Contents:
- Gene and Protein Information
- Database Links
- Selected 3D Structures
- Associated Proteins
- Natural/Endogenous Ligands
- Rank order lists
- Agonists
- Antagonists
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
||||||
| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 332 | 18q21.32 | MC4R | melanocortin 4 receptor | 14,28 |
| Mouse | 7 | 332 | 18 E1 | Mc4r | melanocortin 4 receptor | |
| Rat | 7 | 332 | 18q12.1 | Mc4r | melanocortin 4 receptor | |
| Database Links |
|
| Specialist databases | |
| GPCRdb | mc4r_human (Hs), mc4r_mouse (Mm), mc4r_rat (Rn) |
| Other databases | |
| Alphafold | P32245 (Hs), P56450 (Mm), P70596 (Rn) |
| ChEMBL Target | CHEMBL259 (Hs), CHEMBL3719 (Mm), CHEMBL2700 (Rn) |
| Ensembl Gene | ENSG00000166603 (Hs), ENSMUSG00000047259 (Mm), ENSRNOG00000018692 (Rn) |
| Entrez Gene | 4160 (Hs), 17202 (Mm), 25635 (Rn) |
| Human Protein Atlas | ENSG00000166603 (Hs) |
| KEGG Gene | hsa:4160 (Hs), mmu:17202 (Mm), rno:25635 (Rn) |
| OMIM | 155541 (Hs) |
| Orphanet | ORPHA168091 (Hs) |
| Pharos | P32245 (Hs) |
| RefSeq Nucleotide | NM_005912 (Hs), NM_016977 (Mm), NM_013099 (Rn) |
| RefSeq Protein | NP_005903 (Hs), NP_058673 (Mm), NP_037231 (Rn) |
| UniProtKB | P32245 (Hs), P56450 (Mm), P70596 (Rn) |
| Wikipedia | MC4R (Hs) |
| Selected 3D Structures |
|||||||||||||
|
|
||||||||||||
| Associated Proteins |
||||||||||||
|
||||||||||||
| Natural/Endogenous Ligands |
| ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat} |
| agouti {Sp: Mouse} |
| agouti-related protein {Sp: Human} |
| β-MSH {Sp: Human} |
| α-MSH {Sp: Human, Mouse, Rat} |
| γ-MSH {Sp: Human, Mouse, Rat} |
| β-MSH {Sp: Mouse} , β-MSH {Sp: Rat} |
| Comments: β-MSH is the principal endogenous agonist. Endogenous antagonists are agouti and agouti-related protein. For representations of the rodent orthologues of these peptides see agouti (mouse), agouti (rat) and agouti-related protein (mouse). |
| Potency order of endogenous agonists (Human) |
| β-MSH (POMC, P01189) > α-MSH (POMC, P01189), ACTH (POMC, P01189) > γ-MSH (POMC, P01189) |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| View species-specific agonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The relative potency of melanocortin peptides at the MC4 is β-MSH>α-MSH=ACTH>γ-MSH [26]. Radioligands commonly used to study the MC4 are [125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]AGRP(83-132). RO27-3225 is a selective MC1R and MC4R agonist [4]. cAMP but no binding data were reported. [125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]Nle7-α-MSH are common radioligands used to study MC1, 3, 4 and MC 5. MK-0493 has been reported to be a potent and selective agonist for this receptor [23]. Setmelanotide, an MC4 agonist with 20-fold less activity at MC1 and MC3 receptors, has been approved by FDA for chronic weight management in adult and pediatric patients 6 years of age and older with obesity due to proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency [8]. Bremelanotide, an acid analog of MT-II and a non-selective MC agonist, has been approved by FDA for the treatment of premenopausal women with acquired, generalized hypoactive sexual desire disorder [20]. |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| View species-specific antagonist tables | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Antagonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The pIC50 of full-length recombinant AGRP expressed in bacteria has been reported to be 7.06 [31]. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary Transduction Mechanisms
|
|
| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| References: 14,28 | |
| Secondary Transduction Mechanisms |
|
| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
|
Comments:
Melanocortin activation of the MC4 mobilizes intracellular calcium via an incompletely understood pathway. Non-G protein dependent transduction: Effector/response inwardly rectifying potassium channel, Kir7.1 |
|
| References: 15,27 | |
| Tissue Distribution
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
||||||||
|
| Expression Datasets |
|
|
| Functional Assays
|
||||||||||
|
||||||||||
|
| Physiological Functions
|
||||||||
|
||||||||
|
| Physiological Consequences of Altering Gene Expression
|
||||||||||
|
| Phenotypes, Alleles and Disease Models
|
Mouse data from MGI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Clinically-Relevant Mutations and Pathophysiology
|
||||||||||||||||||
|
||||||||||||||||||
References
1. Adan RA, Szklarczyk AW, Oosterom J, Brakkee JH, Nijenhuis WA, Schaaper WM, Meloen RH, Gispen WH. (1999) Characterization of melanocortin receptor ligands on cloned brain melanocortin receptors and on grooming behavior in the rat. Eur J Pharmacol, 378: 249-258. [PMID:10493100]
2. Al-Obeidi F, Hruby VJ, Castrucci AM, Hadley ME. (1989) Design of potent linear α-melanotropin 4-10 analogues modified in positions 5 and 10. J Med Chem, 32: 174-179. [PMID:2535874]
3. Bednarek MA, MacNeil T, Kalyani RN, Tang R, Van der Ploeg LH, Weinberg DH. (2001) Selective, high affinity peptide antagonists of alpha-melanotropin action at human melanocortin receptor 4: their synthesis and biological evaluation in vitro. J Med Chem, 44 (22): 3665-72. [PMID:11606131]
4. Benoit SC, Schwartz MW, Lachey JL, Hagan MM, Rushing PA, Blake KA, Yagaloff KA, Kurylko G, Franco L, Danhoo W et al.. (2000) A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J Neurosci, 20 (9): 3442-8. [PMID:10777807]
5. Böhm M, Eickelmann M, Li Z, Schneider SW, Oji V, Diederichs S, Barsh GS, Vogt A, Stieler K, Blume-Peytavi U et al.. (2005) Detection of functionally active melanocortin receptors and evidence for an immunoregulatory activity of alpha-melanocyte-stimulating hormone in human dermal papilla cells. Endocrinology, 146 (11): 4635-46. [PMID:16081629]
6. Chaki S, Hirota S, Funakoshi T, Suzuki Y, Suetake S, Okubo T, Ishii T, Nakazato A, Okuyama S. (2003) Anxiolytic-like and antidepressant-like activities of MCL0129 (1-[(S)-2-(4-fluorophenyl)-2-(4-isopropylpiperadin-1-yl)ethyl]-4-[4-(2-methoxynaphthalen-1-yl)butyl]piperazine), a novel and potent nonpeptide antagonist of the melanocortin-4 receptor. J Pharmacol Exp Ther, 304 (2): 818-26. [PMID:12538838]
7. Chhajlani V. (1996) Distribution of cDNA for melanocortin receptor subtypes in human tissues. Biochem Mol Biol Int, 38 (1): 73-80. [PMID:8932521]
8. Clément K, van den Akker E, Argente J, Bahm A, Chung WK, Connors H, De Waele K, Farooqi IS, Gonneau-Lejeune J, Gordon G et al.. (2020) Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials. Lancet Diabetes Endocrinol, 8 (12): 960-970. [PMID:33137293]
9. Conde-Frieboes K, Thøgersen H, Lau JF, Sensfuss U, Hansen TK, Christensen L, Spetzler J, Olsen HB, Nilsson C, Raun K et al.. (2012) Identification and in vivo and in vitro characterization of long acting and melanocortin 4 receptor (MC4-R) selective α-melanocyte-stimulating hormone (α-MSH) analogues. J Med Chem, 55 (5): 1969-77. [PMID:22335602]
10. Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. (1997) Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature, 385 (6612): 165-8. [PMID:8990120]
11. Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S. (2003) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med, 348 (12): 1085-95. [PMID:12646665]
12. Farooqi IS, O'Rahilly S. (2008) Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab, 4 (10): 569-77. [PMID:18779842]
13. Fong TM, Mao C, MacNeil T, Kalyani R, Smith T, Weinberg D, Tota MR, Van der Ploeg LH. (1997) ART (protein product of agouti-related transcript) as an antagonist of MC-3 and MC-4 receptors. Biochem Biophys Res Commun, 237 (3): 629-31. [PMID:9299416]
14. Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T. (1993) Molecular cloning of a novel melanocortin receptor. J Biol Chem, 268 (11): 8246-50. [PMID:8463333]
15. Ghamari-Langroudi M, Digby GJ, Sebag JA, Millhauser GL, Palomino R, Matthews R, Gillyard T, Panaro BL, Tough IR, Cox HM et al.. (2015) G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature, 520 (7545): 94-8. [PMID:25600267]
16. Grieco P, Lavecchia A, Cai M, Trivedi D, Weinberg D, MacNeil T, Van der Ploeg LH, Hruby VJ. (2002) Structure-activity studies of the melanocortin peptides: discovery of potent and selective affinity antagonists for the hMC3 and hMC4 receptors. J Med Chem, 45 (24): 5287-94. [PMID:12431055]
17. Huszar D, Lynch CA, Fairchild-Huntress V, Dunmore JH, Fang Q, Berkemeier LR, Gu W, Kesterson RA, Boston BA, Cone RD et al.. (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell, 88 (1): 131-41. [PMID:9019399]
18. Kask A, Mutulis F, Muceniece R, Pähkla R, Mutule I, Wikberg JE, Rägo L, Schiöth HB. (1998) Discovery of a novel superpotent and selective melanocortin-4 receptor antagonist (HS024): evaluation in vitro and in vivo. Endocrinology, 139 (12): 5006-14. [PMID:9832440]
19. Kiefer LL, Veal JM, Mountjoy KG, Wilkison WO. (1998) Melanocortin receptor binding determinants in the agouti protein. Biochemistry, 37 (4): 991-7. [PMID:9454589]
20. Kingsberg SA, Clayton AH, Portman D, Williams LA, Krop J, Jordan R, Lucas J, Simon JA. (2019) Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol, 134 (5): 899-908. [PMID:31599840]
21. Kishi T, Aschkenasi CJ, Lee CE, Mountjoy KG, Saper CB, Elmquist JK. (2003) Expression of melanocortin 4 receptor mRNA in the central nervous system of the rat. J Comp Neurol, 457 (3): 213-35. [PMID:12541307]
22. Kopanchuk S, Veiksina S, Petrovska R, Mutule I, Szardenings M, Rinken A, Wikberg JE. (2005) Co-operative regulation of ligand binding to melanocortin receptor subtypes: evidence for interacting binding sites. Eur J Pharmacol, 512 (2-3): 85-95. [PMID:15840392]
23. Krishna R, Gumbiner B, Stevens C, Musser B, Mallick M, Suryawanshi S, Maganti L, Zhu H, Han TH, Scherer L et al.. (2009) Potent and selective agonism of the melanocortin receptor 4 with MK-0493 does not induce weight loss in obese human subjects: energy intake predicts lack of weight loss efficacy. Clin Pharmacol Ther, 86 (6): 659-66. [PMID:19741604]
24. Kumar KG, Sutton GM, Dong JZ, Roubert P, Plas P, Halem HA, Culler MD, Yang H, Dixit VD, Butler AA. (2009) Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. Peptides, 30 (10): 1892-900. [PMID:19646498]
25. Liang J, Li L, Jin X, Xu B, Pi L, Liu S, Zhu W, Zhang C, Luan B, Gong L et al.. (2018) Pharmacological effect of human melanocortin-2 receptor accessory protein 2 variants on hypothalamic melanocortin receptors. Endocrine, 61 (1): 94-104. [PMID:29704154]
26. MacNeil DJ, Howard AD, Guan X, Fong TM, Nargund RP, Bednarek MA, Goulet MT, Weinberg DH, Strack AM, Marsh DJ et al.. (2002) The role of melanocortins in body weight regulation: opportunities for the treatment of obesity. Eur J Pharmacol, 440 (2-3): 141-57. [PMID:12007532]
27. Mountjoy KG, Kong PL, Taylor JA, Willard DH, Wilkison WO. (2001) Melanocortin receptor-mediated mobilization of intracellular free calcium in HEK293 cells. Physiol Genomics, 5 (1): 11-9. [PMID:11161002]
28. Mountjoy KG, Mortrud MT, Low MJ, Simerly RB, Cone RD. (1994) Localization of the melanocortin-4 receptor (MC4-R) in neuroendocrine and autonomic control circuits in the brain. Mol Endocrinol, 8 (10): 1298-308. [PMID:7854347]
29. Mountjoy KG, Wild JM. (1998) Melanocortin-4 receptor mRNA expression in the developing autonomic and central nervous systems. Brain Res Dev Brain Res, 107 (2): 309-14. [PMID:9593962]
30. Nickolls SA, Cismowski MI, Wang X, Wolff M, Conlon PJ, Maki RA. (2003) Molecular determinants of melanocortin 4 receptor ligand binding and MC4/MC3 receptor selectivity. J Pharmacol Exp Ther, 304 (3): 1217-27. [PMID:12604699]
31. Rosenfeld RD, Zeni L, Welcher AA, Narhi LO, Hale C, Marasco J, Delaney J, Gleason T, Philo JS, Katta V et al.. (1998) Biochemical, biophysical, and pharmacological characterization of bacterially expressed human agouti-related protein. Biochemistry, 37 (46): 16041-52. [PMID:9819197]
32. Sawyer TK, Sanfilippo PJ, Hruby VJ, Engel MH, Heward CB, Burnett JB, Hadley ME. (1980) 4-Norleucine, 7-D-phenylalanine-alpha-melanocyte-stimulating hormone: a highly potent alpha-melanotropin with ultralong biological activity. Proc Natl Acad Sci USA, 77 (10): 5754-8. [PMID:6777774]
33. Schioth HB, Muceniece R, Wikberg JE, Chhajlani V. (1995) Characterisation of melanocortin receptor subtypes by radioligand binding analysis. Eur J Pharmacol, 288 (3): 311-317. [PMID:7774675]
34. Schiöth HB, Muceniece R, Mutulis F, Bouifrouri AA, Mutule I, Wikberg JE. (1999) Further pharmacological characterization of the selective melanocortin 4 receptor antagonist HS014: comparison with SHU9119. Neuropeptides, 33 (3): 191-6. [PMID:10657491]
35. Schiöth HB, Muceniece R, Wikberg JE. (1996) Characterisation of the melanocortin 4 receptor by radioligand binding. Pharmacol Toxicol, 79 (3): 161-5. [PMID:8884876]
36. Schiöth HB, Mutulis F, Muceniece R, Prusis P, Wikberg JE. (1998) Discovery of novel melanocortin4 receptor selective MSH analogues. Br J Pharmacol, 124 (1): 75-82. [PMID:9630346]
37. Sebhat IK, Martin WJ, Ye Z, Barakat K, Mosley RT, Johnston DB, Bakshi R, Palucki B, Weinberg DH, MacNeil T, Kalyani RN, Tang R, Stearns RA, Miller RR, Tamvakopoulos C, Strack AM, McGowan E, Cashen DE, Drisko JE, Hom GJ, Howard AD, MacIntyre DE, van der Ploeg LH, Patchett AA, Nargund RP. (2002) Design and pharmacology of N-[(3R)-1,2,3,4-tetrahydroisoquinolinium- 3-ylcarbonyl]-(1R)-1-(4-chlorobenzyl)- 2-[4-cyclohexyl-4-(1H-1,2,4-triazol- 1-ylmethyl)piperidin-1-yl]-2-oxoethylamine (1), a potent, selective, melanocortin subtype-4 receptor agonist. J Med Chem , 45: 4589-4593. [PMID:12361385]
38. Skuladottir GV, Jonsson L, Skarphedinsson JO, Mutulis F, Muceniece R, Raine A, Mutule I, Helgason J, Prusis P, Wikberg JE et al.. (1999) Long term orexigenic effect of a novel melanocortin 4 receptor selective antagonist. Br J Pharmacol, 126 (1): 27-34. [PMID:10051117]
39. Vaisse C, Clement K, Durand E, Hercberg S, Guy-Grand B, Froguel P. (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest, 106 (2): 253-62. [PMID:10903341]
40. Van der Ploeg LH, Martin WJ, Howard AD, Nargund RP, Austin CP, Guan X, Drisko J, Cashen D, Sebhat I, Patchett AA et al.. (2002) A role for the melanocortin 4 receptor in sexual function. Proc Natl Acad Sci USA, 99 (17): 11381-6. [PMID:12172010]
41. Yang YK, Dickinson C, Lai YM, Li JY, Gantz I. (2001) Functional properties of an agouti signaling protein variant and characteristics of its cognate radioligand. Am J Physiol Regul Integr Comp Physiol, 281 (6): R1877-86. [PMID:11705773]
42. Yang YK, Fong TM, Dickinson CJ, Mao C, Li JY, Tota MR, Mosley R, Van Der Ploeg LH, Gantz I. (2000) Molecular determinants of ligand binding to the human melanocortin-4 receptor. Biochemistry, 39 (48): 14900-11. [PMID:11101306]
43. Ye Z, Guo L, Barakat KJ, Pollard PG, Palucki BL, Sebhat IK, Bakshi RK, Tang R, Kalyani RN, Vongs A et al.. (2005) Discovery and activity of (1R,4S,6R)-N-[(1R)-2-[4-cyclohexyl-4-[[(1,1-dimethylethyl)amino]carbonyl]-1-piperidinyl]-1-[(4-fluorophenyl)methyl]-2-oxoethyl]-2-methyl-2-azabicyclo[2.2.2]octane-6-carboxamide (3, RY764), a potent and selective melanocortin subtype-4 receptor agonist. Bioorg Med Chem Lett, 15 (15): 3501-5. [PMID:15982875]
44. Yoon YR, Lee TG, Choi MH, Shin SW, Ko YG, Rhyu IJ, Kim DH, Seong JK, Baik JH. (2018) Glucose-regulated protein 78 binds to and regulates the melanocortin-4 receptor. Exp Mol Med, 50 (9): 120. [PMID:30209265]
45. Yu J, Gimenez LE, Hernandez CC, Wu Y, Wein AH, Han GW, McClary K, Mittal SR, Burdsall K, Stauch B et al.. (2020) Determination of the melanocortin-4 receptor structure identifies Ca2+ as a cofactor for ligand binding. Science, 368 (6489): 428-433. [PMID:32327598]
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License