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Details on Person UniProt:Q99836 MYD88
| Class:Id | ReferenceGeneProduct:59755 |
|---|---|
| _chainChangeLog | chain:1-296 added on Fri February 6 2015 |
| _displayName | UniProt:Q99836 MYD88 |
| _timestamp | 2026-02-20 22:46:07 |
| chain | chain:1-296 |
| checksum | CEAE3F6B99524333 |
| comment | 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, PubMed:40638072). 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).SUBUNIT Homodimer. Also forms heterodimers with TIRAP (PubMed:17322885, PubMed:19506249, PubMed:19948740). Binds to TLR2, TLR5, IRAK1, IRAK2 and IRAK4 via their respective TIR domains. Interacts with IL18R1. Interacts with BMX, IL1RL1, IKBKE and IRF7. Interacts with LRRFIP1 and LRRFIP2; this interaction positively regulates Toll-like receptor (TLR) signaling in response to agonist. Interacts with FLII. LRRFIP1 and LRRFIP2 compete with FLII for MYD88-binding. Interacts with IRF1. Upon IL1B treatment, forms a complex with PELI1, IRAK1, IRAK4 and TRAF6; this complex recruits MAP3K7/TAK1, TAB1 and TAB2 to mediate NF-kappa-B activation. Direct binding of SMAD6 to PELI1 prevents the complex formation and hence negatively regulates IL1R-TLR signaling and eventually NF-kappa-B-mediated gene expression. May interact with PIK3AP1. Interacts (via TIR domain) with DHX9 (via H2A and OB-fold regions); this interaction is direct (PubMed:20696886). Interacts with OTUD4 deubiquitinase; the interaction is direct (PubMed:29395066). Interacts with TLR4 (PubMed:36232715).SUBUNIT (Microbial infection) In case of infection, interacts with uropathogenic E.coli protein TcpC; suppressing Toll-like receptor (TLR)-mediated cytokine production.SUBUNIT (Microbial infection) In case of infection, interacts with uropathogenic E.faecalis protein TcpF; suppressing Toll-like receptor (TLR)-mediated cytokine production.SUBUNIT (Microbial infection) In case of infection, interacts with B.melitensis protein TcpB.SUBUNIT (Microbial infection) Interacts with human metapneumovirus protein M2-2; this interaction prevents MYD88-mediated cytokine secretion.SUBUNIT (Microbial infection) Interacts with human cytomegalovirus protein UL88; this interaction degrades MYD88 and reduces innate immune activation.INTERACTION Ubiquitous.DOMAIN The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.PTM 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).PTM (Microbial infection) Ubiquitinated by human herpesvirus 8 (KSHV) protein RTA/ORF50, leading to proteasomal degradation and suppression of TLR4 signaling pathway.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.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).SEQUENCE CAUTION Extended N-terminus.SEQUENCE CAUTION Extended N-terminus. |
| description | recommendedName: fullName evidence="39"Myeloid differentiation primary response protein MyD88 |
| geneName | MYD88 |
| identifier | Q99836 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Antiviral defense Cytoplasm Disease variant Immunity Inflammatory response Innate immunity Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MYD88 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9001911] ENSEMBL:ENSG00000172936 MYD88 [Homo sapiens] |
| secondaryIdentifier | MYD88_HUMAN B4DKH8 B4DKU4 B4DQ60 B4DQ72 J3KPU4 J3KQ87 J3KQJ6 P78397 Q53XS7 |
| sequenceLength | 296 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8973353] UniProt:Q99836-1 MYD88 [Homo sapiens] [ReferenceIsoform:8973354] UniProt:Q99836-2 MYD88 [Homo sapiens] [ReferenceIsoform:8973355] UniProt:Q99836-3 MYD88 [Homo sapiens] [ReferenceIsoform:8973356] UniProt:Q99836-4 MYD88 [Homo sapiens] [ReferenceIsoform:8973357] UniProt:Q99836-5 MYD88 [Homo sapiens] [ReferenceIsoform:8973358] UniProt:Q99836-6 MYD88 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:166059] MYD88 [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:937017] MYD88 [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:975123] MYD88 [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:5602329] MyD88 R196C [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5602451] MyD88 E52del [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5602521] MyD88 S34Y [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5602598] MyD88 E65del [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5602612] MyD88 L93P [cytosol] [Homo sapiens] |
| (referenceSequence) | [FragmentDeletionModification:5602425] Deletion of residues 65 to 65 [ReplacedResidue:5602463] L-leucine 93 replaced with L-proline [FragmentDeletionModification:5602470] Deletion of residues 52 to 52 [ReplacedResidue:5602562] L-arginine 196 replaced with L-cysteine [ReplacedResidue:5602728] L-serine 34 replaced with L-tyrosine |
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No pathways have been reviewed or authored by UniProt:Q99836 MYD88 (59755)
