LTC4S_CAVPO
ID LTC4S_CAVPO Reviewed; 150 AA.
AC A6XA80;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Leukotriene C4 synthase;
DE Short=LTC4 synthase;
DE EC=4.4.1.20 {ECO:0000250|UniProtKB:Q16873};
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 Cavia porcellus (Guinea pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Hystricomorpha; Caviidae;
OC Cavia.
OX NCBI_TaxID=10141;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Hartley; TISSUE=Lung;
RA Irikura D., Lam B.K., Austen K.F., Kanaoka Y.;
RT "Molecular cloning, expression, and characterization of guinea pig
RT leukotriene C4 synthase.";
RL Submitted (JUN-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. Can
CC also catalyzes the transfer of a glutathionyl group from glutathione
CC (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin
CC conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator
CC that possess potent anti-inflammatory and proresolving actions.
CC {ECO:0000250|UniProtKB:Q16873}.
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:0000250|UniProtKB:Q16873};
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 -!- 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; DQ090886; AAZ41359.1; -; mRNA.
DR AlphaFoldDB; A6XA80; -.
DR SMR; A6XA80; -.
DR STRING; 10141.ENSCPOP00000016273; -.
DR ChEMBL; CHEMBL1909043; -.
DR DrugCentral; A6XA80; -.
DR eggNOG; ENOG502RZYY; Eukaryota.
DR HOGENOM; CLU_110291_3_2_1; -.
DR InParanoid; A6XA80; -.
DR UniPathway; UPA00879; -.
DR Proteomes; UP000005447; Unassembled WGS sequence.
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: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:0004464; F:leukotriene-C4 synthase activity; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006691; P:leukotriene metabolic process; ISS:UniProtKB.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; ISS: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 2: Evidence at transcript 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_0000378087"
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"
SQ SEQUENCE 150 AA; 16748 MW; 9E0DF0154E56FC9F CRC64;
MKDEVALLAT VTLLGVLLQA YFSLQVIRAR RAHRVSPPLT TGPPEFERVY RAQVNCSEYF
PLFLATLWVA GVYFHEGAAA LCGLVYLFTR LRYFWGYARS AQLRLAPLYA SARALWLLLA
LATLGLLAHF LPAAARAALL RLLRALLRTA
