GPR174

Target id: 145

Nomenclature: GPR174

Family: Class A Orphans

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

This receptor has a proposed ligand; see the Latest Pairings page for more information.

   GtoImmuPdb view: OFF :     Currently no data for GPR174 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 333 Xq13.3 GPR174 G protein-coupled receptor 174
Mouse 7 335 X D Gpr174 G protein-coupled receptor 174
Rat 7 335 Xq31 Gpr174 G protein-coupled receptor 174
Previous and Unofficial Names
FKSG79
Database Links
Specialist databases
GPCRDB gp174_human (Hs), gp174_mouse (Mm)
Other databases
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
lysophosphatidylserine
Comments: Proposed ligand, two publications

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
lysophosphatidylserine Hs Full agonist 7.1 pEC50 2
pEC50 7.1 (EC50 8.1x10-8 M) [2]
Agonist Comments
GPR174 has been shown to be activated by lysophosphatidylserine, with coupling to cAMP and ERK [2,4].
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Clinically-Relevant Mutations and Pathophysiology
Disease:  Graves' disease
Disease Ontology: DOID:12361
References:  1,5
Gene Expression and Pathophysiology Comments
GPR174 was found to be overexpressed in subcutaneous melanomametastases [3].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Nucleotide transition A>C at location X:78497118 associated with risk for Graves' disease. No amino acid change reported.
Global MAF (%):  0.49
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 40|41|43|62
Minor allele count:  C=0.485/802
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
References:  5
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Amino acid change associated with risk for Graves' disease
Amino acid change:  S162P
Nucleotide change:  519C>T
Global MAF (%):  49
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 37|41|46|62
Minor allele count:  C=0.489/811
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
References:  1
Biologically Significant Variant Comments
A number of rare single nucleotide polymorphisms are reported by Chu et al. in their genome-wide assocation study as being associated with Graves' disease. However, with the exception of rs3827440, none of these variants occured at a frequency of more than 5% in the population studied [1].

References

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1. Chu X, Shen M, Xie F, Miao XJ, Shou WH, Liu L, Yang PP, Bai YN, Zhang KY, Yang L et al.. (2013) An X chromosome-wide association analysis identifies variants in GPR174 as a risk factor for Graves' disease. J. Med. Genet.50 (7): 479-85. [PMID:23667180]

2. Inoue A, Ishiguro J, Kitamura H, Arima N, Okutani M, Shuto A, Higashiyama S, Ohwada T, Arai H, Makide K et al.. (2012) TGFα shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods9 (10): 1021-9. [PMID:22983457]

3. Qin Y, Verdegaal EM, Siderius M, Bebelman JP, Smit MJ, Leurs R, Willemze R, Tensen CP, Osanto S. (2011) Quantitative expression profiling of G-protein-coupled receptors (GPCRs) in metastatic melanoma: the constitutively active orphan GPCR GPR18 as novel drug target. Pigment Cell Melanoma Res24 (1): 207-18. [PMID:20880198]

4. Sugita K, Yamamura C, Tabata K, Fujita N. (2013) Expression of orphan G-protein coupled receptor GPR174 in CHO cells induced morphological changes and proliferation delay via increasing intracellular cAMP. Biochem. Biophys. Res. Commun.430 (1): 190-5. [PMID:23178570]

5. Zhao SX, Xue LQ, Liu W, Gu ZH, Pan CM, Yang SY, Zhan M, Wang HN, Liang J, Gao GQ et al.. (2013) Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis. Hum. Mol. Genet.,  [Epub ahead of print]. [PMID:23612905]

Contributors

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How to cite this page

Anthony P. Davenport, Stephen Alexander, Joanna L. Sharman, Adam J. Pawson, Helen E. Benson, Amy E. Monaghan, Wen Chiy Liew, Chido Mpamhanga, Jim Battey, Richard V. Benya, Robert T. Jensen, Sadashiva Karnik, Evi Kostenis, Eliot Spindel, Laura Storjohann, Kalyan Tirupula, Tom I. Bonner, Richard Neubig, Jean-Philippe Pin, Michael Spedding, Anthony Harmar.
Class A Orphans: GPR174. Last modified on 30/06/2015. Accessed on 25/06/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=145.