LY96 lymphocyte antigen 96 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LY96provided by HGNC
Official Full Name: lymphocyte antigen 96provided by HGNC
Primary source: HGNC:HGNC:17156
See related: Ensembl:ENSG00000154589 MIM:605243; AllianceGenome:HGNC:17156
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MD2; MD-2; ly-96; ESOP-1
Summary: 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]
Expression: Broad expression in spleen (RPKM 8.6), appendix (RPKM 8.4) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 8q21.11

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (73991392..74099857)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (74420655..74529114)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (74903627..74941314)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Myeloid differentiation factor-2/LY96, a potential predictive biomarker of metastasis and poor outcomes in prostate cancer: clinical implications as a potential therapeutic target.
Title: Myeloid differentiation factor-2/LY96, a potential predictive biomarker of metastasis and poor outcomes in prostate cancer: clinical implications as a potential therapeutic target.
Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2.
Title: Insights into the molecular basis and mechanism of heme-triggered TLR4 signalling: The role of heme-binding motifs in TLR4 and MD2.
Myeloid differentiation factor-2 activates monocytes in patients with dilated cardiomyopathy.
Title: Myeloid differentiation factor-2 activates monocytes in patients with dilated cardiomyopathy.
Soluble MD-2 and Heme in Sickle Cell Disease Plasma Promote Pro-Inflammatory Signaling in Endothelial Cells.
Title: Soluble MD-2 and Heme in Sickle Cell Disease Plasma Promote Pro-Inflammatory Signaling in Endothelial Cells.
Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling.
Title: Myeloid differentiation 2 deficiency attenuates AngII-induced arterial vascular oxidative stress, inflammation, and remodeling.
HIV-1 Tat - TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-kappaB dependent pathway.
Title: HIV-1 Tat - TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway.
MD2 protein is highly expressed and involved in the occurrence and development of inflammatory bowel disease, and plays an important role in mucosal barrier injury.
Title: The effects and mechanisms of myeloid differentiation protein 2 on intestinal mucosal permeability in mice with chronic colitis.
The data show that mice expressing humanTLR4/ human MD-2 are slightly more susceptible to C. burnetii infection at some intervals than those expressing mouse TLR4.
Title: Expression of human TLR4/myeloid differentiation factor 2 directs an early innate immune response associated with modest increases in bacterial burden during Coxiella burnetii infection.
The lipid A modifications present in LPS 430 and LPS 435 have a moderate effect on the activation of the human TLR4/MD-2 complex.
Title: Structural variants of Salmonella Typhimurium lipopolysaccharide induce less dimerization of TLR4/MD-2 and reduced pro-inflammatory cytokine production in human monocytes.
Viable CD14/TLR4/MD-2 oligomers were assembled at the plasma membrane surface, and lipopolysaccharide exchange was observed between CD14 and TLR4/MD-2.
Title: A Thermodynamic Funnel Drives Bacterial Lipopolysaccharide Transfer in the TLR4 Pathway.

Submit: New GeneRIF Correction See all GeneRIFs (119)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Novel genetic variants modify the effect of smoking on carotid plaque burden in Hispanics. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat interacts physically with the TLR4-MD2 complex and the N-terminal region (residues 1-29) of Tat is involved in the interation with TLR4-MD2	PubMed
Vif	vif	HIV-1 Vif upregulates the expression of lymphocyte antigen 96 (LY96) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S526 (e-PCR)
- UniSTS:82465

D8S417 (e-PCR)
- UniSTS:26203

D8S526 (e-PCR)
- UniSTS:31433

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Toll-like receptor 4 binding	IEA Inferred from Electronic Annotation more info
enables coreceptor activity	TAS Traceable Author Statement more info	PubMed
enables lipopolysaccharide binding	IEA Inferred from Electronic Annotation more info
enables lipopolysaccharide immune receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables lipopolysaccharide immune receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in cellular defense response	TAS Traceable Author Statement more info	PubMed
involved_in cellular response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in detection of lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in innate immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in lipopolysaccharide-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of lipopolysaccharide-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor 4 signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in toll-like receptor 4 signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in endosome membrane	TAS Traceable Author Statement more info
located_in extracellular region	TAS Traceable Author Statement more info
part_of lipopolysaccharide receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of lipopolysaccharide receptor complex	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: lymphocyte antigen 96

Names: myeloid differentiation protein-2; protein MD-2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001195797.2 → NP_001182726.1 lymphocyte antigen 96 isoform 2 precursor

See identical proteins and their annotated locations for NP_001182726.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1. This variant encodes isoform 2, which is shorter than isoform 1.

Source sequence(s)

BC020690, BG435728

Consensus CDS

CCDS56540.1

UniProtKB/Swiss-Prot

Q9Y6Y9

Related

ENSP00000430533.1, ENST00000518893.1

Conserved Domains (1) summary

cl00274
Location:22 → 123

ML; The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of ...
NM_015364.5 → NP_056179.4 lymphocyte antigen 96 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC022868, AC087672

Consensus CDS

CCDS6216.1

UniProtKB/Swiss-Prot

B3Y6A5, E5RJJ7, Q9Y6Y9

Related

ENSP00000284818.2, ENST00000284818.7

Conserved Domains (1) summary

cl00274
Location:22 → 153

ML; The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000008.11 Reference GRCh38.p14 Primary Assembly

Range

73991392..74099857

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017013299.2 → XP_016868788.1 lymphocyte antigen 96 isoform X2
XM_017013300.2 → XP_016868789.1 lymphocyte antigen 96 isoform X3
XM_011517508.3 → XP_011515810.1 lymphocyte antigen 96 isoform X4

Conserved Domains (1) summary

cl00274
Location:22 → 130

ML; The ML (MD-2-related lipid-recognition) domain is present in MD-1, MD-2, GM2 activator protein, Niemann-Pick type C2 (Npc2) protein, phosphatidylinositol/phosphatidylglycerol transfer protein (PG/PI-TP), mite allergen Der p 2 and several proteins of ...
XM_047421662.1 → XP_047277618.1 lymphocyte antigen 96 isoform X1