| + |
ADRB1 | up-regulates activity 
binding
|
GNA14 |
0.247 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257030 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281666 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
(R)-salbutamol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257866 |
|
|
Cricetulus longicaudatus |
|
| pmid |
sentence |
| 20590599 |
Denopamine is the most selective ligand for β1-receptors, with regard to intrinsic activity and efficacy, and clenbuterol, procaterol, zinterol, AZ 40140d and salbutamol are more selective for the β2-adrenoceptor than the β1-adrenoceptor based on intrinsic activity and efficacy. |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
metoprolol | down-regulates activity 
chemical inhibition
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258337 |
|
|
Cricetulus longicaudatus |
CHO Cell |
| pmid |
sentence |
| 10079020 |
In our CHO cells transfected with the human β1- and β2-adrenoceptors, the binding affinities of atenolol, metoprolol, betaxolol and practolol correlate with previously published β1- (P=0.03) and β2-adrenoceptor (P=0.03) binding affinities in human lung tissue |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
ADRB1 | up-regulates activity
binding
|
GNAS |
0.546 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282367 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282101 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256758 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ‚â• -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ‚â• -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ‚â• -1.0. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
ADRB1 | up-regulates activity
binding
|
GNAO1 |
0.293 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282368 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282102 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
ADRB1 | up-regulates activity
binding
|
GNA15 |
0.389 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282369 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 37742189 |
Here, we quantitatively measure the enzymatic activity of GPCRs in living cells and reveal the G protein selectivity of 124 GPCRs with the exact rank order of their G protein preference. Using this information, we establish a classification of GPCRs by functional selectivity, discover the existence of a G12/13-coupled receptor, G15-coupled receptors, and a variety of subclasses for Gi/o-, Gq-, and Gs-coupled receptors, culminating in development of the predictive algorithm of G protein selectivity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-282103 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
practolol | down-regulates activity
chemical inhibition
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258336 |
|
|
Cricetulus longicaudatus |
CHO Cell |
| pmid |
sentence |
| 10079020 |
In our CHO cells transfected with the human β1- and β2-adrenoceptors, the binding affinities of atenolol, metoprolol, betaxolol and practolol correlate with previously published β1- (P=0.03) and β2-adrenoceptor (P=0.03) binding affinities in human lung tissue |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
Cy3-bifunctional dye zwitterion | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257859 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Denopamine is the most selective ligand for β1-receptors, with regard to intrinsic activity and efficacy, and clenbuterol, procaterol, zinterol, AZ 40140d and salbutamol are more selective for the β2-adrenoceptor than the β1-adrenoceptor based on intrinsic activity and efficacy. |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
ARRB2 | down-regulates activity
binding
|
ADRB1 |
0.458 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256502 |
|
|
in vitro |
|
| pmid |
sentence |
| 2163110 |
The protein, termed beta-arrestin, was expressed and partially purified. It inhibited the signaling function of beta ARK-phosphorylated beta-adrenergic receptors by more than 75 percent, but not that of rhodopsin. It is proposed that beta-arrestin in concert with beta ARK effects homologous desensitization of beta-adrenergic receptors |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
clenbuterol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257862 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Denopamine is the most selective ligand for β1-receptors, with regard to intrinsic activity and efficacy, and clenbuterol, procaterol, zinterol, AZ 40140d and salbutamol are more selective for the β2-adrenoceptor than the β1-adrenoceptor based on intrinsic activity and efficacy. |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
N-[2-hydroxy-5-(1-hydroxy-2-{[1-(4-methoxyphenyl)propan-2-yl]amino}ethyl)phenyl]formamide | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257854 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Thus, overall, salmeterol is a highly selective β2-adrenoceptor agonist because of its higher β2-affinity and not because of higher β2-intrinsic efficacy. A similar reasoning can be applied to formoterol, although this agonist has higher intrinsic efficacy at all three receptors (rank 6, 8 and 5 at β1, β2 and β3). |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
arformoterol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257881 |
|
|
in vitro |
|
| pmid |
sentence |
| 20655218 |
Table 1. Human β2- and β1-adrenoceptor binding and calculated log D7.4 values for formoterol, indacaterol, salmeterol, S1319 and the representative library members 11–41 |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
ADRB1 | up-regulates activity
binding
|
GNAQ |
0.29 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281665 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ADRB1 | up-regulates activity
binding
|
GNA12 |
0.264 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281667 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ADRB1 | up-regulates activity
binding
|
GNA13 |
0.247 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281668 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
isoprenaline | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258578 |
|
|
Chlorocebus aethiops |
COS-7 Cell |
| pmid |
sentence |
| 8982677 |
K i values of the agonists for [~25I]iodocyanopindolol binding to the COS-7 cell membranes are shown in Table 1. In the membranes expressing one of the 13-adrenoceptor subtypes, both isoproterenol and T-0509 caused monophasic dis- placement of [~25I]iodocyanopindolol, suggesting a single binding site of the agonists. |
|
| Publications: |
1 |
Organism: |
Chlorocebus Aethiops |
| + |
L-isoprenaline | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257456 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
procaterol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257864 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Denopamine is the most selective ligand for β1-receptors, with regard to intrinsic activity and efficacy, and clenbuterol, procaterol, zinterol, AZ 40140d and salbutamol are more selective for the β2-adrenoceptor than the β1-adrenoceptor based on intrinsic activity and efficacy. |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
fenoterol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257867 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Finally, comparisons of the rank order of ligands for the three different receptors provide information about relative intrinsic efficacies. Fenoterol is a full and efficacious agonist at the β1-adrenoceptor, ranking third out of the agonists studied. It was also a full agonist at the β2- and β3-adrenoceptors with the highest intrinsic efficacy (i.e. top of Tables 4 and and5,5, rank 1). |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
terbutaline | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257870 |
|
|
Cricetulus longicaudatus |
|
| pmid |
sentence |
| 20590599 |
Of the agonists studied here, there was a general trend that those with highest intrinsic efficacy were so across all three receptor subtypes (i.e. at the top of Tables 3–5, e.g. fenoterol, terbutaline, metaproterenol and adrenaline) |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
metaproterenol | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257873 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Of the agonists studied here, there was a general trend that those with highest intrinsic efficacy were so across all three receptor subtypes (i.e. at the top of Tables 3–5, e.g. fenoterol, terbutaline, metaproterenol and adrenaline) |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
ADRB1 | up-regulates activity
binding
|
GNAL |
0.404 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256901 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 31160049 |
Here we systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique G alpha subunit C-termini. For each receptor, we probed chimeric G alpha subunit activation via a transforming growth factor-alpha (TGF alpha) shedding response in HEK293 cells lacking endogenous Gq/11- and G12/13- signaling. | We defined positive coupling if any member of the subfamily scored LogRAi ≥ -1 and negative coupling if all of the members scored LogRAi < -1 (Figure 3A-B). ROC analysis gives AUC = 0.78 (Figure S4A) when considering high-confidence known coupling data and suggested a threshold of LogRAi ≥ -1.0 for defining true couplings. | The score associated to this interaction has a LogRAi ≥ -1.0. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
GOPC | down-regulates
relocalization
|
ADRB1 |
0.336 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-128791 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15358775 |
Overexpression of cal reduces surface expression of beta1ar. Interaction with cal promotes retention of beta1ar within the cell |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
denopamine | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257860 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Denopamine is the most selective ligand for β1-receptors, with regard to intrinsic activity and efficacy, and clenbuterol, procaterol, zinterol, AZ 40140d and salbutamol are more selective for the β2-adrenoceptor than the β1-adrenoceptor based on intrinsic activity and efficacy. |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
adrenaline | up-regulates activity
chemical activation
|
ADRB1 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257876 |
|
|
Cricetulus longicaudatus |
CHO-K1 Cell |
| pmid |
sentence |
| 20590599 |
Of the agonists studied here, there was a general trend that those with highest intrinsic efficacy were so across all three receptor subtypes (i.e. at the top of Tables 3–5, e.g. fenoterol, terbutaline, metaproterenol and adrenaline) |
|
| Publications: |
1 |
Organism: |
Cricetulus Longicaudatus |
| + |
ADRB1 | up-regulates activity
binding
|
GNAZ |
0.247 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-281664 |
|
|
Homo sapiens |
HEK-293A Cell |
| pmid |
sentence |
| 35302493 |
This study describes the development and validation of a genetically encoded ebBRET-based biosensor platform allowing live-cell mapping of GPCR-G protein coupling preferences covering 12 heterotrimeric G proteins. Profiling of 100 therapeutically relevant human GPCRs resulted in 1500 pathway-specific concentration-response curves and revealed a great diversity of coupling profiles ranging from exquisite selectivity to broad promiscuity.In our dataset, which is the first using unmodified GPCRs and Gα proteins (except for Gs), 29% of the receptors coupled to only one family, whereas others displayed more promiscuity by coupling to 2, 3, or 4 families (36%, 25%, and 10%, respectively). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
4.0
ADRB1
- 
- 