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Protein

Melanocortin receptor 5

Gene

MC5R

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins.

GO - Molecular functioni

  1. hormone binding Source: Ensembl
  2. melanocortin receptor activity Source: ProtInc

GO - Biological processi

  1. G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Source: ProtInc
  2. positive regulation of cAMP biosynthetic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Melanocortin receptor 5
Short name:
MC5-R
Alternative name(s):
MC-2
Gene namesi
Name:MC5R
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 18

Organism-specific databases

HGNCiHGNC:6933. MC5R.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3737ExtracellularSequence AnalysisAdd
BLAST
Transmembranei38 – 6124Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini62 – 7312CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei74 – 9724Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini98 – 11417ExtracellularSequence AnalysisAdd
BLAST
Transmembranei115 – 13824Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini139 – 15517CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei156 – 17924Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini180 – 1867ExtracellularSequence Analysis
Transmembranei187 – 21125Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini212 – 23928CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei240 – 26526Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini266 – 2738ExtracellularSequence Analysis
Transmembranei274 – 29724Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini298 – 32528CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. integral component of plasma membrane Source: ProtInc
  2. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi235 – 2351Q → K: 10% increase of binding to alpha-MSH. 1 Publication
Mutagenesisi272 – 2721R → C: 690% increase of binding to alpha-MSH. 1 Publication

Organism-specific databases

PharmGKBiPA30677.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 325325Melanocortin receptor 5PRO_0000069728Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi2 – 21N-linked (GlcNAc...)Sequence Analysis
Glycosylationi15 – 151N-linked (GlcNAc...)Sequence Analysis
Glycosylationi20 – 201N-linked (GlcNAc...)Sequence Analysis
Glycosylationi28 – 281N-linked (GlcNAc...)Sequence Analysis
Lipidationi311 – 3111S-palmitoyl cysteineSequence Analysis
Lipidationi312 – 3121S-palmitoyl cysteineSequence Analysis

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiP33032.
PRIDEiP33032.

PTM databases

PhosphoSiteiP33032.

Expressioni

Tissue specificityi

Expressed in the brain but not in the melanoma cells.

Gene expression databases

BgeeiP33032.
CleanExiHS_MC5R.
ExpressionAtlasiP33032. baseline and differential.
GenevestigatoriP33032.

Organism-specific databases

HPAiHPA042365.

Interactioni

Protein-protein interaction databases

BioGridi110331. 1 interaction.
DIPiDIP-48792N.
IntActiP33032. 2 interactions.
STRINGi9606.ENSP00000318077.

Structurei

3D structure databases

ProteinModelPortaliP33032.
SMRiP33032. Positions 38-312.
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

eggNOGiNOG237265.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP33032.
KOiK04203.
OMAiSLYIHMF.
PhylomeDBiP33032.
TreeFamiTF332646.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001908. Melancort_rcpt.
IPR000621. Melancort_rcpt_5.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF5. PTHR22750:SF5. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01063. MELNOCORTN5R.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P33032-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MNSSFHLHFL DLNLNATEGN LSGPNVKNKS SPCEDMGIAV EVFLTLGVIS
60 70 80 90 100
LLENILVIGA IVKNKNLHSP MYFFVCSLAV ADMLVSMSSA WETITIYLLN
110 120 130 140 150
NKHLVIADAF VRHIDNVFDS MICISVVASM CSLLAIAVDR YVTIFYALRY
160 170 180 190 200
HHIMTARRSG AIIAGIWAFC TGCGIVFILY SESTYVILCL ISMFFAMLFL
210 220 230 240 250
LVSLYIHMFL LARTHVKRIA ALPGASSARQ RTSMQGAVTV TMLLGVFTVC
260 270 280 290 300
WAPFFLHLTL MLSCPQNLYC SRFMSHFNMY LILIMCNSVM DPLIYAFRSQ
310 320
EMRKTFKEII CCRGFRIACS FPRRD
Length:325
Mass (Da):36,601
Last modified:February 1, 1995 - v3
Checksum:i8BEC17E1BDA059BB
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti149 – 1491R → A in AAA59566. (PubMed:8179577)Curated
Sequence conflicti221 – 23414ALPGA…QRTSM → LCPGPALRGRGPAW(PubMed:8396929)CuratedAdd
BLAST
Sequence conflicti297 – 2971F → Y in AAA59566. (PubMed:8179577)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti209 – 2091F → L.2 Publications
Corresponds to variant rs2236700 [ dbSNP | Ensembl ].
VAR_013128

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z25470 Genomic DNA. Translation: CAA80962.1.
L27080 Genomic DNA. Translation: AAA59566.1.
U08353 Genomic DNA. Translation: AAB60376.1.
AY268429 Genomic DNA. Translation: AAP23196.1.
EF444993 Genomic DNA. Translation: ACA06012.1.
CH471113 Genomic DNA. Translation: EAX01504.1.
BC069153 mRNA. Translation: AAH69153.1.
BC069545 mRNA. Translation: AAH69545.1.
BC095531 mRNA. Translation: AAH95531.1.
CCDSiCCDS11868.1.
PIRiJC5592.
JN0764.
RefSeqiNP_005904.1. NM_005913.2.
UniGeneiHs.248145.

Genome annotation databases

EnsembliENST00000324750; ENSP00000318077; ENSG00000176136.
GeneIDi4161.
KEGGihsa:4161.
UCSCiuc010xaf.2. human.

Polymorphism databases

DMDMi729996.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Melanocortin receptor entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z25470 Genomic DNA. Translation: CAA80962.1.
L27080 Genomic DNA. Translation: AAA59566.1.
U08353 Genomic DNA. Translation: AAB60376.1.
AY268429 Genomic DNA. Translation: AAP23196.1.
EF444993 Genomic DNA. Translation: ACA06012.1.
CH471113 Genomic DNA. Translation: EAX01504.1.
BC069153 mRNA. Translation: AAH69153.1.
BC069545 mRNA. Translation: AAH69545.1.
BC095531 mRNA. Translation: AAH95531.1.
CCDSiCCDS11868.1.
PIRiJC5592.
JN0764.
RefSeqiNP_005904.1. NM_005913.2.
UniGeneiHs.248145.

3D structure databases

ProteinModelPortaliP33032.
SMRiP33032. Positions 38-312.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110331. 1 interaction.
DIPiDIP-48792N.
IntActiP33032. 2 interactions.
STRINGi9606.ENSP00000318077.

Chemistry

BindingDBiP33032.
ChEMBLiCHEMBL4608.
GuidetoPHARMACOLOGYi286.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP33032.

Polymorphism databases

DMDMi729996.

Proteomic databases

PaxDbiP33032.
PRIDEiP33032.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000324750; ENSP00000318077; ENSG00000176136.
GeneIDi4161.
KEGGihsa:4161.
UCSCiuc010xaf.2. human.

Organism-specific databases

CTDi4161.
GeneCardsiGC18P013815.
HGNCiHGNC:6933. MC5R.
HPAiHPA042365.
MIMi600042. gene.
neXtProtiNX_P33032.
PharmGKBiPA30677.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG237265.
GeneTreeiENSGT00770000120529.
HOGENOMiHOG000246927.
HOVERGENiHBG108148.
InParanoidiP33032.
KOiK04203.
OMAiSLYIHMF.
PhylomeDBiP33032.
TreeFamiTF332646.

Enzyme and pathway databases

ReactomeiREACT_14819. Peptide ligand-binding receptors.
REACT_19327. G alpha (s) signalling events.

Miscellaneous databases

GeneWikiiMelanocortin_5_receptor.
GenomeRNAii4161.
NextBioi16394.
PROiP33032.
SOURCEiSearch...

Gene expression databases

BgeeiP33032.
CleanExiHS_MC5R.
ExpressionAtlasiP33032. baseline and differential.
GenevestigatoriP33032.

Family and domain databases

InterProiIPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
IPR001908. Melancort_rcpt.
IPR000621. Melancort_rcpt_5.
IPR001671. Melcrt_ACTH_rcpt.
[Graphical view]
PANTHERiPTHR22750:SF5. PTHR22750:SF5. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00237. GPCRRHODOPSN.
PR00534. MCRFAMILY.
PR00535. MELNOCORTINR.
PR01063. MELNOCORTN5R.
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. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  2. "Molecular cloning and characterization of the rat fifth melanocortin receptor."
    Griffon N., Mignon V., Facchinetti P., Diaz J., Schwartz J.-C., Sokoloff P.
    Biochem. Biophys. Res. Commun. 200:1007-1014(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "Cloning, expression, and tissue distribution of a fifth melanocortin receptor subtype."
    Fathi Z., Iben L.G., Parker E.M.
    Neurochem. Res. 20:107-113(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Tissue: Placenta.
  4. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Kopatz S.A., Aronstam R.S., Sharma S.V.
    Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. NHLBI resequencing and genotyping service (RS&G)
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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], VARIANT LEU-209.
  8. "Glutamine235 and arginine272 in human melanocortin 5 receptor determines its low affinity to MSH."
    Fraendberg P.-A., Xu X., Chhajlani V.
    Biochem. Biophys. Res. Commun. 236:489-492(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF GLN-235 AND ARG-272.
  9. "Expression, candidate gene, and population studies of the melanocortin 5 receptor."
    Hatta N., Dixon C., Ray A.J., Phillips S.R., Cunliffe W.J., Dale M., Todd C., Meggit S., Birch-MacHin M.A., Rees J.L.
    J. Invest. Dermatol. 116:564-570(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LEU-209.

Entry informationi

Entry nameiMC5R_HUMAN
AccessioniPrimary (citable) accession number: P33032
Secondary accession number(s): B0YJ34, Q502V1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: February 1, 1995
Last modified: February 4, 2015
This is version 139 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 18
    Human chromosome 18: 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

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.