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P56450

- MC4R_MOUSE

UniProt

P56450 - MC4R_MOUSE

Protein

Melanocortin receptor 4

Gene

Mc4r

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 3 (27 Jul 2011)
      Previous versions | rss
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    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: Ensembl
    4. peptide hormone binding Source: Ensembl
    5. protein 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: Ensembl
    8. regulation of grooming behavior Source: Ensembl
    9. regulation of metabolic process Source: MGI
    10. response to insulin Source: MGI

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    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: Chromosome 18

    Organism-specific databases

    MGIiMGI:99457. Mc4r.

    Subcellular locationi

    GO - Cellular componenti

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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 4343ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini70 – 8112CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini107 – 12317ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini146 – 16520CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini187 – 1915ExtracellularSequence Analysis
    Topological domaini216 – 24833CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini272 – 2809ExtracellularSequence Analysis
    Topological domaini305 – 33228CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei44 – 6926Helical; Name=1Sequence AnalysisAdd
    BLAST
    Transmembranei82 – 10625Helical; Name=2Sequence AnalysisAdd
    BLAST
    Transmembranei124 – 14522Helical; Name=3Sequence AnalysisAdd
    BLAST
    Transmembranei166 – 18621Helical; Name=4Sequence AnalysisAdd
    BLAST
    Transmembranei192 – 21524Helical; Name=5Sequence AnalysisAdd
    BLAST
    Transmembranei249 – 27123Helical; Name=6Sequence AnalysisAdd
    BLAST
    Transmembranei281 – 30424Helical; Name=7Sequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG269550.
    GeneTreeiENSGT00750000117286.
    HOGENOMiHOG000246927.
    HOVERGENiHBG108148.
    InParanoidiQ49NR4.
    KOiK04202.
    OMAiTSLHFWN.
    OrthoDBiEOG7QK0CF.
    TreeFamiTF332646.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    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

    MNSTHHHGMY TSLHLWNRSS YGLHGNASES LGKGHPDGGC YEQLFVSPEV    50
    FVTLGVISLL ENILVIVAIA KNKNLHSPMY FFICSLAVAD MLVSVSNGSE 100
    TIVITLLNST DTDAQSFTVN IDNVIDSVIC SSLLASICSL LSIAVDRYFT 150
    IFYALQYHNI MTVRRVGIII SCIWAACTVS GVLFIIYSDS SAVIICLISM 200
    FFTMLVLMAS LYVHMFLMAR LHIKRIAVLP GTGTIRQGTN MKGAITLTIL 250
    IGVFVVCWAP FFLHLLFYIS CPQNPYCVCF MSHFNLYLIL IMCNAVIDPL 300
    IYALRSQELR KTFKEIICFY PLGGICELSS RY 332
    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. 1 PublicationCurated
    Sequence conflicti291 – 2911I → M in BAA24015. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS29316.1.
    RefSeqi NP_058673.2. NM_016977.4.
    UniGenei Mm.229447.
    Mm.491749.

    3D structure databases

    ProteinModelPortali P56450.
    SMRi P56450. Positions 50-317.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201341. 3 interactions.

    Chemistry

    BindingDBi P56450.
    ChEMBLi CHEMBL3719.
    GuidetoPHARMACOLOGYi 285.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P56450.

    Proteomic databases

    PRIDEi P56450.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000057942 ; ENSMUSP00000054776 ; ENSMUSG00000047259 .
    GeneIDi 17202.
    KEGGi mmu:17202.
    UCSCi uc008ffv.1. mouse.

    Organism-specific databases

    CTDi 4160.
    MGIi MGI:99457. Mc4r.

    Phylogenomic databases

    eggNOGi NOG269550.
    GeneTreei ENSGT00750000117286.
    HOGENOMi HOG000246927.
    HOVERGENi HBG108148.
    InParanoidi Q49NR4.
    KOi K04202.
    OMAi TSLHFWN.
    OrthoDBi EOG7QK0CF.
    TreeFami TF332646.

    Miscellaneous databases

    NextBioi 291586.
    PROi P56450.
    SOURCEi Search...

    Gene expression databases

    Bgeei P56450.
    CleanExi MM_MC4R.
    Genevestigatori P56450.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    IPR000155. Mcort_rcpt_4.
    IPR001908. Melancort_rcpt.
    IPR001671. Melcrt_ACTH_rcpt.
    [Graphical view ]
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00237. GPCRRHODOPSN.
    PR00534. MCRFAMILY.
    PR00535. MELNOCORTINR.
    PR01062. MELNOCORTN4R.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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.
      , 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. 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: October 1, 2014
    This is version 106 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