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Protein

Melanocortin receptor 3

Gene

MC3R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer
Biological processBiological rhythms

Enzyme and pathway databases

ReactomeiR-HSA-375276 Peptide ligand-binding receptors
R-HSA-418555 G alpha (s) signalling events
SIGNORiP41968

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
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000124089.4
HGNCiHGNC:6931 MC3R
MIMi155540 gene
neXtProtiNX_P41968

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 37ExtracellularSequence analysisAdd BLAST37
Transmembranei38 – 63Helical; Name=1Sequence analysisAdd BLAST26
Topological domaini64 – 75CytoplasmicSequence analysisAdd BLAST12
Transmembranei76 – 100Helical; Name=2Sequence analysisAdd BLAST25
Topological domaini101 – 118ExtracellularSequence analysisAdd BLAST18
Transmembranei119 – 140Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini141 – 160CytoplasmicSequence analysisAdd BLAST20
Transmembranei161 – 181Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini182 – 186ExtracellularSequence analysis5
Transmembranei187 – 210Helical; Name=5Sequence analysisAdd BLAST24
Topological domaini211 – 245CytoplasmicSequence analysisAdd BLAST35
Transmembranei246 – 268Helical; Name=6Sequence analysisAdd BLAST23
Topological domaini269 – 277ExtracellularSequence analysis9
Transmembranei278 – 301Helical; Name=7Sequence analysisAdd BLAST24
Topological domaini302 – 323CytoplasmicSequence analysisAdd BLAST22

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi4159
MalaCardsiMC3R
MIMi602025 phenotype
OpenTargetsiENSG00000124089
Orphaneti217031 Obesity due to MC3R deficiency
PharmGKBiPA30675

Chemistry databases

ChEMBLiCHEMBL4644
GuidetoPHARMACOLOGYi284

Polymorphism and mutation databases

BioMutaiMC3R
DMDMi395398606

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000697181 – 323Melanocortin receptor 3Add BLAST323

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi2N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi16N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi28N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi315S-palmitoyl cysteineSequence analysis1

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP41968
PRIDEiP41968

Expressioni

Tissue specificityi

Brain, placental, and gut tissues.

Gene expression databases

BgeeiENSG00000124089
CleanExiHS_MC3R
GenevisibleiP41968 HS

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
MRAPQ8TCY52EBI-9538510,EBI-9538727

Protein-protein interaction databases

BioGridi110329, 1 interactor
DIPiDIP-48790N
IntActiP41968, 2 interactors
STRINGi9606.ENSP00000243911

Chemistry databases

BindingDBiP41968

Structurei

3D structure databases

ProteinModelPortaliP41968
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

eggNOGiKOG3656 Eukaryota
ENOG410XRW9 LUCA
GeneTreeiENSGT00770000120529
HOGENOMiHOG000246927
HOVERGENiHBG108148
InParanoidiP41968
KOiK04201
OMAiVHMFLFA
OrthoDBiEOG091G0BVW
PhylomeDBiP41968
TreeFamiTF332646

Family and domain databases

CDDicd15352 7tmA_MC3R, 1 hit
InterProiView protein in InterPro
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
IPR002122 Mcort_3_rcpt
IPR001908 Melancort_rcpt
IPR001671 Melcrt_ACTH_rcpt
PANTHERiPTHR22750:SF4 PTHR22750:SF4, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00237 GPCRRHODOPSN
PR00534 MCRFAMILY
PR00535 MELNOCORTINR
PR01061 MELNOCORTN3R
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH69105 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH69599 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH96702 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH96737 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH98169 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAH98351 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence AAO72726 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.2 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02007044V → I Have ligand binding and signaling properties similar to wild-type. 2 PublicationsCorresponds to variant dbSNP:rs3827103Ensembl.1
Natural variantiVAR_055000146I → 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 PublicationsCorresponds to variant dbSNP:rs74315393EnsemblClinVar.1
Natural variantiVAR_055001298I → 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 PublicationCorresponds to variant dbSNP:rs121913556EnsemblClinVar.1

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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiMC3R_HUMAN
AccessioniPrimary (citable) accession number: P41968
Secondary accession number(s): Q4KN27, Q9H517
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: July 11, 2012
Last modified: February 28, 2018
This is version 162 of the entry and version 3 of the sequence. See 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

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