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P41968 (MC3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Melanocortin receptor 3

Short name=MC3-R
Gene names
Name:MC3R
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length323 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase.

Subcellular location

Cell membrane; Multi-pass membrane protein.

Tissue specificity

Brain, placental, and gut tissues.

Polymorphism

Genetic variations in MC3R define the body mass index quantitative trait locus 9 (BMIQ9) [MIM:602025]. Variance in body mass index is a susceptibility factor for obesity.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Sequence caution

The sequence AAC13541.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH69105.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH69599.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH96702.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH96737.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH98169.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAH98351.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

The sequence AAO72726.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMGlycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger

Traceable author statement PubMed 8175743. Source: ProtInc

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

homoiothermy

Inferred from electronic annotation. Source: Ensembl

phospholipase C-activating G-protein coupled receptor signaling pathway

Traceable author statement PubMed 8175743. Source: ProtInc

positive regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 19329486PubMed 19743876. Source: BHF-UCL

regulation of blood pressure

Inferred from electronic annotation. Source: Ensembl

regulation of heart rate

Inferred from electronic annotation. Source: Ensembl

sodium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentintegral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionmelanocortin receptor activity

Traceable author statement PubMed 8175743. Source: ProtInc

melanocyte-stimulating hormone receptor activity

Inferred from physical interaction PubMed 19743876. Source: BHF-UCL

neuropeptide binding

Inferred from physical interaction PubMed 15927146. Source: UniProtKB

peptide hormone binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 19329486PubMed 19743876. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 323323Melanocortin receptor 3
PRO_0000069718

Regions

Topological domain1 – 3737Extracellular Potential
Transmembrane38 – 6326Helical; Name=1; Potential
Topological domain64 – 7512Cytoplasmic Potential
Transmembrane76 – 10025Helical; Name=2; Potential
Topological domain101 – 11818Extracellular Potential
Transmembrane119 – 14022Helical; Name=3; Potential
Topological domain141 – 16020Cytoplasmic Potential
Transmembrane161 – 18121Helical; Name=4; Potential
Topological domain182 – 1865Extracellular Potential
Transmembrane187 – 21024Helical; Name=5; Potential
Topological domain211 – 24535Cytoplasmic Potential
Transmembrane246 – 26823Helical; Name=6; Potential
Topological domain269 – 2779Extracellular Potential
Transmembrane278 – 30124Helical; Name=7; Potential
Topological domain302 – 32322Cytoplasmic Potential

Amino acid modifications

Lipidation3151S-palmitoyl cysteine Potential
Glycosylation21N-linked (GlcNAc...) Potential
Glycosylation161N-linked (GlcNAc...) Potential
Glycosylation281N-linked (GlcNAc...) Potential

Natural variations

Natural variant441V → I Have ligand binding and signaling properties similar to wild-type. Ref.1 Ref.7
Corresponds to variant rs3827103 [ dbSNP | Ensembl ].
VAR_020070
Natural variant1461I → N Associated with susceptibility to obesity; completely lacks signaling in response to agonist stimulation; coexpression of the wild-type and the mutant receptor shows that it does not exert dominant-negative activity on wild-type. Ref.6 Ref.7
VAR_055000
Natural variant2981I → S Associated with susceptibility to obesity; in vitro expression studies demonstrate that the mutation causes complete loss of function; transfected cells show diffuse cytoplasmic staining indicating intracellular retention of the receptor. Ref.8
VAR_055001

Sequences

Sequence LengthMass (Da)Tools
P41968 [UniParc].

Last modified July 11, 2012. Version 3.
Checksum: 98B016FC80802A97

FASTA32336,043
        10         20         30         40         50         60 
MNASCCLPSV QPTLPNGSEH LQAPFFSNQS SSAFCEQVFI KPEVFLSLGI VSLLENILVI 

        70         80         90        100        110        120 
LAVVRNGNLH SPMYFFLCSL AVADMLVSVS NALETIMIAI VHSDYLTFED QFIQHMDNIF 

       130        140        150        160        170        180 
DSMICISLVA SICNLLAIAV DRYVTIFYAL RYHSIMTVRK ALTLIVAIWV CCGVCGVVFI 

       190        200        210        220        230        240 
VYSESKMVIV CLITMFFAMM LLMGTLYVHM FLFARLHVKR IAALPPADGV APQQHSCMKG 

       250        260        270        280        290        300 
AVTITILLGV FIFCWAPFFL HLVLIITCPT NPYCICYTAH FNTYLVLIMC NSVIDPLIYA 

       310        320 
FRSLELRNTF REILCGCNGM NLG 

« Hide

References

« Hide 'large scale' references
[1]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-44.
[2]"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].
[3]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]"Identification of the translation start site of the human melanocortin 3 receptor."
Tarnow P., Rediger A., Schulz A., Gruters A., Biebermann H.
Obes. Facts 5:45-51(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSLATIONAL START SITE.
[6]"A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity."
Lee Y.-S., Poh L.K.-S., Loke K.-Y.
J. Clin. Endocrinol. Metab. 87:1423-1426(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASN-146, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.
[7]"Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G protein-coupled receptor activation."
Tao Y.-X., Segaloff D.L.
J. Clin. Endocrinol. Metab. 89:3936-3942(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS ILE-44 AND ASN-146.
[8]"Sporadic mutations in melanocortin receptor 3 in morbid obese individuals."
Mencarelli M., Walker G.E., Maestrini S., Alberti L., Verti B., Brunani A., Petroni M.L., Tagliaferri M., Liuzzi A., Di Blasio A.M.
Eur. J. Hum. Genet. 16:581-586(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SER-298, CHARACTERIZATION OF VARIANT SER-298, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L06155 Genomic DNA. Translation: AAC13541.1. Different initiation.
AY227893 mRNA. Translation: AAO72726.1. Different initiation.
AL139824 Genomic DNA. Translation: CAC15480.2.
BC069105 mRNA. Translation: AAH69105.1. Different initiation.
BC069599 mRNA. Translation: AAH69599.1. Different initiation.
BC096702 mRNA. Translation: AAH96702.1. Different initiation.
BC096737 mRNA. Translation: AAH96737.1. Different initiation.
BC098169 mRNA. Translation: AAH98169.1. Different initiation.
BC098351 mRNA. Translation: AAH98351.1. Different initiation.
CCDSCCDS13449.2.
PIRB46647.
RefSeqNP_063941.3. NM_019888.3.
UniGeneHs.248018.

3D structure databases

ProteinModelPortalP41968.
SMRP41968. Positions 44-314.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110329. 1 interaction.
DIPDIP-48790N.
STRING9606.ENSP00000243911.

Chemistry

BindingDBP41968.
ChEMBLCHEMBL2111323.
GuidetoPHARMACOLOGY284.

Protein family/group databases

GPCRDBSearch...

Polymorphism databases

DMDM395398606.

Proteomic databases

PaxDbP41968.
PRIDEP41968.

Protocols and materials databases

DNASU4159.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000243911; ENSP00000243911; ENSG00000124089.
GeneID4159.
KEGGhsa:4159.
UCSCuc002xxb.2. human.

Organism-specific databases

CTD4159.
GeneCardsGC20P054823.
H-InvDBHIX0040556.
HGNCHGNC:6931. MC3R.
MIM155540. gene.
602025. phenotype.
neXtProtNX_P41968.
Orphanet217031. Obesity due to MC3R deficiency.
PharmGKBPA30675.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG325361.
HOGENOMHOG000246927.
HOVERGENHBG108148.
InParanoidP41968.
KOK04201.
OMAVHMFLFA.
OrthoDBEOG7QK0CF.
PhylomeDBP41968.
TreeFamTF332646.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

BgeeP41968.
CleanExHS_MC3R.
GenevestigatorP41968.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002122. Mcort_3_rcpt.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERPTHR22750:SF4. PTHR22750:SF4. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01061. MELNOCORTN3R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMelanocortin_3_receptor.
GenomeRNAi4159.
NextBio16386.
PROP41968.
SOURCESearch...

Entry information

Entry nameMC3R_HUMAN
AccessionPrimary (citable) accession number: P41968
Secondary accession number(s): Q4KN27, Q9H517
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 11, 2012
Last modified: July 9, 2014
This is version 131 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries