| + |
GRK2 | down-regulates activity 
phosphorylation
|
MC4R |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251453 |
Ser329 |
LGGLCDLsSRY |
Homo sapiens |
|
| pmid |
sentence |
| 12639913 |
Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA and GRK phosphorylation and the subsequent recruitment of β-arrestin to the activated receptor. Replacement by alanine(s) of Thr312 and Ser329/330 in the C-terminal tail resulted in an impaired sequestration of mutated receptors to agonist, whereas mutations of Thr232 or Ser306 did not. This indicates that phosphorylation of these residues by kinases is critical for the internalization of MC4R. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-249673 |
Ser330 |
GGLCDLSsRY |
Homo sapiens |
|
| pmid |
sentence |
| 12639913 |
Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-247770 |
Thr312 |
RSQELRKtFKEIICC |
Homo sapiens |
|
| pmid |
sentence |
| 12639913 |
Mutagenesis studies revealed that Thr312 and Ser329/330 in the C-terminal tail are potential sites for PKA and GRK phosphorylation and may play an essential role in the recruitment of beta-arrestin to the activated receptor. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| + |
PRKACA | down-regulates activity
phosphorylation
|
MC4R |
0.312 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250016 |
Ser329 |
LGGLCDLsSRY |
Homo sapiens |
|
| pmid |
sentence |
| 12639913 |
Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-250017 |
Thr312 |
RSQELRKtFKEIICC |
Homo sapiens |
|
| pmid |
sentence |
| 12639913 |
Activation of MC4R by agonist is associated with protein kinase A (PKA) and GRK phosphorylation of serine/threonine residues in the C-terminal tail of MC4R, followed by -arrestin and dynamin-dependent internalization of the receptor. Thr312 and Ser329/330 in the C-terminal tail of MC4R are potential sites for PKA |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
AGRP | down-regulates
binding
|
MC4R |
0.767 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-51104 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 9311920 |
Recombinant agouti-related protein was a potent, selective antagonist of mc3r and mc4r,. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Leptin Signaling |
| + |
Corticotropin | up-regulates activity 
binding
|
MC4R |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268711 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20371771 |
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
MC4R | up-regulates activity
binding
|
GNAS |
0.501 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268707 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20371771 |
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256797 |
|
|
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: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
ASIP | down-regulates activity
binding
|
MC4R |
0.515 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268708 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20371771 |
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| + |
MC4R | down-regulates 
|
Food intake |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263504 |
|
|
Homo sapiens |
Hypothalamus |
| pmid |
sentence |
| 33094623 |
Enhanced melanocortin signaling in the hypothalamus results in both decreased food intake and increased energy expenditure. Adipose tissue derived hormone leptin induces negative energy balance by stimulating α-MSH and melanocortin-4 receptor (MC4R) (Friedman 1997, Kask et al. 1998). Increased melanocortin signaling in hypotalamus leads not only to decreased food intake but also increases sympathetic nervous system outflow to skeletal muscle, energy expenditure and physical activity |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | Leptin Signaling |
| + |
MC4R | up-regulates activity
binding
|
GNAI3 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257182 |
|
|
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 |
| + |
AGRP | down-regulates activity
binding
|
MC4R |
0.767 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252379 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 10318826 |
AGRP is a potent antagonist of the melanocortin-3 receptor and the MC4R and has also been shown to have a lesser degree of inhibitory action at the melanocortin-5 receptor. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268709 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20371771 |
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| Pathways: | Leptin Signaling |
| + |
MRAP2 | down-regulates activity
binding
|
MC4R |
0.519 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252363 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 19329486 |
We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
Melanotan II | up-regulates activity
binding
|
MC4R |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253066 |
|
|
|
|
| pmid |
sentence |
| 17702843 |
Centrally administered melanotan II (MTII), a synthetic melanocortin 3/4-receptor agonist, decreases adiposity beyond that accountable by food intake decreases. |
|
| Publications: |
1 |
| Tissue: |
Hypothalamus |
| + |
MC4R | up-regulates activity
binding
|
GNA14 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257392 |
|
|
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 |
| + |
MC4R | up-regulates activity
binding
|
GNA12 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257440 |
|
|
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 |
| + |
MC4R | up-regulates activity
binding
|
GNAI1 |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257069 |
|
|
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 |
| + |
MC4R | up-regulates activity
binding
|
GNAL |
0.273 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-256940 |
|
|
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 |
| + |
MC4R | up-regulates activity
binding
|
GNAQ |
0.252 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257336 |
|
|
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 |
| + |
POMC | up-regulates activity
binding
|
MC4R |
0.771 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-268710 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20371771 |
The melanocortin (MC) receptor family consists of five Gs-coupled receptors that control various physiological functions in response to four distinct agonists, adrenocorticotropic hormone (ACTH, also known as corticotrophin) and alpha, beta, and gamma melanocyte-stimulating hormone (MSH), which are derived from the proopiomelanocortin precursor protein, and two inverse agonists, agouti and agouti-related proteins |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252373 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 20694162 |
α-MSH can activate both melanocortin 4 receptors (MC4R) and melanocortin 1 receptors (MC1R) |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Brain |
| Pathways: | Leptin Signaling |
| + |
MRAP | down-regulates activity
binding
|
MC4R |
0.504 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252362 |
|
|
Cricetulus griseus |
CHO Cell |
| pmid |
sentence |
| 19329486 |
We report that MRAP and MRAP2 can interact with all 5 MCRs. This interaction results in MC2R surface expression and signaling. In contrast, MRAP and MRAP2 can reduce MC1R, MC3R, MC4R, and MC5R responsiveness to [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH). MRAP and MRAP2 can reduce the surface expression of MC4R and also the signaling of this receptor. we observed a significant decrease in the cell-surface expression of MC4R and MC5R in the presence of MRAP and MRAP2. It is interesting that MRAP and MRAP2 have opposite effects in the modulation of different MCR family members. |
|
| Publications: |
1 |
Organism: |
Cricetulus Griseus |
| + |
MSH release-inhibiting hormone | up-regulates activity
chemical activation
|
MC4R |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257538 |
|
|
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 |
| + |
MC4R | up-regulates activity
binding
|
GNAZ |
0.254 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-257270 |
|
|
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 |
| + |
MC4R | up-regulates activity
|
GNAS |
0.501 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-253067 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22215617 |
We hypothesize that XLαs may be involved in this regulatory loop by coupling to melanocortin receptors 3 and 4 in the hypothalamus. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
MC4R
- 
- 