LTC4S_BOVIN
ID LTC4S_BOVIN Reviewed; 150 AA.
AC Q2NKS0;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 99.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Hypothalamus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 25-150.
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI11677.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; BC111676; AAI11677.1; ALT_SEQ; mRNA.
DR EMBL; DN547943; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001039563.2; NM_001046098.2.
DR AlphaFoldDB; Q2NKS0; -.
DR SMR; Q2NKS0; -.
DR STRING; 9913.ENSBTAP00000012836; -.
DR PaxDb; Q2NKS0; -.
DR Ensembl; ENSBTAT00000012836; ENSBTAP00000012836; ENSBTAG00000009737.
DR GeneID; 511749; -.
DR KEGG; bta:511749; -.
DR CTD; 4056; -.
DR VEuPathDB; HostDB:ENSBTAG00000009737; -.
DR VGNC; VGNC:31076; LTC4S.
DR eggNOG; ENOG502RZYY; Eukaryota.
DR GeneTree; ENSGT00940000160738; -.
DR HOGENOM; CLU_110291_3_0_1; -.
DR InParanoid; Q2NKS0; -.
DR OMA; MQVIYAR; -.
DR OrthoDB; 1645250at2759; -.
DR TreeFam; TF105328; -.
DR Reactome; R-BTA-9026762; Biosynthesis of maresin conjugates in tissue regeneration (MCTR).
DR Reactome; R-BTA-9026766; Biosynthesis of protectin and resolvin conjugates in tissue regeneration (PCTR and RCTR).
DR UniPathway; UPA00879; -.
DR Proteomes; UP000009136; Chromosome 7.
DR Bgee; ENSBTAG00000009737; Expressed in diaphragm and 98 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
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:0005635; C:nuclear envelope; IBA:GO_Central.
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: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; IEA:Ensembl.
DR GO; GO:0004464; F:leukotriene-C4 synthase activity; ISS:UniProtKB.
DR GO; GO:0008289; F:lipid binding; IEA:Ensembl.
DR GO; GO:0019370; P:leukotriene biosynthetic process; IBA:GO_Central.
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; 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.
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_0000378086"
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; 16701 MW; DF46ADF41C79BA97 CRC64;
MKDEVALLAS VTLLGVLLQA YFSLQVISAR RAFRVSPPLT TGPPEFERIY RAQVNCSEYF
PLFLAMLWVA GIFFHEGAAA LCGLVYLFAR LRYFQGYARS AQQRLAPLYA SARALWLLVA
LAALGLLAHF LPAELRAALL GQLRKLLLRS
