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Q16873 (LTC4S_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Leukotriene C4 synthase

Short name=LTC4 synthase
EC=4.4.1.20
Alternative name(s):
Leukotriene-C(4) synthase
Gene names
Name:LTC4S
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length150 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

Leukotriene C4 = leukotriene A4 + glutathione.

Subunit structure

Homotrimer. Interacts with ALOX5AP and ALOX5. Ref.12 Ref.13 Ref.14

Subcellular location

Nucleus outer membrane; Multi-pass membrane protein. Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.7 Ref.11 Ref.12.

Tissue specificity

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. Ref.7

Involvement in disease

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

Sequence similarities

Belongs to the MAPEG family.

Ontologies

Keywords
   Biological processLeukotriene biosynthesis
   Cellular componentEndoplasmic reticulum
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   Molecular functionLyase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processarachidonic acid metabolic process

Traceable author statement. Source: Reactome

leukotriene biosynthetic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

leukotriene metabolic process

Inferred from direct assay PubMed 8706658. Source: MGI

lipoxin metabolic process

Traceable author statement. Source: Reactome

lipoxygenase pathway

Traceable author statement. Source: Reactome

oxidation-reduction process

Inferred from Biological aspect of Ancestor. Source: GOC

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum

Inferred from direct assay Ref.12. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Traceable author statement Ref.1. Source: ProtInc

intracellular membrane-bounded organelle

Traceable author statement PubMed 1454853. Source: ProtInc

nuclear envelope

Inferred from direct assay Ref.12Ref.7. Source: UniProtKB

nuclear outer membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionenzyme activator activity

Inferred from electronic annotation. Source: InterPro

glutathione peroxidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

glutathione transferase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

leukotriene-C4 synthase activity

Inferred from direct assay PubMed 8706658. Source: MGI

lipid binding

Inferred from direct assay PubMed 8706658. Source: MGI

protein binding

Inferred from physical interaction Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 150150Leukotriene C4 synthase
PRO_0000217748

Regions

Topological domain1 – 66Cytoplasmic Ref.11 Ref.13 Ref.14
Transmembrane7 – 2721Helical
Topological domain28 – 4821Lumenal Ref.11 Ref.13 Ref.14
Transmembrane49 – 6921Helical
Topological domain70 – 734Cytoplasmic Ref.11 Ref.13 Ref.14
Transmembrane74 – 9421Helical
Topological domain95 – 10410Lumenal Ref.11 Ref.13 Ref.14
Transmembrane105 – 12420Helical
Topological domain125 – 15026Cytoplasmic Ref.11 Ref.13 Ref.14
Region51 – 555Glutathione binding
Region58 – 592Glutathione binding
Region93 – 975Glutathione binding

Sites

Active site311Proton donor Probable
Active site1041Proton acceptor Probable
Binding site301Glutathione

Natural variations

Natural variant1421R → Q. Ref.5
Corresponds to variant rs11541078 [ dbSNP | Ensembl ].
VAR_042736

Experimental info

Sequence conflict211Y → G AA sequence Ref.6

Secondary structure

.......... 150
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16873 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 04E269B475063037

FASTA15016,567
        10         20         30         40         50         60 
MKDEVALLAA VTLLGVLLQA YFSLQVISAR RAFRVSPPLT TGPPEFERVY RAQVNCSEYF 

        70         80         90        100        110        120 
PLFLATLWVA GIFFHEGAAA LCGLVYLFAR LRYFQGYARS AQLRLAPLYA SARALWLLVA 

       130        140        150 
LAALGLLAHF LPAALRAALL GRLRTLLPWA 

« Hide

References

« Hide 'large scale' references
[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]"Molecular cloning and expression of human leukotriene-C4 synthase."
Welsch D.J., Creely D.P., Hauser S.D., Mathis K.J., Krivi G.G., Isakson P.C.
Proc. Natl. Acad. Sci. U.S.A. 91:9745-9749(1994) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS34316.1.
PIRI38595.
JC5398.
RefSeqNP_665874.1. NM_145867.1.
UniGeneHs.706741.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ16873.
SMRQ16873. Positions 2-149.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110234. 3 interactions.
DIPDIP-48473N.
STRING9606.ENSP00000292596.

Chemistry

BindingDBQ16873.
ChEMBLCHEMBL1743183.
DrugBankDB00143. Glutathione.

PTM databases

PhosphoSiteQ16873.

Polymorphism databases

DMDM2833283.

Proteomic databases

PRIDEQ16873.

Protocols and materials databases

DNASU4056.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292596; ENSP00000292596; ENSG00000213316.
GeneID4056.
KEGGhsa:4056.
UCSCuc003mko.3. human.

Organism-specific databases

CTD4056.
GeneCardsGC05P179220.
HGNCHGNC:6719. LTC4S.
MIM246530. gene.
neXtProtNX_Q16873.
Orphanet79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBPA235.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG146874.
HOGENOMHOG000116372.
HOVERGENHBG105513.
InParanoidQ16873.
KOK00807.
OMAIFFHQGV.
PhylomeDBQ16873.
TreeFamTF105328.

Enzyme and pathway databases

BioCycMetaCyc:HS08566-MONOMER.
BRENDA4.4.1.20. 2681.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ16873.
SignaLinkQ16873.

Gene expression databases

CleanExHS_LTC4S.
GenevestigatorQ16873.

Family and domain databases

Gene3D1.20.120.550. 1 hit.
InterProIPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view]
PfamPF01124. MAPEG. 1 hit.
[Graphical view]
PRINTSPR00488. 5LPOXGNASEAP.
PROSITEPS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16873.
GeneWikiLeukotriene_C4_synthase.
GenomeRNAi4056.
NextBio15892.
PROQ16873.
SOURCESearch...

Entry information

Entry nameLTC4S_HUMAN
AccessionPrimary (citable) accession number: Q16873
Secondary accession number(s): Q8N6P0, Q9UC73, Q9UD18
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM