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Q9Y6Y9

- LY96_HUMAN

UniProt

Q9Y6Y9 - LY96_HUMAN

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Protein
Lymphocyte antigen 96
Gene
LY96, ESOP1, MD2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

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
Complete GO annotation...

GO - Biological processi

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

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
Complete GO annotation...

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 – 1818 Reviewed prediction
Add
BLAST
Chaini19 – 160142Lymphocyte antigen 96
PRO_0000018619Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi25 ↔ 513 Publications
Glycosylationi26 – 261N-linked (GlcNAc...)1 Publication
Disulfide bondi37 ↔ 1483 Publications
Disulfide bondi95 ↔ 1053 Publications
Glycosylationi114 – 1141N-linked (GlcNAc...)1 Publication

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.4 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

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.

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.
VSP_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.
CCDSiCCDS6216.1. [Q9Y6Y9-1]
RefSeqiNP_001182726.1. NM_001195797.1.
NP_056179.3. NM_015364.4.
UniGeneiHs.726603.

Genome annotation databases

EnsembliENST00000284818; ENSP00000284818; ENSG00000154589.
ENST00000518893; ENSP00000430533; ENSG00000154589.
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 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...

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 .
ENST00000518893 ; ENSP00000430533 ; ENSG00000154589 .
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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 125 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

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