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MC4R Membrane Protein Introduction

Introduction of MC4R

The melanocortin 4 receptor (MC4R) in humans, encoded by the MC4R gene, is a G protein-coupled receptor that binds α-melanocyte stimulating hormone (α-MSH). As a neuropeptide, melanocortin has a well-recognized anti-inflammatory and anti-apoptotic effect in the brain. MC4R, one of the five melanocortin receptors (MCR), is richly present in the brain and is the only MCR expressed in astrocytes.

Basic Information ofMC4R
Protein Name Melanocortin receptor 4
Gene Name MC4R
Organism Homo sapiens (Human)
UniProt ID P32245
Transmembrane Times 7
Length (aa) 332
Sequence MVNSTHRGMHTSLHLWNRSSYRLHSNASESLGKGYSDGGCYEQLFVSPEVFVTLGVISLLENILVIVAIAKNKNLHSPMYFFICSLAVADMLVSVSNGSETIVITLLNSTDTDAQSFTVNIDNVIDSVICSSLLASICSLLSIAVDRYFTIFYALQYHNIMTVKRVGIIISCIWAACTVSGILFIIYSDSSAVIICLITMFFTMLALMASLYVHMFLMARLHIKRIAVLPGTGAIRQGANMKGAITLTILIGVFVVCWAPFFLHLIFYISCPQNPYCVCFMSHFNLYLILIMCNSIIDPLIYALRSQELRKTFKEIICCYPLGGLCDLSSRY

Function of MC4R Membrane Protein

The regulation of MC4R activation is involved in neuronal activity but the molecular mechanisms are still unknown. Based on researches in murine models, MC4 receptors have been reported related to feeding behavior, the regulation of metabolism, sexual behavior, and male erectile function. MC4R mutations are associated with disease such as inherited human obesity. Previously researches have shown that NDP-MSH, an α-MSH analog, stimulated the activation of MC4R and increased brain-derived neurotrophic factor (BDNF) expression in rat astrocytes. MC4R is also involved in the modulation of anxiety- and depressive-like behavior induced by mild or moderate stress. MC4R plays a key role in the regulation of appetite and energy in the brain and the defects of MC4R result in a severe clinical phenotype with lack of satiety and early-onset severe obesity. In addition, it was reported that the MC4 receptor interacted with proopiomelanocortin (POMC).

Structure of MC4R membrane protein. Fig.1 Structure of MC4R membrane protein.

Application of MC4R Membrane Protein in Literature

  1. Fani L., et al. The melanocortin-4 receptor as target for obesity treatment: a systematic review of emerging pharmacological therapeutic options. Int J Obes (Lond). 2014, 38(2):163-9. PubMed ID: 23774329

    This article gives a systematic review of emerging pharmacological therapeutic options for obesity treatment. In summary, although MC4R agonists have developed in phase I and II trials, there are no effective clinical treatments currently for MC4R-deficient obese patients.

  2. Arble D.M., et al. The melanocortin-4 receptor integrates circadian light cues and metabolism. Clin Hemorheol Microcirc. 2015, 156(5):1685-91. PubMed ID: 25730108

    This article reveals Mc4r signaling plays a protective role in minimizing glucose fluctuations due to circadian rhythms and environmental light cues and demonstrate a previously undiscovered connection between circadian biology and glucose metabolism mediated through the melanocortin system.

  3. Ramírez D., et al. Melanocortin 4 receptor activates ERK-cFos pathway to increase brain-derived neurotrophic factor expression in rat astrocytes and hypothalamus. Molecular and Cellular Endocrinology. 2015, 411: 28–37. PubMed ID: 25892444

    This article reports that MC4R-induced BDNF expression in astrocytes refers to ERK-RSK-cFos pathway based on PI3K and Src for the first time. Meanwhile, it is shown that melanocortins induce BDNF expression and ERK-cFos activation in rat hypothalamus.

  4. Serova L.I, et al. Intranasal infusion of melanocortin receptor four (MC4R) antagonist to rats ameliorates development of depression and anxiety related symptoms induced by single prolonged stress. Behavioural Brain Research. 2013, 250:139-47. PubMed ID: 27818940

    This article focuses on whether blockage of central MC4Rs with HS014 before severe traumatic stress may protect against the development of anxiety and depression co-morbid with post-traumatic stress disorder (PTSD) and reveals pronounced resilience effects of HS014 on the development of behavioral symptoms co-morbid with PTSD for the first time.

  5. Chen S, et al. Activation of melanocortin receptor 4 with RO27-3225 attenuates neuroinflammation through AMPK/JNK/p38 MAPK pathway after intracerebral hemorrhage in mice. J Neuroinflammation. 2018, 15(1):106. PubMed ID: 29642894

    This article evaluates the role of MC4R activation on neuroinflammation in a mouse ICH model and reveals that activation of MC4R with RO27-3225 improved the neurobehavioral functions, decreased brain edema, and suppressed microglia/macrophage activation and neutrophil infiltration after ICH.

MC4R Preparation Options

To obtain the soluble and functional target protein, the versatile Magic™ membrane protein production platform in Creative Biolabs enables many flexible options, from which you can always find a better match for your particular project. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-MC4R antibody development services.


Equipped with world-leading technology platforms and professional scientific staff, Creative Biolabs has successfully generated a variety of functional membrane protein targets for our customers. We are pleased to tailor one-stop, custom-oriented service packages and provide lyophilization or freezing service for long-term storage of membrane proteins from weeks to months. Please feel free to contact us for more information.

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