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MC1 receptor
Not curated in GtoImmuPdb
Target id: 282
Nomenclature: MC1 receptor
Family: Melanocortin receptors
Annotation status:
Annotated and reviewed, awaiting update
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Contents:
- Quaternary Structure
- Gene and Protein Information
- Previous and Unofficial Names
- Database Links
- Selected 3D Structures
- Associated Proteins
- Functional Characteristics
- Natural/Endogenous Ligands
- Rank order lists
- Activators
- Inhibitors
- Gating Inhibitors
- Agonists
- Antagonists
- Channel Blockers
- Allosteric Modulators
- Antibodies
- Other Binding Ligands
- Whole Organism Assay Data
- Large-scale Ligand Screening Data
- Immunopharmacology Comments
- Immuno Cell Type Associations
- Immuno Process Associations
- Immuno Disease Associations
- Malaria Pharmacology Comments
- Transduction Mechanisms
- Tissue Distribution
- Expression Datasets
- Functional Assays
- Physiological Functions
- Physiological Consequences of Altering Gene Expression
- Xenobiotics Influencing Gene Expression
- Phenotypes, Alleles and Disease Models
- Clinically-Relevant Mutations and Pathophysiology
- Gene Expression and Pathophysiology
- Biologically Significant Variants
- General Comments
- Available Assays
- References
- Contributors
- How to cite this page
Gene and Protein Information  |
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| class A G protein-coupled receptor | ||||||
| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 7 | 317 | 16q24.3 | MC1R | melanocortin 1 receptor | 26 |
| Mouse | 7 | 315 | 8 72.1 cM | Mc1r | melanocortin 1 receptor | 26 |
| Rat | 7 | 325 | 19q12 | Mc1r | melanocortin 1 receptor | |
| Previous and Unofficial Names |
| MSH-R | melanocortin 1 receptor (alpha melanocyte stimulating hormone receptor) |
| Database Links |
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| Specialist databases | |
| GPCRdb | mshr_human (Hs), mshr_mouse (Mm) |
| Other databases | |
| Alphafold | Q01726 (Hs), Q01727 (Mm) |
| ChEMBL Target | CHEMBL3795 (Hs), CHEMBL4077 (Mm) |
| Ensembl Gene | ENSG00000258839 (Hs), ENSMUSG00000074037 (Mm), ENSRNOG00000038193 (Rn) |
| Entrez Gene | 4157 (Hs), 17199 (Mm), 292083 (Rn) |
| Human Protein Atlas | ENSG00000258839 (Hs) |
| KEGG Gene | hsa:4157 (Hs), mmu:17199 (Mm), rno:292083 (Rn) |
| OMIM | 155555 (Hs) |
| Orphanet | ORPHA139778 (Hs) |
| Pharos | Q01726 (Hs) |
| RefSeq Nucleotide | NM_002386 (Hs), NM_008559 (Mm) |
| RefSeq Protein | NP_002377 (Hs), NP_032585 (Mm) |
| UniProtKB | Q01726 (Hs), Q01727 (Mm) |
| Wikipedia | MC1R (Hs) |
| Associated Proteins |
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| Natural/Endogenous Ligands |
| ACTH {Sp: Human} , ACTH {Sp: Mouse, Rat} |
| agouti {Sp: Mouse} |
| β-MSH {Sp: Human} |
| α-MSH {Sp: Human, Mouse, Rat} |
| γ-MSH {Sp: Human, Mouse, Rat} |
| β-MSH {Sp: Mouse} , β-MSH {Sp: Rat} |
| Comments: α-MSH is the principal endogenous agonist. Endogenous antagonists are agouti and agouti-related protein. For representations of the rodent orthologues of these peptides see agouti (mouse), agouti (rat) and agouti-related protein (mouse). |
| Potency order of endogenous agonists (Human) |
| α-MSH (POMC, P01189) > β-MSH (POMC, P01189) > ACTH (POMC, P01189), γ-MSH (POMC, P01189) |
Download all structure-activity data for this target as a CSV file 
| Agonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Agonist Comments | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| The human MC1 compared to the mouse MC1 is "supersensitive" to the melanocortin peptides [24]. A selective MC1 receptor agonist with nanomolar potency has recently been described [13]. cAMP but no binding data were published. Ro27-3225 is a selective MC1R and MC4R agonist [2]. cAMP but no binding data were published. [125I]NDP-MSH, [125I]MT-II, [125I]SHU9119, [125I]Nle7-α-MSH are common radioligands used to study MC1, 3, 4 and MC5. |
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| Antagonists | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary Transduction Mechanisms
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| Transducer | Effector/Response |
| Gs family | Adenylyl cyclase stimulation |
| References: 24 | |
| Secondary Transduction Mechanisms |
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| Transducer | Effector/Response |
| G protein (identity unknown) | Other - See Comments |
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Comments:
Melanocortin activation of the murine MC1R mobilizes intracellular calcium via an incompletely understood pathway. Alternative rescue transduction mechanism: (transducer unknown, effector/response protein kinase B (Akt)). This pathway is only activated when there is insufficient production of cAMP due to loss of function mutations and is currently associated with only the protective activity against cancer. |
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| References: 5,25 | |
| Tissue Distribution
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| Expression Datasets |
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| Functional Assays
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| Physiological Functions
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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| Biologically Significant Variants
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| Biologically Significant Variant Comments | ||||||||
| Common variations (polymorphisms) in the MC1R gene are associated with normal differences in skin and hair color. The MC1 receptor regulates the balance between eumelanin (associated with black hair and dark skin that tans easily) and pheomelanin (associated with fair hair, and easily burnt skin on UV exposure) production by melanocytes. MC1 receptor activation favours the production of eumelanin, whereas inactivating variants lead to pheomelanin production. Inactivating receptor polymorphisms are most common in people with red hair, fair skin, freckles, and an increased sensitivity to sun exposure. Inactivating mutations are also associated with increased risk of developing skin cancers, since the inability to produce sufficient eumelanin leaves fair skin more vulnerable to damage from sun exposure. |
| General Comments |
| Bioassays based on frog and lizard skin are also used. [6] |
References
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2. Benoit SC, Schwartz MW, Lachey JL, Hagan MM, Rushing PA, Blake KA, Yagaloff KA, Kurylko G, Franco L, Danhoo W et al.. (2000) A novel selective melanocortin-4 receptor agonist reduces food intake in rats and mice without producing aversive consequences. J Neurosci, 20 (9): 3442-8. [PMID:10777807]
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