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Melanocortin 3 receptor - Wikipedia
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Mammalian protein found in Homo sapiens
MC3R Identifiers Aliases MC3R, BMIQ9, MC3, MC3-R, OB20, OQTL, Melanocortin 3 receptor External IDs OMIM: 155540; MGI: 96929; HomoloGene: 7412; GeneCards: MC3R; OMA:MC3R - orthologs Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.2 Start 56,248,732 bp[1] End 56,249,815 bp[1] Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 H3|2 94.8 cM Start 172,090,412 bp[2] End 172,093,034 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in
- deltoid muscle
- hypothalamus
- prefrontal cortex
- sensory organ
- mucosa of nose
- superior frontal gyrus
- olfactory zone of nasal mucosa
- dorsolateral prefrontal cortex
- wall of uterus
- endometrium
Top expressed in
- embryo
- gastrula
- lumbar subsegment of spinal cord
- meninges
- arcuate nucleus
- skin of abdomen
- nucleus of stria terminalis
- region of wall of ventricular system of neuraxis
- ventricular system
- choroid plexus
More reference expression data BioGPS More reference expression data Gene ontology Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez
4159
17201
Ensembl
ENSG00000124089
ENSMUSG00000038537
UniProt
P41968
P33033
RefSeq (mRNA)
NM_019888
NM_008561
RefSeq (protein)
NP_063941
NP_032587
Location (UCSC) Chr 20: 56.25 – 56.25 Mb Chr 2: 172.09 – 172.09 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse
Melanocortin 3 receptor (MC3R) is a protein that in humans is encoded by the MC3R gene.[5][6]
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.
MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. Humans who carry loss-of-function mutations in MC3R have a later onset of puberty. [7]
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.[8]
Source:[13]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000124089 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038537 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Gantz I, Konda Y, Tashiro T, Shimoto Y, Miwa H, Munzert G, Watson SJ, DelValle J, Yamada T (April 1993). "Molecular cloning of a novel melanocortin receptor". The Journal of Biological Chemistry. 268 (11): 8246–50. doi:10.1016/S0021-9258(18)53088-X. PMID 8463333.
- ^ "Entrez Gene: MC3R melanocortin 3 receptor".
- ^ 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
- ^ Savastano DM, Tanofsky-Kraff M, Han JC, Ning C, Sorg RA, Roza CA, Wolkoff LE, Anandalingam K, Jefferson-George KS, Figueroa RE, Sanford EL, Brady S, Kozlosky M, Schoeller DA, Yanovski JA (October 2009). "Energy intake and energy expenditure among children with polymorphisms of the melanocortin-3 receptor". The American Journal of Clinical Nutrition. 90 (4): 912–20. doi:10.3945/ajcn.2009.27537. PMC 2744620. PMID 19656839.
- ^
- ^ Ericson MD, Shaikh R, Larson CM, Freeman KT, Haskell-Luevano C (January 2021). "Multiresidue Tetrapeptide Substitutions Yield a 140-fold Selective Melanocortin-3 over Melanocortin-4 Receptor Agonist". ACS Medicinal Chemistry Letters. 12 (1): 115–120. doi:10.1021/acsmedchemlett.0c00561. PMC 7812669. PMID 33488972.
- ^ Doering SR, Freeman K, Debevec G, Geer P, Santos RG, Lavoi TM, et al. (May 2021). "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. doi:10.1021/acs.jmedchem.0c02041. PMC 8552302. PMID 33886285.
- ^ Cai M, Mayorov AV, Ying J, Stankova M, Trivedi D, Cabello C, Hruby VJ (August 2005). "Design of novel melanotropin agonists and antagonists with high potency and selectivity for human melanocortin receptors". Peptides. 26 (8): 1481–1485. doi:10.1016/j.peptides.2005.03.020. PMID 15876475. S2CID 45499654.
- ^ "GeneCards®: The Human Gene Database".
- Magenis RE, Smith L, Nadeau JH, Johnson KR, Mountjoy KG, Cone RD (August 1994). "Mapping of the ACTH, MSH, and neural (MC3 and MC4) melanocortin receptors in the mouse and human". Mammalian Genome. 5 (8): 503–8. doi:10.1007/BF00369320. PMID 7949735. S2CID 24047677.
- Konda Y, Gantz I, DelValle J, Shimoto Y, Miwa H, Yamada T (May 1994). "Interaction of dual intracellular signaling pathways activated by the melanocortin-3 receptor". The Journal of Biological Chemistry. 269 (18): 13162–6. doi:10.1016/S0021-9258(17)36813-8. PMID 8175743.
- Gantz I, Tashiro T, Barcroft C, Konda Y, Shimoto Y, Miwa H, Glover T, Munzert G, Yamada T (October 1993). "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" (PDF). Genomics. 18 (1): 166–7. doi:10.1006/geno.1993.1448. hdl:2027.42/30538. PMID 8276410.
- Yang YK, Ollmann MM, Wilson BD, Dickinson C, Yamada T, Barsh GS, Gantz I (March 1997). "Effects of recombinant agouti-signaling protein on melanocortin action". Molecular Endocrinology. 11 (3): 274–80. doi:10.1210/mend.11.3.9898. PMID 9058374.
- Tota MR, Smith TS, Mao C, MacNeil T, Mosley RT, Van der Ploeg LH, Fong TM (January 1999). "Molecular interaction of Agouti protein and Agouti-related protein with human melanocortin receptors". Biochemistry. 38 (3): 897–904. doi:10.1021/bi9815602. PMID 9893984.
- McNulty JC, Thompson DA, Bolin KA, Wilken J, Barsh GS, Millhauser GL (December 2001). "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. doi:10.1021/bi0117192. PMID 11747427.
- Lee YS, Poh LK, Loke KY (March 2002). "A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity". The Journal of Clinical Endocrinology and Metabolism. 87 (3): 1423–6. doi:10.1210/jcem.87.3.8461. PMID 11889220.
- Qian S, Chen H, Weingarth D, Trumbauer ME, Novi DE, Guan X, Yu H, Shen Z, Feng Y, Frazier E, Chen A, Camacho RE, Shearman LP, Gopal-Truter S, MacNeil DJ, Van der Ploeg LH, Marsh DJ (July 2002). "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. doi:10.1128/MCB.22.14.5027-5035.2002. PMC 139785. PMID 12077332.
- Boucher N, Lanouette CM, Larose M, Pérusse L, Bouchard C, Chagnon YC (March 2002). "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. doi:10.1007/BF03402008. PMC 2039979. PMID 12142547.
- Wong J, Love DR, Kyle C, Daniels A, White M, Stewart AW, Schnell AH, Elston RC, Holdaway IM, Mountjoy KG (October 2002). "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. doi:10.1016/S0168-8227(02)00126-2. PMID 12161058.
- Rached M, Buronfosse A, Begeot M, Penhoat A (August 2004). "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. doi:10.1016/j.bbadis.2004.03.009. PMID 15276649.
- Tao YX, Segaloff DL (August 2004). "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. doi:10.1210/jc.2004-0367. PMID 15292330.
- Lapinsh M, Veiksina S, Uhlén S, Petrovska R, Mutule I, Mutulis F, Yahorava S, Prusis P, Wikberg JE (January 2005). "Proteochemometric mapping of the interaction of organic compounds with melanocortin receptor subtypes". Molecular Pharmacology. 67 (1): 50–9. doi:10.1124/mol.104.002857. PMID 15470082. S2CID 13536417.
- Mandrika I, Petrovska R, Wikberg J (January 2005). "Melanocortin receptors form constitutive homo- and heterodimers". Biochemical and Biophysical Research Communications. 326 (2): 349–54. doi:10.1016/j.bbrc.2004.11.036. PMID 15582585.
- de Krom M, de Rijke CE, Hendriks J, van Engeland H, van Elburg AA, Adan RA (December 2005). "Mutation analysis of the agouti related protein promoter region and the melanocortin-3 receptor in anorexia nervosa patients". Psychiatric Genetics. 15 (4): 237. doi:10.1097/00041444-200512000-00003. PMID 16314751.
- Chen M, Aprahamian CJ, Celik A, Georgeson KE, Garvey WT, Harmon CM, Yang Y (January 2006). "Molecular characterization of human melanocortin-3 receptor ligand-receptor interaction". Biochemistry. 45 (4): 1128–37. doi:10.1021/bi0521792. PMID 16430209.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Melanocortin receptor modulators MC1
MC2
MC3
MC4
MC5
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