MYD88

Myeloid differentiation primary response gene (88)
Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations
Available structures PDB 2JS7, 2Z5V, 3MOP
Identifiers
Symbols	MYD88;
External IDs	OMIM: 602170 MGI: 108005 HomoloGene: 1849 GeneCards: MYD88 Gene
Gene Ontology Molecular function • transmembrane receptor activity • Toll binding • death receptor binding • protein binding • TIR domain binding Cellular component • cytoplasm • cytosol • cytosol • plasma membrane • plasma membrane • endosome membrane • endosome membrane • intrinsic to membrane Biological process • toll-like receptor signaling pathway • response to molecule of fungal origin • MyD88-dependent toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • anti-apoptosis • signal transduction • cell surface receptor linked signaling pathway • Toll signaling pathway • response to virus • immunoglobulin mediated immune response • cytokine-mediated signaling pathway • lipopolysaccharide-mediated signaling pathway • response to peptidoglycan • response to lipopolysaccharide • positive regulation of interleukin-17 production • positive regulation of interleukin-23 production • positive regulation of interleukin-6 production • positive regulation of tumor necrosis factor production • toll-like receptor 1 signaling pathway • toll-like receptor 2 signaling pathway • toll-like receptor 4 signaling pathway • regulation of cell proliferation • positive regulation of I-kappaB kinase/NF-kappaB cascade • negative regulation of growth of symbiont in host • positive regulation of chemokine biosynthetic process • innate immune response • type I interferon biosynthetic process • positive regulation of transcription from RNA polymerase II promoter • positive regulation of JNK cascade • nerve growth factor receptor signaling pathway • positive regulation of smooth muscle cell proliferation • positive regulation of lymphocyte proliferation • regulation of inflammatory response • defense response to Gram-positive bacterium • positive regulation of NF-kappaB transcription factor activity • 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	Q0PM15
RefSeq (mRNA)	NM_001172566.1	NM_010851.2
RefSeq (protein)	NP_001166037.1	NP_034981.1
Location (UCSC)	Chr 3: 38.18 – 38.18 Mb	Chr 9: 119.25 – 119.25 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]

Function

In mice, MyD88 is a universal adapter protein as it is used by 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.^[3] The human ortholog MYD88 seems to function similarly, 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.^[4]

Discovery

MyD88 was originally discovered and cloned by Drs Dan A Liebermann and Barbara Hoffman in mice.^[5]

Interactions

Myd88 has been shown to interact with TLR 4,^[6][7][8][9] Interleukin 1 receptor, type I,^[10][11] RAC1,^[12] IRAK2^[9][11][13] and IRAK1.^{[9][13][14][15]} It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease.^[16]

References

1. ^ "Entrez Gene: MYD88 Myeloid differentiation primary response gene (88)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4615. 
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. ^ 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. 
4. ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2688396. 
5. ^ 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. 
6. ^ 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. 
7. ^ Doyle, Sean E; O'Connell Ryan, Vaidya Sagar A, Chow Edward K, Yee Kathleen, Cheng Genhong (Apr. 2003). "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". J. Immunol. (United States) 170 (7): 3565–71. ISSN 0022-1767. PMID 12646618. 
8. ^ Rhee, S H; Hwang D (Nov. 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. 
9. ^ ^{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 (Sep. 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. 
10. ^ Burns, K; Clatworthy J, Martin L, Martinon F, Plumpton C, Maschera B, Lewis A, Ray K, Tschopp J, Volpe F (Jun. 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. 
11. ^ ^{a b} Muzio, M; Ni J, Feng P, Dixit V M (Nov. 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. 
12. ^ Jefferies, C; Bowie A, Brady G, Cooke E L, Li X, O'Neill L A (Jul. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=87113. 
13. ^ ^{a b} Wesche, H; Gao X, Li X, Kirschning C J, Stark G R, Cao Z (Jul. 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. 
14. ^ Chen, Bing-Chang; Wu Wen-Tung, Ho Feng-Ming, Lin Wan-Wan (Jul. 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. 
15. ^ Li, Shyun; Strelow Astrid, Fontana Elizabeth J, Wesche Holger (Apr. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122810. 
16. ^ Lim, JE; Kou J, Song M, Pattanayak A, Jin J, Lalonde R, Fukuchi K (Sept. 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3157279. 

Further reading

• Hardiman G, Rock FL, Balasubramanian S, et al. (1997). "Molecular characterization and modular analysis of human MyD88". Oncogene 13 (11): 2467–75. PMID 8957090. 
• Bonnert TP, Garka KE, Parnet P, et al. (1997). "The cloning and characterization of human MyD88: a member of an IL-1 receptor related family". FEBS Lett. 402 (1): 81–4. doi:10.1016/S0014-5793(96)01506-2. PMID 9013863. 
• Hardiman G, Jenkins NA, Copeland NG, et al. (1998). "Genetic structure and chromosomal mapping of MyD88". Genomics 45 (2): 332–9. doi:10.1006/geno.1997.4940. PMID 9344657. 
• Muzio M, Ni J, Feng P, Dixit VM (1997). "IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling". Science 278 (5343): 1612–5. doi:10.1126/science.278.5343.1612. PMID 9374458. 
• Jaunin F, Burns K, Tschopp J, et al. (1998). "Ultrastructural distribution of the death-domain-containing MyD88 protein in HeLa cells". Exp. Cell Res. 243 (1): 67–75. doi:10.1006/excr.1998.4131. PMID 9716450. 
• Wesche H, Gao X, Li X, et al. (1999). "IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family". J. Biol. Chem. 274 (27): 19403–10. doi:10.1074/jbc.274.27.19403. PMID 10383454. 
• Burns K, Clatworthy J, Martin L, et al. (2000). "Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor". Nat. Cell Biol. 2 (6): 346–51. doi:10.1038/35014038. PMID 10854325. 
• Aliprantis AO, Yang RB, Weiss DS, et al. (2000). "The apoptotic signaling pathway activated by Toll-like receptor-2". EMBO J. 19 (13): 3325–36. doi:10.1093/emboj/19.13.3325. PMC 313930. PMID 10880445. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=313930. 
• Rhee SH, Hwang D (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. 275 (44): 34035–40. doi:10.1074/jbc.M007386200. PMID 10952994. 
• Fitzgerald KA, Palsson-McDermott EM, Bowie AG, et al. (2001). "Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction". Nature 413 (6851): 78–83. doi:10.1038/35092578. PMID 11544529. 
• Tauszig-Delamasure S, Bilak H, Capovilla M, et al. (2002). "Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections". Nat. Immunol. 3 (1): 91–7. doi:10.1038/ni747. PMID 11743586. 
• Bannerman DD, Tupper JC, Kelly JD, et al. (2002). "The Fas-associated death domain protein suppresses activation of NF-κB by LPS and IL-1β". J. Clin. Invest. 109 (3): 419–25. doi:10.1172/JCI14774. PMC 150862. PMID 11828002. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=150862. 
• Tamai R, Sakuta T, Matsushita K, et al. (2002). "Human Gingival CD14+ Fibroblasts Primed with Gamma Interferon Increase Production of Interleukin-8 in Response to Lipopolysaccharide through Up-Regulation of Membrane CD14 and MyD88 mRNA Expression". Infect. Immun. 70 (3): 1272–8. doi:10.1128/IAI.70.3.1272-1278.2002. PMC 127773. PMID 11854210. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=127773. 
• Radons J, Gabler S, Wesche H, et al. (2002). "Identification of essential regions in the cytoplasmic tail of interleukin-1 receptor accessory protein critical for interleukin-1 signaling". J. Biol. Chem. 277 (19): 16456–63. doi:10.1074/jbc.M201000200. PMID 11880380. 
• Janssens S, Burns K, Tschopp J, Beyaert R (2002). "Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88". Curr. Biol. 12 (6): 467–71. doi:10.1016/S0960-9822(02)00712-1. PMID 11909531. 
• Li S, Strelow A, Fontana EJ, Wesche H (2002). "IRAK-4: A novel member of the IRAK family with the properties of an IRAK-kinase". Proc. Natl. Acad. Sci. U.S.A. 99 (8): 5567–72. doi:10.1073/pnas.082100399. PMC 122810. PMID 11960013. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122810. 
• Medvedev AE, Lentschat A, Wahl LM, et al. (2002). "Dysregulation of LPS-induced Toll-like receptor 4-MyD88 complex formation and IL-1 receptor-associated kinase 1 activation in endotoxin-tolerant cells". J. Immunol. 169 (9): 5209–16. PMID 12391239. 
• 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241. 
• Raschi E, Testoni C, Bosisio D, et al. (2003). "Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies". Blood 101 (9): 3495–500. doi:10.1182/blood-2002-08-2349. PMID 12531807. 
• Doyle SE, O'Connell R, Vaidya SA, et al. (2003). "Toll-like receptor 3 mediates a more potent antiviral response than Toll-like receptor 4". J. Immunol. 170 (7): 3565–71. PMID 12646618. 

External links

• MeSH MyD88+Protein