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GPR33

Family: Class A Orphans

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Consequences of Altering Gene Expression
Biologically Significant Variants
General Comments
References
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
Previous and Unofficial Names
G protein-coupled receptor 33, pseudogene
G protein-coupled receptor 33 pseudogene
G protein-coupled receptor 33
Gpr33
Gpr33_predicted
LOC299007
G protein-coupled receptor 33 (predicted)
probable G-protein coupled receptor 33
Database Links
Ensembl ENSG00000214943 (Hs), ENSMUSG00000035148 (Mm), ENSRNOG00000038990 (Rn)
Entrez Gene 2856 (Hs), 14762 (Mm), 299007 (Rn)
GeneCards GPR33 (Hs)
GenitoUrinary Development Molecular Anatomy Project Gpr33 (Mm)
HomoloGene 7345 (Hs)
InterPro Q49SQ1 (Hs), O88416 (Mm), Q49SP8 (Rn)
KEGG Gene hsa:2856 (Hs), mmu:14762 (Mm), rno:299007 (Rn)
OMIM 610118 (Hs)
PharmGKB Gene PA28877 (Hs)
Protein Ontology (PRO) PRO:000001529 (Hs)
RefSeq Nucleotide NM_001197184 (Hs), NR_036675 (Hs), NM_008159 (Mm), NM_001031823 (Rn)
RefSeq Protein NP_001184113 (Hs), NP_032185 (Mm), NP_001026993 (Rn)
TreeFam ENSG00000214943 (Hs), ENSMUSG00000035148 (Mm), ENSRNOG00000038990 (Rn)
UniProt Q49SQ1 (Hs), O88416 (Mm), Q49SP8 (Rn)
Wikipedia GPR33
Orphan and other 7TM receptors
Natural/Endogenous Ligand(s)
Comments: pseudogene in most individuals
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Comments:  The murine ortholog consitutively 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 deliniate functional relevance of the receptor [6].
Biologically Significant Variants
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).
Type:  Single nucletide polymorphisms
Species:  Mouse
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 and 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]

To cite this database page, please use the following:

Amy E. Monaghan.
Class A Orphans: GPR33. Last modified on 16/07/2012. Accessed on 19/06/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=100.


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