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P56450 (MC4R_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Melanocortin receptor 4

Short name=MC4-R
Gene names
Name:Mc4r
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length332 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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). Ref.7

Subunit structure

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. Ref.6 Ref.7

Subcellular location

Cell membrane; Multi-pass membrane protein.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processdiet induced thermogenesis

Inferred from electronic annotation. Source: Ensembl

energy reserve metabolic process

Inferred from electronic annotation. Source: Ensembl

feeding behavior

Inferred from mutant phenotype PubMed 12796784. Source: MGI

insulin secretion

Inferred from genetic interaction PubMed 16141392. Source: MGI

negative regulation of feeding behavior

Inferred from electronic annotation. Source: Ensembl

positive regulation of bone resorption

Inferred from mutant phenotype PubMed 16614075. Source: HGNC

positive regulation of cAMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of grooming behavior

Inferred from electronic annotation. Source: Ensembl

regulation of metabolic process

Inferred from mutant phenotype PubMed 12796784. Source: MGI

response to insulin

Inferred from mutant phenotype PubMed 16141392. Source: MGI

   Cellular_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionmelanocortin receptor activity

Inferred from direct assay PubMed 9454589. Source: MGI

melanocyte-stimulating hormone receptor activity

Inferred from direct assay PubMed 9454589. Source: MGI

neuropeptide binding

Inferred from electronic annotation. Source: Ensembl

peptide hormone binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.6PubMed 9454589. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 332332Melanocortin receptor 4
PRO_0000069724

Regions

Topological domain1 – 4343Extracellular Potential
Transmembrane44 – 6926Helical; Name=1; Potential
Topological domain70 – 8112Cytoplasmic Potential
Transmembrane82 – 10625Helical; Name=2; Potential
Topological domain107 – 12317Extracellular Potential
Transmembrane124 – 14522Helical; Name=3; Potential
Topological domain146 – 16520Cytoplasmic Potential
Transmembrane166 – 18621Helical; Name=4; Potential
Topological domain187 – 1915Extracellular Potential
Transmembrane192 – 21524Helical; Name=5; Potential
Topological domain216 – 24833Cytoplasmic Potential
Transmembrane249 – 27123Helical; Name=6; Potential
Topological domain272 – 2809Extracellular Potential
Transmembrane281 – 30424Helical; Name=7; Potential
Topological domain305 – 33228Cytoplasmic Potential

Amino acid modifications

Lipidation3181S-palmitoyl cysteine Potential
Glycosylation21N-linked (GlcNAc...) Potential
Glycosylation171N-linked (GlcNAc...) Potential
Glycosylation261N-linked (GlcNAc...) Potential
Glycosylation1081N-linked (GlcNAc...) Potential
Disulfide bond84Interchain By similarity

Experimental info

Sequence conflict251G → S in AAG35602. Ref.1
Sequence conflict2911I → M in BAA24015. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P56450 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: BAD7018E30CF4FC1

FASTA33236,959
        10         20         30         40         50         60 
MNSTHHHGMY TSLHLWNRSS YGLHGNASES LGKGHPDGGC YEQLFVSPEV FVTLGVISLL 

        70         80         90        100        110        120 
ENILVIVAIA KNKNLHSPMY FFICSLAVAD MLVSVSNGSE TIVITLLNST DTDAQSFTVN 

       130        140        150        160        170        180 
IDNVIDSVIC SSLLASICSL LSIAVDRYFT IFYALQYHNI MTVRRVGIII SCIWAACTVS 

       190        200        210        220        230        240 
GVLFIIYSDS SAVIICLISM FFTMLVLMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGTN 

       250        260        270        280        290        300 
MKGAITLTIL IGVFVVCWAP FFLHLLFYIS CPQNPYCVCF MSHFNLYLIL IMCNAVIDPL 

       310        320        330 
IYALRSQELR KTFKEIICFY PLGGICELSS RY 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of the melanocortin-4 receptor gene."
Dumont L.M., Wu C.S., Mountjoy K.G.
Submitted (NOV-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 (DEC-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 (JUL-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. expand/collapse author list , 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(2005) [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(2004) [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(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATRNL1.
[7]"Loss of function of the melanocortin 2 receptor accessory protein 2 is associated with mammalian obesity."
Asai M., Ramachandrappa S., Joachim M., Shen Y., Zhang R., Nuthalapati N., Ramanathan V., Strochlic D.E., Ferket P., Linhart K., Ho C., Novoselova T.V., Garg S., Ridderstrale M., Marcus C., Hirschhorn J.N., Keogh J.M., O'Rahilly S. expand/collapse author list , Chan L.F., Clark A.J., Farooqi I.S., Majzoub J.A.
Science 341:275-278(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MRAP2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS29316.1.
RefSeqNP_058673.2. NM_016977.4.
UniGeneMm.229447.
Mm.491749.

3D structure databases

ProteinModelPortalP56450.
SMRP56450. Positions 50-317.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201341. 3 interactions.

Chemistry

BindingDBP56450.
ChEMBLCHEMBL3719.
GuidetoPHARMACOLOGY285.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteP56450.

Proteomic databases

PRIDEP56450.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000057942; ENSMUSP00000054776; ENSMUSG00000047259.
GeneID17202.
KEGGmmu:17202.
UCSCuc008ffv.1. mouse.

Organism-specific databases

CTD4160.
MGIMGI:99457. Mc4r.

Phylogenomic databases

eggNOGNOG269550.
GeneTreeENSGT00750000117286.
HOGENOMHOG000246927.
HOVERGENHBG108148.
InParanoidQ49NR4.
KOK04202.
OMATSLHFWN.
OrthoDBEOG7QK0CF.
TreeFamTF332646.

Gene expression databases

BgeeP56450.
CleanExMM_MC4R.
GenevestigatorP56450.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR000155. Mcort_rcpt_4.
IPR001908. Melancort_rcpt.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01062. MELNOCORTN4R.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio291586.
PROP56450.
SOURCESearch...

Entry information

Entry nameMC4R_MOUSE
AccessionPrimary (citable) accession number: P56450
Secondary accession number(s): Q49NR4, Q9EQM7
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 105 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries