ID   LTC4S_RAT               Reviewed;         150 AA.
AC   Q925U2; G3V6E6;
DT   16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT   17-JUN-2020, sequence version 3.
DT   24-JAN-2024, entry version 107.
DE   RecName: Full=Leukotriene C4 synthase;
DE            Short=LTC4 synthase;
DE            EC=4.4.1.20 {ECO:0000269|PubMed:12445492};
DE   AltName: Full=Glutathione S-transferase LTC4;
DE            EC=2.5.1.- {ECO:0000250|UniProtKB:Q16873};
DE   AltName: Full=Leukotriene-C(4) synthase;
GN   Name=Ltc4s;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12445492; DOI=10.1054/plef.2002.0436;
RA   Abe M., Shibata K., Saruwatar S., Soeda S., Shimeno H., Katsuragi T.;
RT   "cDNA cloning and expression of rat leukotriene C(4) synthase: elevated
RT   expression in rat basophilic leukemia-1 cells after treatment with retinoic
RT   acid.";
RL   Prostaglandins Leukot. Essent. Fatty Acids 67:319-326(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Catalyzes the conjugation of leukotriene A4 with reduced
CC       glutathione (GSH) to form leukotriene C4 with high specificity
CC       (PubMed:12445492). 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 (By similarity). {ECO:0000250|UniProtKB:Q16873,
CC       ECO:0000269|PubMed:12445492}.
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:12445492};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:17619;
CC         Evidence={ECO:0000250|UniProtKB:Q16873};
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:0000250|UniProtKB:Q16873};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53509;
CC         Evidence={ECO:0000250|UniProtKB:Q16873};
CC   -!- ACTIVITY REGULATION: Inhibited by MK886.
CC       {ECO:0000250|UniProtKB:Q16873}.
CC   -!- PATHWAY: Lipid metabolism; leukotriene C4 biosynthesis.
CC       {ECO:0000250|UniProtKB:Q16873}.
CC   -!- SUBUNIT: Homotrimer. Interacts with ALOX5AP and ALOX5.
CC       {ECO:0000250|UniProtKB:Q16873}.
CC   -!- SUBCELLULAR LOCATION: Nucleus outer membrane
CC       {ECO:0000250|UniProtKB:Q16873}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q16873}. Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q16873}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q16873}. Nucleus membrane
CC       {ECO:0000250|UniProtKB:Q16873}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q16873}.
CC   -!- INDUCTION: Up-regulated by all-trans retinoic acid.
CC       {ECO:0000269|PubMed:12445492}.
CC   -!- PTM: Phosphorylation at Ser-36 by RPS6KB1 inhibits the leukotriene-C4
CC       synthase activity. {ECO:0000250|UniProtKB:Q16873}.
CC   -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR   EMBL; AB048790; BAB58882.2; -; mRNA.
DR   EMBL; AABR07029584; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH473948; EDM04261.1; -; Genomic_DNA.
DR   RefSeq; NP_446091.2; NM_053639.2.
DR   RefSeq; XP_008765877.1; XM_008767655.2.
DR   AlphaFoldDB; Q925U2; -.
DR   SMR; Q925U2; -.
DR   STRING; 10116.ENSRNOP00000004359; -.
DR   ChEMBL; CHEMBL2172; -.
DR   PhosphoSitePlus; Q925U2; -.
DR   PaxDb; 10116-ENSRNOP00000004359; -.
DR   GeneID; 114097; -.
DR   KEGG; rno:114097; -.
DR   UCSC; RGD:620677; rat.
DR   AGR; RGD:620677; -.
DR   CTD; 4056; -.
DR   RGD; 620677; Ltc4s.
DR   VEuPathDB; HostDB:ENSRNOG00000003244; -.
DR   eggNOG; ENOG502RZYY; Eukaryota.
DR   HOGENOM; CLU_110291_3_0_1; -.
DR   InParanoid; Q925U2; -.
DR   OrthoDB; 5009707at2759; -.
DR   PhylomeDB; Q925U2; -.
DR   TreeFam; TF105328; -.
DR   BRENDA; 4.4.1.20; 5301.
DR   Reactome; R-RNO-2142688; Synthesis of 5-eicosatetraenoic acids.
DR   Reactome; R-RNO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR   Reactome; R-RNO-2142700; Synthesis of Lipoxins (LX).
DR   Reactome; R-RNO-9026762; Biosynthesis of maresin conjugates in tissue regeneration (MCTR).
DR   Reactome; R-RNO-9026766; Biosynthesis of protectin and resolvin conjugates in tissue regeneration (PCTR and RCTR).
DR   UniPathway; UPA00879; -.
DR   PRO; PR:Q925U2; -.
DR   Proteomes; UP000002494; Chromosome 10.
DR   Proteomes; UP000234681; Chromosome 10.
DR   Bgee; ENSRNOG00000003244; Expressed in ovary and 19 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR   GO; GO:0005635; C:nuclear envelope; ISO:RGD.
DR   GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB.
DR   GO; GO:0005640; C:nuclear outer membrane; ISS:UniProtKB.
DR   GO; GO:0008047; F:enzyme activator activity; IEA:InterPro.
DR   GO; GO:0043295; F:glutathione binding; IDA:RGD.
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; ISO:RGD.
DR   GO; GO:0004464; F:leukotriene-C4 synthase activity; IDA:RGD.
DR   GO; GO:0008289; F:lipid binding; ISO:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR   GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0071299; P:cellular response to vitamin A; IEP:RGD.
DR   GO; GO:0019370; P:leukotriene biosynthetic process; IDA:RGD.
DR   GO; GO:0006691; P:leukotriene metabolic process; ISO:RGD.
DR   GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0048678; P:response to axon injury; IEP:RGD.
DR   GO; GO:0010035; P:response to inorganic substance; IEP:RGD.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR   Gene3D; 1.20.120.550; Membrane associated eicosanoid/glutathione metabolism-like domain; 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   PANTHER; PTHR10250:SF4; LEUKOTRIENE C4 SYNTHASE; 1.
DR   PANTHER; PTHR10250; MICROSOMAL GLUTATHIONE S-TRANSFERASE; 1.
DR   Pfam; PF01124; MAPEG; 1.
DR   PRINTS; PR00488; 5LPOXGNASEAP.
DR   SUPFAM; SSF161084; MAPEG domain-like; 1.
DR   PROSITE; PS01297; FLAP_GST2_LTC4S; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Leukotriene biosynthesis; Lyase; Membrane; Nucleus;
KW   Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW   Transmembrane helix.
FT   CHAIN           1..150
FT                   /note="Leukotriene C4 synthase"
FT                   /id="PRO_0000378088"
FT   TOPO_DOM        1..6
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TRANSMEM        7..27
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TOPO_DOM        28..48
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TRANSMEM        49..69
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TOPO_DOM        70..73
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TRANSMEM        74..94
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TOPO_DOM        95..104
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TRANSMEM        105..124
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   TOPO_DOM        125..150
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   ACT_SITE        31
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   ACT_SITE        104
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   BINDING         30
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   BINDING         51..55
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   BINDING         58..59
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   BINDING         93..97
FT                   /ligand="glutathione"
FT                   /ligand_id="ChEBI:CHEBI:57925"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   MOD_RES         36
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q16873"
FT   CONFLICT        14
FT                   /note="L -> V (in Ref. 1; BAB58882)"
SQ   SEQUENCE   150 AA;  16850 MW;  706DF7B1F4B141BE CRC64;
     MKEETALLAT VTLLGVLLQA YFSLQVISAR RTFHVSPPLT SGPPEFERVF RAQVNCSEYF
     PLFLATLWVA GIFFHEGAAA LCGLFYLFAR LRYFQGYARS AQHRLDPLYA SARALWLLVA
     MAALGLLVHF LPGTLRAALF RWLQVLLPMA
//