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This intronless gene encodes the receptor protein for melanocyte-stimulating hormone (MSH). The encoded protein, a seven pass transmembrane G protein coupled receptor, controls melanogenesis. Two types of melanin exist: red pheomelanin and black eumelanin. Gene mutations that lead to a loss in function are associated with increased pheomelanin production, which leads to lighter skin and hair color. Eumelanin is photoprotective but pheomelanin may contribute to UV-induced skin damage by generating free radicals upon UV radiation. Binding of MSH to its receptor activates the receptor and stimulates eumelanin synthesis. This receptor is a major determining factor in sun sensitivity and is a genetic risk factor for melanoma and non-melanoma skin cancer. Over 30 variant alleles have been identified which correlate with skin and hair color, providing evidence that this gene is an important component in determining normal human pigment variation. [provided by RefSeq, Jul 2008]
MC1R (Melanocortin 1 Receptor) is a Protein Coding gene. Diseases associated with MC1R include Melanoma, Cutaneous Malignant 5 and Skin/Hair/Eye Pigmentation, Variation In, 2. Among its related pathways are Signaling by GPCR and Aldosterone synthesis and secretion. Gene Ontology (GO) annotations related to this gene include G protein-coupled receptor activity and hormone binding. An important paralog of this gene is MC4R.
Melanocortin receptors are activated by members of the melanocortin family: alpha-, beta- and gamma-melanocyte stimulating hormone (MSH) and adrenocorticotropic hormone (ACTH). The melanocortins are involved in a range of physiological functions, including pigmentation and inflammation.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0004930 | G protein-coupled receptor activity | IEA,IBA | 21873635 |
GO:0004977 | melanocortin receptor activity | TAS | 9571181 |
GO:0004980 | melanocyte-stimulating hormone receptor activity | IPI | 19743876 |
GO:0005515 | protein binding | IPI | 19329486 |
GO:0008528 | G protein-coupled peptide receptor activity | TAS | 18292087 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005737 | cytoplasm | IBA | 21873635 |
GO:0005886 | plasma membrane | IDA,TAS | -- |
GO:0005887 | integral component of plasma membrane | TAS | 9571181 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Peptide ligand-binding receptors |
.34
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2 | Signaling by GPCR | ||
3 | Aldosterone synthesis and secretion |
.41
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4 | Melanocyte Development and Pigmentation |
Melanocyte Development and Pigmentation
-
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5 | G alpha (s) signalling events |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0007165 | signal transduction | IEA | -- |
GO:0007186 | G protein-coupled receptor signaling pathway | TAS | -- |
GO:0007187 | G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger | TAS | 9571181 |
GO:0007189 | adenylate cyclase-activating G protein-coupled receptor signaling pathway | IDA | 19329486 |
GO:0007275 | multicellular organism development | TAS | 7581459 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Afamelanotide | Approved, Investigational | Pharma | Target, agonist | 11 | ||
Bremelanotide | Approved, Investigational | Pharma | Target, agonist | 0 | ||
Desipramine | Approved, Investigational | Pharma | 42 | |||
CZEN 002 | Investigational | Pharma | Target | 0 | ||
Melanotan II | Pharma | High affinity melanocortin receptor agonist | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
NDP-MSH |
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Agonist, Full agonist |
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|||
[Nle4,D-Phe7]-alpha-MSH |
|
75921-69-6 |
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||
Melanocyte-stimulating hormone release inhibiting factor |
|
2002-44-0 |
|
|
Compound | Action | Cas Number |
---|---|---|
[Nle4,D-Phe7]-alpha-MSH | Melanocortin receptor agonist | 75921-69-6 |
alpha-MSH | Endogenous melanocortin receptor agonist | 581-05-5 |
Melanocyte-stimulating hormone release inhibiting factor | Inhibitor of alpha-MSH release; inhibits opioid effects in vivo | 2002-44-0 |
Melanotan II | High affinity melanocortin receptor agonist | 121062-08-6 |
THIQ | Potent and selective MC4 receptor agonist | 312637-48-2 |
Compound | Action | Cas Number |
---|---|---|
[Nle4,D-Phe7]-α-MSH | 75921-69-6 | |
BMS 470539 dihydrochloride | MC1 receptor,potent and selective | 457893-92-4 |
HS 014 | 207678-81-7 | |
HS 024 | 212370-59-7 | |
MCL 0020 | 475498-26-1 | |
Melanotan II | 121062-08-6 | |
THIQ | 312637-48-2 | |
α-MSH | 581-05-5 |
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | MC1R 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | MC1R 30 |
|
||
MC1-R 31 |
|
OneToOne | |||
Dog (Canis familiaris) |
Mammalia | MC1R 30 |
|
||
Rat (Rattus norvegicus) |
Mammalia | Mc1r 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Mc1r 30 17 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | MC1R 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | MC1R 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | MC1R 30 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | mc1r 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | mc1r 30 31 |
|
OneToOne | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | -- 31 |
|
ManyToMany | |
-- 31 |
|
ManyToMany |
SNP ID | Clinical significance and condition | Chr 16 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
642519 | Uncertain Significance: Cutaneous malignant melanoma 5 | 89,920,072(+) | A/ACGT | INFRAME_INSERTION | |
645334 | Uncertain Significance: Cutaneous malignant melanoma 5 | 89,919,740(+) | C/T | MISSENSE_VARIANT | |
645959 | Uncertain Significance: Cutaneous malignant melanoma 5 | 89,919,762(+) | C/G | MISSENSE_VARIANT | |
648748 | Uncertain Significance: Cutaneous malignant melanoma 5 | 89,919,674(+) | C/G | MISSENSE_VARIANT | |
651352 | Uncertain Significance: Cutaneous malignant melanoma 5 | 89,919,451(+) | A/G | MISSENSE_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv2762221 | CNV | gain+loss | 21179565 |
nsv1066499 | CNV | loss | 25217958 |
nsv1070371 | CNV | deletion | 25765185 |
nsv428331 | CNV | gain+loss | 18775914 |
nsv482951 | CNV | loss | 15286789 |
nsv509640 | CNV | insertion | 20534489 |
nsv519064 | CNV | loss | 19592680 |
nsv525671 | CNV | loss | 19592680 |
nsv573799 | CNV | gain | 21841781 |
nsv573810 | CNV | loss | 21841781 |
Disorder | Aliases | PubMed IDs |
---|---|---|
melanoma, cutaneous malignant 5 |
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skin/hair/eye pigmentation, variation in, 2 |
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increased analgesia from kappa-opioid receptor agonist, female-specific |
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albinism, oculocutaneous, type ii |
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melanocytic nevus syndrome, congenital |
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