Reviewed, UniProtKB/Swiss-Prot Q01726 (MSHR_HUMAN)

Names and origin

Protein names

Recommended name:
    Melanocyte-stimulating hormone receptor
      Short name=MSH-R
Alternative name(s):
    Melanotropin receptor
    Melanocortin receptor 1
    MC1-R

Gene names

Name:	MC1R
Synonyms:	MSHR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	317 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Melanocytes and corticoadrenal tissue.
Polymorphism	Variations in MC1R are linked to the degree of skin pigmentation (Types I-IV). Type I skin the most lightly pigmented and type IV the most dark pigmented. Partial loss-of-function mutations are associated with fair skin, poor tanning and increased skin cancer risk. Genetic variations in MC1R are associated with variation in skin/hair/eye pigmentation type 2 (SHEP2) [MIM:266300]. Hair, eye and skin pigmentation are among the most visible examples of human phenotypic variation, with a broad normal range that is subject to substantial geographic stratification. In the case of skin, individuals tend to have lighter pigmentation with increasing distance from the equator. By contrast, the majority of variation in human eye and hair color is found among individuals of European ancestry, with most other human populations fixed for brown eyes and black hair.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate Phosphoprotein
Gene Ontology (GO)
Biological process	G-protein signaling, coupled to cyclic nucleotide second messenger Ref.18 Traceable author statement. Source: ProtInc UV protection Ref.14 Traceable author statement. Source: ProtInc multicellular organismal development Ref.14 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.18 Traceable author statement. Source: ProtInc
Molecular function	melanocyte stimulating hormone receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 317	317	Melanocyte-stimulating hormone receptor		PRO_0000069818
Regions
	Topological domain	1 – 37	37	Extracellular Potential
	Transmembrane	38 – 63	26	1 Potential
	Topological domain	64 – 72	9	Cytoplasmic Potential
	Transmembrane	73 – 93	21	2 Potential
	Topological domain	94 – 118	25	Extracellular Potential
	Transmembrane	119 – 140	22	3 Potential
	Topological domain	141 – 163	23	Cytoplasmic Potential
	Transmembrane	164 – 183	20	4 Potential
	Topological domain	184 – 191	8	Extracellular Potential
	Transmembrane	192 – 211	20	5 Potential
	Topological domain	212 – 240	29	Cytoplasmic Potential
	Transmembrane	241 – 266	26	6 Potential
	Topological domain	267 – 279	13	Extracellular Potential
	Transmembrane	280 – 300	21	7 Potential
	Topological domain	301 – 317	17	Cytoplasmic Potential
Amino acid modifications
	Lipidation	315	1	S-palmitoyl cysteine Potential
	Glycosylation	29	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	40	1	I → T Associated with fair hair and light skin; partial loss of function. Ref.8		VAR_013611
	Natural variant	60	1	V → L Associated with SHEP2. dbSNP rs1805005. Ref.10 Ref.16 Ref.21		VAR_013612
	Natural variant	67	1	R → Q Shows a moderate and not significant decrease of cAMP production to NDP-MSH stimulation; shows a decreased responses to low concentrations of NDP-MSH stimulation. dbSNP rs34090186. Ref.5 Ref.9		VAR_009522
	Natural variant	84	1	D → E Susceptibility to melanoma. dbSNP rs1805006. Ref.5 Ref.15 Ref.17		VAR_003507
	Natural variant	89	1	G → R: dbSNP rs34540312.		VAR_042654
	Natural variant	92	1	V → M Associated with SHEP2; predominantly in type I skin; shows a moderate and not significant decreased of cAMP production to NDP-MSH stimulation. dbSNP rs2228479. Ref.10 Ref.16 Ref.21 Ref.5 Ref.17		VAR_003508
	Natural variant	95	1	T → M: dbSNP rs34158934.		VAR_042655
	Natural variant	104	1	G → S: dbSNP rs2229617.		VAR_042656
	Natural variant	120	1	I → T Shows a moderate and not significant decrease of cAMP production to NDP-MSH stimulation; shows decreased responses to low concentrations of NDP-MSH stimulation. dbSNP rs33932559. Ref.9		VAR_042657
	Natural variant	122	1	V → M Associated with fair hair and light skin; partial loss of function. Ref.8		VAR_013613
	Natural variant	147	1	Missing Associated with UV induced sucpetibility to skin damage; virtually unresponsive to NDP-MSH stimulation. Ref.9		VAR_042658
	Natural variant	151	1	R → C Associated with SHEP2; binds to alpha-MSH but cannot be stimulated to produce cAMP. dbSNP rs1805007. Ref.10 Ref.16 Ref.5 Ref.9 Ref.18 Ref.20		VAR_008522
	Natural variant	155	1	I → T: dbSNP rs1110400. Ref.10 Ref.12		VAR_013614
	Natural variant	156	1	V → L: dbSNP rs3212365. Ref.10		VAR_013615
	Natural variant	157	1	T → I Associated with UV induced sucpetibility to skin damage; shows a dramatically decreased cAMP production to NDP-MSH stimulation. Ref.9		VAR_042659
	Natural variant	159	1	P → T Associated with UV induced sucpetibility to skin damage; shows a strong decreased cAMP production to NDP-MSH stimulation. Ref.9		VAR_042660
	Natural variant	160	1	R → W Associated with SHEP2. dbSNP rs1805008. Ref.10 Ref.16 Ref.19		VAR_008523
	Natural variant	162	1	R → P Ref.6		VAR_013632
	Natural variant	163	1	R → Q Shows a moderate and not significant decrease of cAMP production to NDP-MSH stimulation; shows a not significant decrease in cAMP production at any concentrations of NDP-MSH stimulation. dbSNP rs885479. Ref.10 Ref.5 Ref.9		VAR_009523
	Natural variant	166	1	A → G Shows a moderate and not significant decrease of cAMP production to NDP-MSH stimulation; shows a not significant decrease in cAMP production at any concentrations of NDP-MSH stimulation. dbSNP rs35040147. Ref.9		VAR_042661
	Natural variant	171	1	A → S: dbSNP rs35784916.		VAR_042662
	Natural variant	192	1	L → M Shows a moderate and not significant decrease of cAMP production to NDP-MSH stimulation; shows a significant decrease of cAMP production when low concentrations of NDP-MSH is administered. Ref.9		VAR_042663
	Natural variant	196	1	F → L: dbSNP rs3212366. Ref.10		VAR_013616
	Natural variant	294	1	D → H Associated with SHEP2. dbSNP rs1805009. Ref.16 Ref.14		VAR_008524
Experimental info
	Sequence conflict	90	1	S → T Ref.1
	Sequence conflict	90	1	S → T Ref.2
	Sequence conflict	164	1	A → R Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q01726-1 [UniParc]. Last modified December 1, 2000. Version 2. Checksum: CB67405A562C29B2	FASTA	317	34,706
	10 20 30 40 50 60 MAVQGSQRRL LGSLNSTPTA IPQLGLAANQ TGARCLEVSI SDGLFLSLGL VSLVENALVV 70 80 90 100 110 120 ATIAKNRNLH SPMYCFICCL ALSDLLVSGS NVLETAVILL LEAGALVARA AVLQQLDNVI 130 140 150 160 170 180 DVITCSSMLS SLCFLGAIAV DRYISIFYAL RYHSIVTLPR ARRAVAAIWV ASVVFSTLFI 190 200 210 220 230 240 AYYDHVAVLL CLVVFFLAML VLMAVLYVHM LARACQHAQG IARLHKRQRP VHQGFGLKGA 250 260 270 280 290 300 VTLTILLGIF FLCWGPFFLH LTLIVLCPEH PTCGCIFKNF NLFLALIICN AIIDPLIYAF 310 HSQELRRTLK EVLTCSW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The cloning of a family of genes that encode the melanocortin receptors." Mountjoy K.G., Robbins L.S., Mortrud M., Cone R.D. Science 257:1248-1251(1992) [PubMed: 1325670] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Skin.
[2]	"Molecular cloning of a novel melanocortin receptor." Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G., Watson S.J., Delvalle J., Yamada T. J. Biol. Chem. 268:8246-8250(1993) [PubMed: 8463333] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular cloning and expression of the human melanocyte stimulating hormone receptor cDNA." Chhajlani V., Wikberg J.E.S. FEBS Lett. 309:417-420(1992) [PubMed: 1516719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	Erratum Chhajlani V., Wikberg J.E.S. FEBS Lett. 390:238-238(1996) [PubMed: 8706868] [Abstract]
[5]	"High polymorphism at the human melanocortin 1 receptor locus." Rana B.K., Hewett-Emmett D., Jin L., Chang B.H., Sambuughin N., Lin M., Watkins S., Bamshad M., Jorde L.B., Ramsay M., Jenkins T., Li W.H. Genetics 151:1547-1557(1999) [PubMed: 10101176] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-67; GLU-84; MET-92; CYS-151 AND GLN-163.
[6]	"The Pro162 variant is a loss-of-function mutation of the human melanocortin 1 receptor gene." Jimenez-Cervantes C., Olivares C., Gonzalez P., Morandini R., Ghanem G., Garcia-Borron J.C. J. Invest. Dermatol. 117:156-158(2001) [PubMed: 11442765] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PRO-162.
[7]	"The human melanocortin-1 receptor locus: analysis of transcription unit, locus polymorphism and haplotype evolution." Smith A.G., Box N.F., Marks L.H., Chen W., Smit D.J., Wyeth J.R., Huttley G.A., Easteal S., Sturm R.A. Gene 281:81-94(2001) [PubMed: 11750130] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[8]	"Thr40 and Met122 are new partial loss-of-function natural mutations of the human melanocortin 1 receptor." Jimenez-Cervantes C., Germer S., Gonzalez P., Sanchez J., Sanchez C.O., Garcia-Borron J.C. FEBS Lett. 508:44-48(2001) [PubMed: 11707265] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-40 AND MET-122.
[9]	"Identification of novel functional variants of the melanocortin 1 receptor gene originated from Asians." Nakayama K., Soemantri A., Jin F., Dashnyam B., Ohtsuka R., Duanchang P., Isa M.N., Settheetham-Ishida W., Harihara S., Ishida T. Hum. Genet. 119:322-330(2006) [PubMed: 16463023] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-67; THR-120; PHE-147 DEL; CYS-151; ILE-157; THR-159; GLN-163; GLY-166 AND MET-192, CHARACTERIZATION OF VARIANTS GLN-67; THR-120; PHE-147 DEL; CYS-151; ILE-157; THR-159; GLN-163; GLY-166 AND MET-192.
[10]	"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)." Kopatz S.A., Aronstam R.S., Sharma S.V. Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[11]	SeattleSNPs variation discovery resource Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-60; MET-92; CYS-151; THR-155; LEU-156; TRP-160; GLN-163 AND LEU-196.
[12]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT THR-155. Tissue: Skin.
[13]	"Modeling of the three-dimensional structure of the human melanocortin 1 receptor, using an automated method and docking of a rigid cyclic melanocyte-stimulating hormone core peptide." Prusis P., Schioth H.B., Muceniece R., Herzyk P., Afshar M., Hubbard R.E., Wikberg J.E. J. Mol. Graph. Model. 15:307-317(1997) [PubMed: 9640562] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[14]	"Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans." Valverde P., Healy F., Jackson I., Rees J.L., Thody A.J. Nat. Genet. 11:328-330(1995) [PubMed: 7581459] [Abstract] Cited for: VARIANT HIS-294.
[15]	"The Asp84Glu variant of the melanocortin 1 receptor (MC1R) is associated with melanoma." Valverde P., Healy E., Sikkink S., Haldane F., Thody A.J., Carothers A., Jackson I.J., Rees J.L. Hum. Mol. Genet. 5:1663-1666(1996) [PubMed: 8894704] [Abstract] Cited for: VARIANT GLU-84.
[16]	"Characterization of melanocyte stimulating hormone receptor variant alleles in twins with red hair." Box N.F., Wyeth J.R., O'Gorman L.E., Martin N.G., Sturm R.A. Hum. Mol. Genet. 6:1891-1897(1997) [PubMed: 9302268] [Abstract] Cited for: VARIANTS LEU-60; MET-92; CYS-151; TRP-160 AND HIS-294.
[17]	"Identification of common polymorphisms in the coding sequence of the human MSH receptor (MC1R) with possible biological effects." Koppula S.V., Robbins L.S., Lu D., Baack E., White C.R. Jr., Swanson N.A., Cone R.D. Hum. Mutat. 9:30-36(1997) [PubMed: 8990005] [Abstract] Cited for: VARIANTS GLU-84 AND MET-92.
[18]	"Human pigmentation phenotype: a point mutation generates nonfunctional MSH receptor." Fraendberg P.-A., Doufexis M., Kapas S., Chhajlani V. Biochem. Biophys. Res. Commun. 245:490-492(1998) [PubMed: 9571181] [Abstract] Cited for: VARIANT CYS-151.
[19]	"Melanocortin 1 receptor variants in an Irish population." Smith R., Healy E., Siddiqui S., Flanagan N., Steijlen P.M., Rosdahl I., Jacques J.P., Rogers S., Turner R., Jackson I.J., Birch-MacHin M.A., Rees J.L. J. Invest. Dermatol. 111:119-122(1998) [PubMed: 9665397] [Abstract] Cited for: VARIANT TRP-160.
[20]	"Genetic determinants of hair, eye and skin pigmentation in Europeans." Sulem P., Gudbjartsson D.F., Stacey S.N., Helgason A., Rafnar T., Magnusson K.P., Manolescu A., Karason A., Palsson A., Thorleifsson G., Jakobsdottir M., Steinberg S., Palsson S., Jonasson F., Sigurgeirsson B., Thorisdottir K., Ragnarsson R., Benediktsdottir K.R. , Aben K.K., Kiemeney L.A., Olafsson J.H., Gulcher J., Kong A., Thorsteinsdottir U., Stefansson K. Nat. Genet. 39:1443-1452(2007) [PubMed: 17952075] [Abstract] Cited for: VARIANT CYS-151, ASSOCIATION WITH SHEP2.
[21]	"DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed: 18987736] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-60 AND MET-92.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	X65634 Genomic DNA. Translation: CAA46588.1. X67594 mRNA. Translation: CAA47865.1. AF153431 Genomic DNA. Translation: AAD41349.1. AF153432 Genomic DNA. Translation: AAD41350.1. AF153433 Genomic DNA. Translation: AAD41351.1. AF153434 Genomic DNA. Translation: AAD41352.1. AF153435 Genomic DNA. Translation: AAD41353.1. AF153436 Genomic DNA. Translation: AAD41354.1. AF153437 Genomic DNA. Translation: AAD41355.1. AF326275 Genomic DNA. Translation: AAK01121.1. AF263461 Genomic DNA. Translation: AAK58525.1. AY046528 Genomic DNA. Translation: AAL05887.1. AY046529 Genomic DNA. Translation: AAL05888.1. AB241548 Genomic DNA. Translation: BAE94314.1. AY225228 Genomic DNA. Translation: AAO67713.1. AF514787 Genomic DNA. Translation: AAM44861.1. BC007856 mRNA. Translation: AAH07856.1. BC080622 mRNA. Translation: AAH80622.1.
IPI	IPI00816272.
PIR	S29204.
RefSeq	NP_002377.4.
UniGene	Hs.513829
3D structure databases
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q01726.
Genome annotation databases
Ensembl	ENSG00000198211. Homo sapiens. [Contig view]
GeneID	4157.
KEGG	hsa:4157.
Organism-specific databases
GeneCards	GC16P088513.
HGNC	HGNC:6929. MC1R.
MIM	155555. gene. 266300. phenotype.
Orphanet	618. Melanoma, familial.
PharmGKB	PA30673.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q01726.
Gene expression databases
ArrayExpress	Q01726.
Bgee	Q01726.
GermOnline	ENSG00000198211. Homo sapiens.
Family and domain databases
InterPro	IPR000276. 7TM_GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_supfam. IPR001671. Melcrt_ACTH_rcpt. IPR000761. MSH_rcpt. [Graphical view]
PANTHER	PTHR22750:SF2. MSH_rcpt. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR00534. MCRFAMILY. PR00536. MELNOCYTESHR.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16378.
SOURCE	Search...

Entry information

Entry name

MSHR_HUMAN

Accession

Primary (citable) accession number: Q01726
Secondary accession number(s): Q66K38 , Q8WWX6, Q8WWX7, Q96I33, Q96RU4, Q9UBF7, Q9UN58, Q9UN59, Q9UN60, Q9UN61, Q9UN62

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	December 1, 2000
Last modified:	May 5, 2009
This is version 101 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)