MYD88

Domain

The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.

Function

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, PubMed:37971847). Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:15361868, PubMed:19506249, PubMed:24316379). 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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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).

Post-translational modifications

Ubiquitinated; undergoes 'Lys-63'-linked polyubiquitination. OTUD4 specifically hydrolyzes 'Lys-63'-linked polyubiquitinated MYD88 (PubMed:29395066). Deubiquitinated by USP3 that cleaves 'Lys-63'-linked ubiquitin chains leading to inhibition of MYD88-induced NF-kappa-B signaling (PubMed:37971847).

(Microbial infection) Ubiquitinated by human herpesvirus 8 (KSHV) protein RTA/ORF50, leading to proteasomal degradation ans suppression of TLR4 signaling pathway.

Tissue specificity

Ubiquitous.

Cellular localization

• Cytoplasm
• Nucleus

Alternative names

• Myeloid differentiation primary response protein MyD88
• MYD88

Database links

• entrezGene:4615
• omim:602170
• swissprot:Q99836

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Other research areas

• Epigenetics

Molecular weight

33233Da