Homo sapiens Gene: MYD88
Summary
InnateDB Gene IDBG-25713.7
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol MYD88
Gene Name myeloid differentiation primary response 88
Synonyms MYD88D;
Species Homo sapiens
Ensembl Gene ENSG00000172936
Encoded Proteins
myeloid differentiation primary response gene (88)
myeloid differentiation primary response gene (88)
myeloid differentiation primary response gene (88)
myeloid differentiation primary response gene (88)
myeloid differentiation primary response gene (88)
myeloid differentiation primary response gene (88)
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
MYD88 is a Toll/IL-1R homology (TIR) domain containing adaptor which recruits IRAK1 possibly through IRAK4.
MYD88 can interact with bacterial TIR domain containing-proteins (Tcps) identified in Escherichia coli CFT073 (TcpC) and Brucella melitensis (TcpB) and interfere with MYD88-dependent pathway, thus suppressing innate immunity and increasing virulence.
MYD88 binding with interleukin-1 (IL-1) receptor (IL1R1) is required for inducing endocytosis of IL1R1 following ligand binding.
MYD88 is a key adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity.
MYD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF.
TLR-2/MyD88/PI3K/Rac1/Akt pathway mediates LTA-induced MAPKs activation, which in turn initiates the activation of NF-kappaB, and ultimately induces cPLA2/COX-2-dependent PGE2 and IL-6 generation.
MYD88 plays a critical role in reverse cholesterol transport in vitro and in vivo, in part through promoting ATP-binding cassette A1 transporter upregulation, coupling cholesterol trafficking to inflammation through MYD88 and identifying innate immunity as a physiologic signal in cholesterol homeostasis.
MYD88 and IRAK1 autosomal recessive deficiencies impair Toll-like receptor (TLR)- and interleukin-1 receptor-mediated immunity and predispose patients to recurrent life-threatening bacterial diseases, such as invasive pneumococcal disease in particular, in infancy and early childhood, with weak signs of inflammation.
MYD88 is essential in restricting TLR3 signalling and the host protection from unwanted immunopathologies associated with excessive production of IFNB1. MYD88 inhibits TLR3 signalling by impairing IKBKE-mediated induction of IRF3, and consequently the expression IFNB1 and CCL5.
MYD88 is activated by MHC class II in response to staphylococcal enterotoxins and is crucial for the induction of pro-inflammatory cytokines.
MYD88 is a key signalling adapter in TLR signalling. MYD88 aggregates in the cell as distinct foci and co-localizes with IRAK4 in these Myddosomes - the formation of which is required for MYD88 function.
MYD88 is required in dendritic cells stimulated with TLR9 ligand for the enhancement of T cell-dependent antibody response. In addition, MYD88 is required in B cells to facilitate strong anti-viral antibody responses. (Demonstrated in murine model)
MYD88 deficient macrophages displayed impaired interaction with fungal yeast cells and produced low levels of pro-inflammatory cytokines. MYD88 signalling is important in the activation of fungicidal mechanisms and the induction of protective innate immune responses against P. brasiliensis. (Demonstrated in murine model)
MYD88 mediates cytoskeletal remodelling and late spreading of lipopolysaccharide (LPS)-stimulated macrophages. (Demonstrated in mice)
MYD88-dependent recruitment of inflammatory monocytes and dendritic cells to the lungs are key initial cellular responses required for early protection from Burkholderia mallei infection. (Demonstrated in mice)
MYD88 deficiency results in delayed recruitment of phagocytes and defective production of proinflammatory cytokines in response to Salmonella infection. (Demonstrated in mice)
MYD88 signalling in intestinal epithelial cells is crucial for the maintenance of gut microbiota homeostasis. (Demonstrated in mice)
MYD88 mediated production of reactive oxygen species (ROS) is essential for the induction of IL12 by lactic acid bacteria. (Demonstrated in mice)
Following NOD2 activation, IRF4 interacts with MYD88, TRAF6, and RIPK2 and downregulates K63-linked polyubiquitinylation of RICK and TRAF6 leading to disruption of NFkB activation pathways.
Endotoxin tolerance re-programs TLR4 signalling via suppression of PELI1, a positive regulator of MyD88- and TIR domain-containing adapter inducing IFN-β (TRIF)-dependent signalling that promotes K63-linked polyubiquitination of IRAK1, TBK1, and TAK1.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Myd88 restricts West Nile virus (WNV) by inhibiting replication in subsets of cells and modulating expression of chemokines that regulate immune cell migration into the central nervous system.
[Mus musculus] Myd88 signalling plays an important role for resisting primary influenza virus infection but is dispensable for protection against a secondary lethal challenge.
[Mus musculus] Myd88 is essential in restricting Tlr3 signaling and the host protection from unwanted immunopathologies associated with excessive production of Ifnb1. Myd88 inhibits Tlr3 signalling by impairing Ikbke-mediated induction of Irf3, and consequently the expression of Ifnb1 and Ccl5.
[Mus musculus] Myd88 is activated by MHC class II in response to staphylococcal enterotoxins and is crucial for the induction of pro-inflammatory cytokines.
[Mus musculus] MYD88 is a key signalling adapter in TLR signalling. MYD88 aggregates in the cell as distinct foci and co-localizes with IRAK4 in these Myddosomes - the formation of which is required for MYD88 function. (Demonstrated in human)
[Mus musculus] Myd88 is required in dendritic cells stimulated with Tlr9 ligand for the enhancement of T cell-dependent antibody response. In addition, Myd88 is required in B cells to facilitate strong anti-viral antibody responses.
[Mus musculus] Myd88 deficient macrophages displayed impaired interaction with fungal yeast cells and produced low levels of pro-inflammatory cytokines. Myd88 signalling is important in the activation of fungicidal mechanisms and the induction of protective innate immune responses against P. brasiliensis.
[Mus musculus] Myd88 mediates cytoskeletal remodelling and late spreading of lipopolysaccharide (LPS)-stimulated macrophages.
[Mus musculus] Myd88-dependent recruitment of inflammatory monocytes and dendritic cells to the lungs are key initial cellular responses required for early protection from Burkholderia mallei infection.
[Mus musculus] Myd88 deficiency results in delayed recruitment of phagocytes and defective production of proinflammatory cytokines in response to Salmonella infection.
[Mus musculus] Myd88 signalling in intestinal epithelial cells is crucial for the maintenance of gut microbiota homeostasis.
[Mus musculus] Myd88 mediated production of reactive oxygen species (ROS) is essential for the induction of Il12 by lactic acid bacteria.
[Mus musculus] Flagellin-specific IgG1 antibody response is induced through a Tlr5-, inflammasome-, and Myd88-independent pathway.
[Mus musculus] The SF3A/SF3B mRNA splicing complexes regulate the innate immune response in part by regulating Myd88S levels, which modulate the extent of the innate immune response through Tlr4.
[Mus musculus] Mir149 negatively regulates TLR/Myd88 mediated inflammatory responses in macrophages by targeting Myd88 mRNA.
[Mus musculus] Myd88 and Ticam1 pathways differently regulate Tlr4-induced immune responses in B cells.
[Mus musculus] Ticam1 but not Myd88 signalling is critical for the Trl4 protective adjuvant effect in neonates; where Ticam1(-/-) but not Myd88(-/-) neonates are highly susceptible to Escherichia coli peritonitis and bacteremia.
[Mus musculus] Treml4 is an essential positive regulator of Tlr7 signalling. Treml4(-/-) macrophages are hyporesponsive to Tlr7 agonists and fail to produce type I interferons due to impaired phosphorylation of Stat1 by Mapk14 and decreased recruitment of Myd88 to Tlr7.
[Mus musculus] Intracellular Sef/IL-17R (SEFIR) domain of Il17rd targets TIR adaptor proteins Myd88, Tirap, Ticam1, Ticam2 and Traf6 to inhibit TLR downstream signalling.
[Mus musculus] Map1s (Mtap1s) controls bacterial phagocytosis through TLR signalling by interacting directly with Myd88.
[Mus musculus] Hepatocyte Myd88 affects bile acids, gut microbiota and metabolome contributing to regulation of glucose and lipid metabolism.
[Mus musculus] Extracellular RNA of cardiac origin exhibits a potent pro-inflammatory property in vitro and in vivo and induces cytokine production through Tlr7-Myd88 signalling.
Entrez Gene
Summary This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal Toll-interleukin1 receptor domain. Patients with defects in this gene have an increased susceptibility to pyogenic bacterial infections. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]
Gene Information
Type Protein coding
Genomic Location Chromosome 3:38138478-38143022
Strand Forward strand
Band p22.2
Transcripts
ENST00000396334 ENSP00000379625
ENST00000424893 ENSP00000389979
ENST00000417037 ENSP00000401399
ENST00000416282
ENST00000443433 ENSP00000390565
ENST00000421516 ENSP00000391753
ENST00000460295
ENST00000495303 ENSP00000417848
ENST00000481122
ENST00000484513
ENST00000463956
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 129 experimentally validated interaction(s) in this database.
They are also associated with 59 interaction(s) predicted by orthology.
Experimentally validated
Total 129 [view]
Protein-Protein 120 [view]
Protein-DNA 2 [view]
Protein-RNA 0
DNA-DNA 7 [view]
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 59 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0005102 receptor binding
GO:0005121 Toll binding
GO:0005123 death receptor binding
GO:0005149 interleukin-1 receptor binding
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0070976 TIR domain binding
Biological Process
GO:0002224 toll-like receptor signaling pathway
GO:0002238 response to molecule of fungal origin
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007166 cell surface receptor signaling pathway
GO:0007254 JNK cascade
GO:0008063 Toll signaling pathway
GO:0009615 response to virus
GO:0016064 immunoglobulin mediated immune response
GO:0019221 cytokine-mediated signaling pathway
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032481 positive regulation of type I interferon production
GO:0032494 response to peptidoglycan
GO:0032496 response to lipopolysaccharide
GO:0032740 positive regulation of interleukin-17 production
GO:0032747 positive regulation of interleukin-23 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034134 toll-like receptor 2 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034146 toll-like receptor 5 signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034166 toll-like receptor 10 signaling pathway
GO:0038123 toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124 toll-like receptor TLR6:TLR2 signaling pathway
GO:0042127 regulation of cell proliferation
GO:0043066 negative regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0044130 negative regulation of growth of symbiont in host
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045351 type I interferon biosynthetic process
GO:0046330 positive regulation of JNK cascade
GO:0048011 neurotrophin TRK receptor signaling pathway
GO:0048661 positive regulation of smooth muscle cell proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050727 regulation of inflammatory response
GO:0050830 defense response to Gram-positive bacterium
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0070555 response to interleukin-1
GO:0070935 3'-UTR-mediated mRNA stabilization
GO:0071260 cellular response to mechanical stimulus
GO:0090557 establishment of endothelial intestinal barrier
Cellular Component
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0010008 endosome membrane
GO:0014069 postsynaptic density
GO:0043234 protein complex
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
IL1 pathway
REACTOME
RIP-mediated NFkB activation via ZBP1 pathway
MyD88 dependent cascade initiated on endosome pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
p75NTR recruits signalling complexes pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
TRAF6 mediated IRF7 activation pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated NF-kB activation pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Signal Transduction pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Immune System pathway
MyD88-independent cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Signaling by Interleukins pathway
Interleukin-1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
KEGG
Apoptosis pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Toxoplasmosis pathway
INOH
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
PID BIOCARTA
Toll-like receptor pathway [Biocarta view]
Nf-kb signaling pathway [Biocarta view]
Inactivation of gsk3 by akt causes accumulation of b-catenin in alveolar macrophages [Biocarta view]
Signal transduction through il1r [Biocarta view]
Nfkb activation by nontypeable hemophilus influenzae [Biocarta view]
PID NCI
IL1-mediated signaling events
p75(NTR)-mediated signaling
Endogenous TLR signaling
Cross-References
SwissProt Q99836
TrEMBL
UniProt Splice Variant
Entrez Gene 4615
UniGene Hs.82116
RefSeq NM_001172569 NM_001172566 NM_001172567 NM_001172568 NM_002468 XM_005265172
HUGO HGNC:7562
OMIM 602170
CCDS CCDS54566 CCDS2674 CCDS54565 CCDS54567 CCDS54568
HPRD 03703
IMGT
EMBL AB446470 AK296570 AK296716 AK298650 AK298666 AP006309 BC013589 BI524129 BT007376 CH471055 U70451 U84408
GenPept AAB49967 AAC50954 AAH13589 AAP36040 BAG55247 BAG59190 BAG59306 BAG60822 BAG60834 EAW64521
RNA Seq Atlas 4615