P41968 (MC3R_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Melanocortin receptor 3
Short name=MC3-R

Gene names

Name:

MC3R

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase.
Subcellular location	Cell membrane; Multi-pass membrane protein.
Tissue specificity	Brain, placental, and gut tissues.
Polymorphism	Genetic variations in MC3R define the body mass index quantitative trait locus 9 (BMIQ9) [MIM:602025]. Variance in body mass index is a susceptibility factor for obesity.
Sequence similarities	Belongs to the G-protein coupled receptor 1 family.
Sequence caution	The sequence AAC13541.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH69105.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH69599.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH96702.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH96737.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH98169.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAH98351.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence AAO72726.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Glycoprotein Lipoprotein Palmitate
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger Traceable author statement PubMed 8175743. Source: ProtInc adenylate cyclase-modulating G-protein coupled receptor signaling pathway Inferred from electronic annotation. Source: Compara homoiothermy Inferred from electronic annotation. Source: Compara phospholipase C-activating G-protein coupled receptor signaling pathway Traceable author statement PubMed 8175743. Source: ProtInc positive regulation of cAMP biosynthetic process Inferred from direct assay PubMed 19329486PubMed 19743876. Source: BHF-UCL regulation of blood pressure Inferred from electronic annotation. Source: Compara regulation of heart rate Inferred from electronic annotation. Source: Compara sodium ion homeostasis Inferred from electronic annotation. Source: Compara
Cellular_component	integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	melanocyte-stimulating hormone receptor activity Inferred from physical interaction PubMed 19743876. Source: BHF-UCL neuropeptide binding Inferred from physical interaction PubMed 15927146. Source: UniProtKB peptide hormone binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 323	323	Melanocortin receptor 3		PRO_0000069718
Regions
	Topological domain	1 – 37	37	Extracellular Potential
	Transmembrane	38 – 63	26	Helical; Name=1; Potential
	Topological domain	64 – 75	12	Cytoplasmic Potential
	Transmembrane	76 – 100	25	Helical; Name=2; Potential
	Topological domain	101 – 118	18	Extracellular Potential
	Transmembrane	119 – 140	22	Helical; Name=3; Potential
	Topological domain	141 – 160	20	Cytoplasmic Potential
	Transmembrane	161 – 181	21	Helical; Name=4; Potential
	Topological domain	182 – 186	5	Extracellular Potential
	Transmembrane	187 – 210	24	Helical; Name=5; Potential
	Topological domain	211 – 245	35	Cytoplasmic Potential
	Transmembrane	246 – 268	23	Helical; Name=6; Potential
	Topological domain	269 – 277	9	Extracellular Potential
	Transmembrane	278 – 301	24	Helical; Name=7; Potential
	Topological domain	302 – 323	22	Cytoplasmic Potential
Amino acid modifications
	Lipidation	315	1	S-palmitoyl cysteine Potential
	Glycosylation	2	1	N-linked (GlcNAc...) Potential
	Glycosylation	16	1	N-linked (GlcNAc...) Potential
	Glycosylation	28	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	44	1	V → I Have ligand binding and signaling properties similar to wild-type. Ref.1 Ref.7 Corresponds to variant rs3827103 [ dbSNP | Ensembl ].		VAR_020070
	Natural variant	146	1	I → N Associated with susceptibility to obesity; completely lacks signaling in response to agonist stimulation; coexpression of the wild-type and the mutant receptor shows that it does not exert dominant-negative activity on wild-type. Ref.6 Ref.7		VAR_055000
	Natural variant	298	1	I → S Associated with susceptibility to obesity; in vitro expression studies demonstrate that the mutation causes complete loss of function; transfected cells show diffuse cytoplasmic staining indicating intracellular retention of the receptor. Ref.8		VAR_055001

Sequences

	Sequence		Length	Mass (Da)
	P41968 [UniParc]. Last modified July 11, 2012. Version 3. Checksum: 98B016FC80802A97	FASTA	323	36,043
	10 20 30 40 50 60 MNASCCLPSV QPTLPNGSEH LQAPFFSNQS SSAFCEQVFI KPEVFLSLGI VSLLENILVI 70 80 90 100 110 120 LAVVRNGNLH SPMYFFLCSL AVADMLVSVS NALETIMIAI VHSDYLTFED QFIQHMDNIF 130 140 150 160 170 180 DSMICISLVA SICNLLAIAV DRYVTIFYAL RYHSIMTVRK ALTLIVAIWV CCGVCGVVFI 190 200 210 220 230 240 VYSESKMVIV CLITMFFAMM LLMGTLYVHM FLFARLHVKR IAALPPADGV APQQHSCMKG 250 260 270 280 290 300 AVTITILLGV FIFCWAPFFL HLVLIITCPT NPYCICYTAH FNTYLVLIMC NSVIDPLIYA 310 320 FRSLELRNTF REILCGCNGM NLG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of a novel melanocortin receptor." Gantz I., Konda Y., Tashiro T., Shimoto Y., Miwa H., Munzert G., Watson S.J., Delvalle J., Yamada T. J. Biol. Chem. 268:8246-8250(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-44.
[2]	"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 (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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].
[5]	"Identification of the translation start site of the human melanocortin 3 receptor." Tarnow P., Rediger A., Schulz A., Gruters A., Biebermann H. Obes. Facts 5:45-51(2012) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSLATIONAL START SITE.
[6]	"A novel melanocortin 3 receptor gene (MC3R) mutation associated with severe obesity." Lee Y.-S., Poh L.K.-S., Loke K.-Y. J. Clin. Endocrinol. Metab. 87:1423-1426(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ASN-146, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.
[7]	"Functional characterization of melanocortin-3 receptor variants identify a loss-of-function mutation involving an amino acid critical for G protein-coupled receptor activation." Tao Y.-X., Segaloff D.L. J. Clin. Endocrinol. Metab. 89:3936-3942(2004) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF VARIANTS ILE-44 AND ASN-146.
[8]	"Sporadic mutations in melanocortin receptor 3 in morbid obese individuals." Mencarelli M., Walker G.E., Maestrini S., Alberti L., Verti B., Brunani A., Petroni M.L., Tagliaferri M., Liuzzi A., Di Blasio A.M. Eur. J. Hum. Genet. 16:581-586(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SER-298, CHARACTERIZATION OF VARIANT SER-298, ASSOCIATION WITH SUSCEPTIBILITY TO OBESITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L06155 Genomic DNA. Translation: AAC13541.1. Different initiation. AY227893 mRNA. Translation: AAO72726.1. Different initiation. AL139824 Genomic DNA. Translation: CAC15480.2. BC069105 mRNA. Translation: AAH69105.1. Different initiation. BC069599 mRNA. Translation: AAH69599.1. Different initiation. BC096702 mRNA. Translation: AAH96702.1. Different initiation. BC096737 mRNA. Translation: AAH96737.1. Different initiation. BC098169 mRNA. Translation: AAH98169.1. Different initiation. BC098351 mRNA. Translation: AAH98351.1. Different initiation.
IPI	IPI00018253.
PIR	B46647.
RefSeq	NP_063941.3. NM_019888.3.
UniGene	Hs.248018.
3D structure databases
ProteinModelPortal	P41968.
SMR	P41968. Positions 44-314.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48790N.
STRING	9606.ENSP00000243911.
Protein family/group databases
GPCRDB	Search...
Polymorphism databases
DMDM	20141559.
Proteomic databases
PaxDb	P41968.
PRIDE	P41968.
Protocols and materials databases
DNASU	4159.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000243911; ENSP00000243911; ENSG00000124089.
GeneID	4159.
KEGG	hsa:4159.
UCSC	uc002xxb.2. human.
Organism-specific databases
CTD	4159.
GeneCards	GC20P054823.
H-InvDB	HIX0040556.
HGNC	HGNC:6931. MC3R.
MIM	155540. gene. 602025. phenotype.
neXtProt	NX_P41968.
Orphanet	217031. Obesity due MC3R deficiency.
PharmGKB	PA30675.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG325361.
HOGENOM	HOG000246927.
HOVERGEN	HBG108148.
InParanoid	P41968.
KO	K04201.
OMA	VHMFLFA.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P41968.
CleanEx	HS_MC3R.
Genevestigator	P41968.
GermOnline	ENSG00000124089. Homo sapiens.
Family and domain databases
InterPro	IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. IPR002122. Mcort_3_rcpt. IPR001908. Melancort_rcpt. IPR001671. Melcrt_ACTH_rcpt. [Graphical view]
PANTHER	PTHR22750:SF4. PTHR22750:SF4. 1 hit.
Pfam	PF00001. 7tm_1. 1 hit. [Graphical view]
PRINTS	PR00237. GPCRRHODOPSN. PR00534. MCRFAMILY. PR00535. MELNOCORTINR. PR01061. MELNOCORTN3R.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P41968.
ChEMBL	CHEMBL4644.
GenomeRNAi	4159.
NextBio	16386.
SOURCE	Search...

Entry information

Entry name

MC3R_HUMAN

Accession

Primary (citable) accession number: P41968
Secondary accession number(s): Q4KN27, Q9H517

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	July 11, 2012
Last modified:	May 1, 2013
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.