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MC1 receptor

Family: Melanocortin receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
General Comments
References
Gene and Protein Information
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 (alpha melanocyte stimulating hormone receptor) 21
Mouse 7 315 8 E2 Mc1r melanocortin 1 receptor 21
Rat 7 325 19q12 Mc1r melanocortin 1 receptor
Previous and Unofficial Names
MC1R
MSH-R
LOC292083
Mc1r_predicted
melanocortin 1 receptor (predicted)
Mshra
extension recessive yellow
Tob
Database Links
ChEMBL Target
Ensembl
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProt
Wikipedia
Search for 3D structures on the PDB
Search by keyword: Melanocortin receptors MC1 receptor
Natural/Endogenous Ligand(s)
ACTH {Sp: Mouse, Rat} , ACTH {Sp: Human}
α-MSH {Sp: Human, Mouse, Rat}
β-MSH {Sp: Human} , β-MSH {Sp: Mouse} , β-MSH {Sp: Rat}
γ-MSH {Sp: Human, Mouse, Rat}
Rank order of potency (Human)
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]NDP-MSH Hs Full agonist 9.5 pKd 16
SHU9119 Hs Partial agonist 9.2 pKd 12,23
MS05 Hs Full agonist 9.1 pKd 26
HS014 Hs Partial agonist 7.0 pKd 23
NDP-MSH Hs Full agonist 10.0 pIC50 18,24
MT-II Hs Full agonist 9.4 pIC50 1,18
α-MSH {Sp: Human, Mouse, Rat} Hs Full agonist 8.4 pIC50 18
Agonist Comments
The human MC1 compared to the mouse MC1 is "supersensitive" to the melanocortin peptides [19].

A selective MC1 receptor agonist with nanomolar potency has recently been described [11]. 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.

Antagonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
agouti {Sp: Mouse} Mm Inverse agonist 8.6 pKd 15,17
HS024 Hs Antagonist 7.7 pKd 14
ASIP [90-132 (L89Y)] Hs Inverse agonist 8.1 pIC50 29-30
View species-specific antagonist tables

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
References:  19
Secondary Transduction Mechanisms
Transducer Effector/Response
G protein (identity unknown) Other - See Comments
Comments:  Melanocortin activation of the murine MC1R mobilizes intracellular calcium via an incompletely understood pathway.
References:  20
Tissue Distribution
Endothelial cells.
Species:  Human
Technique:  RT-PCR
References:  10
Dermal papilla cells.
Species:  Human
Technique:  RT-PCR and immunofluorescence.
References:  3
Pituitary and testes.
Species:  Human
Technique:  PCR and hybridisation.
References:  7
Neutrophils.
Species:  Human
Technique:  RT-PCR
References:  6
Melanoma cells.
Species:  Human
Technique:  PCR and Northern Blotting.
References:  8
Macrophages.
Species:  Mouse
Technique:  RT-PCR
References:  25
Fibroblasts.
Species:  Mouse
Technique:  RT-PCR and Northern Blotting.
References:  4
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of cAMP in cell lines transfected with the MC1 receptor.
Species:  Human
Tissue:  HEK 293 and COS cells.
Response measured:  Intracellular cAMP accumulation.
References:  19
Measurement of intracellular Ca2+ levels in HEK 293 cells transfected with the MC1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Mobilization of [Ca2+]i.
References:  20
Xenopus melanophore pigment dispersion assay.
Species:  Human
Tissue:  Xenopus melanophores transfected with human MC1.
Response measured:  Melanophore aggregation and dispersion measured by optical density.
References:  13
Measurement of intracellular cAMP levels.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in cAMP levels.
References:  29
Physiological Functions
MC1 expressed by leukocytes may be responsible for some of the anti-inflammatory actions of α-MSH.
Species:  Human
Tissue:  Not Specified
References:  28
In mammals the MC1 expressed by the dermal melanocyte regulates the synthesis of eumelanin (black-brown pigment) versus phaeomelanin (yellow-red pigment). α-MSH acts at the melanocyte MC1 to elevate enzymes like tyrosinase, which are necessary for eumelanin synthesis, replacing synthesis of the default yellow-red phaeolmelanin pigments.
Species:  Mouse
Tissue:  Skin
References:  9
Stimulation of human dermal microvascular endothelial cells (HDMECs) with α-MSH causes an increase in expression of interleukin-8 (IL-8). This may have a role in the anti-inflammatory actions of α-MSH.
Species:  Human
Tissue:  HDMEC cells.
References:  10
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mc1rE-tob Mc1rE-tob/Mc1rE-tob
M. m. domesticus poschiavinus
MGI:99456  MP:0002075 abnormal coat/hair pigmentation
Mc1rtaw Mc1rtaw/Mc1rtaw
M. m. molossinus
MGI:99456  MP:0002075 abnormal coat/hair pigmentation PMID: 15653560 
Mc1rtaw Mc1rtaw/Mc1rtaw
M. m. molossinus
MGI:99456  MP:0000015 abnormal ear pigmentation PMID: 15653560 
Mc1re Mc1re/Mc1re
C57BL/6Ha
MGI:99456  MP:0004382 abnormal hair follicle melanogenesis PMID: 1098946 
Mc1re Mc1re/Mc1re
C57BL/6J-Mc1r/J
MGI:99456  MP:0001224 abnormal keratinocyte apoptosis PMID: 16988713 
Mc1re Mc1re/Mc1re
C57BL/6J-Mc1r/J
MGI:99456  MP:0005077 abnormal melanogenesis PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk Mc1re/Mc1re,Tg(KRT14-Kitl)1Takk/0
involves: C57BL/6 * SJL
MGI:3607789  MGI:99456  MP:0005077 abnormal melanogenesis PMID: 16988713 
Mc1re-J Mc1re-J/Mc1re-J
B6.C-H2-Ab1/KhEg-Mc1r/J
MGI:99456  MP:0001970 abnormal pain threshold PMID: 15277941 
Mc1re Mc1re/Mc1re
C57BL/6
MGI:99456  MP:0001970 abnormal pain threshold PMID: 15994880 
Mc1re Mc1re/Mc1re
involves: C57BL/6Ha
MGI:99456  MP:0006370 abnormal phaeomelanin content PMID: 17652101 
A|Mc1re|Pomctm1Sora|Tg(MC1R)1Jkn a/A,Mc1re/Mc1re,Pomctm1Sora/Pomctm1Sora,Tg(MC1R)1Jkn/?
involves: 129S6/SvEvTac * C57BL/6Ha
MGI:3805879  MGI:87853  MGI:97742  MGI:99456  MP:0006370 abnormal phaeomelanin content PMID: 17652101 
a|Mc1re|Pomctm1Sora|Tg(MC1R)1Jkn a/a,Mc1re/Mc1re,Pomctm1Sora/Pomctm1Sora,Tg(MC1R)1Jkn/?
involves: 129S6/SvEvTac * C57BL/6Ha
MGI:3805879  MGI:87853  MGI:97742  MGI:99456  MP:0006370 abnormal phaeomelanin content PMID: 17652101 
Mc1re Mc1re/Mc1re
C57BL/6J-Mc1r/J
MGI:99456  MP:0002095 abnormal skin pigmentation PMID: 16988713 
Mc1rtaw Mc1rtaw/Mc1rtaw
M. m. molossinus
MGI:99456  MP:0002095 abnormal skin pigmentation PMID: 15653560 
Mc1rE-so Mc1rE-so/Mc1rE-so
C3H
MGI:99456  MP:0002095 abnormal skin pigmentation
Mc1r+|Mc1rE-so Mc1rE-so/Mc1r+
C3H
MGI:99456  MP:0002095 abnormal skin pigmentation
Mc1rtaw Mc1rtaw/Mc1rtaw
M. m. molossinus
MGI:99456  MP:0005174 abnormal tail pigmentation PMID: 15653560 
Mc1re Mc1re/Mc1re
C57BL/6
MGI:99456  MP:0001968 abnormal touch/ nociception PMID: 15994880 
Mc1re Mc1re/Mc1re
C57BL/6
MGI:99456  MP:0004270 analgesia PMID: 15994880 
Adamts20bt|Mc1re Adamts20bt/Adamts20bt,Mc1re/Mc1re
involves: C57BL/6Ha * DBA
MGI:2660628  MGI:99456  MP:0002671 belted PMID: 5713933 
Mc1rE-tob Mc1rE-tob/Mc1rE-tob
M. m. domesticus poschiavinus
MGI:99456  MP:0005409 darkened coat color
Mc1rE-so Mc1rE-so/Mc1rE-so
C3H
MGI:99456  MP:0005409 darkened coat color
Mc1r+|Mc1rE-so Mc1rE-so/Mc1r+
C3H
MGI:99456  MP:0005409 darkened coat color
Mc1re|Mlphln Mc1re/Mc1re,Mlphln/Mlphln
Not Specified
MGI:2176380  MGI:99456  MP:0000371 diluted coat color PMID: 5713933 
Mc1rE-so Mc1rE-so/Mc1rE-so
C3H
MGI:99456  MP:0001188 hyperpigmentation
Mc1r+|Mc1rE-so Mc1rE-so/Mc1r+
C3H
MGI:99456  MP:0001188 hyperpigmentation
Mc1re Mc1re/Mc1re
C57BL/6J-Mc1r/J
MGI:99456  MP:0004227 increased cellular sensitivity to ionizing radiation PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk|Xpctm1Brd Mc1re/Mc1re,Xpctm1Brd/Xpctm1Brd,Tg(KRT14-Kitl)1Takk/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL
MGI:103557  MGI:3607789  MGI:99456  MP:0002020 increased tumor incidence PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk|Xpctm1Brd Mc1re/Mc1re,Xpctm1Brd/Xpctm1Brd,Tg(KRT14-Kitl)1Takk/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL
MGI:103557  MGI:3607789  MGI:99456  MP:0001212 skin lesions PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk|Xpctm1Brd Mc1re/Mc1re,Xpctm1Brd/Xpctm1Brd,Tg(KRT14-Kitl)1Takk/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL
MGI:103557  MGI:3607789  MGI:99456  MP:0004207 squamous cell carcinoma PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk|Xpctm1Brd Mc1re/Mc1re,Xpctm1Brd/Xpctm1Brd,Tg(KRT14-Kitl)1Takk/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL
MGI:103557  MGI:3607789  MGI:99456  MP:0001219 thickened epidermis PMID: 16988713 
Mc1re|Tg(KRT14-Kitl)1Takk|Xpctm1Brd Mc1re/Mc1re,Xpctm1Brd/Xpctm1Brd,Tg(KRT14-Kitl)1Takk/0
involves: 129S7/SvEvBrd * C57BL/6 * SJL
MGI:103557  MGI:3607789  MGI:99456  MP:0001263 weight loss PMID: 16988713 
Ednrbs|Mc1re Ednrbs/Ednrbs,Mc1re/Mc1re
Not Specified
MGI:102720  MGI:99456  MP:0002938 white spotting PMID: 5713933 
Mc1re Mc1re/Mc1re
C57BL/6Ha
MGI:99456  MP:0003136 yellow coat color PMID: 5713933  767180 
Ednrbs|Mc1re Ednrbs/Ednrbs,Mc1re/Mc1re
Not Specified
MGI:102720  MGI:99456  MP:0003136 yellow coat color PMID: 5713933 
Adamts20bt|Mc1re Adamts20bt/Adamts20bt,Mc1re/Mc1re
involves: C57BL/6Ha * DBA
MGI:2660628  MGI:99456  MP:0003136 yellow coat color PMID: 5713933 
Mc1rtaw Mc1rtaw/Mc1rtaw
M. m. molossinus
MGI:99456  MP:0003136 yellow coat color PMID: 15653560 
Mc1re|Mc1rtaw Mc1rtaw/Mc1re
involves: M. m. molossinus * C57BL/6J
MGI:99456  MP:0003136 yellow coat color PMID: 10374067 
Mc1re Mc1re/Mc1re
involves: C57BL/6Ha
MGI:99456  MP:0003136 yellow coat color PMID: 17652101 
A|Ay-Jkn|Mc1re Ay-Jkn/A,Mc1re/Mc1re
involves: C57BL/6Ha * C57BL/6N
MGI:87853  MGI:99456  MP:0003136 yellow coat color PMID: 17652101 
A|Ay-Jkn|Mc1re|Tg(MC1R)1Jkn Ay-Jkn/A,Mc1re/Mc1re,Tg(MC1R)1Jkn/0
involves: C57BL/6Ha * C57BL/6N
MGI:3805879  MGI:87853  MGI:99456  MP:0003136 yellow coat color PMID: 17652101 
A|Mc1re|Pomctm1Sora|Tg(MC1R)1Jkn a/A,Mc1re/Mc1re,Pomctm1Sora/Pomctm1Sora,Tg(MC1R)1Jkn/?
involves: 129S6/SvEvTac * C57BL/6Ha
MGI:3805879  MGI:87853  MGI:97742  MGI:99456  MP:0003136 yellow coat color PMID: 17652101 
a|Mc1re|Pomctm1Sora|Tg(MC1R)1Jkn a/a,Mc1re/Mc1re,Pomctm1Sora/Pomctm1Sora,Tg(MC1R)1Jkn/?
involves: 129S6/SvEvTac * C57BL/6Ha
MGI:3805879  MGI:87853  MGI:97742  MGI:99456  MP:0003136 yellow coat color PMID: 17652101 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Familial melanoma
OMIM: 
Orphanet: 
References: 
Mutations not determined
Disease:  Oculocutaneous albinism type 2
OMIM: 
Orphanet: 
References: 
Mutations not determined
Biologically Significant Variants
The MC1 maps to the extension locus, which was identified by classical geneticists to be one of the major determinants of mammalian coat color. Point mutations of the MC1 that alter its function are responsible for pigmentation phenotypes such as the red fox or yellow mouse.
Type:  Naturally occurring mutations.
Species:  Mouse
References:  22
There is a splice variant of the MC1 receptor termed MC1B, which has an additional 65 amino acids at the predicted intracellular, C-terminal tail. Pharmacologically this splice variant appears to be similar to the MC1 receptor.
Type:  Splice variants.
Species:  Human
References:  27
General Comments
Bioassays based on frog and lizard skin are also used. [5]

REFERENCES

To cite this database page, please use the following:

Tung Fong, Helgi Schiöth, Ira Gantz, Roger D. Cone, Sadaf Farooqi, Carrie Haskell-Luevano, Victor J. Hruby, Kathleen G. Mountjoy, Jeffrey B. Tatro, Jarl E. S. Wikberg.
Melanocortin receptors: MC1 receptor. Last modified on 22/01/2013. Accessed on 24/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=282.


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