Version 5.4
| Bos taurus Gene: MYD88 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Summary | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InnateDB Gene | IDBG-644299.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gene Symbol | MYD88 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Gene Name | Myeloid differentiation primary response protein MyD88 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Synonyms | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Species | Bos taurus | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ensembl Gene | ENSBTAG00000000563 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Encoded Proteins |
Myeloid differentiation primary response protein MyD88
Myeloid differentiation primary response protein MyD88
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| Protein Structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Useful resources | Stemformatics EHFPI ImmGen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| InnateDB Annotation from Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
[Homo sapiens] MYD88 is a Toll/IL-1R homology (TIR) domain containing adaptor which recruits IRAK1 possibly through IRAK4.
[Homo sapiens] 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.
[Homo sapiens] MYD88 binding with interleukin-1 (IL-1) receptor (IL1R1) is required for inducing endocytosis of IL1R1 following ligand binding.
[Homo sapiens] MYD88 is a key adaptor/regulator molecule for the Toll/IL-1R family of receptors for innate immunity.
[Homo sapiens] MYD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF.
[Homo sapiens] 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.
[Homo sapiens] 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.
[Homo sapiens] 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.
[Homo sapiens] 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.
[Homo sapiens] MYD88 is activated by MHC class II in response to staphylococcal enterotoxins and is crucial for the induction of pro-inflammatory cytokines.
[Homo sapiens] 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.
[Homo sapiens] 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)
[Homo sapiens] 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)
[Homo sapiens] MYD88 mediates cytoskeletal remodelling and late spreading of lipopolysaccharide (LPS)-stimulated macrophages. (Demonstrated in mice)
[Homo sapiens] 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)
[Homo sapiens] MYD88 deficiency results in delayed recruitment of phagocytes and defective production of proinflammatory cytokines in response to Salmonella infection. (Demonstrated in mice)
[Homo sapiens] MYD88 signalling in intestinal epithelial cells is crucial for the maintenance of gut microbiota homeostasis. (Demonstrated in mice)
[Homo sapiens] MYD88 mediated production of reactive oxygen species (ROS) is essential for the induction of IL12 by lactic acid bacteria. (Demonstrated in mice)
[Homo sapiens] 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.
[Homo sapiens] 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.
[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.
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| Entrez Gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Summary |
This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000172936:
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] |
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| Gene Information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type | Protein coding | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic Location | Chromosome 22:11646791-11651003 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Strand | Forward strand | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Band | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Transcripts |
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| Interactions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Number of Interactions |
This gene and/or its encoded proteins are associated with 0 experimentally validated interaction(s) in this database.
They are also associated with 116 interaction(s) predicted by orthology.
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| Gene Ontology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular Function |
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| Biological Process |
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| Cellular Component |
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| Orthologs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Species
Homo sapiens
Mus musculus
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Gene ID
Gene Order
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| Pathways | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NETPATH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| REACTOME |
Toll Like Receptor 2 (TLR2) Cascade pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Activated TLR4 signalling pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
MyD88-independent cascade pathway
Cytosolic sensors of pathogen-associated DNA pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
MyD88:Mal cascade initiated on plasma membrane pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Cytokine Signaling in Immune system pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
Immune System pathway
Toll-Like Receptors Cascades pathway
Signal Transduction pathway
TRAF6 mediated NF-kB activation pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
p75NTR recruits signalling complexes pathway
Signalling by NGF pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
MyD88 dependent cascade initiated on endosome pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
TRAF6 mediated IRF7 activation pathway
p75 NTR receptor-mediated signalling pathway
Innate Immune System pathway
Interleukin-1 signaling pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
RIP-mediated NFkB activation via ZBP1 pathway
Signaling by Interleukins pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
MyD88 cascade initiated on plasma membrane pathway
p75NTR signals via NF-kB pathway
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| KEGG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| INOH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PID NCI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Pathway Predictions based on Human Orthology Data | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NETPATH |
IL1 pathway
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| REACTOME |
RIP-mediated NFkB activation via ZBP1 pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated NF-kB activation pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
MyD88-independent cascade pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
MyD88 cascade initiated on plasma membrane pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Interleukin-1 signaling pathway
p75NTR recruits signalling complexes pathway
Signalling by NGF pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Toll-Like Receptors Cascades pathway
p75 NTR receptor-mediated signalling pathway
p75NTR signals via NF-kB pathway
Signal Transduction pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
Immune System pathway
Signaling by Interleukins pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
TRAF6 mediated NF-kB activation pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Toll Like Receptor 2 (TLR2) Cascade pathway
Innate Immune System pathway
MyD88 cascade initiated on plasma membrane pathway
Cytokine Signaling in Immune system pathway
Toll Like Receptor TLR1:TLR2 Cascade pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
Immune System pathway
Toll Like Receptor 5 (TLR5) Cascade pathway
Toll Like Receptor TLR6:TLR2 Cascade pathway
TRAF6 mediated IRF7 activation pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
p75NTR recruits signalling complexes pathway
DEx/H-box helicases activate type I IFN and inflammatory cytokines production pathway
Toll-Like Receptors Cascades pathway
Signaling by Interleukins pathway
p75NTR signals via NF-kB pathway
MyD88 dependent cascade initiated on endosome pathway
Cytosolic sensors of pathogen-associated DNA pathway
Signalling by NGF pathway
RIP-mediated NFkB activation via ZBP1 pathway
Activated TLR4 signalling pathway
Interleukin-1 signaling pathway
MyD88-independent cascade pathway
Signal Transduction pathway
p75 NTR receptor-mediated signalling pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
MyD88:Mal cascade initiated on plasma membrane pathway
TRIF-mediated TLR3/TLR4 signaling pathway
TAK1 activates NFkB by phosphorylation and activation of IKKs complex pathway
Toll Like Receptor 10 (TLR10) Cascade pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
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| KEGG |
Apoptosis pathway
Toll-like receptor signaling pathway pathway
Leishmaniasis pathway
Malaria pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Toxoplasmosis pathway
Toll-like receptor signaling pathway pathway
Apoptosis pathway
Leishmaniasis pathway
Malaria pathway
Toxoplasmosis pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
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| INOH |
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
IL-1 signaling pathway pathway
Toll-like receptor signaling pathway pathway
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| PID NCI |
IL1-mediated signaling events
p75(NTR)-mediated signaling
Endogenous TLR signaling
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| Cross-References | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| SwissProt | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| TrEMBL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Entrez Gene | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UniGene | Bt.48995 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NM_001014382 XM_005222378 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HUGO | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| OMIM | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CCDS | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HPRD | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| IMGT | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| EMBL | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| GenPept | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RNA Seq Atlas | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||