Lymphocyte antigen 96

LY96
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2E56, 2E59, 2Z65, 3FXI, 3ULA, 4G8A
Identifiers
Aliases	LY96, ESOP-1, MD-2, MD2, ly-96, lymphocyte antigen 96
External IDs	OMIM: 605243 MGI: 1341909 HomoloGene: 9109 GeneCards: LY96
Gene ontology Molecular function • coreceptor activity • protein binding • lipopolysaccharide receptor activity Cellular component • intrinsic component of plasma membrane • plasma membrane • extracellular fluid • extracellular region • lipopolysaccharide receptor complex • endosome membrane Biological process • toll-like receptor 4 signaling pathway • immune system process • MyD88-dependent toll-like receptor signaling pathway • positive regulation of lipopolysaccharide-mediated signaling pathway • TRIF-dependent toll-like receptor signaling pathway • cellular defense response • cell surface receptor signaling pathway • response to lipopolysaccharide • positive regulation of tumor necrosis factor production • inflammatory response • cellular response to lipopolysaccharide • detection of lipopolysaccharide • I-kappaB kinase/NF-kappaB signaling • MyD88-independent toll-like receptor signaling pathway • lipopolysaccharide-mediated signaling pathway • negative regulation of MyD88-independent toll-like receptor signaling pathway • innate immune response • necroptotic process • apoptotic signaling pathway Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23643	17087
Ensembl	ENSG00000154589	ENSMUSG00000025779
UniProt	Q9Y6Y9	Q9JHF9
RefSeq (mRNA)	NM_001195797 NM_015364	NM_001159711 NM_016923
RefSeq (protein)	NP_001182726.1 NP_056179.3	NP_001153183.1 NP_058619.1
Location (UCSC)	Chr 8: 73.99 – 74.03 Mb	Chr 1: 16.69 – 16.71 Mb
PubMed search	[1]	[2]
Wikidata

View/Edit Human

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Lymphocyte antigen 96, also known as "MD2," is a protein that in humans is encoded by the LY96 gene.^[3][4][5]

The protein encoded by this gene is involved in binding lipopolysaccharide with TLR4.

The MD-2 protein appears to associate with toll-like receptor 4 on the cell surface and confers responsiveness to lipopolysaccaride (LPS), thus providing a link between the receptor and LPS signaling.^[5]

Interactions

Lymphocyte antigen 96 has been shown to interact with TLR 4.^[3][6]

References

1. "Human PubMed Reference:".
2. "Mouse PubMed Reference:".
3. Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M (Jul 1999). "MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4". J Exp Med. 189 (11): 1777–82. doi:10.1084/jem.189.11.1777. PMC 2193086. PMID 10359581.
4. Abreu MT, Vora P, Faure E, Thomas LS, Arnold ET, Arditi M (Jul 2001). "Decreased expression of Toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide". J Immunol. 167 (3): 1609–16. doi:10.4049/jimmunol.167.3.1609. PMID 11466383.
5. "Entrez Gene: LY96 lymphocyte antigen 96".
6. Re, Fabio; Strominger Jack L (Jun 2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". J. Biol. Chem. United States. 277 (26): 23427–32. doi:10.1074/jbc.M202554200. ISSN 0021-9258. PMID 11976338.

Further reading

• Kato K, Morrison AM, Nakano T, et al. (2000). "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and reproductive systems of embryonic and adult mice". Blood. 96 (1): 362–4. PMID 10891475.
• Dziarski R, Wang Q, Miyake K, et al. (2001). "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". J. Immunol. 166 (3): 1938–44. doi:10.4049/jimmunol.166.3.1938. PMID 11160242.
• Schromm AB, Lien E, Henneke P, et al. (2001). "Molecular Genetic Analysis of an Endotoxin Nonresponder Mutant Cell Line: A Point Mutation in a Conserved Region of Md-2 Abolishes Endotoxin-Induced Signaling". J. Exp. Med. 194 (1): 79–88. doi:10.1084/jem.194.1.79. PMC 2193443. PMID 11435474.
• Visintin A, Mazzoni A, Spitzer JA, Segal DM (2001). "Secreted MD-2 is a large polymeric protein that efficiently confers lipopolysaccharide sensitivity to Toll-like receptor 4". Proc. Natl. Acad. Sci. U.S.A. 98 (21): 12156–61. doi:10.1073/pnas.211445098. PMC 59784. PMID 11593030.
• Akashi S, Nagai Y, Ogata H, et al. (2002). "Human MD-2 confers on mouse Toll-like receptor 4 species-specific lipopolysaccharide recognition". Int. Immunol. 13 (12): 1595–9. doi:10.1093/intimm/13.12.1595. PMID 11717200.
• Abreu MT, Arnold ET, Thomas LS, et al. (2002). "TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells". J. Biol. Chem. 277 (23): 20431–7. doi:10.1074/jbc.M110333200. PMID 11923281.
• Re F, Strominger JL (2002). "Monomeric recombinant MD-2 binds toll-like receptor 4 tightly and confers lipopolysaccharide responsiveness". J. Biol. Chem. 277 (26): 23427–32. doi:10.1074/jbc.M202554200. PMID 11976338.
• Latz E, Visintin A, Lien E, et al. (2003). "Lipopolysaccharide rapidly traffics to and from the Golgi apparatus with the toll-like receptor 4-MD-2-CD14 complex in a process that is distinct from the initiation of signal transduction". J. Biol. Chem. 277 (49): 47834–43. doi:10.1074/jbc.M207873200. PMID 12324469.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Schröder NW, Morath S, Alexander C, et al. (2003). "Lipoteichoic acid (LTA) of Streptococcus pneumoniae and Staphylococcus aureus activates immune cells via Toll-like receptor (TLR)-2, lipopolysaccharide-binding protein (LBP), and CD14, whereas TLR-4 and MD-2 are not involved". J. Biol. Chem. 278 (18): 15587–94. doi:10.1074/jbc.M212829200. PMID 12594207.
• Mullen GE, Kennedy MN, Visintin A, et al. (2003). "The role of disulfide bonds in the assembly and function of MD-2". Proc. Natl. Acad. Sci. U.S.A. 100 (7): 3919–24. doi:10.1073/pnas.0630495100. PMC 153023. PMID 12642668.
• Ohnishi T, Muroi M, Tanamoto K (2004). "MD-2 Is Necessary for the Toll-Like Receptor 4 Protein To Undergo Glycosylation Essential for Its Translocation to the Cell Surface". Clin. Diagn. Lab. Immunol. 10 (3): 405–10. doi:10.1128/cdli.10.3.405-410.2003. PMC 154975. PMID 12738639.
• Thompson PA, Tobias PS, Viriyakosol S, et al. (2003). "Lipopolysaccharide (LPS)-binding protein inhibits responses to cell-bound LPS". J. Biol. Chem. 278 (31): 28367–71. doi:10.1074/jbc.M302921200. PMID 12754215.
• Visintin A, Latz E, Monks BG, et al. (2004). "Lysines 128 and 132 enable lipopolysaccharide binding to MD-2, leading to Toll-like receptor-4 aggregation and signal transduction". J. Biol. Chem. 278 (48): 48313–20. doi:10.1074/jbc.M306802200. PMID 12960171.
• Re F, Strominger JL (2004). "Separate functional domains of human MD-2 mediate Toll-like receptor 4-binding and lipopolysaccharide responsiveness". J. Immunol. 171 (10): 5272–6. doi:10.4049/jimmunol.171.10.5272. PMID 14607928.
• Hamann L, Kumpf O, Müller M, et al. (2005). "A coding mutation within the first exon of the human MD-2 gene results in decreased lipopolysaccharide-induced signaling". Genes Immun. 5 (4): 283–8. doi:10.1038/sj.gene.6364068. PMID 15057266.
• Gruber A, Mancek M, Wagner H, et al. (2004). "Structural model of MD-2 and functional role of its basic amino acid clusters involved in cellular lipopolysaccharide recognition". J. Biol. Chem. 279 (27): 28475–82. doi:10.1074/jbc.M400993200. PMID 15111623.
• Jia HP, Kline JN, Penisten A, et al. (2004). "Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2". Am. J. Physiol. Lung Cell Mol. Physiol. 287 (2): L428–37. doi:10.1152/ajplung.00377.2003. PMID 15121639.

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

External links

• lymphocyte antigen 96, human at the US National Library of Medicine Medical Subject Headings (MeSH)