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GPR42

Family: Free fatty acid receptors, Class A Orphans

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Transduction Mechanisms
Tissue Distribution
Functional Assays
General Comments
References
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
GPR42P
FFAR3L
G protein-coupled receptor 42 pseudogene
Database Links
Ensembl ENSG00000126251 (Hs)
Entrez Gene 2866 (Hs)
GeneCards GPR42 (Hs)
HomoloGene 88719 (Hs)
Human Protein Reference Database 16033 (Hs)
InterPro O15529 (Hs)
KEGG Gene hsa:2866 (Hs)
OMIM 603822 (Hs)
PharmGKB Gene PA28889 (Hs)
RefSeq Nucleotide NM_005304 (Hs)
RefSeq Protein NP_005295 (Hs)
TreeFam ENSG00000126251 (Hs)
UniGene Hs. 533926 (Hs)
UniProt O15529 (Hs)
Wikipedia GPR42
Natural/Endogenous Ligand(s)
Comments: Very closely related to GPR41. Might be 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]. 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, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., Pike, N. B., Strum, J. C., Steplewski, K. M., Murdock, P. R., Holder, J. C., Marshall, F. H., Szekeres, P. G., Wilson, S., Ignar, D. M., Foord, S. M., Wise, A. and Dowell, S. J. (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, S. R., Nguyen, T., Xu, S., Kolakowski, L. F. and O'Dowd, B. F. (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]

To cite this database page, please use the following:

Amy E. Monaghan.
Class A Orphans: GPR42. Last modified on 28/08/2012. Accessed on 25/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=228.


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