Hydroxycarboxylic acid receptor 2

Function

Acts as a high affinity receptor for both nicotinic acid (also known as niacin) and (D)-beta-hydroxybutyrate and mediates increased adiponectin secretion and decreased lipolysis through G(i)-protein-mediated inhibition of adenylyl cyclase. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet. Mediates nicotinic acid-induced apoptosis in mature neutrophils. Receptor activation by nicotinic acid results in reduced cAMP levels which may affect activity of cAMP-dependent protein kinase A and phosphorylation of target proteins, leading to neutrophil apoptosis. The rank order of potency for the displacement of nicotinic acid binding is 5-methyl pyrazole-3-carboxylic acid = pyridine-3-acetic acid > acifran > 5-methyl nicotinic acid = acipimox >> nicotinuric acid = nicotinamide.

Classification

Family (Pfam)

PF00001 7tm_1

InterPro

GPCR_Rhodpsn, GPCR_Rhodpsn_7TM, HCARs

Functional cluster

G Protein-Coupled Receptors

Experimental structures · PDB · 40

• 7XK2 EM 3.10A
• 7ZL9 X-ray 2.70A
• 7ZLY X-ray 2.70A
• 8H2G EM 3.01A
• 8I7V EM 2.77A
• 8I7W EM 3.39A
• 8IHB EM 2.85A
• 8IHF EM 2.97A
• 8IHH EM 3.06A
• 8IHI EM 3.11A
• 8IJ3 EM 3.28A
• 8IJA EM 2.69A
• … and 28 more

A predicted model is available from AlphaFold.

Gene Ontology · 8

• GO:0030054 cell junction
• GO:0005886 plasma membrane
• GO:0070553 nicotinic acid receptor activity
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0050995 negative regulation of lipid catabolic process
• GO:0001781 neutrophil apoptotic process
• GO:0070165 positive regulation of adiponectin secretion
• GO:0033031 positive regulation of neutrophil apoptotic process

Drugs targeting this protein · 1

• SCH-900271 agonist

Related proteins · sequence + function similarity

• Hydroxycarboxylic acid receptor 3 0.99
• Hydroxycarboxylic acid receptor 2 0.99
• Hydroxycarboxylic acid receptor 2 0.99
• Hydroxycarboxylic acid receptor 1 0.96
• Hydroxycarboxylic acid receptor 1 0.95
• Probable G protein-coupled receptor 174 0.94
• Probable G protein-coupled receptor 174 0.94
• Putative P2Y purinoceptor 10 0.93
• Putative P2Y purinoceptor 10 0.92
• Cysteinyl leukotriene receptor 2 0.92
• G protein-coupled receptor 55 0.91
• Cysteinyl leukotriene receptor 2 0.91

Co-cited proteins · studied together in the literature

• Hydroxycarboxylic acid receptor 3 2 shared papers
• Hydroxycarboxylic acid receptor 2 1 shared papers
• Hydroxycarboxylic acid receptor 1 2 shared papers
• Putative vomeronasal receptor-like protein 4 1 shared papers
• Probable G protein-coupled receptor 160 1 shared papers
• Probable G protein-coupled receptor 152 1 shared papers
• Cysteinyl leukotriene receptor 2 1 shared papers
• Probable G protein-coupled receptor 148 1 shared papers
• Putative G protein-coupled receptor GPR32P1 1 shared papers
• Probable G protein-coupled receptor 174 1 shared papers
• Oxoeicosanoid receptor 1 1 shared papers
• GPI ethanolamine phosphate transferase 3, catalytic subunit 1 shared papers

Literature · 5 cited papers

• International union of basic and clinical pharmacology. LXXXII: nomenclature and classification of hydroxy-carboxylic acid receptors (GPR81, GPR109A, and GPR109B). Pharmacol. Rev. · 2011
• Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ. · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Molecular identification of high and low affinity receptors for nicotinic acid. J. Biol. Chem. · 2003
• Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett. · 2002