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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

BioCyciZFISH:ENSG00000124089-MONOMER.
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

HGNCiHGNC:6931. MC3R.

Subcellular locationi

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

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

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...)Sequence analysis1
Glycosylationi16N-linked (GlcNAc...)Sequence analysis1
Glycosylationi28N-linked (GlcNAc...)Sequence 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

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

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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
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 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 rs3827103dbSNPEnsembl.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 rs74315393dbSNPEnsembl.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 rs121913556dbSNPEnsembl.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. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

BindingDBiP41968.
ChEMBLiCHEMBL4644.
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.
DisGeNETi4159.
GeneCardsiMC3R.
H-InvDBHIX0040556.
HGNCiHGNC:6931. MC3R.
MalaCardsiMC3R.
MIMi155540. gene.
602025. phenotype.
neXtProtiNX_P41968.
OpenTargetsiENSG00000124089.
Orphaneti217031. Obesity due to MC3R deficiency.
PharmGKBiPA30675.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000124089-MONOMER.
ReactomeiR-HSA-375276. Peptide ligand-binding receptors.
R-HSA-418555. G alpha (s) signalling events.
SIGNORiP41968.

Miscellaneous databases

GeneWikiiMelanocortin_3_receptor.
GenomeRNAii4159.
PROiP41968.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124089.
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.
SMARTiSM01381. 7TM_GPCR_Srsx. 1 hit.
[Graphical view]
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 152 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

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 one 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.