Reviewed,
UniProtKB/Swiss-Prot Q01726 (MSHR_HUMAN)
Last modified
May 5, 2009.
Version 101.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
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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 |
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| 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 | |
| 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.14Traceable author statement. Source: ProtInc multicellular organismal development Ref.14Traceable 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
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References
| « Hide '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. 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. 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. |
Cross-references
Sequence databases | |
|---|---|
| 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 Q9UN62 | ||||||||
| Entry history |
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| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| 7-transmembrane G-linked receptors List of 7-transmembrane G-linked receptor entries |
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


