<i>GPR42</i> | Free fatty acid receptors | IUPHAR/BPS Guide to PHARMACOLOGY

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GPR42

Target not currently curated in GtoImmuPdb

Target id: 228

Nomenclature: GPR42

Family: Class A Orphans, Free fatty acid receptors

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

Gene and Protein Information
class A G protein-coupled receptor: probable pseudogene
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 - 19q13.1 GPR42 G protein-coupled receptor 42 (gene/pseudogene) 3-4
Previous and Unofficial Names
FFAR1L | GPR41L | FFAR3L
Database Links
Specialist databases
GPCRDB gpr42_human (Hs), gpr42_human (Hs)
Other databases
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
Comments: Very closely related to GPR41. Might be a pseudogene.
Agonist Comments
GPR42 is thought to have arisen as a tandem duplication of GPR41 in the human lineage and has acquired mutations since duplication that abolish its ability to respond to carboxylate ions [1].
Primary Transduction Mechanisms
Comments:  GPR42 appears to have lost the ability to activate Gi family proteins in response to carboxylate ligands due to an amino acid change at position 174 [1].
References: 
Tissue Distribution Comments
RT-PCR detected no signal for GPR42 mRNA in samples of normal human tissues [1] .
Functional Assays
W174R amino acid change is sufficient to restore the response of GPR42 to GPR41 agonist propionate, though at a significantly lower magnitude
Species:  Rat
Tissue:  HEK293T cells
Response measured:  Receptor response to propionate
References:  1
General Comments
Two conflicting hypotheses exist regarding GPR42: the first is that it is a pseudogene, occurring infrequently in human populations as a polymorphic insert [1]. Alternative evidence from genotyping data indicates that GPR42 may be a functional gene in a significant fraction of the population, where Arg174 is present [3]. However, the very close sequence similarity of GPR41 and GPR42 (six nucleotide differences in the coding sequence) make this very difficult to assess. The receptor shares 98% sequence homology with free fatty acid receptor FFA3 (GPR41) [4]. Rodents appear to have only one ortholog of the human GPR41/GPR42 pair, suggesting duplication of the locus has occurred since divergence of primate and human lineages [2].

References

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1. Brown AJ, Goldsworthy SM, Barnes AA, Eilert MM, Tcheang L, Daniels D, Muir AI, Wigglesworth MJ, Kinghorn I, Fraser NJ et al.. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J. Biol. Chem., 278 (13): 11312-9. [PMID:12496283]

2. Brown AJ, Jupe S, Briscoe CP. (2005) A family of fatty acid binding receptors. DNA Cell Biol., 24 (1): 54-61. [PMID:15684720]

3. Liaw CW, Connolly DT. (2009) Sequence polymorphisms provide a common consensus sequence for GPR41 and GPR42. DNA Cell Biol., 28 (11): 555-60. [PMID:19630535]

4. Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O'Dowd BF. (1997) A cluster of four novel human G protein-coupled receptor genes occurring in close proximity to CD22 gene on chromosome 19q13.1. Biochem. Biophys. Res. Commun., 239 (2): 543-7. [PMID:9344866]

Contributors

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