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Protein

Leukotriene C4 synthase

Gene

LTC4S

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4.

Catalytic activityi

Leukotriene C4 = leukotriene A4 + glutathione.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei30Glutathione2 Publications1
Active sitei31Proton donor1 Publication1
Active sitei104Proton acceptor1 Publication1

GO - Molecular functioni

  • enzyme activator activity Source: InterPro
  • glutathione peroxidase activity Source: GO_Central
  • glutathione transferase activity Source: GO_Central
  • leukotriene-C4 synthase activity Source: MGI
  • lipid binding Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Leukotriene biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS08566-MONOMER.
ZFISH:HS08566-MONOMER.
BRENDAi4.4.1.20. 2681.
ReactomeiR-HSA-2142688. Synthesis of 5-eicosatetraenoic acids.
R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-HSA-2142700. Synthesis of Lipoxins (LX).
SABIO-RKQ16873.
SignaLinkiQ16873.

Chemistry databases

SwissLipidsiSLP:000001452.

Names & Taxonomyi

Protein namesi
Recommended name:
Leukotriene C4 synthase (EC:4.4.1.20)
Short name:
LTC4 synthase
Alternative name(s):
Leukotriene-C(4) synthase
Gene namesi
Name:LTC4S
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6719. LTC4S.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 6Cytoplasmic6
Transmembranei7 – 27HelicalAdd BLAST21
Topological domaini28 – 48LumenalAdd BLAST21
Transmembranei49 – 69HelicalAdd BLAST21
Topological domaini70 – 73Cytoplasmic4
Transmembranei74 – 94HelicalAdd BLAST21
Topological domaini95 – 104Lumenal10
Transmembranei105 – 124HelicalAdd BLAST20
Topological domaini125 – 150CytoplasmicAdd BLAST26

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: ProtInc
  • intracellular membrane-bounded organelle Source: ProtInc
  • nuclear envelope Source: UniProtKB
  • nuclear outer membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly.

Organism-specific databases

DisGeNETi4056.
MalaCardsiLTC4S.
OpenTargetsiENSG00000213316.
Orphaneti79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBiPA235.

Chemistry databases

ChEMBLiCHEMBL1743183.
DrugBankiDB00143. Glutathione.
GuidetoPHARMACOLOGYi1391.

Polymorphism and mutation databases

DMDMi2833283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002177481 – 150Leukotriene C4 synthaseAdd BLAST150

Proteomic databases

PaxDbiQ16873.
PeptideAtlasiQ16873.
PRIDEiQ16873.

PTM databases

iPTMnetiQ16873.
PhosphoSitePlusiQ16873.

Expressioni

Tissue specificityi

Detected in lung, platelets and the myelogenous leukemia cell line KG-1 (at protein level). LTC4S activity is present in eosinophils, basophils, mast cells, certain phagocytic mononuclear cells, endothelial cells, vascular smooth muscle cells and platelets.1 Publication

Gene expression databases

CleanExiHS_LTC4S.
ExpressionAtlasiQ16873. differential.
GenevisibleiQ16873. HS.

Interactioni

Subunit structurei

Homotrimer. Interacts with ALOX5AP and ALOX5.3 Publications

Protein-protein interaction databases

BioGridi110234. 4 interactors.
DIPiDIP-48473N.
IntActiQ16873. 1 interactor.
STRINGi9606.ENSP00000292596.

Chemistry databases

BindingDBiQ16873.

Structurei

Secondary structure

1150
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2 – 32Combined sources31
Helixi44 – 73Combined sources30
Helixi76 – 99Combined sources24
Helixi101 – 104Combined sources4
Helixi105 – 145Combined sources41

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PNOX-ray3.30A/B/C/D/E/F/G/H/I/J/K/L1-150[»]
2UUHX-ray2.15A2-150[»]
2UUIX-ray2.00A2-150[»]
3B29X-ray3.20A1-150[»]
3HKKX-ray2.90A2-150[»]
3LEOX-ray2.10A2-150[»]
3PCVX-ray1.90A1-150[»]
4J7TX-ray3.20A2-150[»]
4J7YX-ray2.90A2-150[»]
4JC7X-ray2.70A2-150[»]
4JCZX-ray2.75A2-150[»]
4JRZX-ray2.40A2-150[»]
4WABX-ray2.70A130-150[»]
5HV9X-ray3.00A2-150[»]
ProteinModelPortaliQ16873.
SMRiQ16873.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16873.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni51 – 55Glutathione binding5
Regioni58 – 59Glutathione binding2
Regioni93 – 97Glutathione binding5

Sequence similaritiesi

Belongs to the MAPEG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IX5F. Eukaryota.
ENOG4111JV7. LUCA.
GeneTreeiENSGT00430000030964.
HOGENOMiHOG000116372.
HOVERGENiHBG105513.
InParanoidiQ16873.
KOiK00807.
OMAiIFRAQAN.
OrthoDBiEOG091G12NW.
PhylomeDBiQ16873.
TreeFamiTF105328.

Family and domain databases

Gene3Di1.20.120.550. 1 hit.
InterProiIPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamiPF01124. MAPEG. 1 hit.
[Graphical view]
PRINTSiPR00488. 5LPOXGNASEAP.
PROSITEiPS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q16873-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:150
Mass (Da):16,567
Last modified:November 1, 1996 - v1
Checksum:i04E269B475063037
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti21Y → G AA sequence (PubMed:8446623).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_042736142R → Q.1 PublicationCorresponds to variant rs11541078dbSNPEnsembl.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.
CCDSiCCDS34316.1.
PIRiI38595.
JC5398.
RefSeqiNP_665874.1. NM_145867.1.
UniGeneiHs.706741.

Genome annotation databases

EnsembliENST00000292596; ENSP00000292596; ENSG00000213316.
GeneIDi4056.
KEGGihsa:4056.
UCSCiuc003mko.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS34316.1.
PIRiI38595.
JC5398.
RefSeqiNP_665874.1. NM_145867.1.
UniGeneiHs.706741.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2PNOX-ray3.30A/B/C/D/E/F/G/H/I/J/K/L1-150[»]
2UUHX-ray2.15A2-150[»]
2UUIX-ray2.00A2-150[»]
3B29X-ray3.20A1-150[»]
3HKKX-ray2.90A2-150[»]
3LEOX-ray2.10A2-150[»]
3PCVX-ray1.90A1-150[»]
4J7TX-ray3.20A2-150[»]
4J7YX-ray2.90A2-150[»]
4JC7X-ray2.70A2-150[»]
4JCZX-ray2.75A2-150[»]
4JRZX-ray2.40A2-150[»]
4WABX-ray2.70A130-150[»]
5HV9X-ray3.00A2-150[»]
ProteinModelPortaliQ16873.
SMRiQ16873.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110234. 4 interactors.
DIPiDIP-48473N.
IntActiQ16873. 1 interactor.
STRINGi9606.ENSP00000292596.

Chemistry databases

BindingDBiQ16873.
ChEMBLiCHEMBL1743183.
DrugBankiDB00143. Glutathione.
GuidetoPHARMACOLOGYi1391.
SwissLipidsiSLP:000001452.

PTM databases

iPTMnetiQ16873.
PhosphoSitePlusiQ16873.

Polymorphism and mutation databases

DMDMi2833283.

Proteomic databases

PaxDbiQ16873.
PeptideAtlasiQ16873.
PRIDEiQ16873.

Protocols and materials databases

DNASUi4056.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292596; ENSP00000292596; ENSG00000213316.
GeneIDi4056.
KEGGihsa:4056.
UCSCiuc003mko.4. human.

Organism-specific databases

CTDi4056.
DisGeNETi4056.
GeneCardsiLTC4S.
HGNCiHGNC:6719. LTC4S.
MalaCardsiLTC4S.
MIMi246530. gene.
neXtProtiNX_Q16873.
OpenTargetsiENSG00000213316.
Orphaneti79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBiPA235.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IX5F. Eukaryota.
ENOG4111JV7. LUCA.
GeneTreeiENSGT00430000030964.
HOGENOMiHOG000116372.
HOVERGENiHBG105513.
InParanoidiQ16873.
KOiK00807.
OMAiIFRAQAN.
OrthoDBiEOG091G12NW.
PhylomeDBiQ16873.
TreeFamiTF105328.

Enzyme and pathway databases

BioCyciMetaCyc:HS08566-MONOMER.
ZFISH:HS08566-MONOMER.
BRENDAi4.4.1.20. 2681.
ReactomeiR-HSA-2142688. Synthesis of 5-eicosatetraenoic acids.
R-HSA-2142691. Synthesis of Leukotrienes (LT) and Eoxins (EX).
R-HSA-2142700. Synthesis of Lipoxins (LX).
SABIO-RKQ16873.
SignaLinkiQ16873.

Miscellaneous databases

EvolutionaryTraceiQ16873.
GeneWikiiLeukotriene_C4_synthase.
GenomeRNAii4056.
PROiQ16873.
SOURCEiSearch...

Gene expression databases

CleanExiHS_LTC4S.
ExpressionAtlasiQ16873. differential.
GenevisibleiQ16873. HS.

Family and domain databases

Gene3Di1.20.120.550. 1 hit.
InterProiIPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamiPF01124. MAPEG. 1 hit.
[Graphical view]
PRINTSiPR00488. 5LPOXGNASEAP.
PROSITEiPS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLTC4S_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.