Melanocortin receptor 4 Antibodies

Melanocortin receptor 4 (MC4R)

Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth.

This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP). .

Gene Information

Human
Gene Name:	MC4R
Uniprot:	P32245
Entrez:	4160

Family

Belongs to:
G-protein coupled receptor 1 family

Alternative Names

Fatboy; Glu3; MC4R; MC4-R; melanocortin 4 receptor; melanocortin receptor 4; Melanocortin-4 R; Melanocortin4R; Melanocortin-4R; MGC126851; MGC138197

Molecular Weight

Mass (kDA):
36.943 kDA

Genomic Context

Human
Location:	18q21.32
Sequence:	18; NC_000018.10 (60371062..60372775, complement)

Tissue Specificity

Brain, placental, and gut tissues.

Subcellular Localizations

Cell membrane; Multi-pass membrane protein.

Diseases

• Obesity
• Diabetes Mellitus
• Hyperphagia
• Diabetes Mellitus, Non-insulin-dependent
• Nervousness
• Pediatric Obesity
• Insulin Resistance
• Obesity, Morbid
• Hypertensive Disease
• Hyperinsulinism
• Malignant Neoplasms
• Cachexia

• Dysequilibrium Syndrome
• Pituitary Diseases
• Inflammation
• Eating Disorders
• Insulin Sensitivity
• Haploinsufficiency

Interacting Proteins

• MRAP

Pathways

• Energy Homeostasis
• Feeding Behavior
• Pigmentation
• Regulation Of Energy Homeostasis
• Localization
• Secretion
• Pathogenesis
• Eating Behavior
• Inflammatory Response
• Glucose Homeostasis
• Regulation Of Appetite
• Transport
• Insulin Secretion

• Endocytosis
• Lactation
• Excretion
• Immune Response
• Reverse Transcription
• Translation
• Regulation Of Feeding Behavior

PTMs

• Phosphorylation
• Cleavage
• Oxidation
• Acetylation
• Methylation

• Acylation
• Ubiquitination
• Carboxylation
• Glycosylation
• Amidation

• Iodination

Research Areas

• GPCR
• Neuroscience

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/MC4R

Best Uses Of The MC4R Marker

The receptor MC4R is one the central regulators of appetite. The mAb 1E8a blocks this receptor and reduces the an orexigenic response. Boster scientists are able to submit the results of their research to receive product credits and special samples. This marker is accessible to all scientists around the world. This article will provide the most commonly used applications of the MC4R marker and how it can be beneficial to scientists.

MC4R is a central regulator of appetite

The melanocortin system regulates energy homeostasis and plays a significant role in the body's weight and appetite. MC4R is located in the brainstem, and is highly expressed in the preganglionic parasympathetic neuronal networks of the nucleus tractus's solitaries, as well as the motor nucleus in the dorsal part of the vagus nerve. MC4R regulates appetite and could be lost in order to increase the risk of developing diabetes and obesity.

Several studies have linked the MC4R gene to a higher body mass index (BMI) and an increased risk for type 2 diabetes. A recent study by Leonska-Duniec and colleagues assessed the association between obesity and MC4R gene polymorphisms in Polish women. People with the CC genotype had higher glucose than those with TT genotypes according to the study's authors. However, there was no connection discovered between a person's CC genotype and higher BMI.

There are more than 100 missense mutations within the MC4R gene. The V103I missense mutation enhances the function of MC4R when stimulated. Other missense mutations in MC4R do not affect the function of MC4 receptors and are referred as wild-type (WT)-like mutations. A stop codon has been identified in the MC4R gene that signifies the end of the chain of proteins. This is important because the absence of the MC4 receptor could lead to severe childhood obesity, increased body fat mass, and an excessive hunger.

In molecular genetics a great deal of research has been conducted on the melanocortin-4 receptor gene. It has been proposed that a decrease in the activity of MC4R can lead to obesity. Despite the high prevalence of obesity Researchers have only identified two polymorphisms in MC4R gene that may provide slight protection from obesity. Researchers have also discovered rare mutations in MC4R which totally impair the receptor's ability for signaling and is associated with severe obesity in children.

In the same manner, MC4R is a prominently expressed protein in the hypothalamus. However in mice, the expression of leptin in the hepatocytes in obese subjects was significantly lower than normal-weight mice. This suggests that the MC4R's impact on obese subjects could be due to the genetic resistance. The leptin receptor was not affected by fructose in mice.

The hypothalamus, a tiny brain structure that regulates eating habits, is located in the middle of the brain. These neurons produce various neuropeptides, such as the anorexigenic peptide corticotropin and the thyrotropin. Both peptides are involved in the regulation of appetite. They also regulate appetite, and regulate physical activity. There are a variety of hypothalamic nuclei in the human brain.

The MC4R gene, in addition to MC4R is essential in regulating hunger. This gene regulates blood sugar levels, which is the reason people who are obese have an increased level of glucose. The MC4R gene is a key regulator of hunger during fasting. Incredibly, a genetic link between lepr and trh is known.

1E8a is a mAb that targets MC4R.

mAb 1E8a was shown to bind to MC4R, diminishing the effectiveness of an agonist called -MSH for the receptor MC4R. The results were similar to those observed using a-MSH and MC4R knockout mice. Similarly, the NT peptide of MC4R is a similar influence in rats.

It was first tested in vitro in two separate experiments to determine if the mAb 1E8a binds the receptor MC4R. Immunocytofluorescence was performed on the native form of hMC4R. In both experiments the mAb 1E8a binding mAbs bound to hMC4R, however, it did not bind to the hMC3R. The two subtypes share low homology at the N terminus. However, the extracellular domains are more homological than transmembrane. This makes them the ideal targets for subtype-selective pharmaceutical approaches.

Below is the final conformation for the hMC4R conformation. It displays sodium binding and an exclusive distal arrangement. Additionally it is believed that the NT protein blocks the interaction between mAb1E8a with MC4R. The model also has a high affinity for both types of MC4R. This proves its potential role as a therapeutic target.

The MC4R receptor is part of the central pathway regulating appetite and energy expenditure. To date, four drugs that target the melanocortin receptor have been developed. Setmelanotide blocks MC4R activity, and increases the inverted agonist effect of Agouti protein. The drug also increased food intake in rats after intracerebroventricular administration of mAb 1E8a.

Anti-MC4R Ab 1E8a is extracted from the plasma of rats immunized with synthetic antibodies based on peptides. It blocks MC4R and has anti-inflammatory properties. Anti-MC4R mAbs function as reverse agonists in the absence of MC4R antagonists, and noncompetitive antagonists in presence of the agonist.

The mAb 1E8a targets hMC4R via binding to MCL0129 and mC4R. These antibodies bind to hMC4R by acknowledging the ligand, and then settle at the binding site on hMC4R. The spatial orientation and recognition of the ligand is crucial for MCL0129's N-terminus as well as its ECLs. The Nterm, which is highly flexible, functions as a hook to MCL0129. The Nterm cap's helical component connects to an antagonist.

MC4R has been associated with various other health conditions including obesity and coronavirus infection. Researchers found that scFv1E8a blocked the formation of cAMP within HEK-293 cells treated with scFv 2G2, although there was no effect on basal cAMP production. Thus, the researchers suggest that scFv 1E8a may be an inverted agonist.

Blockade of MC4R reduces the orexigenic response

MC4R inhibits orexigenic responses in mice. MC4R activation inhibits PVN-DAGLa cell 2-AG synthesis and leads to reduction in intake of food. The MC4R selective agonist LY2112688 blocks DAGLa activity within the PVNMC4R neurons, which in turn blocks the effects of MC4R stimulation.

The MC4R's unparalleled ability to regulate energy homeostasis has led its recognition as a significant therapeutic treatment for obesity and cachexia. Previous attempts to activate MC4R signaling were unsuccessful due to undesirable effects. New studies have shown that blocking MC4R inhibits orexigenic response in mice and human subjects.

The results of this study suggest that the genetic impairment of MC4R triggers an orexigenic reaction in female mice. However the sex-dependent effects of the MC4R mutation in humans may point to a different mechanism. The mutation increases locomotion and increases the amount of energy expended. In addition, MC4R genetic defect blocks orexigenic response in male mice.

Furthermore, MC4RDDAGLa mice show an improvement in glucose tolerance and insulin sensitivity. They also exhibit resistance to diabetes and metabolic syndrome. The MC4RDDAGLa mice exhibit increased fat synthesis and improved lipogenesis. MC4RDDAGLa mice can tolerate high levels of glucose and thus are not susceptible to insulin resistance. If you're a diabetic or obese person, MC4RDDAGLa mice can withstand these challenges.

The MC4R is involved in energy balance in the hypothalamus. Molecular analyses of the MC4R signaling pathway have shown the crucial role played by PVN neurons in sustaining energy homeostasis. Pharmacological activation of MC4R suppresses food intake, and increases the expenditure of energy and the metabolism of lipids. In humans, mutations of the MC4R result in metabolic syndrome and hyperphagia in the early stages.

Males are affected by the corticosterone reaction, which is slowed due to MC4R function loss. Females suffer from the opposite effects of MC4R function loss. Females who have impaired MC4R function have higher levels of corticosterone in the basal region and greater responses to acute restraint compared to mice in control.

In mice with a-MSH expression the effects of blocking MC4R were studied. LY2112688 and MC4RDDAGLa served as an analog of MSH. Mice were used in studies by expressing either a MSH or a GFP-mCl receptor. To prevent obesity, mice were kept in whole cells at -70mV. Under isofluorene injections of both LY as well as DO34 were administered.