Biology:Melanocortin 3 receptor
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Short description: Mammalian protein found in Homo sapiens
 Generic protein structure example |
Melanocortin 3 receptor (MC3R) is a protein that in humans is encoded by the MC3R gene.[1][2]
Function
This gene encodes MC3R, a G-protein coupled receptor (GPCR) for melanocyte-stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH) that is expressed in the brain. This gene maps to the same region as the locus for benign neonatal epilepsy. Mice deficient for this gene have increased fat mass, reduced lean mass and decreased food intake, all suggesting a role for the receptor in the regulation of energy homeostasis.[2] MC3R mutations has been linked to reduced growth rate during childhood and a delay in the age of puberty onset.[3]
Research
Studies performed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), found that two specific polymorphisms in the MC3R gene may be associated with pediatric obesity and greater body mass because of greater energy intake. Children who were homozygous for C17A + G241A consumed approximately 38% more than those who did not contain aforementioned polymorphisms. The study concluded that these genetic variants did not affect energy expenditure.[4]
Ligands
- Ac-Val-Gln-(pI)DPhe-DTic-NH2, first MC3 selective agonist, 100x selectivity over MC4.[5]
- Ac-Val-Gln-DBip-DTic-NH2, 140x selectivity over MC4.[6]
- Pyrrolidine bis-cyclic guanidines, non-peptide small molecule MC3 agonists, good selectivity over MC4 but not over MC1 or MC5.[7]
- SHU-9119, mixed MC3/MC4 antagonist.[8]
Evolution
Paralogue[9]
- MC5R
- MC4R
- MC1R
- MC2R
- LPAR1
- S1PR2
- GPR12
- S1PR1
- GPR6
- LPAR2
- S1PR3
- GPR3
- GPR119
- CNR1
- LPAR3
- S1PR5
- S1PR4
- CNR2
See also
References
- ↑ "Molecular cloning of a novel melanocortin receptor". The Journal of Biological Chemistry 268 (11): 8246–50. April 1993. doi:10.1016/S0021-9258(18)53088-X. PMID 8463333.
- ↑ 2.0 2.1 "Entrez Gene: MC3R melanocortin 3 receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4159.
- ↑ Lam, B.Y.H., Williamson, A., Finer, S. et al. MC3R links nutritional state to childhood growth and the timing of puberty. Nature (2021). doi:10.1038/s41586-021-04088-9
- ↑ "Energy intake and energy expenditure among children with polymorphisms of the melanocortin-3 receptor". The American Journal of Clinical Nutrition 90 (4): 912–20. October 2009. doi:10.3945/ajcn.2009.27537. PMID 19656839.
- ↑ "Discovery of Polypharmacological Melanocortin-3 and -4 Receptor Probes and Identification of a 100-Fold Selective nM MC3R Agonist versus a μM MC4R Partial Agonist". Journal of Medicinal Chemistry 62 (5): 2738–2749. March 2019. doi:10.1021/acs.jmedchem.9b00053. PMID 30741545.
- ↑ "Multiresidue Tetrapeptide Substitutions Yield a 140-fold Selective Melanocortin-3 over Melanocortin-4 Receptor Agonist". ACS Medicinal Chemistry Letters 12 (1): 115–120. January 2021. doi:10.1021/acsmedchemlett.0c00561. PMID 33488972.
- ↑ "Discovery of Nanomolar Melanocortin-3 Receptor (MC3R)-Selective Small Molecule Pyrrolidine Bis-Cyclic Guanidine Agonist Compounds Via a High-Throughput "Unbiased" Screening Campaign". Journal of Medicinal Chemistry 64 (9): 5577–5592. May 2021. doi:10.1021/acs.jmedchem.0c02041. PMID 33886285.
- ↑ "Design of novel melanotropin agonists and antagonists with high potency and selectivity for human melanocortin receptors". Peptides 26 (8): 1481–1485. August 2005. doi:10.1016/j.peptides.2005.03.020. PMID 15876475.
- ↑ "GeneCards®: The Human Gene Database". https://www.genecards.org/cgi-bin/carddisp.pl?gene=MC3R&keywords=mc3r#paralogs.
Further reading
- "Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human". Mammalian Genome 5 (8): 503–8. August 1994. doi:10.1007/BF00369320. PMID 7949735.
- "Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor". The Journal of Biological Chemistry 269 (18): 13162–6. May 1994. doi:10.1016/S0021-9258(17)36813-8. PMID 8175743.
- "Localization of the genes encoding the melanocortin-2 (adrenocorticotropic hormone) and melanocortin-3 receptors to chromosomes 18p11.2 and 20q13.2-q13.3 by fluorescence in situ hybridization". Genomics 18 (1): 166–7. October 1993. doi:10.1006/geno.1993.1448. PMID 8276410. https://deepblue.lib.umich.edu/bitstream/2027.42/30538/1/0000171.pdf.
- "Effects of recombinant agouti-signaling protein on melanocortin action". Molecular Endocrinology 11 (3): 274–80. March 1997. doi:10.1210/mend.11.3.9898. PMID 9058374.
- "Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors". Biochemistry 38 (3): 897–904. January 1999. doi:10.1021/bi9815602. PMID 9893984.
- "High-resolution NMR structure of the chemically-synthesized melanocortin receptor binding domain AGRP(87-132) of the agouti-related protein". Biochemistry 40 (51): 15520–7. December 2001. doi:10.1021/bi0117192. PMID 11747427.
- "A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity". The Journal of Clinical Endocrinology and Metabolism 87 (3): 1423–6. March 2002. doi:10.1210/jcem.87.3.8461. PMID 11889220.
- "Neither agouti-related protein nor neuropeptide Y is critically required for the regulation of energy homeostasis in mice". Molecular and Cellular Biology 22 (14): 5027–35. July 2002. doi:10.1128/MCB.22.14.5027-5035.2002. PMID 12077332.
- "A +2138InsCAGACC polymorphism of the melanocortin receptor 3 gene is associated in human with fat level and partitioning in interaction with body corpulence". Molecular Medicine 8 (3): 158–65. March 2002. doi:10.1007/BF03402008. PMID 12142547.
- "Melanocortin-3 receptor gene variants in a Maori kindred with obesity and early onset type 2 diabetes". Diabetes Research and Clinical Practice 58 (1): 61–71. October 2002. doi:10.1016/S0168-8227(02)00126-2. PMID 12161058.
- "Inactivation and intracellular retention of the human I183N mutated melanocortin 3 receptor associated with obesity". Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1689 (3): 229–34. August 2004. doi:10.1016/j.bbadis.2004.03.009. PMID 15276649.
- "Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G protein-coupled receptor activation". The Journal of Clinical Endocrinology and Metabolism 89 (8): 3936–42. August 2004. doi:10.1210/jc.2004-0367. PMID 15292330.
- "Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes". Molecular Pharmacology 67 (1): 50–9. January 2005. doi:10.1124/mol.104.002857. PMID 15470082.
- "Melanocortin receptors form constitutive homo- and heterodimers". Biochemical and Biophysical Research Communications 326 (2): 349–54. January 2005. doi:10.1016/j.bbrc.2004.11.036. PMID 15582585.
- "Mutation analysis of the agouti related protein promoter region and the melanocortin-3 receptor in anorexia nervosa patients". Psychiatric Genetics 15 (4): 237. December 2005. doi:10.1097/00041444-200512000-00003. PMID 16314751.
- "Molecular characterization of human melanocortin-3 receptor ligand-receptor interaction". Biochemistry 45 (4): 1128–37. January 2006. doi:10.1021/bi0521792. PMID 16430209.
External links
- "Melanocortin Receptors: MC3". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2352.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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