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Q16873

- LTC4S_HUMAN

UniProt

Q16873 - LTC4S_HUMAN

Protein

Leukotriene C4 synthase

Gene

LTC4S

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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
    6. protein binding Source: UniProtKB

    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

    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. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    3. integral component of membrane Source: ProtInc
    4. intracellular membrane-bounded organelle Source: ProtInc
    5. nuclear envelope Source: UniProtKB
    6. nuclear outer membrane Source: UniProtKB-SubCell

    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.
    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.
    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

    MKDEVALLAA VTLLGVLLQA YFSLQVISAR RAFRVSPPLT TGPPEFERVY    50
    RAQVNCSEYF PLFLATLWVA GIFFHEGAAA LCGLVYLFAR LRYFQGYARS 100
    AQLRLAPLYA SARALWLLVA LAALGLLAHF LPAALRAALL GRLRTLLPWA 150
    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.
    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.
    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

    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 1, 2014
    This is version 134 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