UniProtKB - Q16873 (LTC4S_HUMAN)
Leukotriene C4 synthase
LTC4S
Functioni
Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4 with high specificity (PubMed:7937884, PubMed:27791009, PubMed:27365393, PubMed:9153254, PubMed:23409838).
Can also catalyzes the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions (PubMed:27791009).
5 PublicationsCatalytic activityi
- EC:4.4.1.205 PublicationsThis reaction proceeds in the backward5 Publications direction.
- (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate + glutathione = (13R)-S-glutathionyl-(14S)-hydroxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate1 PublicationThis reaction proceeds in the forward1 Publication direction.
Activity regulationi
Kineticsi
- KM=70 µM for glutathione1 Publication
- KM=300 µM for glutathione1 Publication
- KM=30 µM for leukotriene A42 Publications
- KM=70.5 µM for 13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid1 Publication
- KM=76 µM for leukotriene A41 Publication
- Vmax=70.5 mmol/min/mg enzyme with 13S,14S-epoxy- 4Z,7Z,9E,11E,16Z,19Z-docosahexaenoic acid as substrate1 Publication
- Vmax=6.7 mmol/min/mg enzyme with leukotriene A4 as substrate1 Publication
pH dependencei
: leukotriene C4 biosynthesis Pathwayi
This protein is involved in the pathway leukotriene C4 biosynthesis, which is part of Lipid metabolism.CuratedView all proteins of this organism that are known to be involved in the pathway leukotriene C4 biosynthesis and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 30 | Glutathione3 Publications | 1 | |
Active sitei | 31 | Proton donor1 Publication | 1 | |
Active sitei | 104 | Proton acceptor1 Publication | 1 |
GO - Molecular functioni
- enzyme activator activity Source: InterPro
- glutathione peroxidase activity Source: GO_Central
- glutathione transferase activity Source: GO_Central
- identical protein binding Source: IntAct
- leukotriene-C4 synthase activity Source: UniProtKB
- lipid binding Source: MGI
GO - Biological processi
- leukotriene biosynthetic process Source: GO_Central
- leukotriene metabolic process Source: UniProtKB
- long-chain fatty acid biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Lyase, Transferase |
Biological process | Leukotriene biosynthesis, Lipid biosynthesis, Lipid metabolism |
Enzyme and pathway databases
BRENDAi | 4.4.1.20, 2681 |
PathwayCommonsi | Q16873 |
Reactomei | R-HSA-2142688, Synthesis of 5-eicosatetraenoic acids R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-2142700, Synthesis of Lipoxins (LX) R-HSA-9026762, Biosynthesis of maresin conjugates in tissue regeneration (MCTR) R-HSA-9026766, Biosynthesis of protectin and resolvin conjugates in tissue regeneration (PCTR and RCTR) |
SABIO-RKi | Q16873 |
SignaLinki | Q16873 |
SIGNORi | Q16873 |
UniPathwayi | UPA00879 |
Chemistry databases
SwissLipidsi | SLP:000001452 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:LTC4S |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6719, LTC4S |
MIMi | 246530, gene |
neXtProti | NX_Q16873 |
VEuPathDBi | HostDB:ENSG00000213316 |
Subcellular locationi
Nucleus
- Nucleus outer membrane 1 Publication; Multi-pass membrane protein
- Nucleus membrane 1 Publication; Multi-pass membrane protein
Endoplasmic reticulum
- Endoplasmic reticulum membrane 2 Publications; Multi-pass membrane protein
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: UniProtKB
Nucleus
- nuclear envelope Source: UniProtKB
- nuclear membrane Source: UniProtKB
- nuclear outer membrane Source: UniProtKB
Other locations
- integral component of membrane Source: ProtInc
- intracellular membrane-bounded organelle Source: ProtInc
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 6 | Cytoplasmic3 Publications | 6 | |
Transmembranei | 7 – 27 | Helical3 PublicationsAdd BLAST | 21 | |
Topological domaini | 28 – 48 | Lumenal3 PublicationsAdd BLAST | 21 | |
Transmembranei | 49 – 69 | Helical3 PublicationsAdd BLAST | 21 | |
Topological domaini | 70 – 73 | Cytoplasmic3 Publications | 4 | |
Transmembranei | 74 – 94 | Helical3 PublicationsAdd BLAST | 21 | |
Topological domaini | 95 – 104 | Lumenal3 Publications | 10 | |
Transmembranei | 105 – 124 | Helical3 PublicationsAdd BLAST | 20 | |
Topological domaini | 125 – 150 | Cytoplasmic3 PublicationsAdd BLAST | 26 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 36 | S → E: Reduced leukotriene-C4 synthase activity by nearly 80%. 1 Publication | 1 | |
Mutagenesisi | 40 | T → A: Leukotriene-C4 synthaseactivity is reduced by 30%. 1 Publication | 1 | |
Mutagenesisi | 51 | R → T or I: Loss of leukotriene-C4 synthase activity. 1 Publication | 1 | |
Mutagenesisi | 55 | N → A: Does not affect leukotriene-C4 synthase activity but substantially increased KM for GSH. 1 Publication | 1 | |
Mutagenesisi | 59 | Y → F: Does not affect leukotriene-C4 synthase activity but substantially increased KM for GSH. 1 Publication | 1 | |
Mutagenesisi | 93 | Y → F: Reduces Leukotriene-C4 synthase activity and increases the optimum for pH-dependent activity. 1 Publication | 1 | |
Mutagenesisi | 97 | Y → F: Does not affect leukotriene-C4 synthase activity but substantially increased KM for GSH. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4056 |
MalaCardsi | LTC4S |
OpenTargetsi | ENSG00000213316 |
PharmGKBi | PA235 |
Miscellaneous databases
Pharosi | Q16873, Tchem |
Chemistry databases
ChEMBLi | CHEMBL1743183 |
DrugBanki | DB00972, Azelastine DB00143, Glutathione |
GuidetoPHARMACOLOGYi | 1391 |
Genetic variation databases
BioMutai | LTC4S |
DMDMi | 2833283 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000217748 | 1 – 150 | Leukotriene C4 synthaseAdd BLAST | 150 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 36 | Phosphoserine; by RPS6KB11 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q16873 |
MassIVEi | Q16873 |
PaxDbi | Q16873 |
PeptideAtlasi | Q16873 |
PRIDEi | Q16873 |
ProteomicsDBi | 61112 |
PTM databases
iPTMneti | Q16873 |
PhosphoSitePlusi | Q16873 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000213316, Expressed in testis and 109 other tissues |
ExpressionAtlasi | Q16873, baseline and differential |
Genevisiblei | Q16873, HS |
Organism-specific databases
HPAi | ENSG00000213316, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q16873
GO - Molecular functioni
- identical protein binding Source: IntAct
Protein-protein interaction databases
BioGRIDi | 110234, 20 interactors |
DIPi | DIP-48473N |
IntActi | Q16873, 9 interactors |
STRINGi | 9606.ENSP00000292596 |
Chemistry databases
BindingDBi | Q16873 |
Miscellaneous databases
RNActi | Q16873, protein |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | Q16873 |
SMRi | Q16873 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16873 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 51 – 55 | Glutathione binding1 Publication | 5 | |
Regioni | 58 – 59 | Glutathione binding1 Publication | 2 | |
Regioni | 93 – 97 | Glutathione binding1 Publication | 5 |
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | ENOG502RZYY, Eukaryota |
GeneTreei | ENSGT00940000160738 |
HOGENOMi | CLU_110291_3_0_1 |
InParanoidi | Q16873 |
OMAi | MQVIYAR |
OrthoDBi | 1609516at2759 |
PhylomeDBi | Q16873 |
TreeFami | TF105328 |
Family and domain databases
Gene3Di | 1.20.120.550, 1 hit |
InterProi | View protein in InterPro IPR001446, 5_LipOase_AP IPR018295, FLAP/GST2/LTC4S_CS IPR023352, MAPEG-like_dom_sf IPR001129, Membr-assoc_MAPEG |
Pfami | View protein in Pfam PF01124, MAPEG, 1 hit |
PRINTSi | PR00488, 5LPOXGNASEAP |
SUPFAMi | SSF161084, SSF161084, 1 hit |
PROSITEi | View protein in PROSITE PS01297, FLAP_GST2_LTC4S, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MKDEVALLAA VTLLGVLLQA YFSLQVISAR RAFRVSPPLT TGPPEFERVY
60 70 80 90 100
RAQVNCSEYF PLFLATLWVA GIFFHEGAAA LCGLVYLFAR LRYFQGYARS
110 120 130 140 150
AQLRLAPLYA SARALWLLVA LAALGLLAHF LPAALRAALL GRLRTLLPWA
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A286YF10 | A0A286YF10_HUMAN | Leukotriene C4 synthase | LTC4S | 104 | Annotation score: | ||
B5MCC3 | B5MCC3_HUMAN | Leukotriene C4 synthase | LTC4S | 93 | Annotation score: | ||
D6RJA1 | D6RJA1_HUMAN | Leukotriene C4 synthase | LTC4S | 69 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 21 | Y → G AA sequence (PubMed:8446623).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_042736 | 142 | R → Q1 PublicationCorresponds to variant dbSNP:rs11541078Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U09353 mRNA Translation: AAA20467.1 U11552 mRNA Translation: AAA50555.1 U50136 Genomic DNA Translation: AAC50476.1 U62025 Genomic DNA Translation: AAB06723.1 BC029498 mRNA Translation: AAH29498.1 |
CCDSi | CCDS34316.1 |
PIRi | I38595 JC5398 |
RefSeqi | NP_665874.1, NM_145867.1 |
Genome annotation databases
Ensembli | ENST00000292596.15; ENSP00000292596.10; ENSG00000213316.10 ENST00000639087.2; ENSP00000492334.1; ENSG00000283887.2 |
GeneIDi | 4056 |
KEGGi | hsa:4056 |
MANE-Selecti | ENST00000292596.15; ENSP00000292596.10; NM_145867.2; NP_665874.1 |
UCSCi | uc003mko.4, human |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U09353 mRNA Translation: AAA20467.1 U11552 mRNA Translation: AAA50555.1 U50136 Genomic DNA Translation: AAC50476.1 U62025 Genomic DNA Translation: AAB06723.1 BC029498 mRNA Translation: AAH29498.1 |
CCDSi | CCDS34316.1 |
PIRi | I38595 JC5398 |
RefSeqi | NP_665874.1, NM_145867.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2PNO | X-ray | 3.30 | A/B/C/D/E/F/G/H/I/J/K/L | 1-150 | [»] | |
2UUH | X-ray | 2.15 | A | 2-150 | [»] | |
2UUI | X-ray | 2.00 | A | 2-150 | [»] | |
3B29 | X-ray | 3.20 | A | 1-150 | [»] | |
3HKK | X-ray | 2.90 | A | 2-150 | [»] | |
3LEO | X-ray | 2.10 | A | 2-150 | [»] | |
3PCV | X-ray | 1.90 | A | 1-150 | [»] | |
4BPM | X-ray | 2.08 | A | 131-150 | [»] | |
4J7T | X-ray | 3.20 | A | 2-150 | [»] | |
4J7Y | X-ray | 2.90 | A | 2-150 | [»] | |
4JC7 | X-ray | 2.70 | A | 2-150 | [»] | |
4JCZ | X-ray | 2.75 | A | 2-150 | [»] | |
4JRZ | X-ray | 2.40 | A | 2-150 | [»] | |
4WAB | X-ray | 2.70 | A | 130-150 | [»] | |
5HV9 | X-ray | 3.00 | A | 2-150 | [»] | |
6R7D | X-ray | 2.35 | A/B/C/D/E/F/G/H/I/J/K/L | 2-150 | [»] | |
AlphaFoldDBi | Q16873 | |||||
SMRi | Q16873 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110234, 20 interactors |
DIPi | DIP-48473N |
IntActi | Q16873, 9 interactors |
STRINGi | 9606.ENSP00000292596 |
Chemistry databases
BindingDBi | Q16873 |
ChEMBLi | CHEMBL1743183 |
DrugBanki | DB00972, Azelastine DB00143, Glutathione |
GuidetoPHARMACOLOGYi | 1391 |
SwissLipidsi | SLP:000001452 |
PTM databases
iPTMneti | Q16873 |
PhosphoSitePlusi | Q16873 |
Genetic variation databases
BioMutai | LTC4S |
DMDMi | 2833283 |
Proteomic databases
jPOSTi | Q16873 |
MassIVEi | Q16873 |
PaxDbi | Q16873 |
PeptideAtlasi | Q16873 |
PRIDEi | Q16873 |
ProteomicsDBi | 61112 |
Protocols and materials databases
Antibodypediai | 17732, 106 antibodies from 22 providers |
DNASUi | 4056 |
Genome annotation databases
Ensembli | ENST00000292596.15; ENSP00000292596.10; ENSG00000213316.10 ENST00000639087.2; ENSP00000492334.1; ENSG00000283887.2 |
GeneIDi | 4056 |
KEGGi | hsa:4056 |
MANE-Selecti | ENST00000292596.15; ENSP00000292596.10; NM_145867.2; NP_665874.1 |
UCSCi | uc003mko.4, human |
Organism-specific databases
CTDi | 4056 |
DisGeNETi | 4056 |
GeneCardsi | LTC4S |
HGNCi | HGNC:6719, LTC4S |
HPAi | ENSG00000213316, Low tissue specificity |
MalaCardsi | LTC4S |
MIMi | 246530, gene |
neXtProti | NX_Q16873 |
OpenTargetsi | ENSG00000213316 |
PharmGKBi | PA235 |
VEuPathDBi | HostDB:ENSG00000213316 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RZYY, Eukaryota |
GeneTreei | ENSGT00940000160738 |
HOGENOMi | CLU_110291_3_0_1 |
InParanoidi | Q16873 |
OMAi | MQVIYAR |
OrthoDBi | 1609516at2759 |
PhylomeDBi | Q16873 |
TreeFami | TF105328 |
Enzyme and pathway databases
UniPathwayi | UPA00879 |
BRENDAi | 4.4.1.20, 2681 |
PathwayCommonsi | Q16873 |
Reactomei | R-HSA-2142688, Synthesis of 5-eicosatetraenoic acids R-HSA-2142691, Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-2142700, Synthesis of Lipoxins (LX) R-HSA-9026762, Biosynthesis of maresin conjugates in tissue regeneration (MCTR) R-HSA-9026766, Biosynthesis of protectin and resolvin conjugates in tissue regeneration (PCTR and RCTR) |
SABIO-RKi | Q16873 |
SignaLinki | Q16873 |
SIGNORi | Q16873 |
Miscellaneous databases
BioGRID-ORCSi | 4056, 4 hits in 1070 CRISPR screens |
ChiTaRSi | LTC4S, human |
EvolutionaryTracei | Q16873 |
GeneWikii | Leukotriene_C4_synthase |
GenomeRNAii | 4056 |
Pharosi | Q16873, Tchem |
PROi | PR:Q16873 |
RNActi | Q16873, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000213316, Expressed in testis and 109 other tissues |
ExpressionAtlasi | Q16873, baseline and differential |
Genevisiblei | Q16873, HS |
Family and domain databases
Gene3Di | 1.20.120.550, 1 hit |
InterProi | View protein in InterPro IPR001446, 5_LipOase_AP IPR018295, FLAP/GST2/LTC4S_CS IPR023352, MAPEG-like_dom_sf IPR001129, Membr-assoc_MAPEG |
Pfami | View protein in Pfam PF01124, MAPEG, 1 hit |
PRINTSi | PR00488, 5LPOXGNASEAP |
SUPFAMi | SSF161084, SSF161084, 1 hit |
PROSITEi | View protein in PROSITE PS01297, FLAP_GST2_LTC4S, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | LTC4S_HUMAN | |
Accessioni | Q16873Primary (citable) accession number: Q16873 Secondary accession number(s): Q8N6P0, Q9UC73, Q9UD18 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | November 1, 1996 | |
Last modified: | May 25, 2022 | |
This is version 188 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families