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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei30 – 301Glutathione2 Publications
Active sitei31 – 311Proton donor1 Publication
Active sitei104 – 1041Proton acceptor1 Publication

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.
BRENDAi4.4.1.20. 2681.
ReactomeiREACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150320. Synthesis of Lipoxins (LX).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
SABIO-RKQ16873.
SignaLinkiQ16873.

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
ProteomesiUP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:6719. LTC4S.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Cytoplasmic
Transmembranei7 – 2721HelicalAdd
BLAST
Topological domaini28 – 4821LumenalAdd
BLAST
Transmembranei49 – 6921HelicalAdd
BLAST
Topological domaini70 – 734Cytoplasmic
Transmembranei74 – 9421HelicalAdd
BLAST
Topological domaini95 – 10410Lumenal
Transmembranei105 – 12420HelicalAdd
BLAST
Topological domaini125 – 15026CytoplasmicAdd
BLAST

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

Orphaneti79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBiPA235.

Chemistry

DrugBankiDB00143. Glutathione.

Polymorphism and mutation databases

DMDMi2833283.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 150150Leukotriene C4 synthasePRO_0000217748Add
BLAST

Proteomic databases

PRIDEiQ16873.

PTM databases

PhosphoSiteiQ16873.

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. baseline.
GenevisibleiQ16873. HS.

Interactioni

Subunit structurei

Homotrimer. Interacts with ALOX5AP and ALOX5.3 Publications

Protein-protein interaction databases

BioGridi110234. 4 interactions.
DIPiDIP-48473N.
STRINGi9606.ENSP00000292596.

Structurei

Secondary structure

1
150
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi2 – 3231Combined sources
Helixi44 – 7330Combined sources
Helixi76 – 9924Combined sources
Helixi101 – 1044Combined sources
Helixi105 – 14541Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliQ16873.
SMRiQ16873. Positions 2-149.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ16873.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni51 – 555Glutathione binding
Regioni58 – 592Glutathione binding
Regioni93 – 975Glutathione binding

Sequence similaritiesi

Belongs to the MAPEG family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG146874.
GeneTreeiENSGT00430000030964.
HOGENOMiHOG000116372.
HOVERGENiHBG105513.
InParanoidiQ16873.
KOiK00807.
OMAiIFRAQAN.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti21 – 211Y → G AA sequence (PubMed:8446623).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti142 – 1421R → Q.1 Publication
Corresponds to variant rs11541078 [ dbSNP | Ensembl ].
VAR_042736

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.3. 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
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[»]
ProteinModelPortaliQ16873.
SMRiQ16873. Positions 2-149.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110234. 4 interactions.
DIPiDIP-48473N.
STRINGi9606.ENSP00000292596.

Chemistry

BindingDBiQ16873.
ChEMBLiCHEMBL1743183.
DrugBankiDB00143. Glutathione.

PTM databases

PhosphoSiteiQ16873.

Polymorphism and mutation databases

DMDMi2833283.

Proteomic databases

PRIDEiQ16873.

Protocols and materials databases

DNASUi4056.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292596; ENSP00000292596; ENSG00000213316.
GeneIDi4056.
KEGGihsa:4056.
UCSCiuc003mko.3. human.

Organism-specific databases

CTDi4056.
GeneCardsiGC05P179220.
HGNCiHGNC:6719. LTC4S.
MIMi246530. gene.
neXtProtiNX_Q16873.
Orphaneti79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBiPA235.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG146874.
GeneTreeiENSGT00430000030964.
HOGENOMiHOG000116372.
HOVERGENiHBG105513.
InParanoidiQ16873.
KOiK00807.
OMAiIFRAQAN.
PhylomeDBiQ16873.
TreeFamiTF105328.

Enzyme and pathway databases

BioCyciMetaCyc:HS08566-MONOMER.
BRENDAi4.4.1.20. 2681.
ReactomeiREACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150320. Synthesis of Lipoxins (LX).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
SABIO-RKQ16873.
SignaLinkiQ16873.

Miscellaneous databases

EvolutionaryTraceiQ16873.
GeneWikiiLeukotriene_C4_synthase.
GenomeRNAii4056.
NextBioi15892.
PROiQ16873.
SOURCEiSearch...

Gene expression databases

CleanExiHS_LTC4S.
ExpressionAtlasiQ16873. baseline.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4."
    Lam B.K., Penrose J.F., Freeman G.J., Austen K.F.
    Proc. Natl. Acad. Sci. U.S.A. 91:7663-7667(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-22 AND 35-48.
    Tissue: Bone marrow.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Molecular cloning of the gene for human leukotriene C4 synthase. Organization, nucleotide sequence, and chromosomal localization to 5q35."
    Penrose J.F., Spector J., Baldasaro M., Xu K., Boyce J., Arm J.P., Austen K.F., Lam B.K.
    J. Biol. Chem. 271:11356-11361(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Molecular cloning of the human leukotriene C4 synthase gene and assignment to chromosome 5q35."
    Bigby T.D., Hodulik C.R., Arden K.C., Fu L.
    Mol. Med. 2:637-646(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-142.
    Tissue: Brain.
  6. "Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase: a homodimeric glutathione S-transferase composed of 18-kDa subunits."
    Nicholson D.W., Ali A., Vaillancourt J.P., Calaycay J.R., Mumford R.A., Zamboni R.J., Ford-Hutchinson A.W.
    Proc. Natl. Acad. Sci. U.S.A. 90:2015-2019(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-35.
  7. "Purification of human lung leukotriene C4 synthase and preparation of a polyclonal antibody."
    Penrose J.F., Spector J., Lam B.K., Friend D.S., Xu K., Jack R.M., Austen K.F.
    Am. J. Respir. Crit. Care Med. 152:283-289(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-19, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    Tissue: Lung.
  8. "Two step purification of human and murine leukotriene C4 synthase."
    Goppelt-Struebe M.
    Biochim. Biophys. Acta 1256:257-261(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-17.
    Tissue: Monocyte.
  9. "Leukotriene C4-synthesis deficiency: a new inborn error of metabolism linked to a fatal developmental syndrome."
    Mayatepek E., Flock B.
    Lancet 352:1514-1517(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN LTC4 SYNTHASE DEFICIENCY.
  10. "Defects in the synthesis of cysteinyl leukotrienes: a new group of inborn errors of metabolism."
    Mayatepek E., Zelezny R., Lehmann W.D., Hammond J.W., Hoffmann G.F.
    J. Inherit. Metab. Dis. 23:404-408(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN LTC4 SYNTHASE DEFICIENCY.
  11. "Membrane localization and topology of leukotriene C4 synthase."
    Christmas P., Weber B.M., McKee M., Brown D., Soberman R.J.
    J. Biol. Chem. 277:28902-28908(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOPOLOGY.
  12. "Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein."
    Strid T., Svartz J., Franck N., Hallin E., Ingelsson B., Soederstroem M., Hammarstroem S.
    Biochem. Biophys. Res. Commun. 381:518-522(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH ALOX5AP AND ALOX5, SUBCELLULAR LOCATION.
  13. "Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis."
    Ago H., Kanaoka Y., Irikura D., Lam B.K., Shimamura T., Austen K.F., Miyano M.
    Nature 448:609-612(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) IN COMPLEX WITH GLUTATHIONE, ACTIVE SITE, TOPOLOGY, SUBUNIT.
  14. "Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase."
    Martinez Molina D., Wetterholm A., Kohl A., McCarthy A.A., Niegowski D., Ohlson E., Hammarberg T., Eshaghi S., Haeggstroem J.Z., Nordlund P.
    Nature 448:613-616(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 2-150 IN COMPLEX WITH GLUTATHIONE, SUBUNIT, TOPOLOGY.

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: June 24, 2015
This is version 139 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

External Data

Dasty 3

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 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.