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Q16873

- LTC4S_HUMAN

UniProt

Q16873 - LTC4S_HUMAN

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Protein

Leukotriene C4 synthase

Gene

LTC4S

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. enzyme activator activity Source: InterPro
  2. glutathione peroxidase activity Source: RefGenome
  3. glutathione transferase activity Source: RefGenome
  4. leukotriene-C4 synthase activity Source: MGI
  5. lipid binding Source: MGI

GO - Biological processi

  1. arachidonic acid metabolic process Source: Reactome
  2. leukotriene biosynthetic process Source: RefGenome
  3. leukotriene metabolic process Source: MGI
  4. lipoxin metabolic process Source: Reactome
  5. lipoxygenase pathway Source: Reactome
  6. oxidation-reduction process Source: GOC
  7. small molecule metabolic process Source: Reactome
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: Chromosome 5

Organism-specific databases

HGNCiHGNC:6719. LTC4S.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB
  2. integral component of membrane Source: ProtInc
  3. intracellular membrane-bounded organelle Source: ProtInc
  4. nuclear envelope Source: UniProtKB
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.

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.
GenevestigatoriQ16873.

Interactioni

Subunit structurei

Homotrimer. Interacts with ALOX5AP and ALOX5.3 Publications

Protein-protein interaction databases

BioGridi110234. 3 interactions.
DIPiDIP-48473N.
STRINGi9606.ENSP00000292596.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 66Cytoplasmic
Topological domaini28 – 4821LumenalAdd
BLAST
Topological domaini70 – 734Cytoplasmic
Topological domaini95 – 10410Lumenal
Topological domaini125 – 15026CytoplasmicAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei7 – 2721HelicalAdd
BLAST
Transmembranei49 – 6921HelicalAdd
BLAST
Transmembranei74 – 9421HelicalAdd
BLAST
Transmembranei105 – 12420HelicalAdd
BLAST

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.
OMAiIFFHQGV.
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:
EMBL
GenBank
DDBJ
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.

Polymorphism databases

DMDMi2833283.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
UniGenei Hs.706741.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
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 [» ]
ProteinModelPortali Q16873.
SMRi Q16873. Positions 2-149.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110234. 3 interactions.
DIPi DIP-48473N.
STRINGi 9606.ENSP00000292596.

Chemistry

BindingDBi Q16873.
ChEMBLi CHEMBL1743183.
DrugBanki DB00143. Glutathione.

PTM databases

PhosphoSitei Q16873.

Polymorphism databases

DMDMi 2833283.

Proteomic databases

PRIDEi Q16873.

Protocols and materials databases

DNASUi 4056.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000292596 ; ENSP00000292596 ; ENSG00000213316 .
GeneIDi 4056.
KEGGi hsa:4056.
UCSCi uc003mko.3. human.

Organism-specific databases

CTDi 4056.
GeneCardsi GC05P179220.
HGNCi HGNC:6719. LTC4S.
MIMi 246530. gene.
neXtProti NX_Q16873.
Orphaneti 79507. Hypotonia - failure to thrive - microcephaly.
PharmGKBi PA235.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG146874.
GeneTreei ENSGT00430000030964.
HOGENOMi HOG000116372.
HOVERGENi HBG105513.
InParanoidi Q16873.
KOi K00807.
OMAi IFFHQGV.
PhylomeDBi Q16873.
TreeFami TF105328.

Enzyme and pathway databases

BioCyci MetaCyc:HS08566-MONOMER.
BRENDAi 4.4.1.20. 2681.
Reactomei REACT_150209. Synthesis of 5-eicosatetraenoic acids.
REACT_150320. Synthesis of Lipoxins (LX).
REACT_150420. Synthesis of Leukotrienes (LT) and Eoxins (EX).
SABIO-RK Q16873.
SignaLinki Q16873.

Miscellaneous databases

EvolutionaryTracei Q16873.
GeneWikii Leukotriene_C4_synthase.
GenomeRNAii 4056.
NextBioi 15892.
PROi Q16873.
SOURCEi Search...

Gene expression databases

CleanExi HS_LTC4S.
ExpressionAtlasi Q16873. baseline.
Genevestigatori Q16873.

Family and domain databases

Gene3Di 1.20.120.550. 1 hit.
InterProi IPR001446. 5_LipOase_AP.
IPR018295. FLAP/GST2/LTC4S_CS.
IPR023352. MAPEG-like_dom.
IPR001129. Membr-assoc_MAPEG.
[Graphical view ]
Pfami PF01124. MAPEG. 1 hit.
[Graphical view ]
PRINTSi PR00488. 5LPOXGNASEAP.
PROSITEi PS01297. FLAP_GST2_LTC4S. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: October 29, 2014
This is version 135 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