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Gene Review

HCAR3  -  hydroxycarboxylic acid receptor 3

Homo sapiens

Synonyms: G-protein coupled receptor 109B, G-protein coupled receptor HM74, G-protein coupled receptor HM74B, GPR109B, HCA3, ...
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High impact information on GPR109B

  • The recent discovery and characterization of a membrane-bound nicotinic acid receptor (HM74) explains niacin's acute inhibition of adipocyte lipolysis, but the role of HM74 in lowering triglycerides is unclear [1].
  • 1-Substituted benzotriazole carboxylic acids have been identified as the first reported examples of selective small-molecule agonists of the human orphan G-protein-coupled receptor GPR109b (HM74), a low-affinity receptor for the HDL-raising drug niacin [2].
  • Both niacin and the structurally distinct HM74/HM74a ligand acifran-induced nuclear expression of PPARgamma protein and enhanced PPARgamma transcriptional activity [3].
  • Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways [3].
  • Thus, three of the newly identified proteins probably belong to a 'leukocyte chemotactic peptide receptor family'. HM74 differs from the other clones with respect to the amino acid homology, suggesting that this may be the receptor for a different type of ligand [4].

Biological context of GPR109B

  • All polypeptides encoded by the cloned cDNAs share common features with the G protein-coupled receptor superfamily, such as seven putative hydrophobic transmembrane domains and, except for HM74, N-linked glycosylation sites near the N-terminus [4].
  • Amino acid sequence comparison reveals that the best match in the protein databases is with the human orphan GPCR called HM74 (33% identity) [5].
  • Here we show that many of the nonsynonymous SNPs listed in public databases for HM74 and HM74A are artifacts resulting from extensive homology between these two genes [6].
  • Moreover, using haplotype analysis, a nearly significant haplotypic association was observed at the HM74 gene [7].

Associations of GPR109B with chemical compounds


Other interactions of GPR109B


  1. Niacin therapy in atherosclerosis. Meyers, C.D., Kamanna, V.S., Kashyap, M.L. Curr. Opin. Lipidol. (2004) [Pubmed]
  2. 1-Alkyl-benzotriazole-5-carboxylic acids are highly selective agonists of the human orphan G-protein-coupled receptor GPR109b. Semple, G., Skinner, P.J., Cherrier, M.C., Webb, P.J., Sage, C.R., Tamura, S.Y., Chen, R., Richman, J.G., Connolly, D.T. J. Med. Chem. (2006) [Pubmed]
  3. Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways. Knowles, H.J., Te Poole, R., Workman, P., Harris, A.L. Biochem. Pharmacol. (2006) [Pubmed]
  4. Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors. Nomura, H., Nielsen, B.W., Matsushima, K. Int. Immunol. (1993) [Pubmed]
  5. Isolation and chromosomal localization of GPR31, a human gene encoding a putative G protein-coupled receptor. Zingoni, A., Rocchi, M., Storlazzi, C.T., Bernardini, G., Santoni, A., Napolitano, M. Genomics (1997) [Pubmed]
  6. Variations in human HM74 (GPR109B) and HM74A (GPR109A) niacin receptors. Zellner, C., Pullinger, C.R., Aouizerat, B.E., Frost, P.H., Kwok, P.Y., Malloy, M.J., Kane, J.P. Hum. Mutat. (2005) [Pubmed]
  7. Analysis of microsatellite markers and single nucleotide polymorphisms in candidate genes for susceptibility to bipolar affective disorder in the chromosome 12Q24.31 region. Shink, E., Harvey, M., Tremblay, M., Gagné, B., Belleau, P., Raymond, C., Labbé, M., Dubé, M.P., Lafrenière, R.G., Barden, N. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2005) [Pubmed]
  8. Characterization of determinants of ligand binding to the nicotinic acid receptor GPR109A (HM74A/PUMA-G). Tunaru, S., Lättig, J., Kero, J., Krause, G., Offermanns, S. Mol. Pharmacol. (2005) [Pubmed]
  9. Nicotinic acid receptor subtypes and their ligands. Soudijn, W., van Wijngaarden, I., Ijzerman, A.P. Med Res Rev (2007) [Pubmed]
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