Melanocortin 1 receptor
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| Location (UCSC) | Chr 16: 89.91 – 89.92 Mb | Chr 8: 124.13 – 124.14 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
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The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a
MC1R is one of the key
In humans, a number of loss-of-function mutations of MC1R have been described, with redheads often having multiple individual loss-of-function mutations, but as of 2001, activating mutations that increase eumelanin synthesis have not been described.[8]
MC1R has also been reported to be involved in cancer (independent of skin coloration), developmental processes, and susceptibility to infections and pain.[9]
Functions
Coloration in mammals
The MC1R protein lies within the
The yellow and black agouti banding pattern observed on most mammalian hair is caused by the pulsative nature of ASIP signalling through MC1R. Exceptions include particoloured bay horses, which have reddish bodies, and black legs, mane, and tail, where ASIP signaling is limited to regions instead of pulsating. Human hair, which is neither banded nor particoloured, is thought to be regulated by α-MSH signaling through MC1R exclusively.
The prevalence of red hair in humans varies considerably worldwide. In the United States, about 25% of the human population carries the mutated melanocortin 1 receptor that causes red hair. With one in four people as carriers, the chance of two people having a child with red hair is about 2% (one in 64).[11] People with freckles and no red hair have an 85% chance of carrying the MC1R gene that is connected to red hair. People with no freckles and no red hair have an 18% chance of carrying the MC1R gene linked to red hair.[12] Eight genes have been identified in humans that control whether the MC1R gene is turned on and the person has red hair.[13]
Coloration in birds
MC1R is responsible for melanic polymorphisms in at least three unrelated species: the bananaquit, the snow goose, and the arctic skua.[14]
Pain in mammals
In mutant yellow-orange mice and human redheads, both with nonfunctional MC1R, both genotypes display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to morphine-metabolite analgesics.[15] These observations suggest a role for mammalian MC1R outside the pigment cell, though the exact mechanism through which the protein can modulate pain sensation is not known.
In a certain genetic background in mice it has been reported that animals lacking MC1R had increased tolerance to capsaicin acting through the TRPV1 receptor and decreased response to chemically induced inflammatory pain.[16]
Humans with MC1R mutations have been reported to need approximately 20% more
Some roles in development
Since
One example at the tissue level showed the involvement of MC1R in the normal and pathological development of
In this study the authors compared normal mice with mice completely lacking MC1R. Even without experimental induction of osteoarthritis, mice without MC1R had less articular cartilage (as shown by the red staining in the image). After experimental induction of osteoarthritis, the defect caused by MC1R was more pronounced.MC1R and infection/inflammation
The involvement of MC1R in a rat model of
Role in cancer independent of skin color
MC1R signalling stimulates
Role in kidney pathology
In other organisms
MC1R has a slightly different function in
Ligands
Agonists
- α-MSH - nonselective peptide full agonist
- β-MSH - nonselective peptide full agonist
- γ-MSH - nonselective peptide full agonist
- ACTH - nonselective peptide full agonist
- Afamelanotide - nonselective peptide full agonist
- BMS-470,539- selective small-molecule full agonist
- Bremelanotide - nonselective peptide full agonist
- Melanotan II - nonselective peptide full agonist
- Modimelanotide - nonselective peptide full agonist
- Setmelanotide - nonselective peptide full agonist
Antagonists
- Agouti signalling peptide- nonselective peptide antagonist
Pigmentation genetics
MC1R
- Laboratory mice[33]
- Dogs[34][35]
- Big cats[36]
- Horses[37]
- Cattle[38]
- Chickens[39]
- Bananaquit[40]
- Gyrfalcon[41]
- Kermode bears[42]
- Rock pocket mice[43]
- Domestic rabbits[32]
- Antarctic fur seals[44]
- Mammoth[45]
A study on unrelated British and Irish individuals demonstrated that over 80% of people with red hair and/or fair skin that tan poorly have a dysfunctional variant of the MC1R gene. This is compared to less than 20% in people with brown or black hair, and less than 4% in people showing a good tanning response.[12]
Asp294His (rs1805009) is a
Other SNPs in the gene, Arg151Cys and Arg160Trp, are also associated with red hair.The
Evolution
Paralogues[51]
- MC4R
- MC3R
- MC5R
- MC2R
- GPR6
- GPR12
- S1PR2
- GPR3
- S1PR1
- LPAR1
- CNR1
- LPAR2
- GPR119
- S1PR3
- S1PR5
- LPAR3
- CNR2
- S1PR4
See also
- Chromatophore
- Melanocyte
- SLC24A5
- Melanin
- Pigment
- Human skin color
- Freckles
- Melanotropin receptor
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000258839 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000074037 – 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.
- PMID 27303435.
- PMID 31649620.
- PMID 12177778.
- PMID 10885670.
- ^ "Red Alert!". 2017-11-02.
- ^ Online Mendelian Inheritance in Man (OMIM): 155555
- ^ "The Red Hair Polymorphisms". Archived from the original on 2019-09-13. Retrieved 20 July 2013.
- ^ S2CID 7980311.
- PMID 30531825.
- PMID 16087416.
- PMID 15994880.
- PMID 20856883.
- PMID 15277908.
- PMID 15731586.
- PMID 25860801.
- PMID 25191747.
- PMID 23457491.
- PMID 27488084.
- S2CID 12806815.
- ^ PMID 26850723.
- S2CID 35603627.
- ^ PMID 11179997.
- PMID 20507942.
- PMID 24498203.
- PMID 16704454.
- PMID 12204775.
- S2CID 24698373.
- ^ PMID 16978179.
- S2CID 12179800.
- S2CID 1755908.
- PMID 17485734.
- S2CID 19021807.
- PMID 11030758.
- S2CID 22044170.
- PMID 8764834.
- S2CID 5685555.
- PMID 22504110.
- S2CID 15846139.
- PMID 12704245.
- PMID 27547348.
- S2CID 20153467.
- PMID 9665397.
- PMID 20445093.
- PMID 11305330.
- PMID 10733465.
- PMID 17182896.
- ^ "GeneCards®: The Human Gene Database".
Further reading
- Millington GW (May 2006). "Proopiomelanocortin (POMC): the cutaneous roles of its melanocortin products and receptors". Clinical and Experimental Dermatology. 31 (3): 407–412. S2CID 25213876.
- Rees J (2003). "The roots of red hair". Wellcome Trust. Archived from the original on 2007-10-30. Retrieved 2007-10-31.
- Roach M (2005). Roots of Desire: The Myth, Meaning and Sexual Power of Red Hair. Bloomsbury USA. pp. 256 pages. ISBN 978-1-58234-344-0.
- Silvers WK (1979). The Coat Colors of Mice. Springer-Verlag. ISBN 978-0-387-90367-5.
- Silvers WK (2003). "The Coat Colors of Mice". Mouse Genome Informatics.
External links
- "Melanocortin Receptors: MC1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2021-01-28. Retrieved 2007-07-23.
- Melanocortin+Receptor+1 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- García-Borrón, Sánchez-Laorden, Jiménez-Cervantes. "Melanocortin-1 receptor structure and functional regulation". Pigment Cell Research. Retrieved April 21, 2024.