793:effector
1751:catalyze
1702:feedback
1616:affinity
1524:integrin
1516:integrin
1496:effector
1293:oxytocin
1229:glucagon
1197:dopamine
1137:bombesin
1053:cysteine
1022:affinity
979:peptides
975:proteins
862:cysteine
763:dopamine
727:-retinal
720:-retinal
674:Secretin
666:Frizzled
661:Adhesion
636:Frizzled
634:(or 6) (
624:(or 5) (
614:(or 4) (
604:(or 3) (
594:(or 2) (
584:(or 1) (
549:liganded
368:proteins
364:peptides
356:hormones
325:agonists
213:RCSB PDB
109:InterPro
102:5001.1.1
8931:, sweet
8906:Class C
8838:PACAPR1
8454:Class B
7663:Relaxin
7585:Motilin
7470:Ghrelin
7435:Galanin
7168:Peptide
6356:Class A
6177:Class F
6161:Class E
6145:Class D
6129:Class C
6113:Class B
6067:Class A
5996:4526412
5942:11 July
5892:4919580
5723:Bibcode
5653:4406311
5645:9872316
5625:Bibcode
5544:2268057
5472:Bibcode
5404:8995214
5238:1301137
5217:Bibcode
5149:8807851
5099:6329291
5050:3465959
4956:1693825
4933:Bibcode
4854:5428143
4805:7108872
4756:5418658
4707:5105198
4686:Bibcode
4650:5347553
4627:Bibcode
4555:2163110
4535:Bibcode
4527:Science
4503:3177959
4432:Bibcode
4400:3184188
4379:Bibcode
4343:3086811
4322:Bibcode
4314:Science
4286:3023143
4265:Bibcode
4229:3074335
4208:Bibcode
4172:3058308
4151:Bibcode
4124:1559802
4094:Bibcode
4086:Science
4067:4407117
4039:Bibcode
3986:Bibcode
3978:Science
3954:3931419
3914:4423750
3886:Bibcode
3811:3336209
3719:7088898
3519:Bibcode
3483:3251606
3460:Bibcode
3359:8081729
3332:8170923
3244:24 June
3166:3689196
3095:5766829
3014:3113327
2976:9708224
2948:Bibcode
2940:Science
2907:3343417
2789:2583103
2768:Bibcode
2760:Science
2688:PF00002
2464:vesicle
2457:dynamin
2289:linking
2138:In the
2088:hormone
1698:isoform
1690:agonist
1464:diffuse
1456:monomer
1311:ligands
1295:); and
1251:(e.g.,
1195:(e.g.,
1088:guanine
1084:protons
987:agonist
957:(7-TM)
915:ADIPOR2
911:ADIPOR1
632:Class F
622:Class E
612:Class D
602:Class C
592:Class B
582:Class A
499:Abilify
344:ligands
174:cd14964
121:PROSITE
77:PF00001
9122:&
9051:GPRC6A
8788:CALCRL
8652:Orphan
7941:Orphan
7932:type 1
7623:Orexin
7611:&
7590:Opioid
7330:Apelin
6003:
5993:
5899:
5889:
5819:(MeSH)
5753:
5746:153653
5743:
5690:
5651:
5643:
5617:Nature
5600:
5592:
5572:Neuron
5551:
5541:
5502:
5492:
5443:
5402:
5361:
5326:
5318:
5283:
5245:
5235:
5188:
5147:
5106:
5096:
5057:
5047:
4963:
4953:
4904:
4896:
4861:
4851:
4812:
4802:
4763:
4753:
4714:
4704:
4657:
4647:
4598:
4553:
4510:
4500:
4458:
4450:
4424:Nature
4407:
4397:
4371:Nature
4350:
4340:
4293:
4283:
4257:Nature
4236:
4226:
4200:Nature
4179:
4169:
4143:Nature
4122:
4114:
4065:
4057:
4031:Nature
4014:
3996:
3961:
3951:
3912:
3904:
3878:Nature
3861:
3853:
3818:
3808:
3769:
3761:
3726:
3716:
3671:
3636:
3598:813484
3596:
3588:
3549:
3542:153653
3539:
3490:
3480:
3400:
3392:
3357:
3330:
3295:
3288:133447
3285:
3214:
3173:
3163:
3102:
3092:
3050:
3012:
2974:
2966:
2914:
2904:
2844:
2834:
2796:
2786:
2640:, and
2495:ERK1/2
2425:kinase
2382:serine
2301:retina
2156:lipase
2154:. The
2064:: the
1927:, and
1921:β-arrs
1901:N-type
1899:- and
1864:α12/13
1747:tissue
1664:α12/13
1660:, and
1600:ligand
1439:trimer
1337:entry
1291:, and
1271:, C5a
1263:, and
1215:, and
1169:opsins
1165:opioid
1063:- and
1010:serine
971:ligand
833:tumors
773:, and
718:11-cis
703:use a
701:opsins
670:Taste2
572:A1-A19
530:genome
514:(23)).
433:α12/13
358:, and
342:. The
338:, and
313:ligand
279:, and
250:bovine
228:PDBsum
202:
192:
138:9.A.14
90:CL0192
63:Symbol
8971:Other
8938:TAS1R
8929:Taste
8827:GLP2R
8822:GLP1R
8775:Other
8640:ELTD1
8613:ADGRL
8571:ADGRG
8537:ADGRE
8508:ADGRC
8479:ADGRB
8460:-like
8342:Opsin
8324:Other
7798:TAS2R
7789:Taste
7617:Sigma
7599:Kappa
7594:Delta
7302:C5a (
7287:Other
6933:Other
6861:FPRL1
6829:CysLT
6647:Other
6598:5-HT2
6568:5-HT1
6563:5-HT3
6362:-like
5791:(PDF)
5784:(PDF)
5649:S2CID
5598:S2CID
5495:22359
5324:S2CID
4902:S2CID
4878:Chest
4456:S2CID
4120:S2CID
4063:S2CID
3910:S2CID
3859:S2CID
3767:S2CID
3594:S2CID
3398:S2CID
2972:S2CID
2622:GRAFS
2618:fungi
2515:Raf-1
2491:c-SRC
2415:well.
1937:CXCR3
1868:αq/11
1800:αq/11
1733:and G
1669:genes
1657:αq/11
1389:and G
1245:lipid
795:bind
751:brain
648:GRAFS
523:genes
520:human
426:αq/11
348:odors
336:yeast
261:GPCRs
66:7tm_1
9076:RAIG
8984:GABA
8817:GIPR
8564:CD97
8412:SREB
8213:137B
8188:109B
8183:109A
7613:Zeta
7570:MCHR
7350:NMBR
7345:GRPR
7340:BRS3
6978:EBI2
6844:LTB4
6768:TAAR
6618:5-HT
6287:EDAR
6001:PMID
5944:2013
5921:2010
5897:PMID
5848:2019
5799:2012
5770:2008
5751:PMID
5688:PMID
5641:PMID
5590:PMID
5549:PMID
5500:PMID
5441:PMID
5400:PMID
5359:PMID
5316:PMID
5281:PMID
5243:PMID
5186:PMID
5145:PMID
5104:PMID
5055:PMID
5031:2012
5008:2006
4961:PMID
4894:PMID
4859:PMID
4810:PMID
4761:PMID
4735:Cell
4712:PMID
4655:PMID
4596:PMID
4551:PMID
4508:PMID
4448:PMID
4405:PMID
4348:PMID
4291:PMID
4234:PMID
4177:PMID
4112:PMID
4055:PMID
4012:PMID
3959:PMID
3902:PMID
3851:PMID
3816:PMID
3759:PMID
3724:PMID
3669:PMID
3634:PMID
3586:PMID
3547:PMID
3488:PMID
3428:2007
3390:PMID
3355:PMID
3328:PMID
3293:PMID
3246:2019
3212:PMID
3171:PMID
3126:2012
3100:PMID
3074:Cell
3048:PMID
3010:PMID
2964:PMID
2912:PMID
2858:2023
2842:PMID
2832:ISBN
2794:PMID
2685:Pfam
2570:GABA
2568:and
2562:GABA
2554:GABA
2478:for
2455:and
2433:AP-2
2326:rate
2268:The
2233:and
2166:and
2066:cAMP
2018:GEFs
1989:ITIM
1961:ERK2
1949:MAPK
1929:Srcs
1925:GRKs
1885:αi/o
1774:αi/o
1766:αi/o
1735:αi/o
1650:αi/o
1610:and
1590:and
1345:The
1339:3SN6
1149:GABA
993:and
913:and
882:1F88
814:and
771:GABA
497:and
485:and
419:αi/o
384:the
379:cAMP
377:the
301:cell
285:GPLR
221:PDBj
217:PDBe
200:ECOD
190:Pfam
162:1gzm
133:TCDB
97:ECOD
86:clan
84:Pfam
72:Pfam
31:GPCR
9070:179
9065:158
9060:156
9056:GPR
8843:GPR
8764:157
8759:155
8754:144
8749:143
8744:133
8739:128
8734:126
8729:125
8724:124
8719:123
8714:116
8709:115
8704:114
8699:113
8694:112
8689:111
8684:110
8660:GPR
8542:EMR
8381:RRH
8376:RGR
8371:1SW
8366:1MW
8361:1LW
8313:183
8308:182
8303:177
8298:176
8293:174
8288:173
8283:171
8278:162
8273:161
8268:160
8263:153
8258:152
8253:151
8248:150
8243:149
8238:148
8233:146
8228:142
8223:141
8218:139
8208:135
8203:132
8198:120
8193:119
8178:103
8173:101
7949:GPR
7485:MAS
7430:FSH
7298:C3a
7184:B/W
7120:PAF
6972:119
6958:GPR
6954:CB2
6949:CB1
6910:),
6887:),
6866:OXE
6483:P2Y
6472:A2B
6467:A2A
5991:PMC
5983:doi
5887:PMC
5879:doi
5875:173
5741:PMC
5731:doi
5719:100
5680:doi
5633:doi
5621:396
5580:doi
5539:PMC
5531:doi
5527:153
5490:PMC
5480:doi
5431:doi
5427:275
5390:doi
5386:272
5351:doi
5308:doi
5273:doi
5233:PMC
5225:doi
5176:doi
5172:277
5135:doi
5094:PMC
5086:doi
5045:PMC
5035:doi
4992:doi
4988:430
4951:PMC
4941:doi
4929:103
4886:doi
4882:124
4849:PMC
4841:doi
4800:PMC
4792:doi
4751:PMC
4743:doi
4739:166
4702:PMC
4694:doi
4645:PMC
4635:doi
4623:114
4586:hdl
4578:doi
4574:115
4543:doi
4531:248
4498:PMC
4490:doi
4440:doi
4428:423
4395:PMC
4387:doi
4375:477
4338:PMC
4330:doi
4318:332
4281:PMC
4273:doi
4261:469
4224:PMC
4216:doi
4204:469
4167:PMC
4159:doi
4147:469
4102:doi
4090:318
4047:doi
4035:450
4004:doi
3982:289
3949:PMC
3941:doi
3894:doi
3882:494
3843:doi
3806:PMC
3798:doi
3751:doi
3714:PMC
3704:doi
3661:doi
3626:doi
3622:390
3578:doi
3537:PMC
3527:doi
3515:100
3478:PMC
3468:doi
3382:doi
3320:doi
3283:PMC
3273:doi
3204:doi
3161:PMC
3153:doi
3090:PMC
3082:doi
3078:172
3040:doi
3002:doi
2956:doi
2944:301
2902:PMC
2894:doi
2824:doi
2784:PMC
2776:doi
2764:318
2519:MEK
2507:Ras
2332:of
2299:in
1881:Gβγ
1852:Rho
1716:or
1694:GEF
1671:or
1574:GDP
1556:GTP
1528:FAK
1431:GEF
1375:GDP
1371:GTP
1335:PDB
1219:);
1155:),
1153:HGF
1092:GEF
1082:to
1034:ERK
805:TLR
722:to
574:).
436:).
406:GTP
402:GDP
208:PDB
169:CDD
9233::
9191:10
9047:))
8915:/
8908::
8812:GR
8679:98
8674:97
8669:64
8664:56
8456::
8168:92
8163:88
8158:87
8153:85
8148:84
8143:83
8138:82
8133:81
8128:78
8123:75
8118:68
8113:65
8108:63
8103:62
8098:61
8093:55
8088:52
8083:50
8078:45
8073:44
8068:42
8063:39
8058:37
8053:35
8048:34
8043:33
8038:32
8033:31
8028:27
8023:26
8018:25
8013:23
8008:22
8003:21
7998:20
7993:19
7988:18
7983:17
7978:15
7973:12
7923:60
7918:50
7913:46
7908:45
7903:43
7898:42
7893:41
7888:40
7883:39
7878:38
7873:31
7868:30
7863:20
7858:19
7853:16
7848:14
7843:13
7838:10
7762:1B
7757:1A
7604:Mu
7534:X4
7529:X3
7524:X2
7519:X1
7494:1L
7365:B2
7360:B1
7311:))
7264:))
7199:FF
6974:))
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