Hydroxycarboxylic acid receptor 2/3 (IPR028017)

Short name: HCAR2/3_rcpt

Overlapping homologous superfamilies


Family relationships


The hydroxycarboxylic acid receptors [PMID: 21454438] are members of the rhodopsin-like G protein-coupled receptor (GPCR) family. There are three hydroxycarboxylic acid receptors, termed HCAR1-3. The family was formerly known as nicotinic acid receptor family, although nicotinic acid only shows submicromolar potency at HCAR2 [PMID: 12563315, PMID: 12522134].

The receptors respond to organic acids, including the endogenous short chain fatty acids, butyric acid and L-lactic acid, as well as the lipid lowering agents nicotinic acid (niacin), acipimox and acifran [PMID: 12646212, PMID: 12563315, PMID: 12522134]. There is an increasing number of synthetic ligands mainly targeted at HCAR2 and HCAR3 receptors [PMID: 19524438, PMID: 19309152]. All three receptors are expressed in adipocytes, and are coupled to Gi type G-proteins mediating antilipolytic effects in fat cells [PMID: 19047060, PMID: 12646212, PMID: 12646212, PMID: 21454438]. HCAR2 and HCAR3 are also expressed in a variety of immune cells including monocytes, macrophages, neutrophils and Langerhans cells [PMID: 17008871, PMID: 19237584]. HCAR1 and HCAR2 are found in most mammalian species, whereas HCAR3 is only present in higher primates [PMID: 21454438]. There is evidence that these receptors can mediate anti-inflammatory effects. HCAR2 has been shown to be a receptor for the anti-dyslipidemic drug nicotinic acid (niacin) as well as for the anti-psoriatic drug monomethyl-fumarate [PMID: 22654812, PMID: 21454438].

This entry represents two members of hydroxycarboxylic acid receptor family, hydroxycarboxylic acid receptor 2 (also known as niacin receptor 1, G protein-coupled receptor 109A, nicotinic acid receptor, HM74A) and hydroxycarboxylic acid receptor 3 (also known as niacin receptor 2, G protein-coupled receptor 109B, low affinity nicotinic acid receptor). The endogenous ligands of HCAR2 and HCAR3 are beta-D-hydroxybutyric acid and 3-hydroxyoctanoic acid, respectively [PMID: 21454438].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004930 G-protein coupled receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.