Free fatty acid receptor 1

Details

Name
Free fatty acid receptor 1
Synonyms
  • G-protein coupled receptor 40
  • GPR40
Gene Name
FFAR1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010479|Free fatty acid receptor 1
MDLPPQLSFGLYVAAFALGFPLNVLAIRGATAHARLRLTPSLVYALNLGCSDLLLTVSLP
LKAVEALASGAWPLPASLCPVFAVAHFFPLYAGGGFLAALSAGRYLGAAFPLGYQAFRRP
CYSWGVCAAIWALVLCHLGLVFGLEAPGGWLDHSNTSLGINTPVNGSPVCLEAWDPASAG
PARFSLSLLLFFLPLAITAFCYVGCLRALARSGLTHRRKLRAAWVAGGALLTLLLCVGPY
NASNVASFLYPNLGGSWRKLGLITGAWSVVLNPLVTGYLGRGPGLKTVCAARTQGGKSQK
Number of residues
300
Molecular Weight
31456.645
Theoretical pI
9.75
GO Classification
Functions
bioactive lipid receptor activity / G-protein coupled receptor activity / guanyl-nucleotide exchange factor activity / lipid binding
Processes
energy reserve metabolic process / G-protein coupled receptor signaling pathway / glucose homeostasis / insulin secretion / positive regulation of calcium ion transport / positive regulation of GTPase activity / positive regulation of insulin secretion / regulation of insulin secretion / response to fatty acid / small molecule metabolic process
Components
integral component of plasma membrane / plasma membrane
General Function
Lipid binding
Specific Function
G-protein coupled receptor for medium and long chain saturated and unsaturated fatty acids that plays an important role in glucose homeostasis. Fatty acid binding increases glucose-stimulated insulin secretion, and may also enhance the secretion of glucagon-like peptide 1 (GLP-1). May also play a role in bone homeostasis; receptor signaling activates pathways that inhibit osteoclast differentiation (By similarity). Ligand binding leads to a conformation change that triggers signaling via G-proteins that activate phospholipase C, leading to an increase of the intracellular calcium concentration. Seems to act through a G(q) and G(i)-mediated pathway.
Pfam Domain Function
Transmembrane Regions
9-31 42-64 80-101 122-142 179-200 224-248 257-279
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0010480|Free fatty acid receptor 1 (FFAR1)
ATGGACCTGCCCCCGCAGCTCTCCTTCGGCCTCTATGTGGCCGCCTTTGCGCTGGGCTTC
CCGCTCAACGTCCTGGCCATCCGAGGCGCGACGGCCCACGCCCGGCTCCGTCTCACCCCT
AGCCTGGTCTACGCCCTGAACCTGGGCTGCTCCGACCTGCTGCTGACAGTCTCTCTGCCC
CTGAAGGCGGTGGAGGCGCTAGCCTCCGGGGCCTGGCCTCTGCCGGCCTCGCTGTGCCCC
GTCTTCGCGGTGGCCCACTTCTTCCCACTCTATGCCGGCGGGGGCTTCCTGGCCGCCCTG
AGTGCAGGCCGCTACCTGGGAGCAGCCTTCCCCTTGGGCTACCAAGCCTTCCGGAGGCCG
TGCTATTCCTGGGGGGTGTGCGCGGCCATCTGGGCCCTCGTCCTGTGTCACCTGGGTCTG
GTCTTTGGGTTGGAGGCTCCAGGAGGCTGGCTGGACCACAGCAACACCTCCCTGGGCATC
AACACACCGGTCAACGGCTCTCCGGTCTGCCTGGAGGCCTGGGACCCGGCCTCTGCCGGC
CCGGCCCGCTTCAGCCTCTCTCTCCTGCTCTTTTTTCTGCCCTTGGCCATCACAGCCTTC
TGCTACGTGGGCTGCCTCCGGGCACTGGCCCGCTCCGGCCTGACGCACAGGCGGAAGCTG
CGGGCCGCCTGGGTGGCCGGCGGGGCCCTCCTCACGCTGCTGCTCTGCGTAGGACCCTAC
AACGCCTCCAACGTGGCCAGCTTCCTGTACCCCAATCTAGGAGGCTCCTGGCGGAAGCTG
GGGCTCATCACGGGTGCCTGGAGTGTGGTGCTTAATCCGCTGGTGACCGGTTACTTGGGA
AGGGGTCCTGGCCTGAAGACAGTGTGTGCGGCAAGAACGCAAGGGGGCAAGTCCCAGAAG
TAA
Chromosome Location
19
Locus
19q13.1
External Identifiers
ResourceLink
UniProtKB IDO14842
UniProtKB Entry NameFFAR1_HUMAN
GenBank Protein ID2612946
GenBank Gene IDAF024687
GenAtlas IDFFAR1
HGNC IDHGNC:4498
General References
  1. Sawzdargo M, George SR, Nguyen T, Xu S, Kolakowski LF, O'Dowd BF: 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. 1997 Oct 20;239(2):543-7. [Article]
  2. 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. [Article]
  3. Briscoe CP, Tadayyon M, Andrews JL, Benson WG, Chambers JK, Eilert MM, Ellis C, Elshourbagy NA, Goetz AS, Minnick DT, Murdock PR, Sauls HR Jr, Shabon U, Spinage LD, Strum JC, Szekeres PG, Tan KB, Way JM, Ignar DM, Wilson S, Muir AI: The orphan G protein-coupled receptor GPR40 is activated by medium and long chain fatty acids. J Biol Chem. 2003 Mar 28;278(13):11303-11. Epub 2002 Dec 19. [Article]
  4. Tomita T, Masuzaki H, Noguchi M, Iwakura H, Fujikura J, Tanaka T, Ebihara K, Kawamura J, Komoto I, Kawaguchi Y, Fujimoto K, Doi R, Shimada Y, Hosoda K, Imamura M, Nakao K: GPR40 gene expression in human pancreas and insulinoma. Biochem Biophys Res Commun. 2005 Dec 30;338(4):1788-90. Epub 2005 Nov 2. [Article]
  5. Sum CS, Tikhonova IG, Neumann S, Engel S, Raaka BM, Costanzi S, Gershengorn MC: Identification of residues important for agonist recognition and activation in GPR40. J Biol Chem. 2007 Oct 5;282(40):29248-55. Epub 2007 Aug 15. [Article]
  6. Sum CS, Tikhonova IG, Costanzi S, Gershengorn MC: Two arginine-glutamate ionic locks near the extracellular surface of FFAR1 gate receptor activation. J Biol Chem. 2009 Feb 6;284(6):3529-36. doi: 10.1074/jbc.M806987200. Epub 2008 Dec 8. [Article]
  7. Kruska N, Reiser G: Phytanic acid and pristanic acid, branched-chain fatty acids associated with Refsum disease and other inherited peroxisomal disorders, mediate intracellular Ca2+ signaling through activation of free fatty acid receptor GPR40. Neurobiol Dis. 2011 Aug;43(2):465-72. doi: 10.1016/j.nbd.2011.04.020. Epub 2011 Apr 30. [Article]
  8. Yabuki C, Komatsu H, Tsujihata Y, Maeda R, Ito R, Matsuda-Nagasumi K, Sakuma K, Miyawaki K, Kikuchi N, Takeuchi K, Habata Y, Mori M: A novel antidiabetic drug, fasiglifam/TAK-875, acts as an ago-allosteric modulator of FFAR1. PLoS One. 2013 Oct 10;8(10):e76280. doi: 10.1371/journal.pone.0076280. eCollection 2013. [Article]
  9. Srivastava A, Yano J, Hirozane Y, Kefala G, Gruswitz F, Snell G, Lane W, Ivetac A, Aertgeerts K, Nguyen J, Jennings A, Okada K: High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Nature. 2014 Sep 4;513(7516):124-7. doi: 10.1038/nature13494. Epub 2014 Jul 20. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00159Icosapentapproved, nutraceuticalyesagonistDetails