LTC4S_RAT
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 03-AUG-2022, entry version 101.
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 PaxDb; Q925U2; -.
DR GeneID; 114097; -.
DR KEGG; rno:114097; -.
DR UCSC; RGD:620677; rat.
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 OMA; MQVIYAR; -.
DR OrthoDB; 1609516at2759; -.
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 tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
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; -; 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 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
