MYD88

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]

Myeloid Differentiation Primary Response 88

Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response (PubMed:15361868, PubMed:18292575, PubMed:33718825).

Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:24316379, PubMed:19506249).

Increases IL-8 transcription (PubMed:9013863).

Involved in IL-18-mediated signaling pathway. Activates IRF1 resulting in its rapid migration into the nucleus to mediate an efficient induction of IFN-beta, NOS2/INOS, and IL12A genes. Upon TLR8 activation by GU-rich single-stranded RNA (GU-rich RNA) derived from viruses such as SARS-CoV-2, SARS-CoV and HIV-1, induces IL1B release through NLRP3 inflammasome activation (PubMed:33718825).

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 (By similarity).

3'-UTR-mediated mRNA stabilization Source: BHF-UCL
Apoptotic process Source: AgBase
Cell surface receptor signaling pathway Source: ProtInc
Cellular response to lipopolysaccharide Source: ARUK-UCL
Cellular response to mechanical stimulus Source: UniProtKB
Cellular response to oxidised low-density lipoprotein particle stimulus Source: ARUK-UCL
Defense response to bacterium Source: BHF-UCL
Defense response to Gram-positive bacterium Source: UniProtKB
Defense response to protozoan Source: ARUK-UCL
Defense response to virus Source: UniProtKB
Establishment of endothelial intestinal barrier Source: Ensembl
Immunoglobulin mediated immune response Source: Ensembl
Induced systemic resistance Source: Ensembl
Innate immune response Source: GO_Central
Interleukin-1-mediated signaling pathway Source: Ensembl
JNK cascade Source: Ensembl
Leukocyte activation involved in inflammatory response Source: Ensembl
Lipopolysaccharide-mediated signaling pathway Source: Ensembl
MyD88-dependent toll-like receptor signaling pathway Source: Ensembl
Neutrophil activation involved in immune response Source: Ensembl
Neutrophil-mediated killing of bacterium Source: Ensembl
Phagocytosis Source: UniProtKB
Positive regulation of chemokine production Source: Ensembl
Positive regulation of cytokine production involved in inflammatory response Source: BHF-UCL
Positive regulation of gene expression Source: ARUK-UCL
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of interleukin-17 production Source: BHF-UCL
Positive regulation of interleukin-1 beta production Source: UniProtKB
Positive regulation of interleukin-23 production Source: BHF-UCL
Positive regulation of interleukin-6 production Source: BHF-UCL
Positive regulation of interleukin-8 production Source: BHF-UCL
Positive regulation of JNK cascade Source: Ensembl
Positive regulation of lymphocyte proliferation Source: Ensembl
Positive regulation of NF-kappaB transcription factor activity Source: AgBase
Positive regulation of NLRP3 inflammasome complex assembly Source: UniProtKB
Positive regulation of smooth muscle cell proliferation Source: Ensembl
Positive regulation of tumor necrosis factor production Source: Ensembl
Positive regulation of type I interferon production Source: BHF-UCL
Regulation of chemokine (C-X-C motif) ligand 1 production Source: Ensembl
Regulation of chemokine (C-X-C motif) ligand 2 production Source: Ensembl
Regulation of inflammatory response Source: BHF-UCL
Regulation of neutrophil migration Source: Ensembl
Response to interleukin-1 Source: BHF-UCL
Response to molecule of fungal origin Source: Ensembl
Response to peptidoglycan Source: Ensembl
Signal transduction Source: ProtInc
Toll-like receptor 8 signaling pathway Source: UniProtKB
Toll signaling pathway Source: GO_Central
Type I interferon signaling pathway Source: BHF-UCL

Nucleus
Cytoplasm

Immunodeficiency 68 (IMD68):
An autosomal recessive primary immunodeficiency characterized by life-threatening, often recurrent, pyogenic bacterial infections, including invasive pneumococcal disease, beginning in infancy or early childhood.
Macroglobulinemia, Waldenstrom, 1 (WM1):
A malignant B-cell neoplasm characterized by lymphoplasmacytic infiltration of the bone marrow and hypersecretion of monoclonal immunoglobulin M (IgM) protein. Clinical features are variable and include anemia, thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. Many patients have asymptomatic or indolent disease.
Defects in MYD88 are frequently found in many hematological malignancies, such as activated B-cell type diffuse large B-cell lymphoma (ABC-DLBCL), cutaneous diffuse large B cell lymphoma (CBCL) and primary central nervous system lymphoma (PCNSL).

Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4 specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88.