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GPR33

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Target not currently curated in GtoImmuPdb

Target id: 100

Nomenclature: GPR33

Family: Class A Orphans with only surrogate ligands

Contents:

Gene and Protein Information Click here for help
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 3
Mouse 7 339 12 C1 Gpr33 G protein-coupled receptor 33
Rat 7 339 6 q23 Gpr33-ps1 G protein-coupled receptor 33, pseudogene 1
Previous and Unofficial Names Click here for help
G protein-coupled receptor 33 (gene/pseudogene) | G protein-coupled receptor 33, pseudogene 1
Database Links Click here for help
Specialist databases
GPCRdb gpr33_human (Hs), gpr33_mouse (Mm), gpr33_ratrt (Rn)
Other databases
Alphafold Q49SQ1 (Hs), O88416 (Mm), Q49SP8 (Rn)
Ensembl Gene ENSG00000214943 (Hs), ENSMUSG00000035148 (Mm), ENSRNOG00000038990 (Rn)
Entrez Gene 2856 (Hs), 14762 (Mm), 299007 (Rn)
Human Protein Atlas ENSG00000214943 (Hs)
KEGG Gene hsa:2856 (Hs), mmu:14762 (Mm), rno:299007 (Rn)
OMIM 610118 (Hs)
Pharos Q49SQ1 (Hs)
RefSeq Nucleotide NR_036675 (Hs), NM_001197184 (Hs), NM_008159 (Mm), NM_001031823 (Rn)
RefSeq Protein NP_001184113 (Hs), NP_032185 (Mm), NP_001026993 (Rn)
UniProtKB Q49SQ1 (Hs), O88416 (Mm), Q49SP8 (Rn)
Wikipedia GPR33 (Hs)
Natural/Endogenous Ligands Click here for help
Comments: pseudogene in most individuals
Immuno Process Associations
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 2 GO processes
GO:0002430 complement receptor mediated signaling pathway IBA
GO:0004875 complement receptor activity IBA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0002430 complement receptor mediated signaling pathway IBA
GO:0004875 complement receptor activity IBA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response IBA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
Comments:  The murine ortholog constitutively activates Gi [4].
References:  2,4-5
Tissue Distribution Click here for help
Spleen, lung, heart, liver, kidney, pancreas, thymus, gonads, leukocytes (pseudogene transcript)
Species:  Human
Technique:  RT-PCR
References:  4
Dendritic cells, spleen, lungs, lymph nodes (mRNA)
Species:  Mouse
Technique:  Quantitative PCR
References:  1
Lung, spleen, testis (macrophage cell line RAW 264.7)
Species:  Mouse
Technique:  RT-PCR
References:  4
Expression Datasets Click here for help

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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 Click here for help
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 Click here for help
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:  rs17097918
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:  rs77195826
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]

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