LTC4S_HUMAN
ID LTC4S_HUMAN Reviewed; 150 AA.
AC Q16873; Q8N6P0; Q9UC73; Q9UD18;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=Leukotriene C4 synthase;
DE Short=LTC4 synthase;
DE EC=4.4.1.20 {ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393, ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884, ECO:0000269|PubMed:9153254};
DE AltName: Full=Glutathione S-transferase LTC4 {ECO:0000305};
DE EC=2.5.1.- {ECO:0000269|PubMed:27791009};
DE AltName: Full=Leukotriene-C(4) synthase;
DE AltName: Full=Leukotriene-C4 synthase;
GN Name=LTC4S;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-22 AND 35-48.
RC TISSUE=Bone marrow;
RX PubMed=8052639; DOI=10.1073/pnas.91.16.7663;
RA Lam B.K., Penrose J.F., Freeman G.J., Austen K.F.;
RT "Expression cloning of a cDNA for human leukotriene C4 synthase, an
RT integral membrane protein conjugating reduced glutathione to leukotriene
RT A4.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7663-7667(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RX PubMed=7937884; DOI=10.1073/pnas.91.21.9745;
RA Welsch D.J., Creely D.P., Hauser S.D., Mathis K.J., Krivi G.G.,
RA Isakson P.C.;
RT "Molecular cloning and expression of human leukotriene-C4 synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9745-9749(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8626689; DOI=10.1074/jbc.271.19.11356;
RA Penrose J.F., Spector J., Baldasaro M., Xu K., Boyce J., Arm J.P.,
RA Austen K.F., Lam B.K.;
RT "Molecular cloning of the gene for human leukotriene C4 synthase.
RT Organization, nucleotide sequence, and chromosomal localization to 5q35.";
RL J. Biol. Chem. 271:11356-11361(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8898379; DOI=10.1007/bf03401647;
RA Bigby T.D., Hodulik C.R., Arden K.C., Fu L.;
RT "Molecular cloning of the human leukotriene C4 synthase gene and assignment
RT to chromosome 5q35.";
RL Mol. Med. 2:637-646(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-142.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PROTEIN SEQUENCE OF 1-35.
RX PubMed=8446623; DOI=10.1073/pnas.90.5.2015;
RA Nicholson D.W., Ali A., Vaillancourt J.P., Calaycay J.R., Mumford R.A.,
RA Zamboni R.J., Ford-Hutchinson A.W.;
RT "Purification to homogeneity and the N-terminal sequence of human
RT leukotriene C4 synthase: a homodimeric glutathione S-transferase composed
RT of 18-kDa subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:2015-2019(1993).
RN [7]
RP PROTEIN SEQUENCE OF 1-19, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=7599836; DOI=10.1164/ajrccm.152.1.7599836;
RA Penrose J.F., Spector J., Lam B.K., Friend D.S., Xu K., Jack R.M.,
RA Austen K.F.;
RT "Purification of human lung leukotriene C4 synthase and preparation of a
RT polyclonal antibody.";
RL Am. J. Respir. Crit. Care Med. 152:283-289(1995).
RN [8]
RP PROTEIN SEQUENCE OF 1-17.
RC TISSUE=Monocyte;
RX PubMed=7766706; DOI=10.1016/0005-2760(95)00031-7;
RA Goppelt-Struebe M.;
RT "Two step purification of human and murine leukotriene C4 synthase.";
RL Biochim. Biophys. Acta 1256:257-261(1995).
RN [9]
RP CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-51; ASN-55; TYR-59; TYR-93 AND
RP TYR-97, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9153254; DOI=10.1074/jbc.272.21.13923;
RA Lam B.K., Penrose J.F., Xu K., Baldasaro M.H., Austen K.F.;
RT "Site-directed mutagenesis of human leukotriene C4 synthase.";
RL J. Biol. Chem. 272:13923-13928(1997).
RN [10]
RP INVOLVEMENT IN LTC4 SYNTHASE DEFICIENCY.
RX PubMed=9820300; DOI=10.1016/s0140-6736(98)01186-6;
RA Mayatepek E., Flock B.;
RT "Leukotriene C4-synthesis deficiency: a new inborn error of metabolism
RT linked to a fatal developmental syndrome.";
RL Lancet 352:1514-1517(1998).
RN [11]
RP INVOLVEMENT IN LTC4 SYNTHASE DEFICIENCY.
RX PubMed=10896305; DOI=10.1023/a:1005664204956;
RA Mayatepek E., Zelezny R., Lehmann W.D., Hammond J.W., Hoffmann G.F.;
RT "Defects in the synthesis of cysteinyl leukotrienes: a new group of inborn
RT errors of metabolism.";
RL J. Inherit. Metab. Dis. 23:404-408(2000).
RN [12]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=12023288; DOI=10.1074/jbc.m203074200;
RA Christmas P., Weber B.M., McKee M., Brown D., Soberman R.J.;
RT "Membrane localization and topology of leukotriene C4 synthase.";
RL J. Biol. Chem. 277:28902-28908(2002).
RN [13]
RP INTERACTION WITH ALOX5AP AND ALOX5, AND SUBCELLULAR LOCATION.
RX PubMed=19233132; DOI=10.1016/j.bbrc.2009.02.074;
RA Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M.,
RA Hammarstroem S.;
RT "Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase
RT and 5-lipoxygenase activating protein.";
RL Biochem. Biophys. Res. Commun. 381:518-522(2009).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, ACTIVE
RP SITE, TOPOLOGY, AND SUBUNIT.
RX PubMed=17632548; DOI=10.1038/nature05936;
RA Ago H., Kanaoka Y., Irikura D., Lam B.K., Shimamura T., Austen K.F.,
RA Miyano M.;
RT "Crystal structure of a human membrane protein involved in cysteinyl
RT leukotriene biosynthesis.";
RL Nature 448:609-612(2007).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-150 IN COMPLEX WITH GLUTATHIONE,
RP SUBUNIT, AND TOPOLOGY.
RX PubMed=17632546; DOI=10.1038/nature06009;
RA Martinez Molina D., Wetterholm A., Kohl A., McCarthy A.A., Niegowski D.,
RA Ohlson E., Hammarberg T., Eshaghi S., Haeggstroem J.Z., Nordlund P.;
RT "Structural basis for synthesis of inflammatory mediators by human
RT leukotriene C4 synthase.";
RL Nature 448:613-616(2007).
RN [16]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND FUNCTION.
RX PubMed=23409838; DOI=10.1021/bi3014104;
RA Ahmad S., Niegowski D., Wetterholm A., Haeggstroem J.Z., Morgenstern R.,
RA Rinaldo-Matthis A.;
RT "Catalytic characterization of human microsomal glutathione S-transferase
RT 2: identification of rate-limiting steps.";
RL Biochemistry 52:1755-1764(2013).
RN [17]
RP CATALYTIC ACTIVITY, FUNCTION, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=27791009; DOI=10.1073/pnas.1607003113;
RA Dalli J., Vlasakov I., Riley I.R., Rodriguez A.R., Spur B.W., Petasis N.A.,
RA Chiang N., Serhan C.N.;
RT "Maresin conjugates in tissue regeneration biosynthesis enzymes in human
RT macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:12232-12237(2016).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-150 OF VARIANT GLU-36 IN
RP COMPLEX WITH GLUTATHIONE, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-36,
RP MASS SPECTROMETRY, MUTAGENESIS OF SER-36 AND THR-40, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND FUNCTION.
RX PubMed=27365393; DOI=10.1074/jbc.m116.735647;
RA Ahmad S., Ytterberg A.J., Thulasingam M., Tholander F., Bergman T.,
RA Zubarev R., Wetterholm A., Rinaldo-Matthis A., Haeggstroem J.Z.;
RT "Phosphorylation of Leukotriene C4 Synthase at Serine 36 Impairs Catalytic
RT Activity.";
RL J. Biol. Chem. 291:18410-18418(2016).
CC -!- FUNCTION: Catalyzes the conjugation of leukotriene A4 with reduced
CC glutathione (GSH) to form leukotriene C4 with high specificity
CC (PubMed:7937884, PubMed:27791009, PubMed:27365393, PubMed:9153254,
CC PubMed:23409838). Can also catalyze the transfer of a glutathionyl
CC group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid
CC to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive
CC lipid mediator that possess potent anti-inflammatory and proresolving
CC actions (PubMed:27791009). {ECO:0000269|PubMed:23409838,
CC ECO:0000269|PubMed:27365393, ECO:0000269|PubMed:27791009,
CC ECO:0000269|PubMed:7937884, ECO:0000269|PubMed:9153254}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=leukotriene C4 = glutathione + leukotriene A4;
CC Xref=Rhea:RHEA:17617, ChEBI:CHEBI:57463, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:57973; EC=4.4.1.20;
CC Evidence={ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393,
CC ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884,
CC ECO:0000269|PubMed:9153254};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17619;
CC Evidence={ECO:0000269|PubMed:23409838, ECO:0000269|PubMed:27365393,
CC ECO:0000269|PubMed:27791009, ECO:0000269|PubMed:7937884,
CC ECO:0000269|PubMed:9153254};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate +
CC glutathione = (13R)-S-glutathionyl-(14S)-hydroxy-
CC (4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate; Xref=Rhea:RHEA:53508,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:131958, ChEBI:CHEBI:137407;
CC Evidence={ECO:0000269|PubMed:27791009};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53509;
CC Evidence={ECO:0000305|PubMed:27791009};
CC -!- ACTIVITY REGULATION: Inhibited by MK886. {ECO:0000269|PubMed:27791009}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=70 uM for glutathione {ECO:0000269|PubMed:27365393};
CC KM=300 uM for glutathione {ECO:0000269|PubMed:23409838};
CC KM=30 uM for leukotriene A4 {ECO:0000269|PubMed:23409838,
CC ECO:0000269|PubMed:27791009};
CC KM=70.5 uM for 13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic
CC acid {ECO:0000269|PubMed:27791009};
CC KM=76 uM for leukotriene A4 {ECO:0000269|PubMed:27365393};
CC Vmax=70.5 mmol/min/mg enzyme with 13S,14S-
CC epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid as substrate
CC {ECO:0000269|PubMed:27791009};
CC Vmax=6.7 mmol/min/mg enzyme with leukotriene A4 as substrate
CC {ECO:0000269|PubMed:27791009};
CC Note=kcat is 19 sec(-1) with glutathione as substrate
CC (PubMed:27365393). kcat is 105 sec(-1) with leukotriene A4 as
CC substrate (PubMed:27365393). {ECO:0000269|PubMed:27365393};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:9153254};
CC -!- PATHWAY: Lipid metabolism; leukotriene C4 biosynthesis. {ECO:0000305}.
CC -!- SUBUNIT: Homotrimer (PubMed:17632548, PubMed:17632546). Interacts with
CC ALOX5AP and ALOX5 (PubMed:19233132). {ECO:0000269|PubMed:17632546,
CC ECO:0000269|PubMed:17632548, ECO:0000269|PubMed:19233132}.
CC -!- INTERACTION:
CC Q16873; P11912: CD79A; NbExp=3; IntAct=EBI-12241118, EBI-7797864;
CC Q16873; Q96BA8: CREB3L1; NbExp=5; IntAct=EBI-12241118, EBI-6942903;
CC Q16873; Q15125: EBP; NbExp=3; IntAct=EBI-12241118, EBI-3915253;
CC Q16873; O14843: FFAR3; NbExp=3; IntAct=EBI-12241118, EBI-17762181;
CC Q16873; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-12241118, EBI-12175685;
CC Q16873; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12241118, EBI-13345167;
CC Q16873; O15529: GPR42; NbExp=3; IntAct=EBI-12241118, EBI-18076404;
CC Q16873; Q16873: LTC4S; NbExp=4; IntAct=EBI-12241118, EBI-12241118;
CC Q16873; Q8TBB6: SLC7A14; NbExp=3; IntAct=EBI-12241118, EBI-5235586;
CC Q16873; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-12241118, EBI-18178701;
CC -!- SUBCELLULAR LOCATION: Nucleus outer membrane
CC {ECO:0000269|PubMed:12023288}; Multi-pass membrane protein. Endoplasmic
CC reticulum membrane {ECO:0000269|PubMed:12023288,
CC ECO:0000269|PubMed:19233132}; Multi-pass membrane protein. Nucleus
CC membrane {ECO:0000269|PubMed:19233132}; Multi-pass membrane protein.
CC -!- TISSUE SPECIFICITY: Detected in lung, platelets and the myelogenous
CC leukemia cell line KG-1 (at protein level). LTC4S activity is present
CC in eosinophils, basophils, mast cells, certain phagocytic mononuclear
CC cells, endothelial cells, vascular smooth muscle cells and platelets.
CC {ECO:0000269|PubMed:7599836}.
CC -!- PTM: Phosphorylation at Ser-36 by RPS6KB1 inhibits the leukotriene-C4
CC synthase activity. {ECO:0000269|PubMed:27365393}.
CC -!- DISEASE: Note=LTC4 synthase deficiency is associated with a
CC neurometabolic developmental disorder characterized by muscular
CC hypotonia, psychomotor retardation, failure to thrive, and
CC microcephaly. {ECO:0000269|PubMed:10896305,
CC ECO:0000269|PubMed:9820300}.
CC -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR EMBL; U09353; AAA20467.1; -; mRNA.
DR EMBL; U11552; AAA50555.1; -; mRNA.
DR EMBL; U50136; AAC50476.1; -; Genomic_DNA.
DR EMBL; U62025; AAB06723.1; -; Genomic_DNA.
DR EMBL; BC029498; AAH29498.1; -; mRNA.
DR CCDS; CCDS34316.1; -.
DR PIR; I38595; I38595.
DR PIR; JC5398; JC5398.
DR RefSeq; NP_665874.1; NM_145867.1.
DR PDB; 2PNO; X-ray; 3.30 A; A/B/C/D/E/F/G/H/I/J/K/L=1-150.
DR PDB; 2UUH; X-ray; 2.15 A; A=2-150.
DR PDB; 2UUI; X-ray; 2.00 A; A=2-150.
DR PDB; 3B29; X-ray; 3.20 A; A=1-150.
DR PDB; 3HKK; X-ray; 2.90 A; A=2-150.
DR PDB; 3LEO; X-ray; 2.10 A; A=2-150.
DR PDB; 3PCV; X-ray; 1.90 A; A=1-150.
DR PDB; 4BPM; X-ray; 2.08 A; A=131-150.
DR PDB; 4J7T; X-ray; 3.20 A; A=2-150.
DR PDB; 4J7Y; X-ray; 2.90 A; A=2-150.
DR PDB; 4JC7; X-ray; 2.70 A; A=2-150.
DR PDB; 4JCZ; X-ray; 2.75 A; A=2-150.
DR PDB; 4JRZ; X-ray; 2.40 A; A=2-150.
DR PDB; 4WAB; X-ray; 2.70 A; A=130-150.
DR PDB; 5HV9; X-ray; 3.00 A; A=2-150.
DR PDB; 6R7D; X-ray; 2.35 A; A/B/C/D/E/F/G/H/I/J/K/L=2-150.
DR PDBsum; 2PNO; -.
DR PDBsum; 2UUH; -.
DR PDBsum; 2UUI; -.
DR PDBsum; 3B29; -.
DR PDBsum; 3HKK; -.
DR PDBsum; 3LEO; -.
DR PDBsum; 3PCV; -.
DR PDBsum; 4BPM; -.
DR PDBsum; 4J7T; -.
DR PDBsum; 4J7Y; -.
DR PDBsum; 4JC7; -.
DR PDBsum; 4JCZ; -.
DR PDBsum; 4JRZ; -.
DR PDBsum; 4WAB; -.
DR PDBsum; 5HV9; -.
DR PDBsum; 6R7D; -.
DR AlphaFoldDB; Q16873; -.
DR SMR; Q16873; -.
DR BioGRID; 110234; 20.
DR DIP; DIP-48473N; -.
DR IntAct; Q16873; 9.
DR STRING; 9606.ENSP00000292596; -.
DR BindingDB; Q16873; -.
DR ChEMBL; CHEMBL1743183; -.
DR DrugBank; DB00972; Azelastine.
DR DrugBank; DB00143; Glutathione.
DR GuidetoPHARMACOLOGY; 1391; -.
DR SwissLipids; SLP:000001452; -.
DR iPTMnet; Q16873; -.
DR PhosphoSitePlus; Q16873; -.
DR BioMuta; LTC4S; -.
DR DMDM; 2833283; -.
DR jPOST; Q16873; -.
DR MassIVE; Q16873; -.
DR PaxDb; Q16873; -.
DR PeptideAtlas; Q16873; -.
DR PRIDE; Q16873; -.
DR ProteomicsDB; 61112; -.
DR Antibodypedia; 17732; 102 antibodies from 21 providers.
DR DNASU; 4056; -.
DR Ensembl; ENST00000292596.15; ENSP00000292596.10; ENSG00000213316.10.
DR Ensembl; ENST00000639087.2; ENSP00000492334.1; ENSG00000283887.2.
DR GeneID; 4056; -.
DR KEGG; hsa:4056; -.
DR MANE-Select; ENST00000292596.15; ENSP00000292596.10; NM_145867.2; NP_665874.1.
DR UCSC; uc003mko.4; human.
DR CTD; 4056; -.
DR DisGeNET; 4056; -.
DR GeneCards; LTC4S; -.
DR HGNC; HGNC:6719; LTC4S.
DR HPA; ENSG00000213316; Low tissue specificity.
DR MalaCards; LTC4S; -.
DR MIM; 246530; gene.
DR neXtProt; NX_Q16873; -.
DR OpenTargets; ENSG00000213316; -.
DR PharmGKB; PA235; -.
DR VEuPathDB; HostDB:ENSG00000213316; -.
DR eggNOG; ENOG502RZYY; Eukaryota.
DR GeneTree; ENSGT00940000160738; -.
DR HOGENOM; CLU_110291_3_0_1; -.
DR InParanoid; Q16873; -.
DR OMA; MQVIYAR; -.
DR OrthoDB; 1609516at2759; -.
DR PhylomeDB; Q16873; -.
DR TreeFam; TF105328; -.
DR BioCyc; MetaCyc:HS08566-MON; -.
DR BRENDA; 4.4.1.20; 2681.
DR PathwayCommons; Q16873; -.
DR Reactome; R-HSA-2142688; Synthesis of 5-eicosatetraenoic acids.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-HSA-2142700; Synthesis of Lipoxins (LX).
DR Reactome; R-HSA-9026762; Biosynthesis of maresin conjugates in tissue regeneration (MCTR).
DR Reactome; R-HSA-9026766; Biosynthesis of protectin and resolvin conjugates in tissue regeneration (PCTR and RCTR).
DR SABIO-RK; Q16873; -.
DR SignaLink; Q16873; -.
DR SIGNOR; Q16873; -.
DR UniPathway; UPA00879; -.
DR BioGRID-ORCS; 4056; 4 hits in 1070 CRISPR screens.
DR ChiTaRS; LTC4S; human.
DR EvolutionaryTrace; Q16873; -.
DR GeneWiki; Leukotriene_C4_synthase; -.
DR GenomeRNAi; 4056; -.
DR Pharos; Q16873; Tchem.
DR PRO; PR:Q16873; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q16873; protein.
DR Bgee; ENSG00000213316; Expressed in right uterine tube and 95 other tissues.
DR ExpressionAtlas; Q16873; baseline and differential.
DR Genevisible; Q16873; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; TAS:ProtInc.
DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB.
DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB.
DR GO; GO:0005640; C:nuclear outer membrane; IDA:UniProtKB.
DR GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR GO; GO:0004602; F:glutathione peroxidase activity; IBA:GO_Central.
DR GO; GO:0004364; F:glutathione transferase activity; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004464; F:leukotriene-C4 synthase activity; IDA:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IDA:MGI.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IBA:GO_Central.
DR GO; GO:0006691; P:leukotriene metabolic process; IDA:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; IDA:UniProtKB.
DR Gene3D; 1.20.120.550; -; 1.
DR InterPro; IPR001446; 5_LipOase_AP.
DR InterPro; IPR018295; FLAP/GST2/LTC4S_CS.
DR InterPro; IPR023352; MAPEG-like_dom_sf.
DR InterPro; IPR001129; Membr-assoc_MAPEG.
DR Pfam; PF01124; MAPEG; 1.
DR PRINTS; PR00488; 5LPOXGNASEAP.
DR SUPFAM; SSF161084; SSF161084; 1.
DR PROSITE; PS01297; FLAP_GST2_LTC4S; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Endoplasmic reticulum;
KW Leukotriene biosynthesis; Lipid biosynthesis; Lipid metabolism; Lyase;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..150
FT /note="Leukotriene C4 synthase"
FT /id="PRO_0000217748"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TOPO_DOM 28..48
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TRANSMEM 49..69
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TOPO_DOM 70..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TRANSMEM 74..94
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TOPO_DOM 95..104
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TRANSMEM 105..124
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT TOPO_DOM 125..150
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12023288,
FT ECO:0000305|PubMed:17632546, ECO:0000305|PubMed:17632548"
FT ACT_SITE 31
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:17632548"
FT ACT_SITE 104
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:17632548"
FT BINDING 30
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:17632546,
FT ECO:0000269|PubMed:17632548, ECO:0000269|PubMed:27365393"
FT BINDING 51..55
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000305|PubMed:17632548"
FT BINDING 58..59
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000305|PubMed:17632548"
FT BINDING 93..97
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000305|PubMed:17632548"
FT MOD_RES 36
FT /note="Phosphoserine; by RPS6KB1"
FT /evidence="ECO:0000269|PubMed:27365393"
FT VARIANT 142
FT /note="R -> Q (in dbSNP:rs11541078)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_042736"
FT MUTAGEN 36
FT /note="S->E: Reduced leukotriene-C4 synthase activity by
FT nearly 80%."
FT /evidence="ECO:0000269|PubMed:27365393"
FT MUTAGEN 40
FT /note="T->A: Leukotriene-C4 synthaseactivity is reduced by
FT 30%."
FT /evidence="ECO:0000269|PubMed:27365393"
FT MUTAGEN 51
FT /note="R->T,I: Loss of leukotriene-C4 synthase activity."
FT /evidence="ECO:0000269|PubMed:9153254"
FT MUTAGEN 55
FT /note="N->A: Does not affect leukotriene-C4 synthase
FT activity but substantially increased KM for GSH."
FT /evidence="ECO:0000269|PubMed:9153254"
FT MUTAGEN 59
FT /note="Y->F: Does not affect leukotriene-C4 synthase
FT activity but substantially increased KM for GSH."
FT /evidence="ECO:0000269|PubMed:9153254"
FT MUTAGEN 93
FT /note="Y->F: Reduces Leukotriene-C4 synthase activity and
FT increases the optimum for pH-dependent activity."
FT /evidence="ECO:0000269|PubMed:9153254"
FT MUTAGEN 97
FT /note="Y->F: Does not affect leukotriene-C4 synthase
FT activity but substantially increased KM for GSH."
FT /evidence="ECO:0000269|PubMed:9153254"
FT CONFLICT 21
FT /note="Y -> G (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 2..32
FT /evidence="ECO:0007829|PDB:3PCV"
FT HELIX 44..73
FT /evidence="ECO:0007829|PDB:3PCV"
FT HELIX 76..99
FT /evidence="ECO:0007829|PDB:3PCV"
FT HELIX 101..104
FT /evidence="ECO:0007829|PDB:3PCV"
FT HELIX 105..145
FT /evidence="ECO:0007829|PDB:3PCV"
SQ SEQUENCE 150 AA; 16567 MW; 04E269B475063037 CRC64;
MKDEVALLAA VTLLGVLLQA YFSLQVISAR RAFRVSPPLT TGPPEFERVY RAQVNCSEYF
PLFLATLWVA GIFFHEGAAA LCGLVYLFAR LRYFQGYARS AQLRLAPLYA SARALWLLVA
LAALGLLAHF LPAALRAALL GRLRTLLPWA
