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Q9Y6Y9 - LY96_HUMAN

UniProt

Q9Y6Y9 - LY96_HUMAN

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Protein

Lymphocyte antigen 96

Gene

LY96

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

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
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
ProteomesiUP000005640: Chromosome 8

Organism-specific databases

HGNCiHGNC:17156. LY96.

Subcellular locationi

Secreted › extracellular space

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 – 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...)1 Publication
Disulfide bondi37 ↔ 148
Disulfide bondi95 ↔ 105
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

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 – 265Combined sources
Beta strandi28 – 369Combined sources
Beta strandi38 – 403Combined sources
Beta strandi45 – 506Combined sources
Beta strandi57 – 659Combined sources
Beta strandi75 – 828Combined sources
Beta strandi90 – 934Combined sources
Beta strandi97 – 1015Combined sources
Helixi103 – 1064Combined sources
Beta strandi113 – 1219Combined sources
Beta strandi129 – 13911Combined sources
Turni140 – 1434Combined sources
Beta strandi144 – 15512Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
GeneTreeiENSGT00390000000742.
HOGENOMiHOG000001152.
HOVERGENiHBG032514.
InParanoidiQ9Y6Y9.
KOiK05400.
OMAiYIPRRDI.
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

        10         20         30         40         50
MLPFLFFSTL FSSIFTEAQK QYWVCNSSDA SISYTYCDKM QYPISINVNP 
        60         70         80         90        100
CIELKRSKGL LHIFYIPRRD LKQLYFNLYI TVNTMNLPKR KEVICRGSDD 
       110        120        130        140        150
DYSFCRALKG ETVNTTISFS FKGIKFSKGK YKCVVEAISG SPEEMLFCLE 
       160
FVILHQPNSN
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:
EMBLi
GenBanki
DDBJi
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. [Q9Y6Y9-2]
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:
EMBLi
GenBanki
DDBJi
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. [Q9Y6Y9-2]
NP_056179.3. NM_015364.4.
UniGeneiHs.726603.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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...

Protein-protein interaction databases

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

Chemistry

ChEMBLiCHEMBL3038512.

PTM databases

PhosphoSiteiQ9Y6Y9.

Polymorphism databases

DMDMi296434574.

Proteomic databases

MaxQBiQ9Y6Y9.
PaxDbiQ9Y6Y9.
PRIDEiQ9Y6Y9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi23643.
GeneCardsiGC08P074953.
HGNCiHGNC:17156. LY96.
HPAiHPA053060.
MIMi605243. gene.
neXtProtiNX_Q9Y6Y9.
PharmGKBiPA134924906.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG46291.
GeneTreeiENSGT00390000000742.
HOGENOMiHOG000001152.
HOVERGENiHBG032514.
InParanoidiQ9Y6Y9.
KOiK05400.
OMAiYIPRRDI.
OrthoDBiEOG7QG45N.
PhylomeDBiQ9Y6Y9.
TreeFamiTF335876.

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.

Miscellaneous databases

EvolutionaryTraceiQ9Y6Y9.
GeneWikiiLymphocyte_antigen_96.
GenomeRNAii23643.
NextBioi46449.
PROiQ9Y6Y9.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y6Y9.
CleanExiHS_LY96.
GenevestigatoriQ9Y6Y9.

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.
ProtoNetiSearch...

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.
+Additional computationally mapped references.

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: January 7, 2015
This is version 129 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.