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Q9Y6Y9

- LY96_HUMAN

UniProt

Q9Y6Y9 - LY96_HUMAN

Protein

Lymphocyte antigen 96

Gene

LY96

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

    Cooperates with TLR4 in the innate immune response to bacterial lipopolysaccharide (LPS), and with TLR2 in the response to cell wall components from Gram-positive and Gram-negative bacteria. Enhances TLR4-dependent activation of NF-kappa-B. Cells expressing both MD2 and TLR4, but not TLR4 alone, respond to LPS.

    GO - Molecular functioni

    1. coreceptor activity Source: ProtInc
    2. lipopolysaccharide receptor activity Source: UniProtKB
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell surface receptor signaling pathway Source: ProtInc
    2. cellular defense response Source: ProtInc
    3. detection of lipopolysaccharide Source: UniProtKB
    4. I-kappaB kinase/NF-kappaB signaling Source: Reactome
    5. inflammatory response Source: UniProtKB-KW
    6. innate immune response Source: Reactome
    7. lipopolysaccharide-mediated signaling pathway Source: GOC
    8. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    9. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    10. positive regulation of lipopolysaccharide-mediated signaling pathway Source: Ensembl
    11. response to lipopolysaccharide Source: MGI
    12. toll-like receptor 2 signaling pathway Source: Reactome
    13. toll-like receptor 3 signaling pathway Source: Reactome
    14. toll-like receptor 4 signaling pathway Source: Reactome
    15. toll-like receptor signaling pathway Source: Reactome
    16. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    17. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    18. TRIF-dependent toll-like receptor signaling pathway Source: Reactome

    Keywords - Biological processi

    Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
    REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lymphocyte antigen 96
    Short name:
    Ly-96
    Alternative name(s):
    ESOP-1
    Protein MD-2
    Gene namesi
    Name:LY96
    Synonyms:ESOP1, MD2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:17156. LY96.

    Subcellular locationi

    GO - Cellular componenti

    1. endosome membrane Source: Reactome
    2. extracellular space Source: UniProtKB-SubCell
    3. lipopolysaccharide receptor complex Source: UniProtKB
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi95 – 951C → Y: Abolishes LPS-response. 1 Publication

    Organism-specific databases

    PharmGKBiPA134924906.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 160142Lymphocyte antigen 96PRO_0000018619Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi25 ↔ 51
    Glycosylationi26 – 261N-linked (GlcNAc...)2 Publications
    Disulfide bondi37 ↔ 148
    Disulfide bondi95 ↔ 105
    Glycosylationi114 – 1141N-linked (GlcNAc...)2 Publications

    Post-translational modificationi

    N-glycosylated; high-mannose.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein

    Proteomic databases

    MaxQBiQ9Y6Y9.
    PaxDbiQ9Y6Y9.
    PRIDEiQ9Y6Y9.

    PTM databases

    PhosphoSiteiQ9Y6Y9.

    Expressioni

    Gene expression databases

    ArrayExpressiQ9Y6Y9.
    BgeeiQ9Y6Y9.
    CleanExiHS_LY96.
    GenevestigatoriQ9Y6Y9.

    Organism-specific databases

    HPAiHPA053060.

    Interactioni

    Subunit structurei

    Heterogeneous homopolymer formed from homodimers; disulfide-linked. Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Binds to the extracellular domains of TLR2 and TLR4. Ligand binding induces interaction with TLR4 and oligomerization of the complex.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    TLR4O002063EBI-1539247,EBI-528701

    Protein-protein interaction databases

    BioGridi117170. 4 interactions.
    DIPiDIP-38571N.
    IntActiQ9Y6Y9. 2 interactions.
    STRINGi9606.ENSP00000284818.

    Structurei

    Secondary structure

    1
    160
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi22 – 265
    Beta strandi28 – 369
    Beta strandi38 – 403
    Beta strandi45 – 506
    Beta strandi57 – 659
    Beta strandi75 – 828
    Beta strandi90 – 934
    Beta strandi97 – 1015
    Helixi103 – 1064
    Beta strandi113 – 1219
    Beta strandi129 – 13911
    Turni140 – 1434
    Beta strandi144 – 15512

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1T2Zmodel-A19-160[»]
    2E56X-ray2.00A17-160[»]
    2E59X-ray2.21A17-160[»]
    2Z65X-ray2.70C/D19-158[»]
    3FXIX-ray3.10C/D19-160[»]
    3ULAX-ray3.60B/D19-158[»]
    4G8AX-ray2.40C/D17-160[»]
    ProteinModelPortaliQ9Y6Y9.
    SMRiQ9Y6Y9. Positions 17-160.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9Y6Y9.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni119 – 1235Interaction with lipopolysaccharide

    Keywords - Domaini

    Signal

    Phylogenomic databases

    eggNOGiNOG46291.
    HOGENOMiHOG000001152.
    HOVERGENiHBG032514.
    InParanoidiQ9Y6Y9.
    KOiK05400.
    OMAiIPRRDIK.
    OrthoDBiEOG7QG45N.
    PhylomeDBiQ9Y6Y9.
    TreeFamiTF335876.

    Family and domain databases

    InterProiIPR014756. Ig_E-set.
    IPR003172. ML_dom.
    [Graphical view]
    PfamiPF02221. E1_DerP2_DerF2. 1 hit.
    [Graphical view]
    SMARTiSM00737. ML. 1 hit.
    [Graphical view]
    SUPFAMiSSF81296. SSF81296. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q9Y6Y9-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MLPFLFFSTL FSSIFTEAQK QYWVCNSSDA SISYTYCDKM QYPISINVNP    50
    CIELKRSKGL LHIFYIPRRD LKQLYFNLYI TVNTMNLPKR KEVICRGSDD 100
    DYSFCRALKG ETVNTTISFS FKGIKFSKGK YKCVVEAISG SPEEMLFCLE 150
    FVILHQPNSN 160
    Length:160
    Mass (Da):18,546
    Last modified:May 18, 2010 - v2
    Checksum:i0F92AFF583637C6B
    GO
    Isoform 2 (identifier: Q9Y6Y9-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         38-68: DKMQYPISINVNPCIELKRSKGLLHIFYIPR → G

    Note: No experimental confirmation available. Gene prediction based on EST data.

    Show »
    Length:130
    Mass (Da):14,933
    Checksum:i7D92D168412B21C7
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti56 – 561R → G.5 Publications
    Corresponds to variant rs6472812 [ dbSNP | Ensembl ].
    VAR_050030
    Natural varianti157 – 1571P → S.
    Corresponds to variant rs11466004 [ dbSNP | Ensembl ].
    VAR_024532

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei38 – 6831DKMQY…FYIPR → G in isoform 2. CuratedVSP_055045Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018549 mRNA. Translation: BAA78717.1.
    AF168121 mRNA. Translation: AAF89635.1.
    AB446498 mRNA. Translation: BAG55275.1.
    AC022868 Genomic DNA. No translation available.
    AC087672 Genomic DNA. No translation available.
    BC020690 mRNA. Translation: AAH20690.1.
    CCDSiCCDS56540.1. [Q9Y6Y9-2]
    CCDS6216.1. [Q9Y6Y9-1]
    RefSeqiNP_001182726.1. NM_001195797.1.
    NP_056179.3. NM_015364.4.
    UniGeneiHs.726603.

    Genome annotation databases

    EnsembliENST00000284818; ENSP00000284818; ENSG00000154589. [Q9Y6Y9-1]
    ENST00000518893; ENSP00000430533; ENSG00000154589. [Q9Y6Y9-2]
    GeneIDi23643.
    KEGGihsa:23643.
    UCSCiuc003yad.3. human. [Q9Y6Y9-1]

    Polymorphism databases

    DMDMi296434574.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB018549 mRNA. Translation: BAA78717.1 .
    AF168121 mRNA. Translation: AAF89635.1 .
    AB446498 mRNA. Translation: BAG55275.1 .
    AC022868 Genomic DNA. No translation available.
    AC087672 Genomic DNA. No translation available.
    BC020690 mRNA. Translation: AAH20690.1 .
    CCDSi CCDS56540.1. [Q9Y6Y9-2 ]
    CCDS6216.1. [Q9Y6Y9-1 ]
    RefSeqi NP_001182726.1. NM_001195797.1.
    NP_056179.3. NM_015364.4.
    UniGenei Hs.726603.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1T2Z model - A 19-160 [» ]
    2E56 X-ray 2.00 A 17-160 [» ]
    2E59 X-ray 2.21 A 17-160 [» ]
    2Z65 X-ray 2.70 C/D 19-158 [» ]
    3FXI X-ray 3.10 C/D 19-160 [» ]
    3ULA X-ray 3.60 B/D 19-158 [» ]
    4G8A X-ray 2.40 C/D 17-160 [» ]
    ProteinModelPortali Q9Y6Y9.
    SMRi Q9Y6Y9. Positions 17-160.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 117170. 4 interactions.
    DIPi DIP-38571N.
    IntActi Q9Y6Y9. 2 interactions.
    STRINGi 9606.ENSP00000284818.

    Chemistry

    ChEMBLi CHEMBL3038513.

    PTM databases

    PhosphoSitei Q9Y6Y9.

    Polymorphism databases

    DMDMi 296434574.

    Proteomic databases

    MaxQBi Q9Y6Y9.
    PaxDbi Q9Y6Y9.
    PRIDEi Q9Y6Y9.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000284818 ; ENSP00000284818 ; ENSG00000154589 . [Q9Y6Y9-1 ]
    ENST00000518893 ; ENSP00000430533 ; ENSG00000154589 . [Q9Y6Y9-2 ]
    GeneIDi 23643.
    KEGGi hsa:23643.
    UCSCi uc003yad.3. human. [Q9Y6Y9-1 ]

    Organism-specific databases

    CTDi 23643.
    GeneCardsi GC08P074953.
    HGNCi HGNC:17156. LY96.
    HPAi HPA053060.
    MIMi 605243. gene.
    neXtProti NX_Q9Y6Y9.
    PharmGKBi PA134924906.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG46291.
    HOGENOMi HOG000001152.
    HOVERGENi HBG032514.
    InParanoidi Q9Y6Y9.
    KOi K05400.
    OMAi IPRRDIK.
    OrthoDBi EOG7QG45N.
    PhylomeDBi Q9Y6Y9.
    TreeFami TF335876.

    Enzyme and pathway databases

    Reactomei REACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
    REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.

    Miscellaneous databases

    EvolutionaryTracei Q9Y6Y9.
    GeneWikii Lymphocyte_antigen_96.
    GenomeRNAii 23643.
    NextBioi 46449.
    PROi Q9Y6Y9.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y6Y9.
    Bgeei Q9Y6Y9.
    CleanExi HS_LY96.
    Genevestigatori Q9Y6Y9.

    Family and domain databases

    InterProi IPR014756. Ig_E-set.
    IPR003172. ML_dom.
    [Graphical view ]
    Pfami PF02221. E1_DerP2_DerF2. 1 hit.
    [Graphical view ]
    SMARTi SM00737. ML. 1 hit.
    [Graphical view ]
    SUPFAMi SSF81296. SSF81296. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. "MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4."
      Shimazu R., Akashi S., Ogata H., Nagai Y., Fukudome K., Miyake K., Kimoto M.
      J. Exp. Med. 189:1777-1782(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-56.
      Tissue: Uterus.
    2. "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and reproductive systems of embryonic and adult mice."
      Kato K., Morrison A.M., Nakano T., Tashiro K., Honjo T.
      Blood 96:362-364(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-56.
    3. "Molecular genetic analysis of an endotoxin nonresponder mutant cell line. A point mutation in a conserved region of MD-2 abolishes endotoxin-induced signaling."
      Schromm A.B., Lien E., Henneke P., Chow J.C., Yoshimura A., Heine H., Latz E., Monks B.G., Schwartz D.A., Miyake K., Golenbock D.T.
      J. Exp. Med. 194:79-88(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), MUTAGENESIS OF CYS-95, VARIANT GLY-56.
    4. "Natural selection in the TLR-related genes in the course of primate evolution."
      Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
      Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT GLY-56.
    5. "DNA sequence and analysis of human chromosome 8."
      Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
      , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
      Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "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] (ISOFORM 1), VARIANT GLY-56.
      Tissue: Liver.
    7. "MD-2 enables Toll-like receptor 2 (TLR2)-mediated responses to lipopolysaccharide and enhances TLR2-mediated responses to Gram-positive and Gram-negative bacteria and their cell wall components."
      Dziarski R., Wang Q., Miyake K., Kirschning C.J., Gupta D.
      J. Immunol. 166:1938-1944(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TLR2 AND TLR4.
    8. "Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4."
      Visintin A., Mazzoni A., Spitzer J.A., Segal D.M.
      Proc. Natl. Acad. Sci. U.S.A. 98:12156-12161(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BONDS, GLYCOSYLATION.
    9. Cited for: INTERCHAIN DISULFIDE BOND.
    10. "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran."
      Kim H.M., Park B.S., Kim J.-I., Kim S.E., Lee J., Oh S.C., Enkhbayar P., Matsushima N., Lee H., Yoo O.J., Lee J.-O.
      Cell 130:906-917(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 19-158 IN COMPLEX WITH TLR4 AND LIPOPOLYSACCHARIDE ANALOG.
    11. "Crystal structures of human MD-2 and its complex with antiendotoxic lipid IVa."
      Ohto U., Fukase K., Miyake K., Satow Y.
      Science 316:1632-1634(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 17-160 IN COMPLEX WITH LIPID IV-A, DISULFIDE BONDS, GLYCOSYLATION AT ASN-26 AND ASN-114.

    Entry informationi

    Entry nameiLY96_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y6Y9
    Secondary accession number(s): B3Y6A5, E5RJJ7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 27, 2002
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 126 of the entry and version 2 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, Reference proteome

    Documents

    1. Human chromosome 8
      Human chromosome 8: 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

    External Data

    Dasty 3