Leukotriene C4 synthase

Leukotriene C4 synthase
Rendering based on PDB 2PNO​.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2PNO​, 2UUH​, 2UUI​, 3B29​, 3HKK​, 3LEO​, 3PCV​, 4J7T​, 4J7Y​, 4JC7​, 4JCZ​, 4JRZ​
Identifiers
Symbols	LTC4S ; MGC33147
External IDs	OMIM: 246530 MGI: 107498 HomoloGene: 7406 ChEMBL: 1743183 GeneCards: LTC4S Gene
EC number	4.4.1.20
Gene ontology Molecular function • glutathione transferase activity • leukotriene-C4 synthase activity • glutathione peroxidase activity • protein binding • enzyme activator activity • lipid binding • glutathione binding • protein heterodimerization activity Cellular component • nuclear envelope • nuclear outer membrane • endoplasmic reticulum • endoplasmic reticulum membrane • integral component of membrane • intracellular membrane-bounded organelle Biological process • leukotriene metabolic process • response to inorganic substance • arachidonic acid metabolic process • leukotriene biosynthetic process • lipoxygenase pathway • response to drug • positive regulation of catalytic activity • small molecule metabolic process • response to axon injury • oxidation-reduction process • cellular response to lipopolysaccharide • cellular response to vitamin A • lipoxin metabolic process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4056	17001
Ensembl	ENSG00000213316	ENSMUSG00000020377
UniProt	Q16873	Q60860
RefSeq (mRNA)	NM_145867	NM_008521
RefSeq (protein)	NP_665874	NP_032547
Location (UCSC)	Chr 5: 179.79 – 179.8 Mb	Chr 11: 50.24 – 50.24 Mb
PubMed search

Leukotriene C4 synthase is an enzyme that in humans is encoded by the LTC4S gene.^[1][2]

The protein encoded by this gene, LTC4S (or glutathione S-transferase II) is an enzyme that converts leukotriene A4 and glutathione to create leukotriene C4. This is a member of MAPEG family of transmembrane proteins. A trimer of Leukotriene C4 synthase is localized on the outer nuclear membrane and endoplasmic reticulum, where it forms a complex with 5-Lipoxygenase-activating protein. This protein is remotely related to microsomal glutathione S-transferase.

Function

The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family includes a number of human proteins, several of which are involved the production of leukotrienes. This gene encodes an enzyme that catalyzes the first step in the biosynthesis of cysteinyl leukotrienes, potent biological compounds derived from arachidonic acid. Leukotrienes have been implicated as mediators of anaphylaxis and inflammatory conditions such as human bronchial asthma. This protein localizes to the nuclear envelope and adjacent endoplasmic reticulum.^[2]

Eicosanoid synthesis. (Leukotrienes at right.)

References

1. Lam BK, Penrose JF, Freeman GJ, Austen KF (Sep 1994). "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 91 (16): 7663–7. doi:10.1073/pnas.91.16.7663. PMC 44462. PMID 8052639.
2. "Entrez Gene: LTC4S leukotriene C4 synthase".

Further reading

• Penrose JF (1999). "LTC4 synthase. Enzymology, biochemistry, and molecular characterization". Clinical reviews in allergy & immunology 17 (1–2): 133–52. doi:10.1007/BF02737601. PMID 10436863.
• Penrose JF, Austen KF (2000). "The biochemical, molecular, and genomic aspects of leukotriene C4 synthase". Proc. Assoc. Am. Physicians 111 (6): 537–46. doi:10.1046/j.1525-1381.1999.99212.x. PMID 10591082.
• Jakobsson PJ, Morgenstern R, Mancini J, et al. (2000). "Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily". Am. J. Respir. Crit. Care Med. 161 (2 Pt 2): S20–4. doi:10.1164/ajrccm.161.supplement_1.ltta-5. PMID 10673221.
• Bigby TD (2000). "The leukotriene C(4) synthase gene and asthma". Am. J. Respir. Cell Mol. Biol. 23 (3): 273–6. doi:10.1165/ajrcmb.23.3.f197. PMID 10970815.
• Penrose JF, Gagnon L, Goppelt-Struebe M, et al. (1993). "Purification of human leukotriene C4 synthase". Proc. Natl. Acad. Sci. U.S.A. 89 (23): 11603–6. doi:10.1073/pnas.89.23.11603. PMC 50601. PMID 1454853.
• Nicholson DW, Ali A, Klemba MW, et al. (1992). "Human leukotriene C4 synthase expression in dimethyl sulfoxide-differentiated U937 cells". J. Biol. Chem. 267 (25): 17849–57. PMID 1517222.
• Penrose JF, Spector J, Lam BK, et al. (1995). "Purification of human lung leukotriene C4 synthase and preparation of a polyclonal antibody". Am. J. Respir. Crit. Care Med. 152 (1): 283–9. doi:10.1164/ajrccm.152.1.7599836. PMID 7599836.
• Söderström M, Morgenstern R, Hammarström S (1995). "Protein-protein interaction affinity chromatography of leukotriene C4 synthase". Protein Expr. Purif. 6 (3): 352–6. doi:10.1006/prep.1995.1046. PMID 7663172.
• Welsch DJ, Creely DP, Hauser SD, et al. (1994). "Molecular cloning and expression of human leukotriene-C4 synthase". Proc. Natl. Acad. Sci. U.S.A. 91 (21): 9745–9. doi:10.1073/pnas.91.21.9745. PMC 44893. PMID 7937884.
• Nicholson DW, Ali A, Vaillancourt JP, et al. (1993). "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. 90 (5): 2015–9. doi:10.1073/pnas.90.5.2015. PMC 46011. PMID 8446623.
• Penrose JF, Spector J, Baldasaro M, et al. (1996). "Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35". J. Biol. Chem. 271 (19): 11356–61. doi:10.1074/jbc.271.19.11356. PMID 8626689.
• Bigby TD, Hodulik CR, Arden KC, Fu L (1997). "Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35". Mol. Med. 2 (5): 637–46. PMC 2230200. PMID 8898379.
• Scoggan KA, Jakobsson PJ, Ford-Hutchinson AW (1997). "Production of leukotriene C4 in different human tissues is attributable to distinct membrane bound biosynthetic enzymes". J. Biol. Chem. 272 (15): 10182–7. doi:10.1074/jbc.272.15.10182. PMID 9092565.
• Sala A, Folco G, Henson PM, Murphy RC (1997). "Pharmacological modulation of human platelet leukotriene C4-synthase". Biochem. Pharmacol. 53 (6): 905–8. doi:10.1016/S0006-2952(96)00819-2. PMID 9113110.
• Spanbroek R, Stark HJ, Janssen-Timmen U, et al. (1998). "5-Lipoxygenase expression in Langerhans cells of normal human epidermis". Proc. Natl. Acad. Sci. U.S.A. 95 (2): 663–8. doi:10.1073/pnas.95.2.663. PMC 18477. PMID 9435249.

External links

• leukotriene-C4 synthase at the US National Library of Medicine Medical Subject Headings (MeSH)
• UMich Orientation of Proteins in Membranes families/superfamily-199 - Eicosanoid and Glutathione metabolism protein family (MAPEG)