2549:, 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.
2283:(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.
2293:: 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.
2064:
2056:
1522:
256:
49:
451:
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.
2200:(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.
485:
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.
1337:
521:
2048:
949:
1114:
1554:
1427:
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996:(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
1991:-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.
2132:
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.
2363:
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
2123:
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
1496:
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
904:
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
472:
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
1117:
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
484:
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
450:
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
2544:
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
2131:
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
2603:
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
2425:
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
459:
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
1000:-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).
1929:
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
690:
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.
2039:. 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.
2010:
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
1404:
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.
1412:
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;
2127:
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.
2429:
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
1118:
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.
524:
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
2318:-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
849:
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
1686:
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
5680:
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".
3240:
1565:, 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
1417:
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.
1849:(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
419:. 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 (
330:, 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 (
1694:
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
1633:
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.
1719:(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
1051:(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
3204:
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".
1974:
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
3626:
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".
3662:
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".
1513:) 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.
2120:
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.
1055:. 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.
1122:
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
3248:
2536:
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.
2639:
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,
905:
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
2002:(immunoreceptor tyrosine-based inhibitory motif) sequence in the B2 receptor is necessary to mediate this interaction and subsequently the antiproliferative effect of bradykinin.
1352:). 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.
4040:
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".
2532:, 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
694:
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
2314:
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
5798:
5626:
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".
829:
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
2351:, 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
2252:, these activated kinases phosphorylate the receptor. The longer the receptor remains active the more kinases are activated and the more receptors are phosphorylated. In
468:
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
2339:(≈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
3383:
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".
1583:. 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
5175:"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"
547:. Although numerous classification schemes have been proposed, the superfamily was classically divided into three main classes (A, B, and C) with no detectable shared
223:
9086:
4433:
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".
2306:
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
1899:
5309:
Santulli G, Trimarco B, Iaccarino G (March 2013). "G-protein-coupled receptor kinase 2 and hypertension: molecular insights and pathophysiological mechanisms".
5389:"The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification"
6340:
3987:
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".
1043:
prevent G-protein coupling and may recruit other proteins, leading to the creation of signaling complexes involved in extracellular-signal regulated kinase (
2860:
1590:
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+/
554:
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
2545:
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
2135:
These signals then can be terminated by cAMP phosphodiesterase, which is an enzyme that degrades cAMP to 5'-AMP and inactivates protein kinase A.
8552:
2442:
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
501:
6044:
4579:
Luttrell LM, Lefkowitz RJ (February 2002). "The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals".
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Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (June 1990). "beta-Arrestin: a protein that regulates beta-adrenergic receptor function".
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1011:
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
7692:
7687:
7682:
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5430:"The interaction of beta-arrestin with the AP-2 adaptor is required for the clustering of beta 2-adrenergic receptor into clathrin-coated pits"
1999:
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molecules, three intracellular loops interacting with G proteins, an N-terminal extracellular region and a C-terminal intracellular region) of
167:
155:
1015:
muscarinic receptors is sufficient, and the six-amino-acid polybasic (KKKRRK) domain in the C-terminus is necessary for its preassembly with G
5352:
Penela P, Ribas C, Mayor F (November 2003). "Mechanisms of regulation of the expression and function of G protein-coupled receptor kinases".
3887:
Venkatakrishnan AJ, Deupi X, Lebon G, Tate CG, Schertler GF, Babu MM (February 2013). "Molecular signatures of G-protein-coupled receptors".
1703:
may also initiate activation of multiple different G-proteins, as it may be capable of stabilizing more than one conformation of the GPCR's
2032:
3797:"G protein-coupled receptors in the hypothalamic paraventricular and supraoptic nuclei--serpentine gateways to neuroendocrine homeostasis"
972:(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
8422:
5836:
2208:
GPCRs become desensitized when exposed to their ligand for a long period of time. There are two recognized forms of desensitization: 1)
8812:
8807:
2949:
King N, Hittinger CT, Carroll SB (July 2003). "Evolution of key cell signaling and adhesion protein families predates animal origins".
17:
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a
Protein Structure Initiative:Biology Network Center aimed at determining the 3D structures of representative GPCR family proteins
2271:
class. cAMP-dependent PKA mediated phosphorylation can cause heterologous desensitisation in receptors other than those activated.
1792:
1126:. Further effect depends on the type of G protein. G proteins are subsequently inactivated by GTPase activating proteins, known as
984:-binding domain that is often covered by EL-2. Ligands may also bind elsewhere, however, as is the case for bulkier ligands (e.g.,
588:
According to the classical A-F system, GPCRs can be grouped into six classes based on sequence homology and functional similarity:
5791:
1360:
through the membrane by the receptor is not completely understood. It is known that in the inactive state, the GPCR is bound to a
8827:
8509:
8504:
8499:
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2529:
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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.
2833:. G Protein-Coupled Receptors in Energy Homeostasis and Obesity Pathogenesis. Vol. 114. Academic Press. pp. 89–107.
1699:(also known as agonist-directed trafficking, or conformation-specific agonism). However, the binding of any single particular
1320:
However, in contrast to other types of receptors that have been studied, wherein ligands bind externally to the membrane, the
932:. In addition, ADIPOR1 and ADIPOR2 are oriented oppositely to GPCRs in the membrane (i.e. GPCRs usually have an extracellular
8494:
7440:
5967:
2170:
1818:
2563:
G-protein-coupled receptor oligomerisation is a widespread phenomenon. One of the best-studied examples is the metabotropic
2359:
that can be generated and limited distance a G-protein can diffuse in 0.03 seconds. For the most part, the RGS proteins are
243:
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5982:"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.
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1594:
binding), which can modify the activity of these enzymes in an additive or synergistic fashion along with the G proteins.
9257:
8481:
7130:
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1788:
1008:
may also bind to a number of different sites, but the eventual effect must be prevention of this TM helix reorientation.
670:
3272:"Phylogenetic analysis of 277 human G-protein-coupled receptors as a tool for the prediction of orphan receptor ligands"
3241:"keyword:"G-protein coupled receptor [KW-0297]" AND organism:"Homo sapiens (Human) [9606]" in UniProtKB"
1373:
8386:
7355:
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2216:, wherein the activated GPCR causes downregulation of a different GPCR. The key reaction of this downregulation is the
2028:
1950:
was necessary for full efficacy chemotaxis of activated T cells. In addition, further scaffolding proteins involved in
1704:
1441:
1105:) domain primarily formed by a combination of IL-2 and IL-3 along with adjacent residues of the associated TM helices.
1102:
1062:
of one or more sites of the C-terminal tail or the intracellular loops. Palmitoylation is the covalent modification of
500:
for their work that was "crucial for understanding how G protein-coupled receptors function". There have been at least
404:
5919:
802:
receptors bind ligands that mediate intercellular communication between cells of the immune system; receptors such as
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2189:(PKC), which phosphorylates many other proteins, changing their catalytic activities, leading to cellular responses.
1970:
In the late 1990s, evidence began accumulating to suggest that some GPCRs are able to signal without G proteins. The
1935:
1914:
706:
GPCRs are involved in a wide variety of physiological processes. Some examples of their physiological roles include:
626:
505:
3152:"The top prescription drugs of 2012 globally: biologics dominate, but small molecule CNS drugs hold on to top spots"
980:
resembling a barrel, with the seven transmembrane helices forming a cavity within the plasma membrane that serves a
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6843:
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1998:
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
1127:
993:
504:
awarded for some aspect of G protein–mediated signaling. As of 2012, two of the top ten global best-selling drugs (
3459:"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.
1349:
662:
616:
5274:
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
1299:
1195:
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469:
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of the first GPCR, rhodopsin, in 2000 and the crystal structure of the first GPCR with a diffusible ligand (β
3576:
3041:
Wettschureck N, Offermanns S (October 2005). "Mammalian G proteins and their cell type specific functions".
1473:, which are now free to modulate the activity of other intracellular proteins. The extent to which they may
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3577:"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
5471:"The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor AP-2 during endocytosis"
1089:
GPCRs respond to extracellular signals mediated by a huge diversity of agonists, ranging from proteins to
1086:
pathways) are also targeted to lipid rafts, this has the effect of facilitating rapid receptor signaling.
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6420:
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4626:"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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2240:) are activated by the signal chain coming from the G protein (that was activated by the receptor) via
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1052:
977:
956:. Click the image for higher resolution to see details regarding the locations of important structures.
897:
822:
574:
227:
54:
4091:
Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, et al. (November 2007).
2767:"High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor"
2765:
Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, et al. (November 2007).
814:. GPCRs are also involved in immune-modulation, e. g. regulating interleukin induction or suppressing
9267:
7434:
7429:
7424:
7194:
7080:
6908:
6890:
6871:
6864:
6383:
6318:
6099:
4093:"GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function"
4009:
2348:
2192:
The effects of Ca are also remarkable: it cooperates with DAG in activating PKC and can activate the
2016:
1958:-containing proteins) may also act as signal transducers. Most often the effector is a member of the
1598:
1576:
is an example of a cellular protein that can be regulated by a G protein, in this case the G protein
1502:
860:
719:
179:
5085:"Biased agonists of the chemokine receptor CXCR3 differentially control chemotaxis and inflammation"
5083:
Smith JS, Nicholson LT, Suwanpradid J, Glenn RA, Knape NM, Alagesan P, et al. (November 2018).
1756:, or AC. While there are ten different AC gene products in mammals, each with subtle differences in
1082:. As many of the downstream transducer and effector molecules of GPCRs (including those involved in
687:) has been proposed for vertebrate GPCRs. They correspond to classical classes C, A, B2, F, and B.
184:
8989:
8858:
8818:
8464:
7388:
7350:
7209:
6998:
6922:
6876:
6366:
6243:
6212:
5827:
2670:
2641:
1979:
1951:
1445:
1361:
1163:
606:
596:
489:
4262:
Warne T, Moukhametzianov R, Baker JG, Nehmé R, Edwards PC, Leslie AG, et al. (January 2011).
3703:) Signals via G-alpha-s and Induces IL-6 and IL-10 Cytokine Secretion in Human Primary Leukocytes"
2407:(β-arrestin-1/2 in most tissues) is increased, at which point β-arrestin may bind and act to both
1097:, but all transduce this signal via a mechanism of G-protein coupling. This is made possible by a
7722:
7717:
7712:
7707:
7702:
7662:
7657:
7574:
7569:
7564:
7554:
7420:
7304:
7272:
7267:
7229:
7224:
7135:
6859:
6109:
6057:
5974:, a database of 3D structural models of all human G-protein coupled receptors, built by the GPCR-
2454:
buds inwardly as a result of interactions between the molecules of clathrin, in a process called
2063:
2055:
1799:
1626:
1159:
1032:
781:
5216:"G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels"
2450:. If enough receptors in the local area recruit clathrin in this manner, they aggregate and the
384:
There are two principal signal transduction pathways involving the G protein-coupled receptors:
7375:
7370:
7287:
7282:
6881:
6482:
6477:
6230:
6088:
4740:
Thomsen AR, Plouffe B, Cahill TJ, Shukla AK, Tarrasch JT, Dosey AM, et al. (August 2016).
4004:
3795:
Hazell GG, Hindmarch CC, Pope GR, Roper JA, Lightman SL, Murphy D, et al. (January 2012).
2624:
2174:
2092:
1995:
1911:
1907:
1903:
1822:
1768:
1696:
1672:
1566:
1457:
1381:
807:
441:
416:
5287:
5173:
Duchene J, Schanstra JP, Pecher C, Pizard A, Susini C, Esteve JP, et al. (October 2002).
928:). However, these 7TMH (7-transmembrane helices) receptors and channels do not associate with
9252:
8920:
7758:
7742:
7737:
7732:
7698:
7653:
7550:
7413:
7408:
7360:
7263:
7258:
7045:
6929:
6772:
6767:
6762:
6751:
6746:
6741:
6736:
6487:
6472:
6349:
6061:
5833:
5720:
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003).
4789:
Nguyen AH, Thomsen AR, Cahill TJ, Huang R, Huang LY, Marcink T, et al. (December 2019).
4683:
Kumari P, Srivastava A, Banerjee R, Ghosh E, Gupta P, Ranjan R, et al. (November 2016).
3516:
Vassilatis DK, Hohmann JG, Zeng H, Li F, Ranchalis JE, Mortrud MT, et al. (April 2003).
3079:
Hauser AS, Chavali S, Masuho I, Jahn LJ, Martemyanov KA, Gloriam DE, Babu MM (January 2018).
2720:
2596:
1862:
1834:
1610:
1584:
1453:
1385:
1365:
1321:
981:
559:
412:
354:
303:
4624:
Cahill TJ, Thomsen AR, Tarrasch JT, Plouffe B, Nguyen AH, Yang F, et al. (March 2017).
2694:
split is based on presumed function rather than signature, as the classical Class B (7tm_2,
8970:
8628:
7940:
7763:
7748:
7325:
7278:
6955:
6934:
6719:
6714:
6709:
6704:
6699:
6292:
6162:
5733:
5635:
5482:
5227:
4943:
4696:
4637:
4545:
4442:
4389:
4332:
4275:
4264:"The structural basis for agonist and partial agonist action on a β(1)-adrenergic receptor"
4218:
4161:
4148:
Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, et al. (January 2011).
4104:
4049:
3996:
3896:
3529:
3470:
2958:
2778:
2682:. Insect GPCRs appear to be in their own group and Taste2 is identified as descending from
2380:
2150:
2080:
2036:
1891:
1688:
1678:). Each sub-class of G-protein consists of multiple proteins, each the product of multiple
1606:
1470:
965:
913:
751:
636:
537:
396:
210:
7614:
7609:
7604:
5134:"Social senses: G-protein-coupled receptor signaling pathways in Dictyostelium discoideum"
4991:"Activation of G protein-coupled receptors entails cysteine modulation of agonist binding"
2496:
At any point in this process, the β-arrestins may also recruit other proteins—such as the
992:), which instead interact with the extracellular loops, or, as illustrated by the class C
896:), was solved. In 2007, the first structure of a human GPCR was solved This human
112:
8:
8793:
7728:
7619:
7403:
7366:
6831:
6460:
6392:
6220:
6104:
6084:
5214:
Chen-Izu Y, Xiao RP, Izu LT, Cheng H, Kuschel M, Spurgeon H, Lakatta EG (November 2000).
4376:
Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, et al. (July 2011).
4205:
Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, et al. (January 2011).
3938:
Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC (January 2014).
2620:
2331:
As mentioned above, G-proteins may terminate their own activation due to their intrinsic
1787:, and vice versa. The level of cytosolic cAMP may then determine the activity of various
1409:
1357:
1005:
917:
864:
578:
28:
5737:
5639:
5486:
5231:
4947:
4700:
4641:
4549:
4446:
4393:
4336:
4279:
4222:
4165:
4108:
4053:
4000:
3900:
3533:
3474:
3016:
2962:
2782:
1617:
molecules. Currently, GPCRs are considered to utilize two primary types of transducers:
9012:
8523:
8347:
7459:
7454:
7449:
7383:
6758:
6731:
6468:
6114:
6006:
5981:
5902:
5877:
5876:
Munk C, Isberg V, Mordalski S, Harpsøe K, Rataj K, Hauser AS, et al. (July 2016).
5659:
5608:
5554:
5529:
5469:
Laporte SA, Oakley RH, Zhang J, Holt JA, Ferguson SS, Caron MG, Barak LS (March 1999).
5334:
5248:
5215:
5109:
5084:
5060:
5033:
4966:
4931:
4912:
4864:
4839:
4815:
4790:
4766:
4741:
4717:
4684:
4660:
4625:
4513:
4488:
4466:
4410:
4377:
4353:
4320:
4296:
4263:
4239:
4206:
4182:
4149:
4130:
4073:
3964:
3939:
3920:
3869:
3821:
3796:
3777:
3729:
3698:
3604:
3493:
3458:
3408:
3176:
3151:
3105:
3080:
2982:
2917:
2892:
2838:
2799:
2766:
2546:
2352:
2020:
1803:
1602:
1506:
1313:
GPCRs that act as receptors for stimuli that have not yet been identified are known as
815:
803:
715:
581:. The very large rhodopsin A group has been further subdivided into 19 subgroups (
555:
338:, although a spontaneous auto-activation of an empty receptor has also been observed.
327:
34:
Class of cell surface receptors coupled to G-protein-associated intracellular signaling
5756:
5721:
5595:
5578:
5365:
5239:
5150:
5133:
5034:"Integrin and GPCR Crosstalk in the Regulation of ASM Contraction Signaling in Asthma"
5006:
3552:
3517:
3321:
Attwood TK, Findlay JB (February 1994). "Fingerprinting G-protein-coupled receptors".
3298:
3288:
3271:
2153:
signal pathway, the extracellular signal molecule binds with the G-protein receptor (G
322:
seven times in the form of six loops (three extracellular loops interacting with
8878:
8822:
8468:
8198:
8193:
7648:
7345:
6694:
6248:
6130:
6011:
5907:
5761:
5698:
5651:
5600:
5559:
5510:
5505:
5470:
5451:
5410:
5369:
5326:
5291:
5253:
5196:
5155:
5114:
5065:
4971:
4904:
4869:
4820:
4771:
4722:
4665:
4606:
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4518:
4458:
4415:
4358:
4301:
4244:
4187:
4122:
4065:
4022:
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3912:
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3826:
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3734:
3679:
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3596:
3557:
3498:
3400:
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3338:
3303:
3222:
3181:
3110:
3058:
3020:
2974:
2922:
2852:
2842:
2804:
2482:
2474:
2419:. Because only the liganded receptor is desensitized by this mechanism, it is called
2241:
2114:
2105:(Ri); stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi);
1865:. Once bound to GTP, Rho can then go on to activate various proteins responsible for
1845:
where it may activate any membrane localized forms of a second ser/thr kinase called
1647:
1573:
1521:
1510:
1345:
1083:
684:
566:
548:
544:
461:
218:
160:
5612:
5338:
4916:
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3426:
3412:
2698:
87:
7673:
7595:
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6053:
6001:
5993:
5897:
5889:
5751:
5741:
5690:
5663:
5643:
5590:
5549:
5541:
5500:
5490:
5441:
5400:
5361:
5318:
5283:
5243:
5235:
5186:
5145:
5104:
5096:
5055:
5045:
5002:
4961:
4951:
4896:
4859:
4851:
4810:
4802:
4761:
4753:
4712:
4704:
4655:
4645:
4596:
4588:
4553:
4508:
4500:
4450:
4405:
4397:
4348:
4340:
4291:
4283:
4234:
4226:
4177:
4169:
4134:
4112:
4077:
4057:
4014:
3959:
3951:
3924:
3904:
3853:
3816:
3808:
3761:
3724:
3714:
3671:
3636:
3588:
3547:
3537:
3488:
3478:
3392:
3330:
3293:
3283:
3214:
3171:
3163:
3100:
3092:
3050:
3012:
2986:
2966:
2912:
2904:
2834:
2827:"Chapter Three - Obestatin Receptor in Energy Homeostasis and Obesity Pathogenesis"
2794:
2786:
2521:
2434:. GRKs may also have GAP domains and so may contribute to inactivation through non-
2356:
2265:
2237:
2186:
2110:
2106:
2102:
1846:
1795:
1757:
1753:
1577:
880:
765:
497:
434:
427:
420:
370:
350:
206:
5853:. University of Edinburgh / International Union of Basic and Clinical Pharmacology
4900:
3608:
1894:–signalling, which can also be important, in particular in the case of activated G
172:
148:
100:
9066:
8853:
8662:
7951:
7633:
7600:
7340:
6637:
6622:
6617:
6612:
6602:
6597:
6592:
6587:
6582:
5971:
5964:
5840:
5785:
Reference for molecular and mathematical models for the initial receptor response
4018:
3844:
Dorsam RT, Gutkind JS (February 2007). "G-protein-coupled receptors and cancer".
3483:
2742:
2725:
2459:
2451:
2388:
2376:
2340:
2217:
2158:
2144:
1842:
1814:
1643:
1414:
1314:
1307:
1090:
1028:
1001:
573:. Despite the lack of sequence homology between classes, all GPCRs have a common
570:
124:
58:
4742:"GPCR-G Protein-β-Arrestin Super-Complex Mediates Sustained G Protein Signaling"
3812:
3218:
8939:
7799:
7627:
6854:
6647:
6642:
6632:
6608:
6578:
6573:
5726:
Proceedings of the
National Academy of Sciences of the United States of America
5475:
Proceedings of the
National Academy of Sciences of the United States of America
4936:
Proceedings of the
National Academy of Sciences of the United States of America
4757:
4630:
Proceedings of the
National Academy of Sciences of the United States of America
4319:
Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, et al. (April 2011).
3955:
3675:
3522:
Proceedings of the
National Academy of Sciences of the United States of America
3096:
3054:
2908:
2891:
Trzaskowski B, Latek D, Yuan S, Ghoshdastider U, Debinski A, Filipek S (2012).
2564:
2533:
2225:
2178:
1898:-coupled GPCRs. The primary effectors of Gβγ are various ion channels, such as
1850:
1683:
1630:
1478:
1461:
1449:
1263:
1215:
1203:
1187:
1171:
1059:
876:
680:
311:
299:
255:
5997:
5322:
5100:
4806:
3334:
1035:
of the intracellular surface for the binding of scaffolding proteins called β-
879:
to stabilize the receptor structure. Some seven-transmembrane helix proteins (
529:
The exact size of the GPCR superfamily is unknown, but at least 831 different
9241:
8994:
8643:
8638:
8633:
7559:
7495:
6563:
6178:
4489:"Inactive-state preassembly of G(q)-coupled receptors and G(q) heterotrimers"
4207:"Structure and function of an irreversible agonist-β(2) adrenoceptor complex"
3719:
3640:
2893:"Action of molecular switches in GPCRs--theoretical and experimental studies"
2659:
2558:
2517:
2336:
2162:
1955:
1942:. Such signaling has been shown to be physiologically relevant, for example,
1724:
1642:
There are three main G-protein-mediated signaling pathways, mediated by four
1486:
1283:
1243:
868:
791:
493:
319:
48:
5923:
5746:
5694:
4956:
4650:
4557:
4344:
4117:
4092:
3542:
2970:
2790:
1711:
of Gα may activate another if the preferred is less available. Furthermore,
8916:
7314:
7308:
6918:
6903:
6726:
6493:
6015:
5911:
5765:
5702:
5604:
5563:
5545:
5514:
5495:
5455:
5446:
5429:
5373:
5330:
5295:
5257:
5200:
5191:
5174:
5118:
5069:
4975:
4908:
4873:
4824:
4791:"Structure of an endosomal signaling GPCR-G protein-β-arrestin megacomplex"
4775:
4726:
4669:
4610:
4522:
4462:
4419:
4362:
4305:
4248:
4191:
4126:
4069:
4026:
3973:
3916:
3865:
3830:
3773:
3738:
3683:
3648:
3600:
3561:
3502:
3404:
3307:
3226:
3185:
3114:
3062:
3003:
Gilman AG (1987). "G proteins: transducers of receptor-generated signals".
2978:
2926:
2856:
2808:
2513:
2455:
2443:
2182:
1866:
1858:
1728:
1541:. Integrin signaling will phosphorylate FAK, which can then decrease GPCR G
1340:
Crystal structure of activated beta-2 adrenergic receptor in complex with G
1275:
1259:
1235:
1183:
1167:
1075:
832:
Cell density sensing: A novel GPCR role in regulating cell density sensing.
811:
795:
612:
602:
509:
5655:
5414:
5159:
5050:
4592:
4565:
4150:"Structure of a nanobody-stabilized active state of the β(2) adrenoceptor"
3369:
3342:
3024:
2825:
Zhang, Jian V.; Li, Lei; Huang, Qingsheng; Ren, Pei-Gen (1 January 2013).
2571:. This so-called constitutive receptor is formed by heterodimerization of
2260:, this phosphorylation results in the switching of the coupling from the G
2005:
1456:(GDP) (or, alternatively, no guanine nucleotide) but active when bound to
754:
bind odorants (olfactory receptors) and pheromones (vomeronasal receptors)
357:
that bind and activate these receptors include light-sensitive compounds,
27:"GPCR" redirects here. For the Great Proletarian Cultural Revolution, see
4855:
4504:
3203:
3130:"The Nobel Prize in Chemistry 2012 Robert J. Lefkowitz, Brian K. Kobilka"
2665:
2490:
2478:
2471:
2463:
2360:
1826:
1572:
Further signal transduction depends on the type of G protein. The enzyme
1211:
1199:
1191:
1071:
1048:
969:
886:
In 2000, the first crystal structure of a mammalian GPCR, that of bovine
6052:
5405:
5388:
4708:
4454:
4401:
4287:
4230:
4173:
4061:
3908:
3765:
2097:
The cAMP signal transduction contains five main characters: stimulative
1336:
9218:
9134:
8361:
6287:
6198:
5679:
5579:"A trafficking checkpoint controls GABA(B) receptor heterodimerization"
2636:
2501:
2408:
2400:
2364:
co-GEF) further contributing to the time resolution of GPCR signaling.
2245:
2197:
2027:), as well as modulation of various other "accessory" proteins such as
1976:
1939:
1854:
1749:
1720:
1618:
1614:
1591:
1482:
1295:
1279:
1267:
1251:
1247:
1155:
1151:
1079:
1067:
1040:
973:
961:
953:
937:
933:
839:
650:
563:
136:
6348:
5893:
5773:
4685:"Functional competence of a partially engaged GPCR-β-arrestin complex"
4601:
3592:
3396:
3356:
Kolakowski LF (1994). "GCRDb: a G-protein-coupled receptor database".
3167:
892:
883:) that resemble GPCRs may contain ion channels, within their protein.
520:
8927:
8848:
6370:
5871:
Data, diagrams and web tools for G protein-coupled receptors (GPCRs).
5866:
5530:"G-protein-coupled receptor phosphorylation: where, when and by whom"
3612:
3457:
Krishnan A, Almén MS, Fredriksson R, Schiöth HB (2012). Xue C (ed.).
2438:
mechanisms as well. A combination of these mechanisms may also occur.
2396:
2307:
2221:
2012:
1771:(ATP) to cAMP, and all are directly stimulated by G-proteins of the G
1765:
1562:
1435:
1231:
1227:
1223:
1219:
1143:
1139:
1123:
1024:
929:
887:
799:
785:
777:
769:
744:
743:
The gustatory sense (taste): GPCRs in taste cells mediate release of
723:
666:
408:
362:
342:
331:
315:
61:
4932:"Some G protein heterotrimers physically dissociate in living cells"
4378:"Crystal structure of the β2 adrenergic receptor-Gs protein complex"
3857:
2595:
R2 in heterologous systems leads to retention of the subunit in the
2231:
912:
GPCRs exhibit a similar structure to some other proteins with seven
9152:
9130:
6194:
5975:
5878:"GPCRdb: the G protein-coupled receptor database - an introduction"
2739:, a technique for control of cell signaling through synthetic GPCRs
2730:
2679:
2653:
2486:
2447:
2404:
2297:
2071:
There are two principal signal transduction pathways involving the
1984:
despite the absence of the associated G protein α- and β-subunits.
1943:
1931:
1761:
1712:
1622:
1597:
The signaling pathways activated through a GPCR are limited by the
1534:
1533:
GPCRs downstream signals have been shown to possibly interact with
1526:
1408:
It is believed that a receptor molecule exists in a conformational
1303:
1239:
1207:
1147:
1063:
1036:
960:
In terms of structure, GPCRs are characterized by an extracellular
948:
872:
773:
676:
646:
307:
119:
5647:
2047:
1775:
class. In contrast, however, interaction with Gα subunits of the G
1324:
of GPCRs typically bind within the transmembrane domain. However,
1113:
909:
confirmed that the Gα binds to a cavity created by this movement.
8223:
7933:
7928:
7923:
7918:
7913:
7908:
7903:
7898:
7893:
7888:
7883:
7878:
7873:
7868:
7863:
7858:
7853:
7848:
7544:
7539:
7534:
7529:
3697:
Saroz Y, Kho DT, Glass M, Graham ES, Grimsey NL (December 2019).
3127:
2932:
2890:
2623:
mediated by the superfamily of GPCRs dates back to the origin of
2612:
R1 causes masking of a retention signal of functional receptors.
2467:
2098:
1708:
1700:
1553:
1493:
1474:
1466:
1328:
are activated by cleavage of part of their extracellular domain.
1098:
1094:
997:
989:
985:
925:
921:
734:
727:
378:
374:
366:
335:
131:
5428:
Laporte SA, Oakley RH, Holt JA, Barak LS, Caron MG (July 2000).
4090:
3937:
2764:
2615:
1779:
type inhibits AC from generating cAMP. Thus, a GPCR coupled to G
9105:
9100:
9095:
9090:
9080:
9075:
9070:
9061:
9006:
9001:
8963:
8958:
8953:
8915:
8798:
8774:
8769:
8764:
8759:
8754:
8749:
8744:
8739:
8734:
8729:
8724:
8719:
8714:
8709:
8704:
8699:
8694:
8616:
8611:
8606:
8601:
8538:
8533:
8528:
8436:
8381:
8376:
8371:
8342:
8323:
8318:
8313:
8308:
8303:
8298:
8293:
8288:
8283:
8278:
8273:
8268:
8263:
8258:
8253:
8248:
8243:
8238:
8233:
8228:
8218:
8213:
8208:
8203:
8183:
7843:
7838:
7833:
7828:
7823:
7818:
7813:
7524:
7519:
7514:
7509:
7474:
7165:
6988:
6982:
6552:
6547:
6537:
6532:
5722:"The G protein-coupled receptor repertoires of human and mouse"
4887:
Brass LF (September 2003). "Thrombin and platelet activation".
3518:"The G protein-coupled receptor repertoires of human and mouse"
3456:
2580:
2572:
2435:
2392:
2332:
2311:
2166:
1605:
of the GPCR itself but ultimately determined by the particular
1175:
1020:
758:
540:
323:
260:
238:
5387:
Krueger KM, Daaka Y, Pitcher JA, Lefkowitz RJ (January 1997).
5082:
4990:
4261:
2512:(MAPK) signaling through, for example, phosphorylation of the
1665:
1658:
1651:
871:. These extracellular loops also contain two highly conserved
9201:
8892:
8887:
8689:
8684:
8679:
8674:
8650:
8596:
8591:
8586:
8431:
8426:
8416:
8411:
8352:
8178:
8173:
8168:
8163:
8158:
8153:
8148:
8143:
8138:
8133:
8128:
8123:
8118:
8113:
8108:
8103:
8098:
8093:
8088:
8083:
8078:
8073:
8068:
8063:
8058:
8053:
8048:
8043:
8038:
8033:
8028:
8023:
8018:
8013:
8008:
8003:
7998:
7993:
7988:
7983:
7504:
7469:
7319:
7159:
7154:
7149:
7144:
7139:
7125:
7119:
7114:
7109:
7104:
7099:
7094:
7089:
7084:
7074:
7069:
7064:
7059:
7054:
7049:
7017:
6977:
6972:
6895:
6807:
6802:
6797:
6792:
6787:
6782:
6542:
6527:
6522:
6517:
6512:
6507:
6502:
6497:
4682:
4039:
3886:
2936:
Text was copied from this source, which is available under a
2632:
2628:
2525:
2411:
hinder G-protein coupling as well as initiate the process of
1971:
1947:
1838:
1679:
1426:
1255:
1179:
843:
761:
711:
658:
533:
530:
381:. G protein-coupled receptors are involved in many diseases.
346:
5386:
5172:
4623:
4321:"Structure of an agonist-bound human A2A adenosine receptor"
3986:
747:
in response to bitter-, umami- and sweet-tasting substances.
9196:
9191:
9186:
9181:
9176:
9171:
9166:
9161:
9156:
8574:
8567:
8562:
8557:
8366:
8356:
7978:
7973:
7968:
7963:
7623:
7499:
6993:
6297:
5946:
2695:
2286:
Phosphorylation of the receptor can have two consequences:
1959:
1918:
1538:
657:
More recently, an alternative classification system called
358:
200:
143:
107:
94:
82:
9128:
5875:
4930:
Digby GJ, Lober RM, Sethi PR, Lambert NA (November 2006).
4739:
1917:, as well as some isoforms of AC and PLC, along with some
1460:(GTP). Upon receptor activation, the GEF domain, in turn,
1421:
8391:
5308:
2477:. At this point, the adapter molecules and clathrin have
4788:
4432:
3794:
2403:
tail. Upon GRK phosphorylation, the GPCR's affinity for
2326:
1364:
complex. Binding of an agonist to the GPCR results in a
5719:
4535:
4375:
4204:
4147:
3515:
3382:
3078:
2831:
Progress in
Molecular Biology and Translational Science
2212:, in which the activated GPCR is downregulated; and 2)
2006:
GPCR-independent signaling by heterotrimeric G-proteins
1817:(PLCβ), which catalyzes the cleavage of membrane-bound
1444:
domain may be bound to an also inactive α-subunit of a
1019:
proteins. In particular, the C-terminus often contains
314:
and activate cellular responses. They are coupled with
5576:
5468:
5427:
4929:
3040:
2335:
capability. However, this reaction proceeds at a slow
2138:
3128:
Royal Swedish Academy of Sciences (10 October 2012).
952:
Two-dimensional schematic of a generic GPCR set in a
5213:
5131:
2948:
2042:
5847:"IUPHAR/BPS Guide to PHARMACOLOGY Database (GPCRs)"
5311:
High Blood Pressure & Cardiovascular Prevention
5273:
3696:
3143:
3121:
3036:
3034:
943:
543:) have been predicted to code for them from genome
5979:
5625:
1924:
1900:G-protein-regulated inwardly rectifying K channels
1841:release from the ER, while DAG diffuses along the
1368:in the receptor that is transmitted to the bound G
1070:, and has the effect of targeting the receptor to
4988:
4840:"The year in G protein-coupled receptor research"
4578:
3751:
2886:
2884:
2882:
2880:
2878:
2232:Phosphorylation by cAMP-dependent protein kinases
1078:-rich microdomains of the plasma membrane called
867:. The extracellular parts of the receptor can be
757:Behavioral and mood regulation: Receptors in the
9239:
5980:Zhang J, Yang J, Jang R, Zhang Y (August 2015).
5577:Margeta-Mitrovic M, Jan YN, Jan LY (July 2000).
5351:
5132:Kim JY, Haastert PV, Devreotes PN (April 1996).
4486:
4482:
4480:
3031:
2604:functional receptor. It has been shown that GABA
2462:due to the actions of two other proteins called
2446:, which in turn recruits another protein called
1637:
863:that possess seven membrane-spanning domains or
821:Autonomic nervous system transmission: Both the
512:) act by targeting G protein-coupled receptors.
407:(GEF). The GPCR can then activate an associated
5675:
5673:
5269:
5267:
4487:Qin K, Dong C, Wu G, Lambert NA (August 2011).
4318:
3625:
3452:
3450:
3448:
3199:
3197:
3195:
2824:
2760:
2758:
2737:Receptor activated solely by a synthetic ligand
2302:: The phosphorylated receptor can be linked to
1646:of G-proteins distinguished from each other by
1058:A final common structural theme among GPCRs is
4084:
4033:
3940:"Insights into the structure of class B GPCRs"
3320:
2875:
2733:, a class of drug candidates targeted at GPCRs
2067:The effect of Ri and Gi in cAMP signal pathway
2059:The effect of Rs and Gs in cAMP signal pathway
2051:Activation effects of cAMP on protein kinase A
1783:counteracts the actions of a GPCR coupled to G
1561:If a receptor in an active state encounters a
1396:dimer and from the receptor. The dissociated G
341:G protein-coupled receptors are found only in
6334:
6038:
4477:
3880:
3843:
3074:
3072:
2998:
2996:
2616:Origin and diversification of the superfamily
1946:signaling mediated by the chemokine receptor
1890:The above descriptions ignore the effects of
835:Homeostasis modulation (e.g., water balance).
259:The seven-transmembrane α-helix structure of
5670:
5570:
5521:
5462:
5421:
5345:
5302:
5276:Annual Review of Pharmacology and Toxicology
5264:
5207:
4923:
4880:
4837:
4831:
4782:
4733:
4676:
4617:
4572:
4426:
4369:
4312:
4255:
4198:
4141:
3980:
3931:
3788:
3707:ACS Pharmacology & Translational Science
3655:
3619:
3574:
3445:
3269:
3192:
2755:
2631:, and have been classified according to the
2196:pathway, in which calcium-modulated protein
1388:which in turn triggers the dissociation of G
1372:subunit of the heterotrimeric G protein via
460:breakthroughs involved determination of the
6365:
5619:
5380:
5031:
4529:
3661:
2942:
2938:Attribution 2.5 Generic (CC BY 2.5) licence
2820:
2818:
2701:) is used to identify both in the studies.
2552:
2539:
2485:back to the plasma membrane or targeted to
1066:(Cys) residues via addition of hydrophobic
476:Seven years later, the crystallization of β
454:
373:, and vary in size from small molecules to
276:seven-(pass)-transmembrane domain receptors
8463:
6341:
6327:
6045:
6031:
3355:
3069:
2993:
2274:
2033:guanine-nucleotide dissociation inhibitors
47:
6005:
5901:
5826:at the U.S. National Library of Medicine
5755:
5745:
5594:
5553:
5504:
5494:
5445:
5404:
5288:10.1146/annurev.pharmtox.44.101802.121558
5247:
5190:
5149:
5108:
5059:
5049:
4965:
4955:
4863:
4814:
4795:Nature Structural & Molecular Biology
4765:
4716:
4659:
4649:
4600:
4512:
4409:
4352:
4295:
4238:
4181:
4116:
4008:
3963:
3820:
3728:
3718:
3551:
3541:
3492:
3482:
3297:
3287:
3175:
3104:
2916:
2798:
2678:GPCR receptor family before the split of
1877:also couple to other sub-classes, often G
1525:Proposed downstream interactions between
334:-like family). They are all activated by
6239:Serine/threonine-specific protein kinase
5920:"G Protein-Coupled Receptors on the NET"
4995:Journal of Molecular Structure: Theochem
3149:
2815:
2458:. Once the pit has been pinched off the
2062:
2054:
2046:
1798:(PKA) family. Thus cAMP is considered a
1552:
1520:
1425:
1335:
1331:
1112:
947:
519:
300:group of evolutionarily related proteins
254:
3081:"Pharmacogenomics of GPCR Drug Targets"
1505:, or GAP. In fact, many of the primary
1501:, or RGS proteins, which are a type of
1422:G-protein activation/deactivation cycle
818:-induced immune responses from T cells.
14:
9240:
7491:Luteinizing hormone/choriogonadotropin
3002:
2236:Cyclic AMP-dependent protein kinases (
2203:
2086:
1987:In mammalian cells, the much-studied β
1930:G-protein-dependent signaling such as
1497:allosteric modulating proteins called
1039:(β-arr). Once bound, β-arrestins both
726:, for example, uses the conversion of
701:
9127:
8914:
8495:Brain-specific angiogenesis inhibitor
8462:
6364:
6322:
6026:
5527:
4886:
4838:Millar RP, Newton CL (January 2010).
3575:Xiao X, Wang P, Chou KC (July 2009).
3433:from the original on 21 February 2008
2347:that, when bound to Gα through their
2327:Mechanisms of GPCR signal termination
2171:phosphatidylinositol 4,5-bisphosphate
1819:phosphatidylinositol 4,5-bisphosphate
854:
750:The sense of smell: Receptors of the
6303:Lipoprotein receptor-related protein
5804:from the original on 18 October 2012
2863:from the original on 17 January 2023
2711:G protein-coupled receptors database
2627:. Mammalian-like GPCRs are found in
2157:) on the cell surface and activates
1557:G-protein-coupled receptor mechanism
810:and engage target cell types in the
558:, while the remaining receptors are
5792:"The Nobel Prize in Chemistry 2012"
5434:The Journal of Biological Chemistry
5393:The Journal of Biological Chemistry
5179:The Journal of Biological Chemistry
3270:Joost P, Methner A (October 2002).
3017:10.1146/annurev.bi.56.070187.003151
2664:cAMP receptors before the split of
2173:(PIP2) into two second messengers:
2139:Phosphatidylinositol signal pathway
1873:(ROCK). Most GPCRs that couple to G
1440:When the receptor is inactive, the
920:and adiponectin receptors 1 and 2 (
24:
5713:
4989:Rubenstein LA, Lanzara RG (1998).
3944:Trends in Pharmacological Sciences
3581:Journal of Computational Chemistry
2839:10.1016/B978-0-12-386933-3.00003-0
2281:G protein-coupled receptor kinases
2175:inositol 1,4,5-trisphosphate (IP3)
1821:(PIP2) into the second messengers
976:. The GPCR arranges itself into a
405:guanine nucleotide exchange factor
25:
9289:
5817:
3289:10.1186/gb-2002-3-11-research0063
2520:, or recruit the proteins of the
2043:Details of cAMP and PIP2 pathways
1613:, as well as the availability of
1499:regulators of G-protein signaling
1477:, however, is limited due to the
1133:
1047:) pathway activation or receptor
940:, whereas ADIPORs are inverted).
627:Fungal mating pheromone receptors
515:
8844:Growth-hormone-releasing hormone
5032:Teoh CM, Tam JK, Tran T (2012).
5013:from the original on 16 May 2011
2931:
2587:subunits. Expression of the GABA
2510:mitogen-activated protein kinase
1885:
994:metabotropic glutamate receptors
944:Structure–function relationships
8804:Corticotropin-releasing hormone
6147:Metabotropic glutamate receptor
5882:British Journal of Pharmacology
5683:Molecular Biology and Evolution
5534:British Journal of Pharmacology
5166:
5125:
5076:
5025:
4982:
3837:
3801:Frontiers in Neuroendocrinology
3745:
3690:
3568:
3509:
3419:
3376:
3349:
3314:
3263:
3233:
1925:G-protein-independent signaling
1734:
7466:Gonadotropin-releasing hormone
6270:Tumor necrosis factor receptor
1823:inositol (1,4,5) trisphosphate
1760:distribution or function, all
1750:cyclic-adenosine monophosphate
1489:added to the C-termini of Gγ.
1292:gonadotropin-releasing hormone
13:
1:
8884:Vasoactive intestinal peptide
7754:Thyrotropin-releasing hormone
6308:Progestin and adipoQ receptor
5596:10.1016/S0896-6273(00)00012-X
5366:10.1016/S0898-6568(03)00099-8
5240:10.1016/S0006-3495(00)76495-2
5151:10.1016/S1074-5521(96)90103-9
5007:10.1016/S0166-1280(98)90217-2
4901:10.1378/chest.124.3_suppl.18S
3005:Annual Review of Biochemistry
2748:
2481:, and the receptor is either
2417:clathrin-mediated endocytosis
2367:In addition, the GPCR may be
1833:found in the membrane of the
1638:G-protein-dependent signaling
1481:of Gα and the presence of an
1300:thyrotropin-releasing hormone
1196:vasoactive intestinal peptide
1162:), hepatocyte growth factor (
1101:-nucleotide exchange factor (
696:pseudo amino acid composition
470:cryogenic electron microscopy
415:bound to the G protein for a
195:Available protein structures:
4019:10.1126/science.289.5480.739
3754:Journal of Leukocyte Biology
3484:10.1371/journal.pone.0029817
2716:List of MeSH codes (D12.776)
2498:non-receptor tyrosine kinase
2432:heterologous desensitization
2214:heterologous desensitization
2101:receptor (Rs) or inhibitory
1625:. Because β-arr's have high
1548:
1516:
1326:protease-activated receptors
1288:follicle-stimulating hormone
1108:
57:in complex with the partial
7:
9248:G protein-coupled receptors
7669:Prolactin-releasing peptide
6354:G protein-coupled receptors
6283:-Acetylglucosamine receptor
6265:Asialoglycoprotein receptor
6095:Protease-activated receptor
5824:G-protein-coupled+receptors
3813:10.1016/j.yfrne.2011.07.002
3699:"Cannabinoid Receptor 2 (CB
3664:Protein and Peptide Letters
3219:10.1016/j.ygeno.2006.04.001
2897:Current Medicinal Chemistry
2704:
2371:itself. This can occur as:
1965:
1609:stabilized by a particular
1448:. These "G-proteins" are a
1278:); peptide hormones (e.g.,
536:(or about 4% of the entire
268:G protein-coupled receptors
10:
9294:
9258:Integral membrane proteins
6275:Immunoglobulin superfamily
6070:G protein-coupled receptor
4758:10.1016/j.cell.2016.07.004
3956:10.1016/j.tips.2013.11.001
3676:10.2174/092986610791112693
3097:10.1016/j.cell.2017.11.033
3055:10.1152/physrev.00003.2005
2909:10.2174/092986712799320556
2829:. In Tao, Ya-Xiong (ed.).
2556:
2421:homologous desensitization
2264:class of G-protein to the
2210:homologous desensitization
2181:(DAG). IP3 binds with the
2161:, which is located on the
2142:
2090:
2073:G protein-linked receptors
1853:activates proteins called
1791:as well as members of the
1740:The effector of both the G
1469:and a tightly interacting
1433:
1358:transduction of the signal
1272:platelet-activating factor
1027:(Thr) residues that, when
861:integral membrane proteins
292:G protein-linked receptors
55:beta-2 adrenergic receptor
26:
18:G-protein-coupled receptor
9211:
9145:
9141:
9123:
8980:
8938:
8934:
8910:
8784:
8661:
8480:
8476:
8458:
8333:
7950:
7798:
7791:
7297:
7185:
7178:
6943:
6830:
6821:
6657:
6562:
6459:
6391:
6382:
6378:
6360:
6257:
6229:
6211:
6187:
6171:
6155:
6139:
6123:
6100:Neurotransmitter receptor
6077:
6068:
5998:10.1016/j.str.2015.06.007
5943:"PSI GPCR Network Center"
5936:a classification of GPCRs
5323:10.1007/s40292-013-0001-8
5101:10.1126/scisignal.aaq1075
4807:10.1038/s41594-019-0330-y
3156:ACS Chemical Neuroscience
3150:Lindsley CW (June 2013).
2399:residues of IL-3 and the
2355:due to limited amount of
2220:of the intracellular (or
2017:receptor tyrosine kinases
1919:phosphoinositide-3-kinase
1915:voltage-gated Ca channels
1752:(cAMP)-generating enzyme
1503:GTPase-activating protein
1492:Because Gα also has slow
720:electromagnetic radiation
237:
217:
199:
194:
190:
178:
166:
154:
142:
130:
118:
106:
93:
81:
73:
68:
46:
41:
8990:Calcium-sensing receptor
8859:Methuselah-like proteins
6244:Receptor tyrosine kinase
6213:Ligand-gated ion channel
5828:Medical Subject Headings
5774:"GPCR Reference Library"
3720:10.1021/acsptsci.9b00049
3641:10.1016/j.ab.2009.04.009
3358:Receptors & Channels
2674:family evolved from the
2599:. Expression of the GABA
2553:Receptor oligomerization
2540:GPCR cellular regulation
2413:receptor internalization
2379:, wherein the change in
1952:subcellular localization
1857:, which in turn tosolic
1446:heterotrimeric G-protein
1362:heterotrimeric G protein
1142:stimulatory molecules);
607:Secretin receptor family
502:seven other Nobel Prizes
490:Nobel Prize in Chemistry
455:History and significance
318:. They pass through the
7136:Sphingosine-1-phosphate
7024:Hydroxycarboxylic acids
6110:Biogenic amine receptor
5970:1 February 2016 at the
5747:10.1073/pnas.0230374100
5528:Tobin AB (March 2008).
5138:Chemistry & Biology
4957:10.1073/pnas.0607116103
4844:Molecular Endocrinology
4651:10.1073/pnas.1701529114
4581:Journal of Cell Science
4558:10.1126/science.2163110
4493:Nature Chemical Biology
4345:10.1126/science.1202793
4118:10.1126/science.1150609
3629:Analytical Biochemistry
3543:10.1073/pnas.0230374100
3385:Pharmacological Reviews
3335:10.1093/protein/7.2.195
2971:10.1126/science.1083853
2791:10.1126/science.1150577
2387:(GRKs), which go on to
2385:GPCR-Regulating Kinases
2275:Phosphorylation by GRKs
2079:signal pathway and the
1715:pathways may result in
1374:protein domain dynamics
1158:, γ-aminobutyric acid (
838:Involved in growth and
764:bind several different
722:into cellular signals.
480:-adrenergic receptor (β
9017:Metabotropic glutamate
6231:Enzyme-linked receptor
6089:Prostaglandin receptor
6062:cell surface receptors
5546:10.1038/sj.bjp.0707662
5496:10.1073/pnas.96.7.3712
5447:10.1074/jbc.M002581200
5192:10.1074/jbc.M202744200
3846:Nature Reviews. Cancer
2383:allows recruitment of
2093:cAMP-dependent pathway
2068:
2060:
2052:
1996:bradykinin receptor B2
1769:adenosine triphosphate
1717:receptor modifications
1697:functional selectivity
1558:
1530:
1458:guanosine triphosphate
1431:
1353:
1119:
957:
808:inflammatory mediators
718:reaction to translate
710:The visual sense: The
617:Metabotropic glutamate
526:
304:cell surface receptors
284:heptahelical receptors
264:
9278:Protein superfamilies
7046:Lysophosphatidic acid
6350:Cell surface receptor
5695:10.1093/molbev/msr061
4689:Nature Communications
4593:10.1242/jcs.115.3.455
3043:Physiological Reviews
2721:Metabotropic receptor
2597:endoplasmic reticulum
2224:) receptor domain by
2111:protein kinase A
2066:
2058:
2050:
1994:In kidney cells, the
1835:endoplasmic reticulum
1809:The effector of the G
1796:protein kinase A
1556:
1524:
1485:moiety that has been
1454:Guanosine diphosphate
1429:
1366:conformational change
1339:
1332:Conformational change
1116:
951:
914:transmembrane domains
865:transmembrane helices
812:inflammatory response
569:or are classified as
523:
258:
8971:Vomeronasal receptor
7941:Vomeronasal receptor
6293:Transferrin receptor
5839:3 April 2015 at the
5540:(Suppl 1): S167–76.
4895:(3 Suppl): 18S–25S.
4856:10.1210/me.2009-0473
4505:10.1038/nchembio.642
3282:(11): RESEARCH0063.
3251:on 15 September 2020
2504:—which may activate
2151:phosphatidylinositol
2081:phosphatidylinositol
2037:protein phosphatases
1802:and PKA a secondary
964:, followed by seven
918:microbial rhodopsins
902:-adrenergic receptor
752:olfactory epithelium
637:Cyclic AMP receptors
397:phosphatidylinositol
288:serpentine receptors
9273:Signal transduction
8864:Parathyroid hormone
6824:signaling molecules
6221:Purinergic receptor
6105:Purinergic receptor
6085:Eicosanoid receptor
5738:2003PNAS..100.4903V
5640:1998Natur.396..679W
5487:1999PNAS...96.3712L
5406:10.1074/jbc.272.1.5
5354:Cellular Signalling
5232:2000BpJ....79.2547C
5220:Biophysical Journal
5051:10.1155/2012/341282
4948:2006PNAS..10317789D
4709:10.1038/ncomms13416
4701:2016NatCo...713416K
4642:2017PNAS..114.2562C
4550:1990Sci...248.1547L
4455:10.1038/nature01705
4447:2003Natur.423..762Y
4402:10.1038/nature10361
4394:2011Natur.477..549R
4337:2011Sci...332..322X
4288:10.1038/nature09746
4280:2011Natur.469..241W
4231:10.1038/nature09665
4223:2011Natur.469..236R
4174:10.1038/nature09648
4166:2011Natur.469..175R
4109:2007Sci...318.1266R
4062:10.1038/nature06325
4054:2007Natur.450..383R
4001:2000Sci...289..739P
3909:10.1038/nature11896
3901:2013Natur.494..185V
3766:10.1189/jlb.0712328
3534:2003PNAS..100.4903V
3475:2012PLoSO...729817K
3323:Protein Engineering
2963:2003Sci...301..361K
2783:2007Sci...318.1258C
2657:, evolved from the
2621:Signal transduction
2591:R1 without the GABA
2547:degradative enzymes
2375:a direct result of
2204:Receptor regulation
2087:cAMP signal pathway
1869:regulation such as
1829:(DAG). IP3 acts on
875:residues that form
804:histamine receptors
702:Physiological roles
579:signal transduction
556:olfactory receptors
328:amino acid residues
29:Cultural Revolution
9013:Glutamate receptor
8398:Protease-activated
6163:Pheromone receptor
6115:Olfactory receptor
5038:Journal of Allergy
3091:(1–2): 41–54.e19.
2608:R2 binding to GABA
2333:GTP→GDP hydrolysis
2250:feedback mechanism
2069:
2061:
2053:
2021:cytokine receptors
1764:the conversion of
1723:ligand under most
1603:tertiary structure
1559:
1531:
1511:adenylate cyclases
1494:GTP→GDP hydrolysis
1432:
1392:subunit from the G
1380:subunit exchanges
1354:
1120:
978:tertiary structure
958:
855:Receptor structure
716:photoisomerization
527:
411:by exchanging the
392:signal pathway and
265:
9263:Molecular biology
9235:
9234:
9231:
9230:
9227:
9226:
9119:
9118:
9115:
9114:
8906:
8905:
8902:
8901:
8454:
8453:
8450:
8449:
8446:
8445:
7787:
7786:
7174:
7173:
6817:
6816:
6316:
6315:
6249:Guanylate cyclase
6207:
6206:
6131:Secretin receptor
6054:Membrane proteins
5894:10.1111/bph.13509
5095:(555): eaaq1075.
5089:Science Signaling
4801:(12): 1123–1131.
4636:(10): 2562–2567.
4544:(4962): 1547–50.
4103:(5854): 1266–73.
3593:10.1002/jcc.21163
3397:10.1124/pr.57.2.5
3168:10.1021/cn400107y
2777:(5854): 1258–65.
2377:ligand occupation
2322:-adrenoreceptors.
2242:adenylate cyclase
2115:phosphodiesterase
1921:(PI3K) isoforms.
1815:phospholipase C-β
1754:adenylate cyclase
1684:splice variations
1648:sequence homology
1574:adenylate cyclase
1537:signals, such as
1376:. The activated G
1194:, members of the
1084:negative feedback
842:of some types of
766:neurotransmitters
740:for this purpose.
577:and mechanism of
551:between classes.
549:sequence homology
545:sequence analysis
462:crystal structure
371:neurotransmitters
351:choanoflagellates
274:), also known as
253:
252:
249:
248:
244:structure summary
16:(Redirected from
9285:
9268:Protein families
9143:
9142:
9125:
9124:
8936:
8935:
8912:
8911:
8478:
8477:
8460:
8459:
7796:
7795:
7183:
7182:
7081:Lysophospholipid
6828:
6827:
6389:
6388:
6384:Neurotransmitter
6380:
6379:
6362:
6361:
6343:
6336:
6329:
6320:
6319:
6075:
6074:
6047:
6040:
6033:
6024:
6023:
6019:
6009:
5992:(8): 1538–1549.
5961:
5956:
5954:
5945:. Archived from
5938:
5933:
5931:
5922:. Archived from
5915:
5905:
5888:(14): 2195–207.
5873:
5862:
5860:
5858:
5813:
5811:
5809:
5803:
5796:
5787:
5782:
5780:
5769:
5759:
5749:
5707:
5706:
5677:
5668:
5667:
5634:(6712): 679–82.
5623:
5617:
5616:
5598:
5574:
5568:
5567:
5557:
5525:
5519:
5518:
5508:
5498:
5466:
5460:
5459:
5449:
5425:
5419:
5418:
5408:
5384:
5378:
5377:
5349:
5343:
5342:
5306:
5300:
5299:
5271:
5262:
5261:
5251:
5211:
5205:
5204:
5194:
5185:(43): 40375–83.
5170:
5164:
5163:
5153:
5129:
5123:
5122:
5112:
5080:
5074:
5073:
5063:
5053:
5029:
5023:
5022:
5020:
5018:
4986:
4980:
4979:
4969:
4959:
4942:(47): 17789–94.
4927:
4921:
4920:
4884:
4878:
4877:
4867:
4835:
4829:
4828:
4818:
4786:
4780:
4779:
4769:
4737:
4731:
4730:
4720:
4680:
4674:
4673:
4663:
4653:
4621:
4615:
4614:
4604:
4587:(Pt 3): 455–65.
4576:
4570:
4569:
4533:
4527:
4526:
4516:
4484:
4475:
4474:
4430:
4424:
4423:
4413:
4388:(7366): 549–55.
4373:
4367:
4366:
4356:
4316:
4310:
4309:
4299:
4259:
4253:
4252:
4242:
4217:(7329): 236–40.
4202:
4196:
4195:
4185:
4160:(7329): 175–80.
4145:
4139:
4138:
4120:
4088:
4082:
4081:
4037:
4031:
4030:
4012:
4010:10.1.1.1012.2275
3995:(5480): 739–45.
3984:
3978:
3977:
3967:
3935:
3929:
3928:
3895:(7436): 185–94.
3884:
3878:
3877:
3841:
3835:
3834:
3824:
3792:
3786:
3785:
3749:
3743:
3742:
3732:
3722:
3694:
3688:
3687:
3659:
3653:
3652:
3623:
3617:
3616:
3615:on 9 April 2017.
3611:. Archived from
3572:
3566:
3565:
3555:
3545:
3513:
3507:
3506:
3496:
3486:
3454:
3443:
3442:
3440:
3438:
3423:
3417:
3416:
3380:
3374:
3373:
3353:
3347:
3346:
3318:
3312:
3311:
3301:
3291:
3267:
3261:
3260:
3258:
3256:
3247:. Archived from
3237:
3231:
3230:
3201:
3190:
3189:
3179:
3147:
3141:
3140:
3138:
3136:
3125:
3119:
3118:
3108:
3076:
3067:
3066:
3038:
3029:
3028:
3000:
2991:
2990:
2946:
2940:
2935:
2930:
2920:
2888:
2873:
2872:
2870:
2868:
2822:
2813:
2812:
2802:
2762:
2686:. Note that the
2625:multicellularity
2524:directly (i.e.,
2357:second messenger
2238:protein kinase A
2187:protein kinase C
2113:(PKA); and cAMP
2107:adenylyl cyclase
2103:hormone receptor
2083:signal pathway.
1954:of GPCRs (e.g.,
1847:protein kinase C
1800:second messenger
1793:ser/thr-specific
1748:pathways is the
1599:primary sequence
1509:proteins (e.g.,
1415:inverse agonists
1315:orphan receptors
1308:endocannabinoids
1002:Inverse agonists
895:
881:channelrhodopsin
571:orphan receptors
498:Robert Lefkowitz
298:), form a large
192:
191:
51:
39:
38:
21:
9293:
9292:
9288:
9287:
9286:
9284:
9283:
9282:
9238:
9237:
9236:
9223:
9207:
9137:
9111:
8998:
8976:
8930:
8898:
8780:
8657:
8472:
8442:
8329:
7946:
7783:
7389:Cholecystokinin
7293:
7170:
6999:Free fatty acid
6939:
6823:
6822:Metabolites and
6813:
6653:
6558:
6455:
6374:
6356:
6347:
6317:
6312:
6258:Other/ungrouped
6253:
6225:
6203:
6183:
6167:
6151:
6135:
6119:
6064:
6051:
5972:Wayback Machine
5952:
5950:
5949:on 25 July 2013
5941:
5929:
5927:
5926:on 23 July 2011
5918:
5865:
5856:
5854:
5851:IUPHAR Database
5845:
5841:Wayback Machine
5820:
5807:
5805:
5801:
5794:
5790:
5778:
5776:
5772:
5716:
5714:Further reading
5711:
5710:
5678:
5671:
5624:
5620:
5575:
5571:
5526:
5522:
5467:
5463:
5440:(30): 23120–6.
5426:
5422:
5385:
5381:
5350:
5346:
5307:
5303:
5272:
5265:
5212:
5208:
5171:
5167:
5130:
5126:
5081:
5077:
5030:
5026:
5016:
5014:
4987:
4983:
4928:
4924:
4885:
4881:
4836:
4832:
4787:
4783:
4738:
4734:
4681:
4677:
4622:
4618:
4577:
4573:
4534:
4530:
4485:
4478:
4441:(6941): 762–9.
4431:
4427:
4374:
4370:
4331:(6027): 322–7.
4317:
4313:
4274:(7329): 241–4.
4260:
4256:
4203:
4199:
4146:
4142:
4089:
4085:
4048:(7168): 383–7.
4038:
4034:
3985:
3981:
3936:
3932:
3885:
3881:
3858:10.1038/nrc2069
3842:
3838:
3793:
3789:
3750:
3746:
3702:
3695:
3691:
3660:
3656:
3624:
3620:
3573:
3569:
3514:
3510:
3455:
3446:
3436:
3434:
3425:
3424:
3420:
3381:
3377:
3354:
3350:
3319:
3315:
3268:
3264:
3254:
3252:
3245:www.uniprot.org
3239:
3238:
3234:
3202:
3193:
3148:
3144:
3134:
3132:
3126:
3122:
3077:
3070:
3049:(4): 1159–204.
3039:
3032:
3001:
2994:
2957:(5631): 361–3.
2947:
2943:
2903:(8): 1090–109.
2889:
2876:
2866:
2864:
2849:
2823:
2816:
2763:
2756:
2751:
2743:TOG superfamily
2726:Orphan receptor
2707:
2618:
2611:
2607:
2602:
2594:
2590:
2584:
2576:
2568:
2561:
2555:
2542:
2470:, it is now an
2460:plasma membrane
2329:
2321:
2317:
2277:
2269:
2263:
2257:
2234:
2226:protein kinases
2218:phosphorylation
2206:
2163:plasma membrane
2159:phospholipase C
2156:
2147:
2145:IP3/DAG pathway
2141:
2095:
2089:
2045:
2008:
1990:
1968:
1927:
1897:
1888:
1880:
1876:
1843:plasma membrane
1837:(ER) to elicit
1812:
1786:
1782:
1778:
1774:
1747:
1743:
1737:
1689:βγ combinations
1676:
1669:
1662:
1655:
1640:
1581:
1551:
1544:
1519:
1465:yield a Gα-GTP
1438:
1424:
1403:
1399:
1395:
1391:
1379:
1371:
1343:
1334:
1204:biogenic amines
1136:
1111:
1091:biogenic amines
1053:desensitization
1031:, increase the
1018:
1014:
946:
908:
901:
891:
877:disulfide bonds
857:
827:parasympathetic
704:
518:
492:was awarded to
483:
479:
467:
457:
445:
438:
431:
424:
399:signal pathway.
156:OPM superfamily
64:
59:inverse agonist
35:
32:
23:
22:
15:
12:
11:
5:
9291:
9281:
9280:
9275:
9270:
9265:
9260:
9255:
9250:
9233:
9232:
9229:
9228:
9225:
9224:
9222:
9221:
9215:
9213:
9209:
9208:
9206:
9205:
9199:
9194:
9189:
9184:
9179:
9174:
9169:
9164:
9159:
9149:
9147:
9139:
9138:
9121:
9120:
9117:
9116:
9113:
9112:
9110:
9109:
9103:
9098:
9093:
9084:
9078:
9073:
9064:
9059:
9053:
9048:
9043:
9038:
9033:
9028:
9023:
9010:
9004:
8996:
8992:
8986:
8984:
8978:
8977:
8975:
8974:
8968:
8967:
8966:
8961:
8956:
8945:
8943:
8932:
8931:
8908:
8907:
8904:
8903:
8900:
8899:
8897:
8896:
8890:
8881:
8876:
8870:
8861:
8856:
8851:
8846:
8841:
8835:
8830:
8825:
8816:
8810:
8801:
8796:
8790:
8788:
8782:
8781:
8779:
8778:
8772:
8767:
8762:
8757:
8752:
8747:
8742:
8737:
8732:
8727:
8722:
8717:
8712:
8707:
8702:
8697:
8692:
8687:
8682:
8677:
8667:
8665:
8659:
8658:
8656:
8655:
8654:
8653:
8648:
8647:
8646:
8641:
8636:
8621:
8620:
8619:
8614:
8609:
8604:
8599:
8594:
8589:
8579:
8578:
8577:
8572:
8571:
8570:
8565:
8560:
8545:
8544:
8543:
8542:
8541:
8536:
8531:
8516:
8515:
8514:
8513:
8512:
8507:
8502:
8486:
8484:
8474:
8473:
8456:
8455:
8452:
8451:
8448:
8447:
8444:
8443:
8441:
8440:
8434:
8429:
8420:
8414:
8409:
8404:
8395:
8389:
8384:
8379:
8374:
8369:
8364:
8359:
8350:
8345:
8343:Adrenomedullin
8339:
8337:
8331:
8330:
8328:
8327:
8321:
8316:
8311:
8306:
8301:
8296:
8291:
8286:
8281:
8276:
8271:
8266:
8261:
8256:
8251:
8246:
8241:
8236:
8231:
8226:
8221:
8216:
8211:
8206:
8201:
8196:
8191:
8186:
8181:
8176:
8171:
8166:
8161:
8156:
8151:
8146:
8141:
8136:
8131:
8126:
8121:
8116:
8111:
8106:
8101:
8096:
8091:
8086:
8081:
8076:
8071:
8066:
8061:
8056:
8051:
8046:
8041:
8036:
8031:
8026:
8021:
8016:
8011:
8006:
8001:
7996:
7991:
7986:
7981:
7976:
7971:
7966:
7956:
7954:
7948:
7947:
7945:
7944:
7938:
7937:
7936:
7931:
7926:
7921:
7916:
7911:
7906:
7901:
7896:
7891:
7886:
7881:
7876:
7871:
7866:
7861:
7856:
7851:
7846:
7841:
7836:
7831:
7826:
7821:
7816:
7805:
7803:
7793:
7789:
7788:
7785:
7784:
7782:
7781:
7775:
7770:
7761:
7756:
7751:
7746:
7740:
7735:
7726:
7720:
7715:
7710:
7705:
7696:
7690:
7685:
7680:
7671:
7666:
7660:
7651:
7646:
7640:
7631:
7617:
7612:
7607:
7598:
7593:
7587:
7578:
7572:
7567:
7562:
7557:
7548:
7542:
7537:
7532:
7527:
7522:
7517:
7512:
7507:
7502:
7493:
7488:
7483:
7478:
7472:
7463:
7457:
7452:
7443:
7438:
7432:
7427:
7421:Formyl peptide
7418:
7417:
7416:
7411:
7401:
7395:
7386:
7381:
7380:
7379:
7373:
7364:
7358:
7353:
7343:
7338:
7332:
7323:
7317:
7311:
7301:
7299:
7295:
7294:
7292:
7291:
7285:
7276:
7270:
7261:
7252:
7246:
7241:
7236:
7227:
7222:
7216:
7207:
7201:
7191:
7189:
7180:
7176:
7175:
7172:
7171:
7169:
7168:
7163:
7157:
7152:
7147:
7142:
7133:
7128:
7123:
7117:
7112:
7107:
7102:
7097:
7092:
7087:
7078:
7072:
7067:
7062:
7057:
7052:
7043:
7042:
7041:
7036:
7031:
7021:
7015:
7010:
7005:
6996:
6991:
6986:
6980:
6975:
6962:
6953:
6947:
6945:
6941:
6940:
6938:
6937:
6932:
6927:
6926:
6925:
6916:
6911:
6906:
6893:
6879:
6874:
6869:
6868:
6867:
6862:
6852:
6846:
6836:
6834:
6825:
6819:
6818:
6815:
6814:
6812:
6811:
6805:
6800:
6795:
6790:
6785:
6776:
6770:
6765:
6756:
6755:
6754:
6749:
6744:
6739:
6729:
6724:
6723:
6722:
6717:
6712:
6707:
6702:
6692:
6686:
6681:
6676:
6671:
6661:
6659:
6655:
6654:
6652:
6651:
6645:
6640:
6635:
6626:
6620:
6615:
6606:
6600:
6595:
6590:
6585:
6568:
6566:
6560:
6559:
6557:
6556:
6550:
6545:
6540:
6535:
6530:
6525:
6520:
6515:
6510:
6505:
6500:
6491:
6485:
6480:
6475:
6465:
6463:
6457:
6456:
6454:
6453:
6448:
6443:
6438:
6432:
6427:
6418:
6412:
6407:
6397:
6395:
6386:
6376:
6375:
6358:
6357:
6346:
6345:
6338:
6331:
6323:
6314:
6313:
6311:
6310:
6305:
6300:
6295:
6290:
6285:
6277:
6272:
6267:
6261:
6259:
6255:
6254:
6252:
6251:
6246:
6241:
6235:
6233:
6227:
6226:
6224:
6223:
6217:
6215:
6209:
6208:
6205:
6204:
6202:
6201:
6191:
6189:
6185:
6184:
6182:
6181:
6175:
6173:
6169:
6168:
6166:
6165:
6159:
6157:
6153:
6152:
6150:
6149:
6143:
6141:
6137:
6136:
6134:
6133:
6127:
6125:
6121:
6120:
6118:
6117:
6112:
6107:
6102:
6097:
6092:
6081:
6079:
6072:
6066:
6065:
6050:
6049:
6042:
6035:
6027:
6021:
6020:
5962:
5939:
5916:
5863:
5843:
5834:GPCR Cell Line
5831:
5819:
5818:External links
5816:
5815:
5814:
5788:
5770:
5715:
5712:
5709:
5708:
5689:(9): 2471–80.
5669:
5618:
5569:
5520:
5461:
5420:
5379:
5360:(11): 973–81.
5344:
5301:
5282:(1): 559–609.
5263:
5226:(5): 2547–56.
5206:
5165:
5124:
5075:
5024:
4981:
4922:
4879:
4830:
4781:
4752:(4): 907–919.
4732:
4675:
4616:
4571:
4528:
4476:
4425:
4368:
4311:
4254:
4197:
4140:
4083:
4032:
3979:
3930:
3879:
3836:
3787:
3744:
3713:(6): 414–428.
3700:
3689:
3654:
3618:
3587:(9): 1414–23.
3567:
3508:
3444:
3418:
3375:
3348:
3329:(2): 195–203.
3313:
3276:Genome Biology
3262:
3232:
3191:
3142:
3120:
3068:
3030:
2992:
2941:
2874:
2847:
2814:
2753:
2752:
2750:
2747:
2746:
2745:
2740:
2734:
2728:
2723:
2718:
2713:
2706:
2703:
2617:
2614:
2609:
2605:
2600:
2592:
2588:
2582:
2574:
2566:
2557:Main article:
2554:
2551:
2541:
2538:
2440:
2439:
2427:
2423:
2328:
2325:
2324:
2323:
2319:
2315:
2294:
2276:
2273:
2267:
2261:
2258:-adrenoceptors
2255:
2233:
2230:
2205:
2202:
2179:diacylglycerol
2154:
2143:Main article:
2140:
2137:
2091:Main article:
2088:
2085:
2044:
2041:
2007:
2004:
1988:
1967:
1964:
1926:
1923:
1895:
1887:
1884:
1883:
1882:
1878:
1874:
1851:allosterically
1827:diacylglycerol
1810:
1807:
1784:
1780:
1776:
1772:
1745:
1741:
1736:
1733:
1674:
1667:
1660:
1653:
1639:
1636:
1631:phosphorylated
1587:-bound state.
1579:
1550:
1547:
1542:
1518:
1515:
1479:palmitoylation
1462:allosterically
1423:
1420:
1401:
1397:
1393:
1389:
1377:
1369:
1341:
1333:
1330:
1264:prostaglandins
1216:norepinephrine
1172:neuropeptide Y
1135:
1134:Ligand binding
1132:
1110:
1107:
1060:palmitoylation
1029:phosphorylated
1016:
1012:
945:
942:
936:, cytoplasmic
906:
899:
856:
853:
852:
851:
850:transcription.
847:
836:
833:
830:
819:
790:Regulation of
788:
755:
748:
741:
703:
700:
655:
654:
640:
630:
620:
610:
600:
597:Rhodopsin-like
538:protein-coding
517:
516:Classification
514:
481:
477:
465:
456:
453:
443:
436:
429:
422:
401:
400:
393:
251:
250:
247:
246:
241:
235:
234:
221:
215:
214:
204:
197:
196:
188:
187:
182:
176:
175:
170:
164:
163:
158:
152:
151:
146:
140:
139:
134:
128:
127:
122:
116:
115:
110:
104:
103:
98:
91:
90:
85:
79:
78:
75:
71:
70:
66:
65:
52:
44:
43:
33:
9:
6:
4:
3:
2:
9290:
9279:
9276:
9274:
9271:
9269:
9266:
9264:
9261:
9259:
9256:
9254:
9251:
9249:
9246:
9245:
9243:
9220:
9217:
9216:
9214:
9210:
9203:
9200:
9198:
9195:
9193:
9190:
9188:
9185:
9183:
9180:
9178:
9175:
9173:
9170:
9168:
9165:
9163:
9160:
9158:
9154:
9151:
9150:
9148:
9144:
9140:
9136:
9132:
9126:
9122:
9107:
9104:
9102:
9099:
9097:
9094:
9092:
9088:
9085:
9082:
9079:
9077:
9074:
9072:
9068:
9065:
9063:
9060:
9057:
9054:
9052:
9049:
9047:
9044:
9042:
9039:
9037:
9034:
9032:
9029:
9027:
9024:
9022:
9018:
9014:
9011:
9008:
9005:
9003:
8999:
8993:
8991:
8988:
8987:
8985:
8983:
8979:
8972:
8969:
8965:
8962:
8960:
8957:
8955:
8952:
8951:
8950:
8947:
8946:
8944:
8941:
8937:
8933:
8929:
8925:
8922:
8918:
8913:
8909:
8894:
8891:
8889:
8885:
8882:
8880:
8877:
8874:
8871:
8869:
8865:
8862:
8860:
8857:
8855:
8852:
8850:
8847:
8845:
8842:
8839:
8836:
8834:
8831:
8829:
8826:
8824:
8820:
8817:
8814:
8811:
8809:
8805:
8802:
8800:
8797:
8795:
8792:
8791:
8789:
8787:
8783:
8776:
8773:
8771:
8768:
8766:
8763:
8761:
8758:
8756:
8753:
8751:
8748:
8746:
8743:
8741:
8738:
8736:
8733:
8731:
8728:
8726:
8723:
8721:
8718:
8716:
8713:
8711:
8708:
8706:
8703:
8701:
8698:
8696:
8693:
8691:
8688:
8686:
8683:
8681:
8678:
8676:
8672:
8669:
8668:
8666:
8664:
8660:
8652:
8649:
8645:
8642:
8640:
8637:
8635:
8632:
8631:
8630:
8627:
8626:
8625:
8622:
8618:
8615:
8613:
8610:
8608:
8605:
8603:
8600:
8598:
8595:
8593:
8590:
8588:
8585:
8584:
8583:
8580:
8576:
8573:
8569:
8566:
8564:
8561:
8559:
8556:
8555:
8554:
8551:
8550:
8549:
8546:
8540:
8537:
8535:
8532:
8530:
8527:
8526:
8525:
8522:
8521:
8520:
8517:
8511:
8508:
8506:
8503:
8501:
8498:
8497:
8496:
8493:
8492:
8491:
8488:
8487:
8485:
8483:
8479:
8475:
8470:
8466:
8461:
8457:
8438:
8435:
8433:
8430:
8428:
8424:
8421:
8418:
8415:
8413:
8410:
8408:
8405:
8403:
8399:
8396:
8393:
8390:
8388:
8385:
8383:
8380:
8378:
8375:
8373:
8370:
8368:
8365:
8363:
8360:
8358:
8354:
8351:
8349:
8346:
8344:
8341:
8340:
8338:
8336:
8332:
8325:
8322:
8320:
8317:
8315:
8312:
8310:
8307:
8305:
8302:
8300:
8297:
8295:
8292:
8290:
8287:
8285:
8282:
8280:
8277:
8275:
8272:
8270:
8267:
8265:
8262:
8260:
8257:
8255:
8252:
8250:
8247:
8245:
8242:
8240:
8237:
8235:
8232:
8230:
8227:
8225:
8222:
8220:
8217:
8215:
8212:
8210:
8207:
8205:
8202:
8200:
8197:
8195:
8192:
8190:
8187:
8185:
8182:
8180:
8177:
8175:
8172:
8170:
8167:
8165:
8162:
8160:
8157:
8155:
8152:
8150:
8147:
8145:
8142:
8140:
8137:
8135:
8132:
8130:
8127:
8125:
8122:
8120:
8117:
8115:
8112:
8110:
8107:
8105:
8102:
8100:
8097:
8095:
8092:
8090:
8087:
8085:
8082:
8080:
8077:
8075:
8072:
8070:
8067:
8065:
8062:
8060:
8057:
8055:
8052:
8050:
8047:
8045:
8042:
8040:
8037:
8035:
8032:
8030:
8027:
8025:
8022:
8020:
8017:
8015:
8012:
8010:
8007:
8005:
8002:
8000:
7997:
7995:
7992:
7990:
7987:
7985:
7982:
7980:
7977:
7975:
7972:
7970:
7967:
7965:
7961:
7958:
7957:
7955:
7953:
7949:
7942:
7939:
7935:
7932:
7930:
7927:
7925:
7922:
7920:
7917:
7915:
7912:
7910:
7907:
7905:
7902:
7900:
7897:
7895:
7892:
7890:
7887:
7885:
7882:
7880:
7877:
7875:
7872:
7870:
7867:
7865:
7862:
7860:
7857:
7855:
7852:
7850:
7847:
7845:
7842:
7840:
7837:
7835:
7832:
7830:
7827:
7825:
7822:
7820:
7817:
7815:
7812:
7811:
7810:
7807:
7806:
7804:
7801:
7797:
7794:
7792:Miscellaneous
7790:
7779:
7776:
7774:
7771:
7769:
7765:
7762:
7760:
7757:
7755:
7752:
7750:
7747:
7744:
7741:
7739:
7736:
7734:
7730:
7727:
7724:
7721:
7719:
7716:
7714:
7711:
7709:
7706:
7704:
7700:
7697:
7694:
7691:
7689:
7686:
7684:
7681:
7679:
7675:
7672:
7670:
7667:
7664:
7661:
7659:
7655:
7652:
7650:
7647:
7644:
7641:
7639:
7635:
7632:
7629:
7625:
7621:
7618:
7616:
7613:
7611:
7608:
7606:
7602:
7599:
7597:
7594:
7591:
7588:
7586:
7582:
7579:
7576:
7573:
7571:
7568:
7566:
7563:
7561:
7558:
7556:
7552:
7549:
7546:
7543:
7541:
7538:
7536:
7533:
7531:
7528:
7526:
7523:
7521:
7518:
7516:
7513:
7511:
7508:
7506:
7503:
7501:
7497:
7494:
7492:
7489:
7487:
7484:
7482:
7479:
7476:
7473:
7471:
7467:
7464:
7461:
7458:
7456:
7453:
7451:
7447:
7444:
7442:
7439:
7436:
7433:
7431:
7428:
7426:
7422:
7419:
7415:
7412:
7410:
7407:
7406:
7405:
7402:
7399:
7396:
7394:
7390:
7387:
7385:
7382:
7377:
7374:
7372:
7368:
7365:
7362:
7359:
7357:
7354:
7352:
7349:
7348:
7347:
7344:
7342:
7339:
7336:
7333:
7331:
7327:
7324:
7321:
7318:
7316:
7312:
7310:
7306:
7305:Anaphylatoxin
7303:
7302:
7300:
7296:
7289:
7286:
7284:
7280:
7277:
7274:
7271:
7269:
7265:
7262:
7260:
7256:
7253:
7250:
7247:
7245:
7242:
7240:
7237:
7235:
7231:
7228:
7226:
7223:
7220:
7217:
7215:
7211:
7208:
7205:
7202:
7200:
7196:
7193:
7192:
7190:
7188:
7184:
7181:
7177:
7167:
7164:
7161:
7158:
7156:
7153:
7151:
7148:
7146:
7143:
7141:
7137:
7134:
7132:
7129:
7127:
7124:
7121:
7118:
7116:
7113:
7111:
7108:
7106:
7103:
7101:
7098:
7096:
7093:
7091:
7088:
7086:
7082:
7079:
7076:
7073:
7071:
7068:
7066:
7063:
7061:
7058:
7056:
7053:
7051:
7047:
7044:
7040:
7037:
7035:
7032:
7030:
7027:
7026:
7025:
7022:
7019:
7016:
7014:
7011:
7009:
7006:
7004:
7000:
6997:
6995:
6992:
6990:
6987:
6984:
6981:
6979:
6976:
6974:
6970:
6966:
6963:
6961:
6957:
6954:
6952:
6949:
6948:
6946:
6942:
6936:
6933:
6931:
6928:
6924:
6920:
6917:
6915:
6912:
6910:
6907:
6905:
6901:
6897:
6894:
6892:
6888:
6885:
6884:
6883:
6882:Prostaglandin
6880:
6878:
6875:
6873:
6870:
6866:
6863:
6861:
6858:
6857:
6856:
6853:
6850:
6847:
6845:
6841:
6838:
6837:
6835:
6833:
6829:
6826:
6820:
6809:
6806:
6804:
6801:
6799:
6796:
6794:
6791:
6789:
6786:
6784:
6780:
6777:
6774:
6771:
6769:
6766:
6764:
6760:
6757:
6753:
6750:
6748:
6745:
6743:
6740:
6738:
6735:
6734:
6733:
6730:
6728:
6725:
6721:
6718:
6716:
6713:
6711:
6708:
6706:
6703:
6701:
6698:
6697:
6696:
6693:
6690:
6687:
6685:
6682:
6680:
6677:
6675:
6672:
6670:
6666:
6665:Acetylcholine
6663:
6662:
6660:
6656:
6649:
6646:
6644:
6641:
6639:
6636:
6634:
6630:
6627:
6624:
6621:
6619:
6616:
6614:
6610:
6607:
6604:
6601:
6599:
6596:
6594:
6591:
6589:
6586:
6584:
6580:
6577:
6575:
6570:
6569:
6567:
6565:
6561:
6554:
6551:
6549:
6546:
6544:
6541:
6539:
6536:
6534:
6531:
6529:
6526:
6524:
6521:
6519:
6516:
6514:
6511:
6509:
6506:
6504:
6501:
6499:
6495:
6492:
6489:
6486:
6484:
6481:
6479:
6476:
6474:
6470:
6467:
6466:
6464:
6462:
6458:
6452:
6449:
6447:
6444:
6442:
6439:
6436:
6433:
6431:
6428:
6426:
6422:
6419:
6416:
6413:
6411:
6408:
6406:
6402:
6399:
6398:
6396:
6394:
6390:
6387:
6385:
6381:
6377:
6372:
6368:
6363:
6359:
6355:
6351:
6344:
6339:
6337:
6332:
6330:
6325:
6324:
6321:
6309:
6306:
6304:
6301:
6299:
6296:
6294:
6291:
6289:
6286:
6284:
6282:
6278:
6276:
6273:
6271:
6268:
6266:
6263:
6262:
6260:
6256:
6250:
6247:
6245:
6242:
6240:
6237:
6236:
6234:
6232:
6228:
6222:
6219:
6218:
6216:
6214:
6210:
6200:
6196:
6193:
6192:
6190:
6186:
6180:
6179:cAMP receptor
6177:
6176:
6174:
6170:
6164:
6161:
6160:
6158:
6154:
6148:
6145:
6144:
6142:
6138:
6132:
6129:
6128:
6126:
6122:
6116:
6113:
6111:
6108:
6106:
6103:
6101:
6098:
6096:
6093:
6090:
6086:
6083:
6082:
6080:
6076:
6073:
6071:
6067:
6063:
6059:
6055:
6048:
6043:
6041:
6036:
6034:
6029:
6028:
6025:
6017:
6013:
6008:
6003:
5999:
5995:
5991:
5987:
5983:
5977:
5973:
5969:
5966:
5963:
5960:
5948:
5944:
5940:
5937:
5925:
5921:
5917:
5913:
5909:
5904:
5899:
5895:
5891:
5887:
5883:
5879:
5872:
5868:
5864:
5852:
5848:
5844:
5842:
5838:
5835:
5832:
5829:
5825:
5822:
5821:
5800:
5793:
5789:
5786:
5775:
5771:
5767:
5763:
5758:
5753:
5748:
5743:
5739:
5735:
5732:(8): 4903–8.
5731:
5727:
5723:
5718:
5717:
5704:
5700:
5696:
5692:
5688:
5684:
5676:
5674:
5665:
5661:
5657:
5653:
5649:
5648:10.1038/25354
5645:
5641:
5637:
5633:
5629:
5622:
5614:
5610:
5606:
5602:
5597:
5592:
5589:(1): 97–106.
5588:
5584:
5580:
5573:
5565:
5561:
5556:
5551:
5547:
5543:
5539:
5535:
5531:
5524:
5516:
5512:
5507:
5502:
5497:
5492:
5488:
5484:
5481:(7): 3712–7.
5480:
5476:
5472:
5465:
5457:
5453:
5448:
5443:
5439:
5435:
5431:
5424:
5416:
5412:
5407:
5402:
5398:
5394:
5390:
5383:
5375:
5371:
5367:
5363:
5359:
5355:
5348:
5340:
5336:
5332:
5328:
5324:
5320:
5316:
5312:
5305:
5297:
5293:
5289:
5285:
5281:
5277:
5270:
5268:
5259:
5255:
5250:
5245:
5241:
5237:
5233:
5229:
5225:
5221:
5217:
5210:
5202:
5198:
5193:
5188:
5184:
5180:
5176:
5169:
5161:
5157:
5152:
5147:
5144:(4): 239–43.
5143:
5139:
5135:
5128:
5120:
5116:
5111:
5106:
5102:
5098:
5094:
5090:
5086:
5079:
5071:
5067:
5062:
5057:
5052:
5047:
5043:
5039:
5035:
5028:
5012:
5008:
5004:
5000:
4996:
4992:
4985:
4977:
4973:
4968:
4963:
4958:
4953:
4949:
4945:
4941:
4937:
4933:
4926:
4918:
4914:
4910:
4906:
4902:
4898:
4894:
4890:
4883:
4875:
4871:
4866:
4861:
4857:
4853:
4850:(1): 261–74.
4849:
4845:
4841:
4834:
4826:
4822:
4817:
4812:
4808:
4804:
4800:
4796:
4792:
4785:
4777:
4773:
4768:
4763:
4759:
4755:
4751:
4747:
4743:
4736:
4728:
4724:
4719:
4714:
4710:
4706:
4702:
4698:
4694:
4690:
4686:
4679:
4671:
4667:
4662:
4657:
4652:
4647:
4643:
4639:
4635:
4631:
4627:
4620:
4612:
4608:
4603:
4598:
4594:
4590:
4586:
4582:
4575:
4567:
4563:
4559:
4555:
4551:
4547:
4543:
4539:
4532:
4524:
4520:
4515:
4510:
4506:
4502:
4499:(10): 740–7.
4498:
4494:
4490:
4483:
4481:
4472:
4468:
4464:
4460:
4456:
4452:
4448:
4444:
4440:
4436:
4429:
4421:
4417:
4412:
4407:
4403:
4399:
4395:
4391:
4387:
4383:
4379:
4372:
4364:
4360:
4355:
4350:
4346:
4342:
4338:
4334:
4330:
4326:
4322:
4315:
4307:
4303:
4298:
4293:
4289:
4285:
4281:
4277:
4273:
4269:
4265:
4258:
4250:
4246:
4241:
4236:
4232:
4228:
4224:
4220:
4216:
4212:
4208:
4201:
4193:
4189:
4184:
4179:
4175:
4171:
4167:
4163:
4159:
4155:
4151:
4144:
4136:
4132:
4128:
4124:
4119:
4114:
4110:
4106:
4102:
4098:
4094:
4087:
4079:
4075:
4071:
4067:
4063:
4059:
4055:
4051:
4047:
4043:
4036:
4028:
4024:
4020:
4016:
4011:
4006:
4002:
3998:
3994:
3990:
3983:
3975:
3971:
3966:
3961:
3957:
3953:
3949:
3945:
3941:
3934:
3926:
3922:
3918:
3914:
3910:
3906:
3902:
3898:
3894:
3890:
3883:
3875:
3871:
3867:
3863:
3859:
3855:
3851:
3847:
3840:
3832:
3828:
3823:
3818:
3814:
3810:
3806:
3802:
3798:
3791:
3783:
3779:
3775:
3771:
3767:
3763:
3759:
3755:
3748:
3740:
3736:
3731:
3726:
3721:
3716:
3712:
3708:
3704:
3693:
3685:
3681:
3677:
3673:
3670:(5): 559–67.
3669:
3665:
3658:
3650:
3646:
3642:
3638:
3634:
3630:
3622:
3614:
3610:
3606:
3602:
3598:
3594:
3590:
3586:
3582:
3578:
3571:
3563:
3559:
3554:
3549:
3544:
3539:
3535:
3531:
3528:(8): 4903–8.
3527:
3523:
3519:
3512:
3504:
3500:
3495:
3490:
3485:
3480:
3476:
3472:
3469:(1): e29817.
3468:
3464:
3460:
3453:
3451:
3449:
3432:
3428:
3422:
3414:
3410:
3406:
3402:
3398:
3394:
3391:(2): 279–88.
3390:
3386:
3379:
3371:
3367:
3363:
3359:
3352:
3344:
3340:
3336:
3332:
3328:
3324:
3317:
3309:
3305:
3300:
3295:
3290:
3285:
3281:
3277:
3273:
3266:
3250:
3246:
3242:
3236:
3228:
3224:
3220:
3216:
3213:(3): 263–73.
3212:
3208:
3200:
3198:
3196:
3187:
3183:
3178:
3173:
3169:
3165:
3161:
3157:
3153:
3146:
3131:
3124:
3116:
3112:
3107:
3102:
3098:
3094:
3090:
3086:
3082:
3075:
3073:
3064:
3060:
3056:
3052:
3048:
3044:
3037:
3035:
3026:
3022:
3018:
3014:
3011:(1): 615–49.
3010:
3006:
2999:
2997:
2988:
2984:
2980:
2976:
2972:
2968:
2964:
2960:
2956:
2952:
2945:
2939:
2934:
2928:
2924:
2919:
2914:
2910:
2906:
2902:
2898:
2894:
2887:
2885:
2883:
2881:
2879:
2862:
2858:
2854:
2850:
2848:9780123869333
2844:
2840:
2836:
2832:
2828:
2821:
2819:
2810:
2806:
2801:
2796:
2792:
2788:
2784:
2780:
2776:
2772:
2768:
2761:
2759:
2754:
2744:
2741:
2738:
2735:
2732:
2729:
2727:
2724:
2722:
2719:
2717:
2714:
2712:
2709:
2708:
2702:
2700:
2697:
2693:
2689:
2685:
2681:
2677:
2673:
2672:
2668:. Later, the
2667:
2663:
2661:
2660:Dictyostelium
2656:
2655:
2650:
2649:
2644:
2643:
2638:
2634:
2630:
2626:
2622:
2613:
2598:
2586:
2578:
2570:
2560:
2559:GPCR oligomer
2550:
2548:
2537:
2535:
2531:
2527:
2523:
2519:
2515:
2511:
2507:
2503:
2499:
2494:
2492:
2488:
2484:
2480:
2476:
2473:
2469:
2465:
2461:
2457:
2453:
2449:
2445:
2437:
2433:
2428:
2424:
2422:
2418:
2414:
2410:
2406:
2402:
2398:
2394:
2390:
2389:phosphorylate
2386:
2382:
2378:
2374:
2373:
2372:
2370:
2365:
2362:
2358:
2354:
2350:
2346:
2342:
2338:
2334:
2313:
2309:
2305:
2301:
2299:
2295:
2292:
2291:Translocation
2289:
2288:
2287:
2284:
2282:
2272:
2270:
2259:
2251:
2248:(cAMP). In a
2247:
2243:
2239:
2229:
2227:
2223:
2219:
2215:
2211:
2201:
2199:
2195:
2190:
2188:
2184:
2180:
2176:
2172:
2168:
2164:
2160:
2152:
2146:
2136:
2133:
2129:
2125:
2121:
2118:
2116:
2112:
2108:
2104:
2100:
2094:
2084:
2082:
2078:
2074:
2065:
2057:
2049:
2040:
2038:
2034:
2030:
2026:
2022:
2018:
2014:
2003:
2001:
1997:
1992:
1985:
1983:
1982:
1981:D. discoideum
1978:
1973:
1963:
1961:
1957:
1953:
1949:
1945:
1941:
1937:
1933:
1922:
1920:
1916:
1913:
1909:
1905:
1901:
1893:
1886:Gβγ signaling
1872:
1868:
1864:
1860:
1856:
1852:
1848:
1844:
1840:
1836:
1832:
1831:IP3 receptors
1828:
1824:
1820:
1816:
1808:
1805:
1801:
1797:
1794:
1790:
1770:
1767:
1763:
1759:
1755:
1751:
1739:
1738:
1732:
1730:
1726:
1725:physiological
1722:
1718:
1714:
1710:
1706:
1702:
1698:
1692:
1690:
1685:
1681:
1677:
1670:
1663:
1656:
1649:
1645:
1635:
1632:
1628:
1624:
1620:
1616:
1612:
1608:
1604:
1600:
1595:
1593:
1588:
1586:
1582:
1575:
1570:
1568:
1564:
1555:
1546:
1540:
1536:
1528:
1523:
1514:
1512:
1508:
1504:
1500:
1495:
1490:
1488:
1484:
1480:
1476:
1472:
1468:
1463:
1459:
1455:
1451:
1447:
1443:
1437:
1428:
1419:
1416:
1411:
1406:
1387:
1383:
1375:
1367:
1363:
1359:
1351:
1347:
1338:
1329:
1327:
1323:
1318:
1316:
1311:
1309:
1305:
1301:
1297:
1293:
1289:
1285:
1284:anaphylatoxin
1281:
1277:
1273:
1269:
1265:
1261:
1258:mediators of
1257:
1253:
1249:
1245:
1244:acetylcholine
1241:
1237:
1233:
1229:
1225:
1221:
1217:
1213:
1209:
1205:
1201:
1197:
1193:
1189:
1185:
1181:
1177:
1173:
1169:
1168:melanocortins
1165:
1161:
1157:
1153:
1149:
1145:
1141:
1131:
1129:
1125:
1115:
1106:
1104:
1100:
1096:
1092:
1087:
1085:
1081:
1077:
1073:
1069:
1065:
1061:
1056:
1054:
1050:
1046:
1042:
1038:
1034:
1030:
1026:
1022:
1009:
1007:
1003:
999:
995:
991:
987:
983:
979:
975:
971:
967:
966:transmembrane
963:
955:
950:
941:
939:
935:
931:
927:
923:
919:
915:
910:
903:
894:
889:
884:
882:
878:
874:
870:
866:
862:
848:
845:
841:
837:
834:
831:
828:
824:
820:
817:
813:
809:
805:
801:
797:
794:activity and
793:
792:immune system
789:
787:
783:
779:
775:
771:
767:
763:
760:
756:
753:
749:
746:
742:
739:
737:
732:
730:
725:
721:
717:
713:
709:
708:
707:
699:
697:
692:
688:
686:
682:
678:
674:
673:
668:
664:
660:
652:
648:
644:
641:
638:
634:
631:
628:
624:
621:
618:
614:
611:
608:
604:
601:
598:
594:
591:
590:
589:
586:
584:
580:
576:
572:
568:
565:
561:
557:
552:
550:
546:
542:
539:
535:
532:
522:
513:
511:
507:
506:Advair Diskus
503:
499:
495:
494:Brian Kobilka
491:
486:
474:
471:
463:
452:
448:
446:
439:
432:
425:
418:
414:
410:
406:
398:
394:
391:
387:
386:
385:
382:
380:
376:
372:
368:
364:
360:
356:
352:
348:
344:
339:
337:
333:
329:
325:
321:
320:cell membrane
317:
313:
309:
305:
301:
297:
293:
289:
285:
281:
280:7TM receptors
277:
273:
269:
262:
257:
245:
242:
240:
236:
233:
229:
225:
222:
220:
216:
212:
208:
205:
202:
198:
193:
189:
186:
183:
181:
177:
174:
171:
169:
165:
162:
159:
157:
153:
150:
147:
145:
141:
138:
135:
133:
129:
126:
123:
121:
117:
114:
111:
109:
105:
102:
99:
96:
92:
89:
86:
84:
80:
76:
72:
67:
63:
60:
56:
50:
45:
40:
37:
30:
19:
9253:Biochemistry
8981:
8948:
8921:Metabotropic
8785:
8670:
8623:
8581:
8547:
8518:
8489:
8334:
7959:
7808:
7759:Urotensin-II
7699:Somatostatin
7654:Prokineticin
7551:Melanocortin
7254:
7187:Neuropeptide
7126:Oxoglutarate
6968:
6930:Prostacyclin
6899:
6886:
6839:
6727:GHB receptor
6628:
6571:
6353:
6280:
6069:
5989:
5985:
5958:
5951:. Retrieved
5947:the original
5935:
5928:. Retrieved
5924:the original
5885:
5881:
5870:
5855:. Retrieved
5850:
5806:. Retrieved
5784:
5777:. Retrieved
5729:
5725:
5686:
5682:
5631:
5627:
5621:
5586:
5582:
5572:
5537:
5533:
5523:
5478:
5474:
5464:
5437:
5433:
5423:
5396:
5392:
5382:
5357:
5353:
5347:
5314:
5310:
5304:
5279:
5275:
5223:
5219:
5209:
5182:
5178:
5168:
5141:
5137:
5127:
5092:
5088:
5078:
5041:
5037:
5027:
5015:. Retrieved
4998:
4994:
4984:
4939:
4935:
4925:
4892:
4888:
4882:
4847:
4843:
4833:
4798:
4794:
4784:
4749:
4745:
4735:
4692:
4688:
4678:
4633:
4629:
4619:
4584:
4580:
4574:
4541:
4537:
4531:
4496:
4492:
4438:
4434:
4428:
4385:
4381:
4371:
4328:
4324:
4314:
4271:
4267:
4257:
4214:
4210:
4200:
4157:
4153:
4143:
4100:
4096:
4086:
4045:
4041:
4035:
3992:
3988:
3982:
3950:(1): 12–22.
3947:
3943:
3933:
3892:
3888:
3882:
3852:(2): 79–94.
3849:
3845:
3839:
3807:(1): 45–66.
3804:
3800:
3790:
3760:(4): 521–8.
3757:
3753:
3747:
3710:
3706:
3692:
3667:
3663:
3657:
3635:(1): 68–73.
3632:
3628:
3621:
3613:the original
3584:
3580:
3570:
3525:
3521:
3511:
3466:
3462:
3435:. Retrieved
3421:
3388:
3384:
3378:
3361:
3357:
3351:
3326:
3322:
3316:
3279:
3275:
3265:
3253:. Retrieved
3249:the original
3244:
3235:
3210:
3206:
3162:(6): 905–7.
3159:
3155:
3145:
3133:. Retrieved
3123:
3088:
3084:
3046:
3042:
3008:
3004:
2954:
2950:
2944:
2900:
2896:
2865:. Retrieved
2830:
2774:
2770:
2691:
2687:
2683:
2675:
2669:
2666:opisthokonts
2658:
2652:
2647:
2640:
2619:
2562:
2543:
2514:small GTPase
2495:
2456:opsonization
2441:
2381:conformation
2369:desensitized
2366:
2345:RGS proteins
2330:
2303:
2296:
2290:
2285:
2278:
2249:
2235:
2207:
2191:
2183:IP3 receptor
2148:
2134:
2130:
2126:
2122:
2119:
2096:
2070:
2009:
1993:
1986:
1980:
1969:
1928:
1889:
1867:cytoskeleton
1859:small GTPase
1789:ion channels
1735:Gα signaling
1731:conditions.
1729:experimental
1693:
1641:
1629:only to the
1607:conformation
1596:
1589:
1571:
1560:
1532:
1491:
1439:
1407:
1384:in place of
1355:
1319:
1312:
1276:leukotrienes
1260:inflammation
1236:metabotropic
1198:family, and
1184:somatostatin
1137:
1128:RGS proteins
1121:
1088:
1076:sphingolipid
1057:
1010:
959:
911:
885:
869:glycosylated
858:
796:inflammation
768:, including
735:
728:
705:
693:
689:
671:
656:
587:
553:
528:
487:
475:
458:
449:
402:
383:
345:, including
340:
310:outside the
306:that detect
295:
291:
287:
283:
279:
275:
271:
267:
266:
36:
8629:Latrophilin
7764:Vasopressin
7749:Thyrotropin
7326:Angiotensin
7279:Neurotensin
6956:Cannabinoid
6935:Thromboxane
6288:Neuropilins
5930:10 November
5317:(1): 5–12.
3437:10 December
2522:ERK cascade
2508:, or other
2491:degradation
2479:dissociated
2464:amphiphysin
2361:promiscuous
2222:cytoplasmic
2169:hydrolyzes
2035:(GDIs) and
1855:calmodulins
1813:pathway is
1644:sub-classes
1623:β-arrestins
1410:equilibrium
1268:prostanoids
1212:epinephrine
1200:vasopressin
1192:tachykinins
1080:lipid rafts
1072:cholesterol
1068:acyl groups
1049:endocytosis
1006:antagonists
823:sympathetic
619:/pheromone)
168:OPM protein
69:Identifiers
9242:Categories
9219:Smoothened
9212:Smoothened
9135:Smoothened
8794:Calcitonin
7729:Tachykinin
7626:, but not
7620:Nociceptin
7486:Kisspeptin
7404:Endothelin
7367:Bradykinin
7255:Neuromedin
6832:Eicosanoid
6461:Purinergic
6393:Adrenergic
6199:smoothened
5965:GPCR-HGmod
5857:6 February
5808:10 October
5399:(1): 5–8.
5044:: 341282.
5017:14 January
4602:10161/7805
3427:"InterPro"
3364:(1): 1–7.
3135:10 October
2867:24 October
2749:References
2662:discoideum
2637:eukaryotic
2534:polymerize
2483:trafficked
2409:sterically
2405:β-arrestin
2401:C-terminal
2353:resolution
2349:GAP domain
2246:cyclic AMP
2198:calmodulin
2194:CaM kinase
1977:slime mold
1956:PDZ-domain
1944:β-arrestin
1871:Rho-kinase
1825:(IP3) and
1721:endogenous
1619:G-proteins
1615:transducer
1592:calmodulin
1545:activity.
1487:covalently
1483:isoprenoid
1434:See also:
1296:neurokinin
1280:calcitonin
1252:chemokines
1248:muscarinic
1178:peptides,
1156:endothelin
1152:bradykinin
1041:sterically
974:C-terminus
962:N-terminus
954:lipid raft
938:C-terminus
934:N-terminus
930:G proteins
916:, such as
859:GPCRs are
840:metastasis
698:approach.
651:Smoothened
564:endogenous
363:pheromones
343:eukaryotes
316:G proteins
207:structures
53:The human
9129:Class F:
8928:pheromone
8924:glutamate
8348:Olfactory
7384:Chemokine
7166:Succinate
6951:Bile acid
6759:Melatonin
6732:Histamine
6572:(all but
6564:Serotonin
6469:Adenosine
6371:Rhodopsin
6058:receptors
5986:Structure
5978:pipeline
5779:11 August
5001:: 57–71.
4695:: 13416.
4005:CiteSeerX
2731:Pepducins
2684:Rhodopsin
2680:nematodes
2642:Rhodopsin
2487:lysosomes
2472:endocytic
2397:threonine
2308:rhodopsin
2025:JAK/STATs
2013:integrins
1902:(GIRKs),
1766:cytosolic
1563:G protein
1549:Signaling
1517:Crosstalk
1471:Gβγ dimer
1436:G protein
1250:effect);
1238:effect);
1232:glutamate
1228:melatonin
1224:serotonin
1220:histamine
1144:adenosine
1140:olfactory
1124:G protein
1109:Mechanism
1037:arrestins
1025:threonine
1023:(Ser) or
988:or large
970:α-helices
888:rhodopsin
800:chemokine
786:glutamate
778:histamine
770:serotonin
759:mammalian
745:gustducin
736:all-trans
724:Rhodopsin
667:Rhodopsin
663:Glutamate
575:structure
567:compounds
562:by known
488:The 2012
409:G protein
377:to large
332:rhodopsin
308:molecules
302:that are
263:rhodopsin
137:PDOC00210
125:IPR000276
62:carazolol
9153:Frizzled
9146:Frizzled
9131:Frizzled
8973:, type 2
8879:Secretin
8819:Glucagon
8524:Cadherin
8482:Adhesion
8469:Secretin
7802:, bitter
7649:Oxytocin
7346:Bombesin
6994:Estrogen
6695:Dopamine
6195:Frizzled
6016:26190572
5976:I-TASSER
5968:Archived
5912:27155948
5867:"GPCRdb"
5837:Archived
5799:Archived
5766:12679517
5703:21402729
5613:15430860
5605:10939334
5564:18193069
5515:10097102
5456:10770944
5374:14499340
5339:45674941
5331:23532739
5296:14744258
5258:11053129
5201:12177051
5119:30401786
5070:23056062
5011:Archived
4976:17095603
4917:22279536
4909:12970120
4874:20019124
4825:31740855
4776:27499021
4727:27827372
4670:28223524
4611:11861753
4523:21873996
4471:52860797
4463:12802337
4420:21772288
4363:21393508
4306:21228877
4249:21228876
4192:21228869
4127:17962519
4070:17952055
4027:10926528
3974:24359917
3917:23407534
3874:10996598
3866:17251915
3831:21802439
3782:21897008
3774:23345392
3739:32259074
3684:19594431
3649:19364489
3601:19037861
3562:12679517
3503:22238661
3463:PLOS ONE
3431:Archived
3413:34541683
3405:15914470
3308:12429062
3227:16753280
3207:Genomics
3186:24024784
3115:29249361
3063:16183910
2979:12869759
2927:22300046
2861:Archived
2857:23317783
2809:17962520
2705:See also
2692:Adhesion
2688:Secretin
2676:Adhesion
2671:Secretin
2654:Frizzled
2648:Adhesion
2569:receptor
2500:(nRTK),
2452:membrane
2448:clathrin
2415:through
2391:various
2341:isoforms
2304:arrestin
2298:Arrestin
2019:(RTKs),
1966:Examples
1962:family.
1804:effector
1762:catalyze
1713:feedback
1627:affinity
1535:integrin
1527:integrin
1507:effector
1304:oxytocin
1240:glucagon
1208:dopamine
1148:bombesin
1064:cysteine
1033:affinity
990:peptides
986:proteins
873:cysteine
774:dopamine
738:-retinal
731:-retinal
685:Secretin
677:Frizzled
672:Adhesion
647:Frizzled
645:(or 6) (
635:(or 5) (
625:(or 4) (
615:(or 3) (
605:(or 2) (
595:(or 1) (
560:liganded
379:proteins
375:peptides
367:hormones
336:agonists
224:RCSB PDB
120:InterPro
113:5001.1.1
8942:, sweet
8917:Class C
8849:PACAPR1
8465:Class B
7674:Relaxin
7596:Motilin
7481:Ghrelin
7446:Galanin
7179:Peptide
6367:Class A
6188:Class F
6172:Class E
6156:Class D
6140:Class C
6124:Class B
6078:Class A
6007:4526412
5953:11 July
5903:4919580
5734:Bibcode
5664:4406311
5656:9872316
5636:Bibcode
5555:2268057
5483:Bibcode
5415:8995214
5249:1301137
5228:Bibcode
5160:8807851
5110:6329291
5061:3465959
4967:1693825
4944:Bibcode
4865:5428143
4816:7108872
4767:5418658
4718:5105198
4697:Bibcode
4661:5347553
4638:Bibcode
4566:2163110
4546:Bibcode
4538:Science
4514:3177959
4443:Bibcode
4411:3184188
4390:Bibcode
4354:3086811
4333:Bibcode
4325:Science
4297:3023143
4276:Bibcode
4240:3074335
4219:Bibcode
4183:3058308
4162:Bibcode
4135:1559802
4105:Bibcode
4097:Science
4078:4407117
4050:Bibcode
3997:Bibcode
3989:Science
3965:3931419
3925:4423750
3897:Bibcode
3822:3336209
3730:7088898
3530:Bibcode
3494:3251606
3471:Bibcode
3370:8081729
3343:8170923
3255:24 June
3177:3689196
3106:5766829
3025:3113327
2987:9708224
2959:Bibcode
2951:Science
2918:3343417
2800:2583103
2779:Bibcode
2771:Science
2699:PF00002
2475:vesicle
2468:dynamin
2300:linking
2149:In the
2099:hormone
1709:isoform
1701:agonist
1475:diffuse
1467:monomer
1322:ligands
1306:); and
1262:(e.g.,
1206:(e.g.,
1099:guanine
1095:protons
998:agonist
968:(7-TM)
926:ADIPOR2
922:ADIPOR1
643:Class F
633:Class E
623:Class D
613:Class C
603:Class B
593:Class A
510:Abilify
355:ligands
185:cd14964
132:PROSITE
88:PF00001
9133:&
9062:GPRC6A
8799:CALCRL
8663:Orphan
7952:Orphan
7943:type 1
7634:Orexin
7622:&
7601:Opioid
7341:Apelin
6014:
6004:
5910:
5900:
5830:(MeSH)
5764:
5757:153653
5754:
5701:
5662:
5654:
5628:Nature
5611:
5603:
5583:Neuron
5562:
5552:
5513:
5503:
5454:
5413:
5372:
5337:
5329:
5294:
5256:
5246:
5199:
5158:
5117:
5107:
5068:
5058:
4974:
4964:
4915:
4907:
4872:
4862:
4823:
4813:
4774:
4764:
4725:
4715:
4668:
4658:
4609:
4564:
4521:
4511:
4469:
4461:
4435:Nature
4418:
4408:
4382:Nature
4361:
4351:
4304:
4294:
4268:Nature
4247:
4237:
4211:Nature
4190:
4180:
4154:Nature
4133:
4125:
4076:
4068:
4042:Nature
4025:
4007:
3972:
3962:
3923:
3915:
3889:Nature
3872:
3864:
3829:
3819:
3780:
3772:
3737:
3727:
3682:
3647:
3609:813484
3607:
3599:
3560:
3553:153653
3550:
3501:
3491:
3411:
3403:
3368:
3341:
3306:
3299:133447
3296:
3225:
3184:
3174:
3113:
3103:
3061:
3023:
2985:
2977:
2925:
2915:
2855:
2845:
2807:
2797:
2651:, and
2506:ERK1/2
2436:kinase
2393:serine
2312:retina
2167:lipase
2165:. The
2075:: the
1938:, and
1932:β-arrs
1912:N-type
1910:- and
1875:α12/13
1758:tissue
1675:α12/13
1671:, and
1611:ligand
1450:trimer
1348:entry
1302:, and
1282:, C5a
1274:, and
1226:, and
1180:opsins
1176:opioid
1074:- and
1021:serine
982:ligand
844:tumors
784:, and
729:11-cis
714:use a
712:opsins
681:Taste2
583:A1-A19
541:genome
525:(23)).
444:α12/13
369:, and
353:. The
349:, and
324:ligand
290:, and
261:bovine
239:PDBsum
213:
203:
149:9.A.14
101:CL0192
74:Symbol
8982:Other
8949:TAS1R
8940:Taste
8838:GLP2R
8833:GLP1R
8786:Other
8651:ELTD1
8624:ADGRL
8582:ADGRG
8548:ADGRE
8519:ADGRC
8490:ADGRB
8471:-like
8353:Opsin
8335:Other
7809:TAS2R
7800:Taste
7628:Sigma
7610:Kappa
7605:Delta
7313:C5a (
7298:Other
6944:Other
6872:FPRL1
6840:CysLT
6658:Other
6609:5-HT2
6579:5-HT1
6574:5-HT3
6373:-like
5802:(PDF)
5795:(PDF)
5660:S2CID
5609:S2CID
5506:22359
5335:S2CID
4913:S2CID
4889:Chest
4467:S2CID
4131:S2CID
4074:S2CID
3921:S2CID
3870:S2CID
3778:S2CID
3605:S2CID
3409:S2CID
2983:S2CID
2633:GRAFS
2629:fungi
2526:Raf-1
2502:c-SRC
2426:well.
1948:CXCR3
1879:αq/11
1811:αq/11
1744:and G
1680:genes
1668:αq/11
1400:and G
1256:lipid
806:bind
762:brain
659:GRAFS
534:genes
531:human
437:αq/11
359:odors
347:yeast
272:GPCRs
77:7tm_1
9087:RAIG
8995:GABA
8828:GIPR
8575:CD97
8423:SREB
8224:137B
8199:109B
8194:109A
7624:Zeta
7581:MCHR
7361:NMBR
7356:GRPR
7351:BRS3
6989:EBI2
6855:LTB4
6779:TAAR
6629:5-HT
6298:EDAR
6012:PMID
5955:2013
5932:2010
5908:PMID
5859:2019
5810:2012
5781:2008
5762:PMID
5699:PMID
5652:PMID
5601:PMID
5560:PMID
5511:PMID
5452:PMID
5411:PMID
5370:PMID
5327:PMID
5292:PMID
5254:PMID
5197:PMID
5156:PMID
5115:PMID
5066:PMID
5042:2012
5019:2006
4972:PMID
4905:PMID
4870:PMID
4821:PMID
4772:PMID
4746:Cell
4723:PMID
4666:PMID
4607:PMID
4562:PMID
4519:PMID
4459:PMID
4416:PMID
4359:PMID
4302:PMID
4245:PMID
4188:PMID
4123:PMID
4066:PMID
4023:PMID
3970:PMID
3913:PMID
3862:PMID
3827:PMID
3770:PMID
3735:PMID
3680:PMID
3645:PMID
3597:PMID
3558:PMID
3499:PMID
3439:2007
3401:PMID
3366:PMID
3339:PMID
3304:PMID
3257:2019
3223:PMID
3182:PMID
3137:2012
3111:PMID
3085:Cell
3059:PMID
3021:PMID
2975:PMID
2923:PMID
2869:2023
2853:PMID
2843:ISBN
2805:PMID
2696:Pfam
2581:GABA
2579:and
2573:GABA
2565:GABA
2489:for
2466:and
2444:AP-2
2337:rate
2279:The
2244:and
2177:and
2077:cAMP
2029:GEFs
2000:ITIM
1972:ERK2
1960:MAPK
1940:Srcs
1936:GRKs
1896:αi/o
1785:αi/o
1777:αi/o
1746:αi/o
1661:αi/o
1621:and
1601:and
1356:The
1350:3SN6
1160:GABA
1004:and
924:and
893:1F88
825:and
782:GABA
508:and
496:and
430:αi/o
395:the
390:cAMP
388:the
312:cell
296:GPLR
232:PDBj
228:PDBe
211:ECOD
201:Pfam
173:1gzm
144:TCDB
108:ECOD
97:clan
95:Pfam
83:Pfam
42:GPCR
9081:179
9076:158
9071:156
9067:GPR
8854:GPR
8775:157
8770:155
8765:144
8760:143
8755:133
8750:128
8745:126
8740:125
8735:124
8730:123
8725:116
8720:115
8715:114
8710:113
8705:112
8700:111
8695:110
8671:GPR
8553:EMR
8392:RRH
8387:RGR
8382:1SW
8377:1MW
8372:1LW
8324:183
8319:182
8314:177
8309:176
8304:174
8299:173
8294:171
8289:162
8284:161
8279:160
8274:153
8269:152
8264:151
8259:150
8254:149
8249:148
8244:146
8239:142
8234:141
8229:139
8219:135
8214:132
8209:120
8204:119
8189:103
8184:101
7960:GPR
7496:MAS
7441:FSH
7309:C3a
7195:B/W
7131:PAF
6983:119
6969:GPR
6965:CB2
6960:CB1
6921:),
6898:),
6877:OXE
6494:P2Y
6483:A2B
6478:A2A
6002:PMC
5994:doi
5898:PMC
5890:doi
5886:173
5752:PMC
5742:doi
5730:100
5691:doi
5644:doi
5632:396
5591:doi
5550:PMC
5542:doi
5538:153
5501:PMC
5491:doi
5442:doi
5438:275
5401:doi
5397:272
5362:doi
5319:doi
5284:doi
5244:PMC
5236:doi
5187:doi
5183:277
5146:doi
5105:PMC
5097:doi
5056:PMC
5046:doi
5003:doi
4999:430
4962:PMC
4952:doi
4940:103
4897:doi
4893:124
4860:PMC
4852:doi
4811:PMC
4803:doi
4762:PMC
4754:doi
4750:166
4713:PMC
4705:doi
4656:PMC
4646:doi
4634:114
4597:hdl
4589:doi
4585:115
4554:doi
4542:248
4509:PMC
4501:doi
4451:doi
4439:423
4406:PMC
4398:doi
4386:477
4349:PMC
4341:doi
4329:332
4292:PMC
4284:doi
4272:469
4235:PMC
4227:doi
4215:469
4178:PMC
4170:doi
4158:469
4113:doi
4101:318
4058:doi
4046:450
4015:doi
3993:289
3960:PMC
3952:doi
3905:doi
3893:494
3854:doi
3817:PMC
3809:doi
3762:doi
3725:PMC
3715:doi
3672:doi
3637:doi
3633:390
3589:doi
3548:PMC
3538:doi
3526:100
3489:PMC
3479:doi
3393:doi
3331:doi
3294:PMC
3284:doi
3215:doi
3172:PMC
3164:doi
3101:PMC
3093:doi
3089:172
3051:doi
3013:doi
2967:doi
2955:301
2913:PMC
2905:doi
2835:doi
2795:PMC
2787:doi
2775:318
2530:MEK
2518:Ras
2343:of
2310:in
1892:Gβγ
1863:Rho
1727:or
1705:GEF
1682:or
1585:GDP
1567:GTP
1539:FAK
1442:GEF
1386:GDP
1382:GTP
1346:PDB
1230:);
1166:),
1164:HGF
1103:GEF
1093:to
1045:ERK
816:TLR
733:to
585:).
447:).
417:GTP
413:GDP
219:PDB
180:CDD
9244::
9202:10
9058:))
8926:/
8919::
8823:GR
8690:98
8685:97
8680:64
8675:56
8467::
8179:92
8174:88
8169:87
8164:85
8159:84
8154:83
8149:82
8144:81
8139:78
8134:75
8129:68
8124:65
8119:63
8114:62
8109:61
8104:55
8099:52
8094:50
8089:45
8084:44
8079:42
8074:39
8069:37
8064:35
8059:34
8054:33
8049:32
8044:31
8039:27
8034:26
8029:25
8024:23
8019:22
8014:21
8009:20
8004:19
7999:18
7994:17
7989:15
7984:12
7934:60
7929:50
7924:46
7919:45
7914:43
7909:42
7904:41
7899:40
7894:39
7889:38
7884:31
7879:30
7874:20
7869:19
7864:16
7859:14
7854:13
7849:10
7773:1B
7768:1A
7615:Mu
7545:X4
7540:X3
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