GPR50

Protein-coding gene in humans

GPR50

Identifiers

Aliases

GPR50, H9, Mel1c, G protein-coupled receptor 50

External IDs

OMIM: 300207 MGI: 1333877 HomoloGene: 3113 GeneCards: GPR50

Gene location (Human)

Chr.	X chromosome (human)^[1]

Band	Xq28	Start	151,176,584 bp^[1]
Band	Xq28	End	151,181,465 bp^[1]

Gene location (Mouse)

Chr.	X chromosome (mouse)^[2]

Band	X A7.3\|X 36.98 cM	Start	70,707,273 bp^[2]
Band	X A7.3\|X 36.98 cM	End	70,712,863 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

anterior pituitary

smooth muscle tissue

placenta

hypothalamus

ganglionic eminence

lymph node

islet of Langerhans

uterus

connective tissue

adipose tissue

Top expressed in

median eminence

arcuate nucleus

intestinal villus

entorhinal cortex

tracheobronchial tree

dorsomedial hypothalamic nucleus

abdominal wall

mammillary body

secondary oocyte

yolk sac

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	melatonin receptor activity G protein-coupled receptor activity protein binding signal transducer activity identical protein binding
Cellular component	integral component of membrane integral component of plasma membrane membrane nucleoplasm plasma membrane
Biological process	cell-cell signaling G protein-coupled receptor signaling pathway signal transduction
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


9248


14765

Ensembl


ENSG00000102195


ENSMUSG00000056380

UniProt


Q13585


O88495

RefSeq (mRNA)


NM_004224


NM_010340 NM_001308501

RefSeq (protein)


NP_004215


NP_001295430 NP_034470

Location (UCSC)

Chr X: 151.18 – 151.18 Mb

Chr X: 70.71 – 70.71 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

G protein-coupled receptor 50 is a protein which in humans is encoded by the GPR50 gene.^[5]^[6]^[7]

Function

GPR50 is a member of the G protein-coupled receptor family of integral membrane proteins and is most closely related to the melatonin receptor.^[6] GPR50 is able to heterodimerize with both the MT₁ and MT₂ melatonin receptor subtypes. While GPR50 has no effect on MT₂ function, GPR50 prevented MT₁ from both binding melatonin and coupling to G proteins.^[8] GPR50 is the mammalian ortholog of melatonin receptor Mel1c described in non-mammalian vertebrates. ^[9]

Clinical significance

Certain polymorphisms of the GPR50 gene in females are associated with increased risk of developing bipolar affective disorder, major depressive disorder, and schizophrenia.^[10] Other GPR50 gene polymorphism are associated with higher fasting circulating triglyceride levels and lower circulating High-density lipoprotein levels.^[11]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000102195 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000056380 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: GPR50 G protein-coupled receptor 50".
^ ^a ^b Reppert SM, Weaver DR, Ebisawa T, Mahle CD, Kolakowski LF (May 1996). "Cloning of a melatonin-related receptor from human pituitary". FEBS Letters. 386 (2–3): 219–24. doi:10.1016/0014-5793(96)00437-1. PMID 8647286.
^ Gubitz AK, Reppert SM (January 1999). "Assignment of the melatonin-related receptor to human chromosome X (GPR50) and mouse chromosome X (Gpr50)". Genomics. 55 (2): 248–51. doi:10.1006/geno.1998.5661. PMID 9933574.
^ Levoye A, Dam J, Ayoub MA, Guillaume JL, Couturier C, Delagrange P, Jockers R (July 2006). "The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization". The EMBO Journal. 25 (13): 3012–23. doi:10.1038/sj.emboj.7601193. PMC 1500982. PMID 16778767.
^ Dufourny L, Levasseur A, Migaud M, Callebaut I, Pontarotti P, Malpaux B, Monget P (2008). "GPR50 is the mammalian ortholog of Mel1c: Evidence of rapid evolution in mammals". BMC Evolutionary Biology. 8 (1): 105. Bibcode:2008BMCEE...8..105D. doi:10.1186/1471-2148-8-105. PMC 2323367. PMID 18400093.
^ Thomson PA, Wray NR, Thomson AM, Dunbar DR, Grassie MA, Condie A, Walker MT, Smith DJ, Pulford DJ, Muir W, Blackwood DH, Porteous DJ (May 2005). "Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor". Molecular Psychiatry. 10 (5): 470–8. doi:10.1038/sj.mp.4001593. PMID 15452587.
^ Bhattacharyya S, Luan J, Challis B, Keogh J, Montague C, Brennand J, Morten J, Lowenbeim S, Jenkins S, Farooqi IS, Wareham NJ, O'Rahilly S (April 2006). "Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levels". Journal of Lipid Research. 47 (4): 761–6. doi:10.1194/jlr.M500338-JLR200. PMID 16436372.

Reppert SM, Weaver DR, Ebisawa T, et al. (1996). "Cloning of a melatonin-related receptor from human pituitary". FEBS Lett. 386 (2–3): 219–24. doi:10.1016/0014-5793(96)00437-1. PMID 8647286.
Gubitz AK, Reppert SM (1999). "Assignment of the melatonin-related receptor to human chromosome X (GPR50) and mouse chromosome X (Gpr50)". Genomics. 55 (2): 248–51. doi:10.1006/geno.1998.5661. PMID 9933574.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Slominski A, Pisarchik A, Zbytek B, et al. (2003). "Functional activity of serotoninergic and melatoninergic systems expressed in the skin". J. Cell. Physiol. 196 (1): 144–53. doi:10.1002/jcp.10287. PMID 12767050. S2CID 24534729.
Suzuki Y, Yamashita R, Shirota M, et al. (2004). "Sequence Comparison of Human and Mouse Genes Reveals a Homologous Block Structure in the Promoter Regions". Genome Res. 14 (9): 1711–8. doi:10.1101/gr.2435604. PMC 515316. PMID 15342556.
Thomson PA, Wray NR, Thomson AM, et al. (2005). "Sex-specific association between bipolar affective disorder in women and GPR50, an X-linked orphan G protein-coupled receptor". Mol. Psychiatry. 10 (5): 470–8. doi:10.1038/sj.mp.4001593. PMID 15452587.
Bhattacharyya S, Luan J, Challis B, et al. (2006). "Sequence variants in the melatonin-related receptor gene (GPR50) associate with circulating triglyceride and HDL levels". J. Lipid Res. 47 (4): 761–6. doi:10.1194/jlr.M500338-JLR200. PMID 16436372.
Levoye A, Dam J, Ayoub MA, et al. (2006). "The orphan GPR50 receptor specifically inhibits MT1 melatonin receptor function through heterodimerization". EMBO J. 25 (13): 3012–23. doi:10.1038/sj.emboj.7601193. PMC 1500982. PMID 16778767.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3
Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)
Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)
Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine D1 D2 D3 D4 D5 GHB receptor Histamine H1 H2 H3 H4 Melatonin (1A 1B 1C) TAAR (1 2 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 1 2 FPRL1 OXE Prostaglandin DP (1 2), EP (1 2 3 4), FP Prostacyclin Thromboxane
Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Hydroxycarboxylic acids 1 2 3 Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide

B/W (1
2)
FF (1
2)
S
Y (1
2
4
5)
Neuromedin (B
U (1
2))
Neurotensin (1
2)

Other

Anaphylatoxin (C3a
C5a (1
2))
Angiotensin (1
2)
Apelin
Bombesin
- BRS3
- GRPR
- NMBR)
- Bradykinin (B1
- B2)
Chemokine
Cholecystokinin (A
B)
Endothelin
- A
- B
Formyl peptide (1
2
3)
FSH
Galanin (1
2
3)
Gonadotropin-releasing hormone (1
2)
Ghrelin
Kisspeptin
Luteinizing hormone/choriogonadotropin
MAS (1
1L
D
E
F
G
X1
X2
X3
X4)
Melanocortin (1
2
3
4
5)
MCHR (1
2)
Motilin
Opioid (Delta
Kappa
Mu
Nociceptin & Zeta, but not Sigma)
Orexin (1
2)
Oxytocin
Prokineticin (1
2)
Prolactin-releasing peptide
Relaxin (1
2
3
4)
Somatostatin (1
2
3
4
5)
Tachykinin (1
2
3)
Thyrotropin
Thyrotropin-releasing hormone
Urotensin-II
Vasopressin (1A
1B
2)

Miscellaneous

Taste, bitter	TAS2R 1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60 Vomeronasal receptor type 1
Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)
Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin-like

Adhesion	ADGRB Brain-specific angiogenesis inhibitor 1 2 3 ADGRC Cadherin 1 2 3 ADGRE EMR 1 2 3 CD97 ADGRG 1 2 3 4 5 6 7 ADGRL Latrophilin 1 2 3 ELTD1
Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)
Other	Calcitonin CALCRL Corticotropin-releasing hormone (1 2) Glucagon (GR GIPR GLP1R GLP2R) Growth-hormone-releasing hormone PACAPR1 GPR Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste, sweet	TAS1R 1 2 3 Vomeronasal receptor, type 2
Other	Calcium-sensing receptor GABA_B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)