Hydroxycarboxylic acid receptor 2

NameHydroxycarboxylic acid receptor 2
Synonyms
  • G-protein coupled receptor 109A
  • G-protein coupled receptor HM74A
  • GPR109A
  • HCA2
  • HM74A
  • Niacin receptor 1
  • NIACR1
  • Nicotinic acid receptor
Gene NameHCAR2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0010442|Hydroxycarboxylic acid receptor 2
MNRHHLQDHFLEIDKKNCCVFRDDFIVKVLPPVLGLEFIFGLLGNGLALWIFCFHLKSWK
SSRIFLFNLAVADFLLIICLPFLMDNYVRRWDWKFGDIPCRLMLFMLAMNRQGSIIFLTV
VAVDRYFRVVHPHHALNKISNRTAAIISCLLWGITIGLTVHLLKKKMPIQNGGANLCSSF
SICHTFQWHEAMFLLEFFLPLGIILFCSARIIWSLRQRQMDRHAKIKRAITFIMVVAIVF
VICFLPSVVVRIRIFWLLHTSGTQNCEVYRSVDLAFFITLSFTYMNSMLDPVVYYFSSPS
FPNFFSTLINRCLQRKMTGEPDNNRSTSVELTGDPNKTRGAPEALMANSGEPWSPSYLGP
TSP
Number of residues363
Molecular Weight41849.08
Theoretical pI9.37
GO Classification
Functions
  • nicotinic acid receptor activity
Processes
  • negative regulation of lipid catabolic process
  • positive regulation of neutrophil apoptotic process
  • neutrophil apoptotic process
  • positive regulation of adiponectin secretion
Components
  • plasma membrane
  • cell junction
  • integral component of membrane
General FunctionNicotinic acid receptor activity
Specific FunctionActs 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.
Pfam Domain Function
Transmembrane Regions34-54 64-84 103-123 143-163 193-213 230-250 274-294
GenBank Protein ID28975188
UniProtKB IDQ8TDS4
UniProtKB Entry NameHCAR2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010443|Hydroxycarboxylic acid receptor 2 (HCAR2)
ATGAATCGGCACCATCTGCAGGATCACTTTCTGGAAATAGACAAGAAGAACTGCTGTGTG
TTCCGAGATGACTTCATTGTCAAGGTGTTGCCGCCGGTGTTGGGGCTGGAGTTTATCTTC
GGGCTTCTGGGCAATGGCCTTGCCCTGTGGATTTTCTGTTTCCACCTCAAGTCCTGGAAA
TCCAGCCGGATTTTCCTGTTCAACCTGGCAGTGGCTGACTTTCTACTGATCATCTGCCTG
CCCTTCCTGATGGACAACTATGTGAGGCGTTGGGACTGGAAGTTTGGGGACATCCCTTGC
CGGCTGATGCTCTTCATGTTGGCTATGAACCGCCAGGGCAGCATCATCTTCCTCACGGTG
GTGGCGGTAGACAGGTATTTCCGGGTGGTCCATCCCCACCACGCCCTGAACAAGATCTCC
AATCGGACAGCAGCCATCATCTCTTGCCTTCTGTGGGGCATCACTATTGGCCTGACAGTC
CACCTCCTGAAGAAGAAGATGCCGATCCAGAATGGCGGTGCAAATTTGTGCAGCAGCTTC
AGCATCTGCCATACCTTCCAGTGGCACGAAGCCATGTTCCTCCTGGAGTTCTTCCTGCCC
CTGGGCATCATCCTGTTCTGCTCAGCCAGAATTATCTGGAGCCTGCGGCAGAGACAAATG
GACCGGCATGCCAAGATCAAGAGAGCCATCACCTTCATCATGGTGGTGGCCATCGTCTTT
GTCATCTGCTTCCTTCCCAGCGTGGTTGTGCGGATCCGCATCTTCTGGCTCCTGCACACT
TCGGGCACGCAGAATTGTGAAGTGTACCGCTCGGTGGACCTGGCGTTCTTTATCACTCTC
AGCTTCACCTACATGAACAGCATGCTGGACCCCGTGGTGTACTACTTCTCCAGCCCATCC
TTTCCCAACTTCTTCTCCACTTTGATCAACCGCTGCCTCCAGAGGAAGATGACAGGTGAG
CCAGATAATAACCGCAGCACGAGCGTCGAGCTCACAGGGGACCCCAACAAAACCAGAGGC
GCTCCAGAGGCGTTAATGGCCAACTCCGGTGAGCCATGGAGCCCCTCTTATCTGGGCCCA
ACCTCTCCTTAA
GenBank Gene IDAY148884
GeneCard IDNot Available
GenAtlas IDGPR109A
HGNC IDHGNC:24827
Chromosome Location12
Locus12q24.31
References
  1. Wise A, Foord SM, Fraser NJ, Barnes AA, Elshourbagy N, Eilert M, Ignar DM, Murdock PR, Steplewski K, Green A, Brown AJ, Dowell SJ, Szekeres PG, Hassall DG, Marshall FH, Wilson S, Pike NB: Molecular identification of high and low affinity receptors for nicotinic acid. J Biol Chem. 2003 Mar 14;278(11):9869-74. Epub 2003 Jan 9. 12522134
  2. Takeda S, Kadowaki S, Haga T, Takaesu H, Mitaku S: Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett. 2002 Jun 5;520(1-3):97-101. 12044878
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  4. Kostylina G, Simon D, Fey MF, Yousefi S, Simon HU: Neutrophil apoptosis mediated by nicotinic acid receptors (GPR109A). Cell Death Differ. 2008 Jan;15(1):134-42. Epub 2007 Oct 12. 17932499
  5. Offermanns S, Colletti SL, Lovenberg TW, Semple G, Wise A, IJzerman AP: International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B). Pharmacol Rev. 2011 Jun;63(2):269-90. doi: 10.1124/pr.110.003301. Epub 2011 Mar 31. 21454438