<i>GPR42</i> | Class A Orphans | IUPHAR/BPS Guide to PHARMACOLOGY

GPR42

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

   GtoImmuPdb view: OFF :     Currently no data for GPR42 in GtoImmuPdb

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, Pike NB, Strum JC, Steplewski KM, Murdock PR, Holder JC, Marshall FH, Szekeres PG, Wilson S, Ignar DM, Foord SM, Wise A, Dowell SJ. (2003) The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem, 278: 11312-11319. [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: 543-547. [PMID:9344866]

Contributors

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How to cite this page

Leigh Stoddart, Nick Holliday.
Class A Orphans: GPR42. Last modified on 20/02/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=228.