<i>GPR33</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

GPR33

Target id: 100

Nomenclature: GPR33

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

   GtoImmuPdb view: OFF :     Currently no data for GPR33 in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor: pseudogene in most individuals
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 333 14q12 GPR33 G protein-coupled receptor 33 (gene/pseudogene) 3
Mouse 7 339 12 C1 Gpr33 G protein-coupled receptor 33
Rat 7 339 6 q23 Gpr33 G protein-coupled receptor 33
Database Links
Specialist databases
GPCRDB gpr33_human (Hs), gpr33_mouse (Mm), gpr33_ratrt (Rn)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Comments: pseudogene in most individuals
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  The murine ortholog constitutively activates Gi [4].
References:  2,4-5
Tissue Distribution
Spleen, lung, heart, liver, kidney, pancreas, thymus, gonads, leukocytes (pseudogene transcript)
Species:  Human
Technique:  RT-PCR
References:  4
Lung, spleen, testis (macrophage cell line RAW 264.7)
Species:  Mouse
Technique:  RT-PCR
References:  4
Dendritic cells, spleen, lungs, lymph nodes (mRNA)
Species:  Mouse
Technique:  Quantitative PCR
References:  1
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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Functional Assays
Gln, Trp and Thr substitutions at position 3.50 do not alter receptor expression at the cell surface but reduce basal receptor activity.
Species:  Mouse
Tissue:  COS-7 Cells
Response measured:  Reduced basal receptor activity
References:  5
I122F and Y225N abolish basal receptor activity; this is attributed to altered cell surface expression.
Species:  Mouse
Tissue:  COS-7 Cells
Response measured:  Inhibition of basal receptor activity
References:  2
The Ala to Asp mutation in the DRY motif at the TMD3/ICL2 transition results in reduced basal receptor activity caused by stabilisation of the inactive receptor conformation.
Species:  Mouse
Tissue:  COS-7 Cells
Response measured:  Reduced receptor activity
References:  4
Physiological Consequences of Altering Gene Expression Comments
GPR33 deficient mouse (carrying the Y225N mutation) does not show any obviously altered fertility, morphologic development, major organs or blood cell counts. Macrophage specific function should be assessed to delineate functional relevance of the receptor [6].
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  R143H
Global MAF (%):  6
Subpopulation MAF (%):  AFR|AMR|EUR: 5|6|10
Minor allele count:  T=0.055/121
SNP accession: 
Validation:  1000 Genomes, HapMap, Frequency
Type:  Single nucleotide polymorphism
Species:  Human
Amino acid change:  M79L
Global MAF (%):  1
Subpopulation MAF (%):  AFR|AMR: 5|1
Minor allele count:  A=0.012/27
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes
Type:  Single nucleotide polymorphism
Species:  Mouse
Description:  Arg->His polymorphism in DRY motif of GPR33 does not alter receptor function in vitro (for other GPCR this polymorphism has been shown to increase β-arrestin mediated desensitisation).
References:  5
General Comments
Human GPR33 contains a premature stop codon within the coding sequence of the second intracellular loop [4]. Pseudogenes of GPR33 predominantly occur in rodents (rat) and primates but not other mammals [4]. Receptor inactivation may have occurred due to a rodent-hominoid-specific pathogen [1]. Murine GPR33 expression is regulated by toll like receptors and AP-1/NFκB signalling pathways in cell culture and in vivo. Manganese also increase receptor mRNA expression in dendritic cells via an unknown mechanism [1].

References

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1. Bohnekamp J, Böselt I, Saalbach A, Tönjes A, Kovacs P, Biebermann H, Manvelyan HM, Polte T, Gasperikova D, Lkhagvasuren S, Baier L, Stumvoll M, Römpler H, Schöneberg T. (2010) Involvement of the chemokine-like receptor GPR33 in innate immunity. Biochem. Biophys. Res. Commun., 396 (2): 272-7. [PMID:20399748]

2. Grosse J, Tarnow P, Römpler H, Schneider B, Sedlmeier R, Huffstadt U, Korthaus D, Nehls M, Wattler S, Schöneberg T, Biebermann H, Augustin M. (2006) N-ethyl-N-nitrosourea-based generation of mouse models for mutant G protein-coupled receptors. Physiol. Genomics, 26 (3): 209-17. [PMID:16720677]

3. Marchese A, Nguyen T, Malik P, Xu S, Cheng R, Xie Z, Heng HH, George SR, Kolakowski LF, O'Dowd BF. (1998) Cloning genes encoding receptors related to chemoattractant receptors. Genomics, 50 (2): 281-6. [PMID:9653656]

4. Römpler H, Schulz A, Pitra C, Coop G, Przeworski M, Pääbo S, Schöneberg T. (2005) The rise and fall of the chemoattractant receptor GPR33. J. Biol. Chem., 280 (35): 31068-75. [PMID:15987686]

5. Römpler H, Yu HT, Arnold A, Orth A, Schöneberg T. (2006) Functional consequences of naturally occurring DRY motif variants in the mammalian chemoattractant receptor GPR33. Genomics, 87 (6): 724-32. [PMID:16595170]

6. Süsens U, Hermans-Borgmeyer I, Urny J, Schaller HC. (2006) Characterisation and differential expression of two very closely related G-protein-coupled receptors, GPR139 and GPR142, in mouse tissue and during mouse development. Neuropharmacology, 50 (4): 512-20. [PMID:16378626]

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: GPR33. Last modified on 31/07/2015. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=100.