MYD88

Myeloid differentiation primary response 88
Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2JS7, 2Z5V, 3MOP, 4DOM, 4EO7
Identifiers
Symbols	MYD88; MYD88D
External IDs	OMIM: 602170 MGI: 108005 HomoloGene: 1849 ChEMBL: 5919 GeneCards: MYD88 Gene
Gene Ontology Molecular function • death receptor binding • protein binding • identical protein binding • TIR domain binding Cellular component • cytosol • plasma membrane • endosome membrane Biological process • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • inflammatory response • signal transduction • cell surface receptor signaling pathway • positive regulation of interleukin-17 production • positive regulation of interleukin-23 production • positive regulation of interleukin-6 production • toll-like receptor 2 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • negative regulation of apoptotic process • positive regulation of I-kappaB kinase/NF-kappaB cascade • innate immune response • neurotrophin TRK receptor signaling pathway • regulation of inflammatory response • response to interleukin-1 • 3'-UTR-mediated mRNA stabilization • cellular response to mechanical stimulus Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4615	17874
Ensembl	ENSG00000172936	ENSMUSG00000032508
UniProt	Q99836	P22366
RefSeq (mRNA)	NM_001172566	NM_010851
RefSeq (protein)	NP_001166037	NP_034981
Location (UCSC)	Chr 3: 38.18 – 38.18 Mb	Chr 9: 119.34 – 119.34 Mb
PubMed search
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Myeloid differentiation primary response gene (88) (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.^[1][2]

Model organisms

Model organisms have been used in the study of MYD88 function. The gene was originally discovered and cloned by Dan Liebermann and Barbara Hoffman in mice.^[3] In that species it is a universal adapter protein as it is used by almost all TLRs (except TLR 3) to activate the transcription factor NF-κB. Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK.^[4] It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease.^[5]

A conditional knockout mouse line, called Myd88^{tm1a(EUCOMM)Wtsi[9][10]} was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[11][12][13] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[7][14] Twenty-one tests were carried out on homozygous mutant animals, revealing one abnormality: male mutants had an increased susceptibility to bacterial infection.

Function

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.^[15] 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 ^[16] and Waldenstrom's Macroglobulinemia ^[17]

Interactions

Myd88 has been shown to interact with TLR 4,^{[18][19][20][21]} Interleukin 1 receptor, type I,^[22][23] RAC1,^[24] IRAK2^[21][23][25] and IRAK1.^{[21][25][26][27]}

References

Further reading

External links

• MyD88 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)