Hmdb loader
Identification
HMDB Protein ID HMDBP13842
Secondary Accession Numbers None
Name Myeloid differentiation primary response protein MyD88
Synonyms Not Available
Gene Name MYD88
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:9697844). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:9575168, PubMed:9697844). Increases IL-8 transcription. Involved in IL-18-mediated signaling pathway (PubMed:9697844). Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes (PubMed:17018642). Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses, induces IL1B release through NLRP3 inflammasome activation (By similarity). MyD88-mediated signaling in intestinal epithelial cells is crucial for maintenance of gut homeostasis and controls the expression of the antimicrobial lectin REG3G in the small intestine (PubMed:17635956, PubMed:21998396). Mediates leukocyte recruitment at the inflammatory site (PubMed:18941239).Defective in its ability to induce IRAK phosphorylation and NF-kappa-B activation and can function as a negative regulator of activation by IL-1 or lipopolysaccharide (LPS).
Pathways
  • African trypanosomiasis
  • Chagas disease
  • Coronavirus disease - COVID-19
  • Epstein-Barr virus infection
  • Hepatitis B
  • Herpes simplex virus 1 infection
  • Human immunodeficiency virus 1 infection
  • Influenza A
  • Legionellosis
  • Leishmaniasis
  • Lipid and atherosclerosis
  • Malaria
  • MAPK signaling pathway
  • Measles
  • NF-kappa B signaling pathway
  • NOD-like receptor signaling pathway
  • PD-L1 expression and PD-1 checkpoint pathway in cancer
  • Pertussis
  • Salmonella infection
  • Toll-like receptor signaling pathway
  • Toxoplasmosis
  • Tuberculosis
  • Yersinia infection
Reactions Not Available
GO Classification
Biological Process
3'-UTR-mediated mRNA stabilization
lipopolysaccharide-mediated signaling pathway
defense response to Gram-positive bacterium
interleukin-1-mediated signaling pathway
transmembrane receptor protein serine/threonine kinase signaling pathway
type I interferon-mediated signaling pathway
immunoglobulin mediated immune response
phagocytosis
positive regulation of tumor necrosis factor production
positive regulation of chemokine production
cellular response to oxidised low-density lipoprotein particle stimulus
positive regulation of cytokine production involved in inflammatory response
positive regulation of interleukin-6 production
positive regulation of interleukin-8 production
defense response to protozoan
cellular response to mechanical stimulus
establishment of endothelial intestinal barrier
regulation of tumor necrosis factor production
positive regulation of interleukin-17 production
neutrophil activation involved in immune response
induced systemic resistance
leukocyte activation involved in inflammatory response
neutrophil-mediated killing of bacterium
positive regulation of interleukin-23 production
positive regulation of lymphocyte proliferation
regulation of chemokine (C-X-C motif) ligand 1 production
regulation of chemokine (C-X-C motif) ligand 2 production
regulation of interleukin-6 production
regulation of neutrophil migration
response to peptidoglycan
positive regulation of smooth muscle cell proliferation
innate immune response
regulation of cell proliferation
regulation of inflammatory response
response to lipopolysaccharide
inflammatory response
cellular response to lipopolysaccharide
positive regulation of gene expression
apoptotic process
cell surface receptor signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB cascade
regulation of gene expression
immune response
positive regulation of NF-kappaB transcription factor activity
positive regulation of JNK cascade
response to molecule of fungal origin
Toll signaling pathway
defense response to bacterium
response to interleukin-1
MyD88-dependent toll-like receptor signaling pathway
JNK cascade
cytokine-mediated signaling pathway
positive regulation of type I interferon production
response to virus
Cellular Component
protein-containing complex
nucleus
plasma membrane
postsynaptic density
cytosol
cytoplasm
Molecular Function
TIR domain binding
identical protein binding
receptor binding
Toll binding
protein self-association
Toll-like receptor binding
interleukin-1 receptor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 296
Molecular Weight 33752.575
Theoretical pI 5.512
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P22366
UniProtKB/Swiss-Prot Entry Name MYD88_MOUSE
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Huttlin EL, Jedrychowski MP, Elias JE, Goswami T, Rad R, Beausoleil SA, Villen J, Haas W, Sowa ME, Gygi SP: A tissue-specific atlas of mouse protein phosphorylation and expression. Cell. 2010 Dec 23;143(7):1174-89. doi: 10.1016/j.cell.2010.12.001. [PubMed:21183079 ]
  3. Bonnert TP, Garka KE, Parnet P, Sonoda G, Testa JR, Sims JE: The cloning and characterization of human MyD88: a member of an IL-1 receptor related family. FEBS Lett. 1997 Jan 27;402(1):81-4. doi: 10.1016/s0014-5793(96)01506-2. [PubMed:9013863 ]
  4. Hardiman G, Jenkins NA, Copeland NG, Gilbert DJ, Garcia DK, Naylor SL, Kastelein RA, Bazan JF: Genetic structure and chromosomal mapping of MyD88. Genomics. 1997 Oct 15;45(2):332-9. doi: 10.1006/geno.1997.4940. [PubMed:9344657 ]
  5. Lord KA, Hoffman-Liebermann B, Liebermann DA: Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6. Oncogene. 1990 Jul;5(7):1095-7. [PubMed:2374694 ]
  6. Burns K, Martinon F, Esslinger C, Pahl H, Schneider P, Bodmer JL, Di Marco F, French L, Tschopp J: MyD88, an adapter protein involved in interleukin-1 signaling. J Biol Chem. 1998 May 15;273(20):12203-9. doi: 10.1074/jbc.273.20.12203. [PubMed:9575168 ]
  7. Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S: Targeted disruption of the MyD88 gene results in loss of IL-1- and IL-18-mediated function. Immunity. 1998 Jul;9(1):143-50. doi: 10.1016/s1074-7613(00)80596-8. [PubMed:9697844 ]
  8. Janssens S, Burns K, Tschopp J, Beyaert R: Regulation of interleukin-1- and lipopolysaccharide-induced NF-kappaB activation by alternative splicing of MyD88. Curr Biol. 2002 Mar 19;12(6):467-71. doi: 10.1016/s0960-9822(02)00712-1. [PubMed:11909531 ]
  9. Negishi H, Fujita Y, Yanai H, Sakaguchi S, Ouyang X, Shinohara M, Takayanagi H, Ohba Y, Taniguchi T, Honda K: Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program. Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15136-41. doi: 10.1073/pnas.0607181103. Epub 2006 Oct 3. [PubMed:17018642 ]
  10. Brandl K, Plitas G, Schnabl B, DeMatteo RP, Pamer EG: MyD88-mediated signals induce the bactericidal lectin RegIII gamma and protect mice against intestinal Listeria monocytogenes infection. J Exp Med. 2007 Aug 6;204(8):1891-900. doi: 10.1084/jem.20070563. Epub 2007 Jul 16. [PubMed:17635956 ]
  11. Babcock AA, Toft-Hansen H, Owens T: Signaling through MyD88 regulates leukocyte recruitment after brain injury. J Immunol. 2008 Nov 1;181(9):6481-90. doi: 10.4049/jimmunol.181.9.6481. [PubMed:18941239 ]
  12. Vaishnava S, Yamamoto M, Severson KM, Ruhn KA, Yu X, Koren O, Ley R, Wakeland EK, Hooper LV: The antibacterial lectin RegIIIgamma promotes the spatial segregation of microbiota and host in the intestine. Science. 2011 Oct 14;334(6053):255-8. doi: 10.1126/science.1209791. [PubMed:21998396 ]
  13. Troutman TD, Hu W, Fulenchek S, Yamazaki T, Kurosaki T, Bazan JF, Pasare C: Role for B-cell adapter for PI3K (BCAP) as a signaling adapter linking Toll-like receptors (TLRs) to serine/threonine kinases PI3K/Akt. Proc Natl Acad Sci U S A. 2012 Jan 3;109(1):273-8. doi: 10.1073/pnas.1118579109. Epub 2011 Dec 20. [PubMed:22187460 ]
  14. Zhao Y, Mudge MC, Soll JM, Rodrigues RB, Byrum AK, Schwarzkopf EA, Bradstreet TR, Gygi SP, Edelson BT, Mosammaparast N: OTUD4 Is a Phospho-Activated K63 Deubiquitinase that Regulates MyD88-Dependent Signaling. Mol Cell. 2018 Feb 1;69(3):505-516.e5. doi: 10.1016/j.molcel.2018.01.009. [PubMed:29395066 ]