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Protein

Melanocortin receptor 4

Gene

Mc4r

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP) (By similarity).By similarity

GO - Molecular functioni

  • melanocortin receptor activity Source: RGD
  • melanocyte-stimulating hormone receptor activity Source: Ensembl
  • neuropeptide binding Source: Ensembl
  • peptide hormone binding Source: RGD

GO - Biological processi

  • diet induced thermogenesis Source: RGD
  • energy reserve metabolic process Source: RGD
  • feeding behavior Source: RGD
  • insulin secretion Source: Ensembl
  • negative regulation of feeding behavior Source: RGD
  • positive regulation of bone resorption Source: Ensembl
  • positive regulation of cAMP biosynthetic process Source: Ensembl
  • regulation of feeding behavior Source: RGD
  • regulation of grooming behavior Source: RGD
  • response to insulin Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Melanocortin receptor 4
Short name:
MC4-R
Gene namesi
Name:Mc4r
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi3057. Mc4r.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4343ExtracellularSequence analysisAdd
BLAST
Transmembranei44 – 6926Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini70 – 8112CytoplasmicSequence analysisAdd
BLAST
Transmembranei82 – 10625Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini107 – 12317ExtracellularSequence analysisAdd
BLAST
Transmembranei124 – 14522Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini146 – 16520CytoplasmicSequence analysisAdd
BLAST
Transmembranei166 – 18621Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini187 – 1915ExtracellularSequence analysis
Transmembranei192 – 21524Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini216 – 24833CytoplasmicSequence analysisAdd
BLAST
Transmembranei249 – 27123Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini272 – 2809ExtracellularSequence analysis
Transmembranei281 – 30424Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini305 – 33228CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • nucleus Source: RGD
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2700.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 332332Melanocortin receptor 4PRO_0000069726Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...)Sequence analysis
Glycosylationi17 – 171N-linked (GlcNAc...)Sequence analysis
Glycosylationi26 – 261N-linked (GlcNAc...)Sequence analysis
Disulfide bondi84 – 84InterchainPROSITE-ProRule annotation
Lipidationi318 – 3181S-palmitoyl cysteineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP70596.
PRIDEiP70596.

PTM databases

PhosphoSiteiP70596.

Expressioni

Tissue specificityi

Brain, enriched in the striatum, nucleus accumbens, and periaqueductal gray.

Gene expression databases

GenevisibleiP70596. RN.

Interactioni

Subunit structurei

Interacts with ATRNL1 (By similarity). Homodimer; disulfide-linked, also forms higher order oligomers. Interacts with MGRN1, but does not undergo MGRN1-mediated ubiquitination; this interaction competes with GNAS-binding and thus inhibits agonist-induced cAMP production. Interacts with MRAP and MRAP2; these associated factors increase ligand-sensitivity and generation of cAMP (By similarity).By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025223.

Chemistry

BindingDBiP70596.

Structurei

3D structure databases

ProteinModelPortaliP70596.
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.
InParanoidiP70596.
KOiK04202.
OMAiGTGTIRQ.
OrthoDBiEOG7QK0CF.
PhylomeDBiP70596.
TreeFamiTF332646.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000155. Mcort_rcpt_4.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01062. MELNOCORTN4R.
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.

P70596-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSTHHHGMY TSLHLWNRSS HGLHGNASES LGKGHSDGGC YEQLFVSPEV
60 70 80 90 100
FVTLGVISLL ENILVIVAIA KNKNLHSPMY FFICSLAVAD MLVSVSNGSE
110 120 130 140 150
TIVITLLNST DTDAQSFTVN IDNVIDSVIC SSLLASICSL LSIAVDRYFT
160 170 180 190 200
IFYALQYHNI MTVRRVGIII SCIWAACTVS GVLFIIYSDS SAVIICLITM
210 220 230 240 250
FFTMLVLMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGAN MKGAITLTIL
260 270 280 290 300
IGVFVVCWAP FFLHLLFYIS CPQNPYCVCF MSHFNLYLIL IMCNAVIDPL
310 320 330
IYALRSQELR KTFKEIICFY PLGGICELPG RY
Length:332
Mass (Da):36,887
Last modified:February 1, 1997 - v1
Checksum:iE0E9BAC7E7D168E6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67863 mRNA. Translation: AAB36517.1.
PIRiB57055.
RefSeqiNP_037231.1. NM_013099.3.
UniGeneiRn.10620.

Genome annotation databases

EnsembliENSRNOT00000025223; ENSRNOP00000025223; ENSRNOG00000018692.
GeneIDi25635.
KEGGirno:25635.
UCSCiRGD:3057. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67863 mRNA. Translation: AAB36517.1.
PIRiB57055.
RefSeqiNP_037231.1. NM_013099.3.
UniGeneiRn.10620.

3D structure databases

ProteinModelPortaliP70596.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000025223.

Chemistry

BindingDBiP70596.
ChEMBLiCHEMBL2700.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP70596.

Proteomic databases

PaxDbiP70596.
PRIDEiP70596.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000025223; ENSRNOP00000025223; ENSRNOG00000018692.
GeneIDi25635.
KEGGirno:25635.
UCSCiRGD:3057. rat.

Organism-specific databases

CTDi4160.
RGDi3057. Mc4r.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP70596.
KOiK04202.
OMAiGTGTIRQ.
OrthoDBiEOG7QK0CF.
PhylomeDBiP70596.
TreeFamiTF332646.

Enzyme and pathway databases

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

Miscellaneous databases

NextBioi607451.
PROiP70596.

Gene expression databases

GenevisibleiP70596. RN.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000155. Mcort_rcpt_4.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01062. MELNOCORTN4R.
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...

Publicationsi

  1. "Morphine down-regulates melanocortin-4 receptor expression in brain regions that mediate opiate addiction."
    Alvaro J.D., Tatro J.B., Quillan J.M., Fogliano M., Eisenhard M., Lerner M.R., Nestler E.J., Duman R.S.
    Mol. Pharmacol. 50:583-591(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.

Entry informationi

Entry nameiMC4R_RAT
AccessioniPrimary (citable) accession number: P70596
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: May 11, 2016
This is version 114 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. 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.