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 4

Gene

Mc4r

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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).1 Publication

GO - Molecular functioni

  1. melanocortin receptor activity Source: MGI
  2. melanocyte-stimulating hormone receptor activity Source: MGI
  3. neuropeptide binding Source: MGI
  4. peptide hormone binding Source: Ensembl
  5. ubiquitin protein ligase binding Source: MGI

GO - Biological processi

  1. diet induced thermogenesis Source: Ensembl
  2. energy reserve metabolic process Source: Ensembl
  3. feeding behavior Source: MGI
  4. insulin secretion Source: MGI
  5. negative regulation of feeding behavior Source: Ensembl
  6. positive regulation of bone resorption Source: HGNC
  7. positive regulation of cAMP biosynthetic process Source: MGI
  8. regulation of grooming behavior Source: Ensembl
  9. regulation of metabolic process Source: MGI
  10. response to insulin Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_313192. G alpha (s) signalling events.
REACT_319210. Peptide ligand-binding receptors.

Names & Taxonomyi

Protein namesi
Recommended name:
Melanocortin receptor 4
Short name:
MC4-R
Gene namesi
Name:Mc4r
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:99457. 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

  1. integral component of membrane Source: UniProtKB-KW
  2. nucleus Source: Ensembl
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 332332Melanocortin receptor 4PRO_0000069724Add
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
Glycosylationi108 – 1081N-linked (GlcNAc...)Sequence Analysis
Lipidationi318 – 3181S-palmitoyl cysteineSequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PRIDEiP56450.

PTM databases

PhosphoSiteiP56450.

Expressioni

Gene expression databases

BgeeiP56450.
CleanExiMM_MC4R.
GenevestigatoriP56450.

Interactioni

Subunit structurei

Interacts with ATRNL1. 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 (By similarity). Interacts with MRAP and MRAP2; these associated factors increase ligand-sensitivity and generation of cAMP.By similarity2 Publications

Protein-protein interaction databases

BioGridi201341. 3 interactions.

Structurei

3D structure databases

ProteinModelPortaliP56450.
SMRiP56450. Positions 50-317.
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

eggNOGiNOG269550.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP56450.
KOiK04202.
OMAiMHTSLHF.
OrthoDBiEOG7QK0CF.
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.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P56450-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNSTHHHGMY TSLHLWNRSS YGLHGNASES LGKGHPDGGC 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 SAVIICLISM
210 220 230 240 250
FFTMLVLMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGTN MKGAITLTIL
260 270 280 290 300
IGVFVVCWAP FFLHLLFYIS CPQNPYCVCF MSHFNLYLIL IMCNAVIDPL
310 320 330
IYALRSQELR KTFKEIICFY PLGGICELSS RY
Length:332
Mass (Da):36,959
Last modified:July 27, 2011 - v3
Checksum:iBAD7018E30CF4FC1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti25 – 251G → S in AAG35602 (Ref. 1) Curated
Sequence conflicti291 – 2911I → M in BAA24015 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201662 Genomic DNA. Translation: AAG35602.1.
AY684813 Genomic DNA. Translation: AAV92649.1.
AY684814 Genomic DNA. Translation: AAV92650.1.
AY684815 Genomic DNA. Translation: AAV92651.1.
AY684818 Genomic DNA. Translation: AAV92654.1.
AY684819 Genomic DNA. Translation: AAV92655.1.
AY684820 Genomic DNA. Translation: AAV92656.1.
AK136793 mRNA. Translation: BAE23130.1.
BC116957 mRNA. Translation: AAI16958.1.
BC116959 mRNA. Translation: AAI16960.1.
AB009664 Genomic DNA. Translation: BAA24015.1.
CCDSiCCDS29316.1.
RefSeqiNP_058673.2. NM_016977.4.
UniGeneiMm.229447.
Mm.491749.

Genome annotation databases

EnsembliENSMUST00000057942; ENSMUSP00000054776; ENSMUSG00000047259.
GeneIDi17202.
KEGGimmu:17202.
UCSCiuc008ffv.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF201662 Genomic DNA. Translation: AAG35602.1.
AY684813 Genomic DNA. Translation: AAV92649.1.
AY684814 Genomic DNA. Translation: AAV92650.1.
AY684815 Genomic DNA. Translation: AAV92651.1.
AY684818 Genomic DNA. Translation: AAV92654.1.
AY684819 Genomic DNA. Translation: AAV92655.1.
AY684820 Genomic DNA. Translation: AAV92656.1.
AK136793 mRNA. Translation: BAE23130.1.
BC116957 mRNA. Translation: AAI16958.1.
BC116959 mRNA. Translation: AAI16960.1.
AB009664 Genomic DNA. Translation: BAA24015.1.
CCDSiCCDS29316.1.
RefSeqiNP_058673.2. NM_016977.4.
UniGeneiMm.229447.
Mm.491749.

3D structure databases

ProteinModelPortaliP56450.
SMRiP56450. Positions 50-317.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201341. 3 interactions.

Chemistry

BindingDBiP56450.
ChEMBLiCHEMBL3719.
GuidetoPHARMACOLOGYi285.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP56450.

Proteomic databases

PRIDEiP56450.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000057942; ENSMUSP00000054776; ENSMUSG00000047259.
GeneIDi17202.
KEGGimmu:17202.
UCSCiuc008ffv.1. mouse.

Organism-specific databases

CTDi4160.
MGIiMGI:99457. Mc4r.

Phylogenomic databases

eggNOGiNOG269550.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP56450.
KOiK04202.
OMAiMHTSLHF.
OrthoDBiEOG7QK0CF.
TreeFamiTF332646.

Enzyme and pathway databases

ReactomeiREACT_313192. G alpha (s) signalling events.
REACT_319210. Peptide ligand-binding receptors.

Miscellaneous databases

NextBioi291586.
PROiP56450.
SOURCEiSearch...

Gene expression databases

BgeeiP56450.
CleanExiMM_MC4R.
GenevestigatoriP56450.

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.
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. "Characterization of the melanocortin-4 receptor gene."
    Dumont L.M., Wu C.S., Mountjoy K.G.
    Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/Sv.
  2. Morooka Y., Oomizu S., Takeuchi S., Takahashi S.
    Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 112-295.
    Strain: ICR.
    Tissue: Pituitary anterior lobe.
  3. "Analysis of Mc4r locus in DIO and DR mice."
    Reichwald K., Petz U., Klingenspor M., Platzer M.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: A/J, AKR/J, C57BL/6J, CAST/Ei, SJL/J and SWR/J.
    Tissue: Spleen.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Diencephalon.
  5. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  6. "Characterization of a novel binding partner of the melanocortin-4 receptor: attractin-like protein."
    Haqq A.M., Rene P., Kishi T., Khong K., Lee C.E., Liu H., Friedman J.M., Elmquist J.K., Cone R.D.
    Biochem. J. 376:595-605(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ATRNL1.
  7. Cited for: FUNCTION, INTERACTION WITH MRAP2.

Entry informationi

Entry nameiMC4R_MOUSE
AccessioniPrimary (citable) accession number: P56450
Secondary accession number(s): Q49NR4, Q9EQM7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: April 1, 2015
This is version 111 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.