Human Gene LY96 (uc003yad.3) Description and Page Index
  Description: Homo sapiens lymphocyte antigen 96 (LY96), transcript variant 1, mRNA.
RefSeq Summary (NM_015364): This gene encodes a protein which associates with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccyaride (LPS), thus providing a link between the receptor and LPS signaling. Studies of the mouse ortholog suggest that this gene may be involved in endotoxin neutralization. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2010].
Transcript (Including UTRs)
   Position: hg19 chr8:74,903,564-74,941,307 Size: 37,744 Total Exon Count: 5 Strand: +
Coding Region
   Position: hg19 chr8:74,903,678-74,941,289 Size: 37,612 Coding Exon Count: 5 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr8:74,903,564-74,941,307)mRNA (may differ from genome)Protein (160 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Lymphocyte antigen 96; Short=Ly-96; AltName: Full=ESOP-1; AltName: Full=Protein MD-2; Flags: Precursor;
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: 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.
INTERACTION: O00206:TLR4; NbExp=3; IntAct=EBI-1539247, EBI-528701;
SUBCELLULAR LOCATION: Secreted, extracellular space.
PTM: N-glycosylated; high-mannose.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): LY96
CDC HuGE Published Literature: LY96

-  MalaCards Disease Associations
  MalaCards Gene Search: LY96
Diseases sorted by gene-association score: intestinal botulism (17), wound botulism (16), interstitial emphysema (16), parametritis (15), neurotic disorder (12), neurogenic bowel (11), patellofemoral pain syndrome (8), melioidosis (8), breast abscess (7), foodborne botulism (7), infant botulism (7), neonatal abstinence syndrome (7), miller-dieker lissencephaly syndrome (7), spastic hemiplegia (6), irak4 deficiency (6), myd88 deficiency (6), developmental coordination disorder (6), calcific tendinitis (5)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 37.74 RPKM in Spleen
Total median expression: 273.65 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -24.70114-0.217 Picture PostScript Text
3' UTR 0.00180.000 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR014756 - Ig_E-set
IPR003172 - MD-2_lipid-recog

Pfam Domains:
PF02221 - ML domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- Model

- X-ray MuPIT

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2Z65 - X-ray MuPIT 3FXI - X-ray MuPIT 3ULA - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q9Y6Y9
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 Protein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001875 lipopolysaccharide receptor activity
GO:0005515 protein binding
GO:0015026 coreceptor activity

Biological Process:
GO:0002224 toll-like receptor signaling pathway
GO:0002376 immune system process
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0006968 cellular defense response
GO:0007166 cell surface receptor signaling pathway
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0031666 positive regulation of lipopolysaccharide-mediated signaling pathway
GO:0032496 response to lipopolysaccharide
GO:0032497 detection of lipopolysaccharide
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034128 negative regulation of MyD88-independent toll-like receptor signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0045087 innate immune response
GO:0070266 necroptotic process
GO:0071222 cellular response to lipopolysaccharide
GO:0097190 apoptotic signaling pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0031226 intrinsic component of plasma membrane
GO:0046696 lipopolysaccharide receptor complex

-  Descriptions from all associated GenBank mRNAs
  LQ740453 - Sequence 7 from Patent WO2018083189.
AB018549 - Homo sapiens MD-2 mRNA, complete cds.
BC020690 - Homo sapiens lymphocyte antigen 96, mRNA (cDNA clone MGC:22424 IMAGE:4767246), complete cds.
AF168121 - Homo sapiens ESOP1 (ESOP1) mRNA, complete cds.
AB590737 - Synthetic construct DNA, clone: pFN21AE1645, Homo sapiens LY96 gene for lymphocyte antigen 96, without stop codon, in Flexi system.
KJ893425 - Synthetic construct Homo sapiens clone ccsbBroadEn_02819 LY96 gene, encodes complete protein.
KR711233 - Synthetic construct Homo sapiens clone CCSBHm_00021336 LY96 (LY96) mRNA, encodes complete protein.
KR711234 - Synthetic construct Homo sapiens clone CCSBHm_00021337 LY96 (LY96) mRNA, encodes complete protein.
GU059938 - Homo sapiens MD-2 mimetic protein precursor variant (LY96) mRNA, complete cds, alternatively spliced.
AB446498 - Homo sapiens MD2 mRNA for MD2 protein, complete cds.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04620 - Toll-like receptor signaling pathway
hsa05130 - Pathogenic Escherichia coli infection

Reactome (by CSHL, EBI, and GO)

Protein Q9Y6Y9 (Reactome details) participates in the following event(s):

R-HSA-166041 Transfer of LPS onto TLR4
R-HSA-5432825 HMGB1 binds TLR4:LY96
R-HSA-5432849 S100A8:S100A9 binds TLR4:LY96
R-HSA-5432852 SFTPA/SFTPD binds TLR4:LY96
R-HSA-6805943 S100A1 binds TLR4:LY96
R-HSA-8870678 Cleaved fibrinogen products bind TLR4:LY96
R-HSA-2201293 Endocytosis of TLR4:LY96:LPS:CD14
R-HSA-166168 TLR4:LY96:LPS:CD14 recruits TRAM (TICAM2)
R-HSA-2201316 Activated TLR2/4 interacts with MAL(TIRAP)
R-HSA-166175 TRAM:TLR4:LY96:LPS:CD14 recruits TRIF (TICAM1)
R-HSA-166072 MyD88 forms a complex with MAL:activated TLR2/4
R-HSA-2201322 MAL is phosphorylated by BTK
R-HSA-2559414 Activated TLR2/4:MAL interacts with BTK
R-HSA-168921 TRIF:activated TLR3/TLR4 complex recruits RIP1
R-HSA-936985 Activated TLR4:TICAM1 recruits TRAF6
R-HSA-2201338 TRAF3 binds TICAM1:activated TLR4 complex
R-HSA-2559568 SARM binds TICAM1:TRAM:TLR4:LY96:LPS:CD14
R-HSA-937075 Phosphorylated TAK1 leaves activated TLR receptor complex
R-HSA-937079 MyD88 oligomerization within the complex of activated TLR:Mal:MyD88
R-HSA-166082 IRAK4 binds to the activated TLR receptor:Mal:MyD88 complex
R-HSA-168915 K63-linked ubiquitination of RIP1 bound to the activated TLR complex
R-HSA-2562541 TLR4-induced ripoptosome assembly
R-HSA-936947 Activated TLR4:TICAM1:K63pUb-TRAF6 recruits TAK1complex
R-HSA-937029 IKBKG subunit of IKK complex binds polyubiquinated RIP1
R-HSA-5362486 TANK binds K63-poly-Ub-TRAF3:TICAM1:activated TLR4
R-HSA-2562564 Caspase-8 processing within TLR4 complex
R-HSA-2569057 RIP3 binds TRIF to mediate necroptosis
R-HSA-937022 IRAK4 autophosphorylation in the complex with activated TLR:MyD88:Mal
R-HSA-166091 IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex
R-HSA-166362 Dissociation of hp-IRAK1:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-2262775 Dissociation of p-IRAK2:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex
R-HSA-936951 Activation of TAK1 complex bound to activated TLR4 complex
R-HSA-936941 Recruitment of TBK1/IKK epsilon to K63-pUb-TANK:K63-pUb-TRAF3:TRIF:activated TLR4 followed by their phosphorylation
R-HSA-166286 Multiple IRAK1 autophosphorylation steps
R-HSA-166284 Second phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166119 First phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal
R-HSA-166363 TRAF6 binds to hp- IRAK1
R-HSA-937059 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:Mal:activated TLR complex
R-HSA-2262777 TRAF6 binds to p-IRAK2
R-HSA-166271 IRF3/IRF7 recruitment to p-TBK1/p-IKK epsilon bound to the activated TLR4
R-HSA-166245 Phosphorylation of IRF-3/IRF7 and their release from the activated TLR complex
R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade
R-HSA-5686938 Regulation of TLR by endogenous ligand
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane
R-HSA-168249 Innate Immune System
R-HSA-166166 MyD88-independent TLR4 cascade
R-HSA-5602498 MyD88 deficiency (TLR2/4)
R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade
R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade
R-HSA-168256 Immune System
R-HSA-937041 IKK complex recruitment mediated by RIP1
R-HSA-937072 TRAF6-mediated induction of TAK1 complex within TLR4 complex
R-HSA-936964 Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon
R-HSA-5603041 IRAK4 deficiency (TLR2/4)
R-HSA-5602358 Diseases associated with the TLR signaling cascade
R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade
R-HSA-2562578 TRIF-mediated programmed cell death
R-HSA-140534 Ligand-dependent caspase activation
R-HSA-937061 TRIF(TICAM1)-mediated TLR4 signaling
R-HSA-5260271 Diseases of Immune System
R-HSA-5357769 Caspase activation via extrinsic apoptotic signalling pathway
R-HSA-1643685 Disease
R-HSA-975163 IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation
R-HSA-9014325 TICAM1,TRAF6-dependent induction of TAK1 complex
R-HSA-109581 Apoptosis
R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation
R-HSA-168164 Toll Like Receptor 3 (TLR3) Cascade
R-HSA-5357801 Programmed Cell Death
R-HSA-975155 MyD88 dependent cascade initiated on endosome
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade

-  Other Names for This Gene
  Alternate Gene Symbols: B3Y6A5, ESOP1, LY96_HUMAN, MD2, NM_015364, NP_056179, Q9Y6Y9
UCSC ID: uc003yad.3
RefSeq Accession: NM_015364
Protein: Q9Y6Y9 (aka LY96_HUMAN)
CCDS: CCDS6216.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_015364.4
exon count: 5CDS single in 3' UTR: no RNA size: 642
ORF size: 483CDS single in intron: no Alignment % ID: 99.84
txCdsPredict score: 1130.00frame shift in genome: no % Coverage: 95.79
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.