From Wikipedia, the free encyclopedia
  (Redirected from Myd88)
Jump to: navigation, search
Myeloid differentiation primary response 88
Toll-like receptor pathways revised.jpg
Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols MYD88 ; MYD88D
External IDs OMIM602170 MGI108005 HomoloGene1849 ChEMBL: 5919 GeneCards: MYD88 Gene
RNA expression pattern
PBB GE MYD88 209124 at tn.png
More reference expression data
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 [1] [2]

Myeloid differentiation primary response gene 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.[1][2]

Model organisms[edit]

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 Myd88tm1a(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.


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]


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]

Gene polymorphisms[edit]

Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified and for some of them an association with susceptibility to various infective disease [28] and also with susceptibility to some autoimmune diseases like ulcerative colitis was found. [29]


  1. ^ "Entrez Gene: MYD88 Myeloid differentiation primary response gene (88)". 
  2. ^ Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE (January 1997). "The cloning and characterization of human MyD88: a member of an IL-1 receptor related family". FEBS Letters 402 (1): 81–4. doi:10.1016/S0014-5793(96)01506-2. PMID 9013863. 
  3. ^ Lord KA, Hoffman-Liebermann B, Liebermann DA (1990). "Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6". Oncogene 5 (7): 1095–7. PMID 2374694. 
  4. ^ Arancibia SA, Beltrán CJ, Aguirre IM, Silva P, Peralta AL, Malinarich F, Hermoso MA. (2007). "Toll-like receptors are key participants in innate immune responses". Biological research 40 (2): 97–112. doi:10.4067/S0716-97602007000200001. PMID 18064347. 
  5. ^ Lim, JE; Kou J; Song M; Pattanayak A; Jin J; Lalonde R; Fukuchi K (September 2011). "MyD88 Deficiency Ameliorates β-Amyloidosis in an Animal Model of Alzheimer's Disease". Am. J. Pathol. (United States) 179 (3): 1095–103. doi:10.1016/j.ajpath.2011.05.045. PMC 3157279. PMID 21763676. 
  6. ^ "Salmonella infection data for Myd88". Wellcome Trust Sanger Institute. 
  7. ^ a b Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. 
  8. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  9. ^ "International Knockout Mouse Consortium". 
  10. ^ "Mouse Genome Informatics". 
  11. ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.  edit
  12. ^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718. 
  13. ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. 
  14. ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism.". Genome Biol 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. 
  15. ^ von Bernuth H, Picard C, Jin Z et al. (August 2008). "Pyogenic Bacterial Infections in Humans with MyD88 Deficiency". Science 321 (5889): 691–6. doi:10.1126/science.1158298. PMC 2688396. PMID 18669862. 
  16. ^ Ngo et al, Nature 2011
  17. ^ Treon et al, NEJM 2012
  18. ^ Chuang, Tsung-Hsien; Ulevitch Richard J (May 2004). "Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors". Nat. Immunol. (United States) 5 (5): 495–502. doi:10.1038/ni1066. ISSN 1529-2908. PMID 15107846. 
  19. ^ Doyle, Sean E; O'Connell Ryan, Vaidya Sagar A, Chow Edward K, Yee Kathleen, Cheng Genhong (April 2003). "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". J. Immunol. (United States) 170 (7): 3565–71. doi:10.4049/jimmunol.170.7.3565. ISSN 0022-1767. PMID 12646618. 
  20. ^ Rhee, S H; Hwang D (November 2000). "Murine TOLL-like receptor 4 confers lipopolysaccharide responsiveness as determined by activation of NF kappa B and expression of the inducible cyclooxygenase". J. Biol. Chem. (UNITED STATES) 275 (44): 34035–40. doi:10.1074/jbc.M007386200. ISSN 0021-9258. PMID 10952994. 
  21. ^ a b c Fitzgerald, K A; Palsson-McDermott E M, Bowie A G, Jefferies C A, Mansell A S, Brady G, Brint E, Dunne A, Gray P, Harte M T, McMurray D, Smith D E, Sims J E, Bird T A, O'Neill L A (September 2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction". Nature (England) 413 (6851): 78–83. doi:10.1038/35092578. ISSN 0028-0836. PMID 11544529. 
  22. ^ Burns, K; Clatworthy J; Martin L; Martinon F; Plumpton C; Maschera B; Lewis A; Ray K; Tschopp J; Volpe F (June 2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nat. Cell Biol. (ENGLAND) 2 (6): 346–51. doi:10.1038/35014038. ISSN 1465-7392. PMID 10854325. 
  23. ^ a b Muzio, M; Ni J; Feng P; Dixit V M (November 1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science (UNITED STATES) 278 (5343): 1612–5. doi:10.1126/science.278.5343.1612. ISSN 0036-8075. PMID 9374458. 
  24. ^ Jefferies, C; Bowie A; Brady G; Cooke E L; Li X; O'Neill L A (July 2001). "Transactivation by the p65 Subunit of NF-κB in Response to Interleukin-1 (IL-1) Involves MyD88, IL-1 Receptor-Associated Kinase 1, TRAF-6, and Rac1". Mol. Cell. Biol. (United States) 21 (14): 4544–52. doi:10.1128/MCB.21.14.4544-4552.2001. ISSN 0270-7306. PMC 87113. PMID 11416133. 
  25. ^ a b Wesche, H; Gao X; Li X; Kirschning C J; Stark G R; Cao Z (July 1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". J. Biol. Chem. (UNITED STATES) 274 (27): 19403–10. doi:10.1074/jbc.274.27.19403. ISSN 0021-9258. PMID 10383454. 
  26. ^ Chen, Bing-Chang; Wu Wen-Tung; Ho Feng-Ming; Lin Wan-Wan (July 2002). "Inhibition of interleukin-1beta -induced NF-kappa B activation by calcium/calmodulin-dependent protein kinase kinase occurs through Akt activation associated with interleukin-1 receptor-associated kinase phosphorylation and uncoupling of MyD88". J. Biol. Chem. (United States) 277 (27): 24169–79. doi:10.1074/jbc.M106014200. ISSN 0021-9258. PMID 11976320. 
  27. ^ Li, Shyun; Strelow Astrid; Fontana Elizabeth J; Wesche Holger (April 2002). "IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (8): 5567–72. doi:10.1073/pnas.082100399. ISSN 0027-8424. PMC 122810. PMID 11960013. 
  28. ^ Netea MG (2012). "Genetic variation in Toll-like receptors and disease susceptibility..". Nat Immunol 13 (6): 535–42. doi:10.1038/ni.2284. PMID 22610250. 
  29. ^ Matsunaga K (Jan 2014). "The 1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis.". J Mol Med Rep 9 (1): 28–32. doi:10.3892/mmr.2013.1769. PMID 24189845. 

Further reading[edit]

External links[edit]