Gene Symbol: mc4r
Description: melanocortin 4 receptor
Alias: MC4-R, si:dkey-151m6.62, zMC4, melanocortin receptor 4
Species: zebrafish
Products:     mc4r

Top Publications

  1. Zhang C, Forlano P, Cone R. AgRP and POMC neurons are hypophysiotropic and coordinately regulate multiple endocrine axes in a larval teleost. Cell Metab. 2012;15:256-64 pubmed publisher
    ..mediates this phenotypic variation in Xiphophorus and encodes variant alleles of the melanocortin-4 receptor (MC4R)...
  2. Haitina T, Klovins J, Takahashi A, Löwgren M, Ringholm A, Enberg J, et al. Functional characterization of two melanocortin (MC) receptors in lamprey showing orthology to the MC1 and MC4 receptor subtypes. BMC Evol Biol. 2007;7:101 pubmed
    ..This study shows presence of MC receptors in agnathans indicating early signs of specific functions of melanocortin receptor subtypes. ..
  3. Selz Y, Braasch I, Hoffmann C, Schmidt C, Schultheis C, Schartl M, et al. Evolution of melanocortin receptors in teleost fish: the melanocortin type 1 receptor. Gene. 2007;401:114-22 pubmed publisher
    ..Protein sequence comparison between fish and mammalian Mc1r revealed a remarkable concordance between evolutionary and functional analyses for the identification of residues and regions critical for receptor function...
  4. Piccinetti C, Migliarini B, Olivotto I, Coletti G, Amici A, Carnevali O. Appetite regulation: the central role of melatonin in Danio rerio. Horm Behav. 2010;58:780-5 pubmed publisher
    ..For the first time, in fact, melatonin control of food intake by the modulation of leptin, MC4R, ghrelin, NPY and CB1 gene expression was evaluated...
  5. Logan D, Bryson Richardson R, Taylor M, Currie P, Jackson I. Sequence characterization of teleost fish melanocortin receptors. Ann N Y Acad Sci. 2003;994:319-30 pubmed
    ..We have confirmed the sequences of these 10 genes and show the comparison of the amino acid sequences of the encoded proteins with the orthologous receptor in other vertebrates. ..
  6. Forner Piquer I, Maradonna F, Gioacchini G, Santangeli S, Allarà M, Piscitelli F, et al. Dose-Specific Effects of Di-Isononyl Phthalate on the Endocannabinoid System and on Liver of Female Zebrafish. Endocrinology. 2017;158:3462-3476 pubmed publisher
    ..These findings suggest that replacement of DEHP with DiNP should be considered with caution because of observed adverse DiNP effects on aquatic organisms. ..
  7. Shainer I, Buchshtab A, Hawkins T, Wilson S, Cone R, Gothilf Y. Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish. Sci Rep. 2017;7:44777 pubmed publisher
  8. Piccinetti C, Migliarini B, Olivotto I, Simoniello M, Giorgini E, Carnevali O. Melatonin and peripheral circuitries: insights on appetite and metabolism in Danio rerio. Zebrafish. 2013;10:275-82 pubmed publisher stimulating molecules involved in appetite inhibition, such as leptin (LPT), in the liver and intestine and MC4R, a melanocortin system receptor, in the liver...
  9. Skugor A, Tveiten H, Johnsen H, Andersen Ø. Multiplicity of Buc copies in Atlantic salmon contrasts with loss of the germ cell determinant in primates, rodents and axolotl. BMC Evol Biol. 2016;16:232 pubmed
    ..The extra-ovarian expression of salmon buc genes and the presence of a second zebrafish bucL gene suggest additional functions not related to germ cell specification. ..

More Information


  1. Kobayashi Y, Tsuchiya K, Yamanome T, Schioth H, Kawauchi H, Takahashi A. Food deprivation increases the expression of melanocortin-4 receptor in the liver of barfin flounder, Verasper moseri. Gen Comp Endocrinol. 2008;155:280-7 pubmed
    ..The MC system has a role in both pigmentation and the regulation of energy homeostasis, in which MC4R, one of the five MC receptors, has a key role...
  2. Gupta A, Christensen R, Rayla A, Lakshmanan A, Stormo G, Wolfe S. An optimized two-finger archive for ZFN-mediated gene targeting. Nat Methods. 2012;9:588-90 pubmed publisher
    ..Using this archive, we introduced lesions at 9 of 11 target sites in the zebrafish genome. ..
  3. Guillot R, Cortés R, Navarro S, Mischitelli M, García Herranz V, Sánchez E, et al. Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach. Horm Behav. 2016;82:87-100 pubmed publisher
    ..The information provided herein will help to elucidate new central systems involved in control of obesity and should be of invaluable use for sustaining fish production systems. ..
  4. Xie S, Bian W, Wang C, Junaid M, Zou J, Pei D. A novel technique based on in vitro oocyte injection to improve CRISPR/Cas9 gene editing in zebrafish. Sci Rep. 2016;6:34555 pubmed publisher
    ..Due to high throughputs, simplicity and flexible design, this novel strategy will provide an efficient alternative to increase the speed of generating heritable mutants in zebrafish by using CRISPR/Cas9 system. ..
  5. Zhang C, Song Y, Thompson D, Madonna M, Millhauser G, Toro S, et al. Pineal-specific agouti protein regulates teleost background adaptation. Proc Natl Acad Sci U S A. 2010;107:20164-71 pubmed publisher
  6. Cortés R, Teles M, Oliveira M, Fierro Castro C, Tort L, Cerdá Reverter J. Effects of acute handling stress on short-term central expression of orexigenic/anorexigenic genes in zebrafish. Fish Physiol Biochem. 2018;44:257-272 pubmed publisher
    ..By contrast, the anorexigenic precursors tested, i.e., cart peptides and pomc, exhibited increased expression after acute stress, suggesting their involvement in the anorexigenic effects. ..
  7. Kumar A, Bhandari A, Sinha R, Goyal P, Grapputo A. Spliceosomal intron insertions in genome compacted ray-finned fishes as evident from phylogeny of MC receptors, also supported by a few other GPCRs. PLoS ONE. 2011;6:e22046 pubmed publisher
    ..In addition to repetitive elements, genome compaction is now believed to be a new hallmark that promotes intron insertions, as it requires rapid DNA breakage and subsequent repair processes to gain back normal functionality. ..
  8. Shimada Y, Hirano M, Nishimura Y, Tanaka T. A high-throughput fluorescence-based assay system for appetite-regulating gene and drug screening. PLoS ONE. 2012;7:e52549 pubmed publisher
    ..In conclusion, we have developed an assay that uses zebrafish, which can be applied to high-throughput screening and target gene discovery for appetite suppressants and enhancers. ..
  9. Schioth H, Lagerström M, Watanobe H, Jonsson L, Vergoni A, Ringholm A, et al. Functional role, structure, and evolution of the melanocortin-4 receptor. Ann N Y Acad Sci. 2003;994:74-83 pubmed
    ..The MC-4 receptor has been remarkably conserved in structure and pharmacology for more than 400 million years, implying that the receptor participated in vital physiological functions early in vertebrate evolution. ..
  10. Renquist B, Zhang C, Williams S, Cone R. Development of an assay for high-throughput energy expenditure monitoring in the zebrafish. Zebrafish. 2013;10:343-52 pubmed publisher
  11. Josep Agulleiro M, Cortés R, Fernández Durán B, Navarro S, Guillot R, Meimaridou E, et al. Melanocortin 4 receptor becomes an ACTH receptor by coexpression of melanocortin receptor accessory protein 2. Mol Endocrinol. 2013;27:1934-45 pubmed publisher
    ..In this paper, we demonstrate that MRAP2a enables MC4R, a canonical MSH receptor, to be activated by ACTH with a similar sensitivity to that exhibited by MC2R...
  12. Wang H, Semenova S, Kuusela S, Panula P, Lehtonen S. Tankyrases regulate glucoregulatory mechanisms and somatic growth via the central melanocortin system in zebrafish larvae. FASEB J. 2015;29:4435-48 pubmed publisher
    ..of TNKS1b suppressed the expression of melanocortin receptor 3 and increased the expression of melanocortin receptor 4. The collective data suggest that TNKS1b modulates glucoregulatory mechanisms and the somatic growth of ..
  13. Falcinelli S, Rodiles A, Unniappan S, Picchietti S, Gioacchini G, Merrifield D, et al. Probiotic treatment reduces appetite and glucose level in the zebrafish model. Sci Rep. 2016;6:18061 pubmed publisher
    ..rhamnosus in the treatment of impaired glucose tolerance and food intake disorders by gut microbiota manipulation. ..
  14. Martella A, Silvestri C, Maradonna F, Gioacchini G, Allarà M, Radaelli G, et al. Bisphenol A Induces Fatty Liver by an Endocannabinoid-Mediated Positive Feedback Loop. Endocrinology. 2016;157:1751-63 pubmed publisher
    ..We conclude that BPA is able to produce hepatosteatosis in zebrafish and human hepatocytes by up-regulating the endocannabinoid system. ..
  15. Sebag J, Zhang C, Hinkle P, Bradshaw A, Cone R. Developmental control of the melanocortin-4 receptor by MRAP2 proteins in zebrafish. Science. 2013;341:278-81 pubmed publisher
    The melanocortin-4 receptor (MC4R) is essential for control of energy homeostasis in vertebrates. MC4R interacts with melanocortin receptor accessory protein 2 (MRAP2) in vitro, but its functions in vivo are unknown...
  16. Sánchez E, Rubio V, Thompson D, Metz J, Flik G, Millhauser G, et al. Phosphodiesterase inhibitor-dependent inverse agonism of agouti-related protein on melanocortin 4 receptor in sea bass (Dicentrarchus labrax). Am J Physiol Regul Integr Comp Physiol. 2009;296:R1293-306 pubmed publisher
    The melanocortin 4 receptor (MC4R) is a G protein-coupled receptor mainly expressed in the central nervous system of vertebrates...