Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.^[5][6] originally discovered in the laboratory of Dan A. Liebermann (Lord et al. Oncogene 1990) as a Myeloid differentiation primary response gene.

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MYD88
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2JS7, 2Z5V, 3MOP, 4DOM, 4EO7
Identifiers
Aliases	MYD88, MYD88D, myeloid differentiation primary response 88, innate immune signal transduction adaptor, MYD88 innate immune signal transduction adaptor, IMD68
External IDs	OMIM: 602170 MGI: 108005 HomoloGene: 1849 GeneCards: MYD88
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3p22.2 Start 38,138,478 bp[1] End 38,143,022 bp[1]
Gene location (Mouse) Chr. Chromosome 9 (mouse)[2] Band 9 F3|9 71.33 cM Start 119,165,000 bp[2] End 119,170,477 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte blood periodontal fiber palpebral conjunctiva bone marrow spongy bone appendix lower lobe of lung jejunal mucosa spleen Top expressed in right lung lobe lip ankle joint uterus esophagus blood duodenum epithelium of stomach spleen carotid body More reference expression data BioGPS More reference expression data
Gene ontology Molecular function death receptor binding protein binding TIR domain binding identical protein binding protein self-association Toll-like receptor binding Cellular component cytosol plasma membrane endosome membrane cytoplasm nucleus Biological process response to interleukin-1 immune system process negative regulation of apoptotic process MyD88-dependent toll-like receptor signaling pathway toll-like receptor signaling pathway cell surface receptor signaling pathway cellular response to mechanical stimulus regulation of inflammatory response positive regulation of interleukin-6 production positive regulation of I-kappaB kinase/NF-kappaB signaling toll-like receptor 9 signaling pathway positive regulation of interleukin-17 production inflammatory response 3'-UTR-mediated mRNA stabilization positive regulation of type I interferon production positive regulation of interleukin-23 production signal transduction defense response to Gram-positive bacterium positive regulation of NF-kappaB transcription factor activity apoptotic process innate immune response type I interferon signaling pathway positive regulation of gene expression positive regulation of interleukin-8 production defense response to bacterium interleukin-1-mediated signaling pathway cellular response to oxidised low-density lipoprotein particle stimulus positive regulation of cytokine production involved in inflammatory response phagocytosis Toll signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4615 17874 Ensembl ENSG00000172936 ENSMUSG00000032508 UniProt Q99836 P22366 RefSeq (mRNA) NM_001172566 NM_001172567 NM_001172568 NM_001172569 NM_002468 NM_001365876 NM_001365877 NM_001374787 NM_001374788 NM_010851 RefSeq (protein) NP_001166037 NP_001166038 NP_001166039 NP_001166040 NP_002459 NP_001352805 NP_001352806 NP_001361716 NP_001361717 NP_034981 Location (UCSC) Chr 3: 38.14 – 38.14 Mb Chr 9: 119.17 – 119.17 Mb PubMed search [3] [4]
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The MYD88 gene provides instructions for making a protein involved in signaling within immune cells. The MyD88 protein acts as an adapter, connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell.

In innate immunity, the MyD88 plays a pivotal role in immune cell activation through Toll-like receptors (TLRs), which belong to large group of pattern recognition receptors (PRR). In general, these receptors sense common patterns which are shared by various pathogens – Pathogen-associated molecular pattern (PAMPs), or which are produced/released during cellular damage – damage-associated molecular patterns (DAMPs).^[7]

TLRs are homologous to Toll receptors, which were first described in the onthogenesis of fruit flies Drosophila, being responsible for dorso-ventral development. Hence, TLRs have been proved in all animals from insects to mammals. TLRs are located either on the cellular surface (TLR1, TLR2, TLR4, TLR5, TLR6) or within endosomes (TLR3, TLR7, TLR8, TLR9) sensing extracellular or phagocytosed pathogens, respectively. TLRs are integral membrane glycoproteins with typical semicircular-shaped extracellular parts containing leucine-rich repeats responsible for ligand binding, and Intracellular parts containing Toll-Interleukin receptor (TIR) domain.^[8]

After ligand binding, all TLRs apart from TLR3, interact with adaptor protein MyD88. Another adaptor protein, which is activated by TLR3 and TLR4, is called TIR domain-containing adapter-inducing IFN-β (TRIF). Subsequently, these proteins activate two important transcription factors:

• NF-κB is a dimeric protein responsible for expression of various inflammatory cytokines, chemokines and adhesion and costimulatory molecules, which in turn triggers acute inflammation and stimulation of adaptive immunity
• IRFs is a group of proteins responsible for expression of type I interferons setting the so-called antiviral state of a cell.

TLR7 and TLR9 activate both NF-κB and IRF3 through MyD88-dependent and TRIF-independent pathway, respectively.^[8]

The human ortholog MYD88 seems to function similarly to mice, since the immunological phenotype of human cells deficient in MYD88 is similar to cells from MyD88 deficient mice. However, available evidence suggests that MYD88 is dispensable for human resistance to common viral infections and to all but a few pyogenic bacterial infections, demonstrating a major difference between mouse and human immune responses.^[9] Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of diffuse large B-cell lymphoma^[10] and Waldenström's macroglobulinemia.^[11]

Myd88 has been shown to interact with:

Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified. and for some of them an association with susceptibility to various infectious diseases^[22] and to some autoimmune diseases like ulcerative colitis was found.^[23]