GPR50

G protein-coupled receptor 50

Identifiers

GPR50 ; H9; Mel1c

External IDs

OMIM: 300207 MGI: 1333877 HomoloGene: 3113 IUPHAR: 107 GeneCards: GPR50 Gene

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

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr X:
151.18 – 151.18 Mb

Chr X:
71.66 – 71.67 Mb

PubMed search

G protein-coupled receptor 50 is a protein which in humans is encoded by the GPR50 gene.^[1]^[2]^[3]

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.^[2] 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.^[4] GPR50 is the mammalian ortholog of melatonin receptor Mel1c described in non-mammalian vertebrates. ^[5]

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.^[6] Other GPR50 gene polymorphism are associated with higher fasting circulating triglyceride levels and lower circulating High-density lipoprotein levels.^[7]

References

↑ "Entrez Gene: GPR50 G protein-coupled receptor 50".
1 2 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: 105. 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. 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. replacement character in |first5= at position 2 (help)
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) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 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) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) 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) 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) GHB receptor 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

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 77 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	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) 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)

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)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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GPR50

Function

Clinical significance

References

Further reading