Leukotriene C4 synthase

Details

Name
Leukotriene C4 synthase
Synonyms
  • 4.4.1.20
  • Leukotriene-C(4) synthase
  • LTC4 synthase
Gene Name
LTC4S
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016318|Leukotriene C4 synthase
MKDEVALLAAVTLLGVLLQAYFSLQVISARRAFRVSPPLTTGPPEFERVYRAQVNCSEYF
PLFLATLWVAGIFFHEGAAALCGLVYLFARLRYFQGYARSAQLRLAPLYASARALWLLVA
LAALGLLAHFLPAALRAALLGRLRTLLPWA
Number of residues
150
Molecular Weight
16566.465
Theoretical pI
10.4
GO Classification
Functions
enzyme activator activity / glutathione binding / glutathione peroxidase activity / glutathione transferase activity / leukotriene-C4 synthase activity / lipid binding
Processes
arachidonic acid metabolic process / cellular response to lipopolysaccharide / cellular response to vitamin A / leukotriene biosynthetic process / leukotriene metabolic process / lipoxin metabolic process / lipoxygenase pathway / oxidation-reduction process / response to axon injury / response to drug / response to inorganic substance / small molecule metabolic process
Components
endoplasmic reticulum / endoplasmic reticulum membrane / integral component of membrane / intracellular membrane-bounded organelle / nuclear envelope / nuclear outer membrane
General Function
Lipid binding
Specific Function
Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.
Pfam Domain Function
Transmembrane Regions
7-27 49-69 74-94 105-124
Cellular Location
Nucleus outer membrane
Gene sequence
>lcl|BSEQ0016319|Leukotriene C4 synthase (LTC4S)
ATGAAGGACGAGGTAGCTCTACTGGCTGCTGTCACCCTCCTGGGAGTCCTGCTGCAAGCC
TACTTCTCCCTGCAGGTGATCTCGGCGCGCAGGGCCTTCCGCGTGTCGCCGCCGCTCACC
ACCGGCCCACCCGAGTTCGAGCGCGTCTACCGAGCCCAGGTGAACTGCAGCGAGTACTTC
CCGCTGTTCCTCGCCACGCTCTGGGTCGCCGGCATCTTCTTTCATGAAGGGGCGGCGGCC
CTGTGCGGCCTGGTCTACCTGTTCGCGCGCCTCCGCTACTTCCAGGGCTACGCGCGCTCC
GCGCAGCTCAGGCTGGCACCGCTGTACGCGAGCGCGCGCGCCCTCTGGCTGCTGGTGGCG
CTGGCTGCGCTCGGCCTGCTCGCCCACTTCCTCCCGGCCGCGCTGCGCGCCGCGCTCCTC
GGACGGCTCCGGACGCTGCTGCCGTGGGCCTGA
Chromosome Location
5
Locus
5q35
External Identifiers
ResourceLink
UniProtKB IDQ16873
UniProtKB Entry NameLTC4S_HUMAN
GenBank Protein ID520485
GenBank Gene IDU09353
GenAtlas IDLTC4S
HGNC IDHGNC:6719
General References
  1. Lam BK, Penrose JF, Freeman GJ, Austen KF: Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7663-7. [PubMed:8052639]
  2. Welsch DJ, Creely DP, Hauser SD, Mathis KJ, Krivi GG, Isakson PC: Molecular cloning and expression of human leukotriene-C4 synthase. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9745-9. [PubMed:7937884]
  3. Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, Austen KF, Lam BK: Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35. J Biol Chem. 1996 May 10;271(19):11356-61. [PubMed:8626689]
  4. Bigby TD, Hodulik CR, Arden KC, Fu L: Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35. Mol Med. 1996 Sep;2(5):637-46. [PubMed:8898379]
  5. 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. [PubMed:15489334]
  6. Nicholson DW, Ali A, Vaillancourt JP, Calaycay JR, Mumford RA, Zamboni RJ, Ford-Hutchinson AW: Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase: a homodimeric glutathione S-transferase composed of 18-kDa subunits. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2015-9. [PubMed:8446623]
  7. Penrose JF, Spector J, Lam BK, Friend DS, Xu K, Jack RM, Austen KF: Purification of human lung leukotriene C4 synthase and preparation of a polyclonal antibody. Am J Respir Crit Care Med. 1995 Jul;152(1):283-9. [PubMed:7599836]
  8. Goppelt-Struebe M: Two step purification of human and murine leukotriene C4 synthase. Biochim Biophys Acta. 1995 May 17;1256(2):257-61. [PubMed:7766706]
  9. Mayatepek E, Flock B: Leukotriene C4-synthesis deficiency: a new inborn error of metabolism linked to a fatal developmental syndrome. Lancet. 1998 Nov 7;352(9139):1514-7. [PubMed:9820300]
  10. Mayatepek E, Zelezny R, Lehmann WD, Hammond JW, Hoffmann GF: Defects in the synthesis of cysteinyl leukotrienes: a new group of inborn errors of metabolism. J Inherit Metab Dis. 2000 Jun;23(4):404-8. [PubMed:10896305]
  11. Christmas P, Weber BM, McKee M, Brown D, Soberman RJ: Membrane localization and topology of leukotriene C4 synthase. J Biol Chem. 2002 Aug 9;277(32):28902-8. Epub 2002 May 21. [PubMed:12023288]
  12. Strid T, Svartz J, Franck N, Hallin E, Ingelsson B, Soderstrom M, Hammarstrom S: Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein. Biochem Biophys Res Commun. 2009 Apr 17;381(4):518-22. doi: 10.1016/j.bbrc.2009.02.074. Epub 2009 Feb 20. [PubMed:19233132]
  13. Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M: Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature. 2007 Aug 2;448(7153):609-12. Epub 2007 Jul 15. [PubMed:17632548]
  14. Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggstrom JZ, Nordlund P: Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature. 2007 Aug 2;448(7153):613-6. Epub 2007 Jul 15. [PubMed:17632546]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00143Glutathioneapproved, investigational, nutraceuticalunknownDetails
DB00972AzelastineapprovedunknowninhibitorDetails