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Q9Y6Y9 (LY96_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lymphocyte antigen 96

Short name=Ly-96
Alternative name(s):
ESOP-1
Protein MD-2
Gene names
Name:LY96
Synonyms:ESOP1, MD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length160 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.7 Ref.8 Ref.9 Ref.11

Subcellular location

Secretedextracellular space.

Post-translational modification

N-glycosylated; high-mannose. Ref.8 Ref.11

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSignal
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

cell surface receptor signaling pathway

Traceable author statement Ref.1. Source: ProtInc

cellular defense response

Traceable author statement Ref.1. Source: ProtInc

detection of lipopolysaccharide

Inferred from direct assay PubMed 19252480. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement. Source: Reactome

lipopolysaccharide-mediated signaling pathway

Inferred from direct assay PubMed 19252480. Source: GOC

positive regulation of lipopolysaccharide-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

response to lipopolysaccharide

Inferred from direct assay PubMed 12594207. Source: MGI

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentendosome membrane

Traceable author statement. Source: Reactome

extracellular space

Inferred from electronic annotation. Source: UniProtKB-SubCell

lipopolysaccharide receptor complex

Inferred from direct assay PubMed 19252480. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncoreceptor activity

Traceable author statement Ref.1. Source: ProtInc

lipopolysaccharide receptor activity

Inferred from direct assay PubMed 19252480. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 19252480. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TLR4O002063EBI-1539247,EBI-528701

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9Y6Y9-1)

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.
Isoform 2 (identifier: Q9Y6Y9-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 160142Lymphocyte antigen 96
PRO_0000018619

Regions

Region119 – 1235Interaction with lipopolysaccharide

Amino acid modifications

Glycosylation261N-linked (GlcNAc...) Ref.11
Glycosylation1141N-linked (GlcNAc...) Ref.11
Disulfide bond25 ↔ 51 Ref.8 Ref.9 Ref.11
Disulfide bond37 ↔ 148 Ref.8 Ref.9 Ref.11
Disulfide bond95 ↔ 105 Ref.8 Ref.9 Ref.11

Natural variations

Alternative sequence38 – 6831DKMQY…FYIPR → G in isoform 2.
VSP_055045
Natural variant561R → G. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6
Corresponds to variant rs6472812 [ dbSNP | Ensembl ].
VAR_050030
Natural variant1571P → S.
Corresponds to variant rs11466004 [ dbSNP | Ensembl ].
VAR_024532

Experimental info

Mutagenesis951C → Y: Abolishes LPS-response. Ref.3

Secondary structure

......................... 160
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: 0F92AFF583637C6B

FASTA16018,546
        10         20         30         40         50         60 
MLPFLFFSTL FSSIFTEAQK QYWVCNSSDA SISYTYCDKM QYPISINVNP CIELKRSKGL 

        70         80         90        100        110        120 
LHIFYIPRRD LKQLYFNLYI TVNTMNLPKR KEVICRGSDD DYSFCRALKG ETVNTTISFS 

       130        140        150        160 
FKGIKFSKGK YKCVVEAISG SPEEMLFCLE FVILHQPNSN 

« Hide

Isoform 2 [UniParc].

Checksum: 7D92D168412B21C7
Show »

FASTA13014,933

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"The role of disulfide bonds in the assembly and function of MD-2."
Mullen G.E.D., Kennedy M.N., Visintin A., Mazzoni A., Leifer C.A., Davies D.R., Segal D.M.
Proc. Natl. Acad. Sci. U.S.A. 100:3919-3924(2003) [PubMed] [Europe PMC] [Abstract]
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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS6216.1.
RefSeqNP_001182726.1. NM_001195797.1.
NP_056179.3. NM_015364.4.
UniGeneHs.726603.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9Y6Y9.
SMRQ9Y6Y9. Positions 17-160.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117170. 4 interactions.
DIPDIP-38571N.
IntActQ9Y6Y9. 2 interactions.
STRING9606.ENSP00000284818.

Chemistry

ChEMBLCHEMBL3038513.

PTM databases

PhosphoSiteQ9Y6Y9.

Polymorphism databases

DMDM296434574.

Proteomic databases

MaxQBQ9Y6Y9.
PaxDbQ9Y6Y9.
PRIDEQ9Y6Y9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284818; ENSP00000284818; ENSG00000154589.
ENST00000518893; ENSP00000430533; ENSG00000154589.
GeneID23643.
KEGGhsa:23643.
UCSCuc003yad.3. human.

Organism-specific databases

CTD23643.
GeneCardsGC08P074953.
HGNCHGNC:17156. LY96.
HPAHPA053060.
MIM605243. gene.
neXtProtNX_Q9Y6Y9.
PharmGKBPA134924906.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46291.
HOGENOMHOG000001152.
HOVERGENHBG032514.
InParanoidQ9Y6Y9.
KOK05400.
OMAIPRRDIK.
OrthoDBEOG7QG45N.
PhylomeDBQ9Y6Y9.
TreeFamTF335876.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

ArrayExpressQ9Y6Y9.
BgeeQ9Y6Y9.
CleanExHS_LY96.
GenevestigatorQ9Y6Y9.

Family and domain databases

InterProIPR014756. Ig_E-set.
IPR003172. ML_dom.
[Graphical view]
PfamPF02221. E1_DerP2_DerF2. 1 hit.
[Graphical view]
SMARTSM00737. ML. 1 hit.
[Graphical view]
SUPFAMSSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ9Y6Y9.
GeneWikiLymphocyte_antigen_96.
GenomeRNAi23643.
NextBio46449.
PROQ9Y6Y9.
SOURCESearch...

Entry information

Entry nameLY96_HUMAN
AccessionPrimary (citable) accession number: Q9Y6Y9
Secondary accession number(s): B3Y6A5, E5RJJ7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM