Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Melanocortin receptor 3

Gene

MC3R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain.By similarity

GO - Molecular functioni

  • melanocortin receptor activity Source: ProtInc
  • melanocyte-stimulating hormone receptor activity Source: BHF-UCL
  • neuropeptide binding Source: UniProtKB
  • peptide hormone binding Source: Ensembl

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Biological rhythms

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Melanocortin receptor 3
Short name:
MC3-R
Gene namesi
Name:MC3R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:6931. MC3R.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737ExtracellularSequence AnalysisAdd
BLAST
Transmembranei38 – 6326Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini64 – 7512CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei76 – 10025Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini101 – 11818ExtracellularSequence AnalysisAdd
BLAST
Transmembranei119 – 14022Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini141 – 16020CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei161 – 18121Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini182 – 1865ExtracellularSequence Analysis
Transmembranei187 – 21024Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini211 – 24535CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei246 – 26823Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini269 – 2779ExtracellularSequence Analysis
Transmembranei278 – 30124Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini302 – 32322CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

MIMi602025. phenotype.
Orphaneti217031. Obesity due to MC3R deficiency.
PharmGKBiPA30675.

Polymorphism and mutation databases

BioMutaiMC3R.
DMDMi395398606.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 323323Melanocortin receptor 3PRO_0000069718Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...)Sequence Analysis
Glycosylationi16 – 161N-linked (GlcNAc...)Sequence Analysis
Glycosylationi28 – 281N-linked (GlcNAc...)Sequence Analysis
Lipidationi315 – 3151S-palmitoyl cysteineSequence Analysis

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP41968.
PRIDEiP41968.

Expressioni

Tissue specificityi

Brain, placental, and gut tissues.

Gene expression databases

BgeeiP41968.
CleanExiHS_MC3R.
GenevisibleiP41968. HS.

Interactioni

Protein-protein interaction databases

BioGridi110329. 1 interaction.
DIPiDIP-48790N.
IntActiP41968. 2 interactions.
STRINGi9606.ENSP00000243911.

Structurei

3D structure databases

ProteinModelPortaliP41968.
SMRiP41968. Positions 44-314.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG325361.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP41968.
KOiK04201.
OMAiVHMFLFA.
OrthoDBiEOG7QK0CF.
PhylomeDBiP41968.
TreeFamiTF332646.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002122. Mcort_3_rcpt.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF4. PTHR22750:SF4. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01061. MELNOCORTN3R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P41968-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNASCCLPSV QPTLPNGSEH LQAPFFSNQS SSAFCEQVFI KPEVFLSLGI
60 70 80 90 100
VSLLENILVI LAVVRNGNLH SPMYFFLCSL AVADMLVSVS NALETIMIAI
110 120 130 140 150
VHSDYLTFED QFIQHMDNIF DSMICISLVA SICNLLAIAV DRYVTIFYAL
160 170 180 190 200
RYHSIMTVRK ALTLIVAIWV CCGVCGVVFI VYSESKMVIV CLITMFFAMM
210 220 230 240 250
LLMGTLYVHM FLFARLHVKR IAALPPADGV APQQHSCMKG AVTITILLGV
260 270 280 290 300
FIFCWAPFFL HLVLIITCPT NPYCICYTAH FNTYLVLIMC NSVIDPLIYA
310 320
FRSLELRNTF REILCGCNGM NLG
Length:323
Mass (Da):36,043
Last modified:July 11, 2012 - v3
Checksum:i98B016FC80802A97
GO

Sequence cautioni

The sequence AAC13541.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH69105.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH69599.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH96702.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH96737.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH98169.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH98351.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAO72726.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Polymorphismi

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti44 – 441V → I Have ligand binding and signaling properties similar to wild-type. 2 Publications
Corresponds to variant rs3827103 [ dbSNP | Ensembl ].
VAR_020070
Natural varianti146 – 1461I → 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. 2 Publications
VAR_055000
Natural varianti298 – 2981I → 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. 1 Publication
VAR_055001

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13449.2.
PIRiB46647.
RefSeqiNP_063941.3. NM_019888.3.
UniGeneiHs.248018.

Genome annotation databases

EnsembliENST00000243911; ENSP00000243911; ENSG00000124089.
GeneIDi4159.
KEGGihsa:4159.
UCSCiuc002xxb.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13449.2.
PIRiB46647.
RefSeqiNP_063941.3. NM_019888.3.
UniGeneiHs.248018.

3D structure databases

ProteinModelPortaliP41968.
SMRiP41968. Positions 44-314.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110329. 1 interaction.
DIPiDIP-48790N.
IntActiP41968. 2 interactions.
STRINGi9606.ENSP00000243911.

Chemistry

BindingDBiP41968.
ChEMBLiCHEMBL2111323.
GuidetoPHARMACOLOGYi284.

Protein family/group databases

GPCRDBiSearch...

Polymorphism and mutation databases

BioMutaiMC3R.
DMDMi395398606.

Proteomic databases

PaxDbiP41968.
PRIDEiP41968.

Protocols and materials databases

DNASUi4159.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000243911; ENSP00000243911; ENSG00000124089.
GeneIDi4159.
KEGGihsa:4159.
UCSCiuc002xxb.2. human.

Organism-specific databases

CTDi4159.
GeneCardsiGC20P054823.
H-InvDBHIX0040556.
HGNCiHGNC:6931. MC3R.
MIMi155540. gene.
602025. phenotype.
neXtProtiNX_P41968.
Orphaneti217031. Obesity due to MC3R deficiency.
PharmGKBiPA30675.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG325361.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP41968.
KOiK04201.
OMAiVHMFLFA.
OrthoDBiEOG7QK0CF.
PhylomeDBiP41968.
TreeFamiTF332646.

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiMelanocortin_3_receptor.
GenomeRNAii4159.
NextBioi16386.
PROiP41968.
SOURCEiSearch...

Gene expression databases

BgeeiP41968.
CleanExiHS_MC3R.
GenevisibleiP41968. HS.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR002122. Mcort_3_rcpt.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF4. PTHR22750:SF4. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01061. MELNOCORTN3R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. Cited for: VARIANT SER-298, CHARACTERIZATION OF VARIANT SER-298, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.

Entry informationi

Entry nameiMC3R_HUMAN
AccessioniPrimary (citable) accession number: P41968
Secondary accession number(s): Q4KN27, Q9H517
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 11, 2012
Last modified: July 22, 2015
This is version 141 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.