MYD88 (MYD88 innate immune signal transduction adaptor)

Gene

• Entrez ID: 4615
• Gene name: MYD88 innate immune signal transduction adaptor
• Gene symbol: MYD88
• Synonyms: IMD68, MYD88D
• Chromosome: 3
• Chromosome location: 3p22.2
• 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]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs137853064	C>A,G,T	Pathogenic	Non coding transcript variant, missense variant, intron variant, coding sequence variant
rs387907272	T>C	Likely-pathogenic, uncertain-significance, pathogenic	Stop lost, missense variant, coding sequence variant, terminator codon variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT007368	hsa-miR-203a-3p	Luciferase reporter assay, qRT-PCR, Western blot	23522925
MIRT020533	hsa-miR-155-5p	Western blot	21030878
MIRT054356	hsa-miR-21-5p	Chip, ELISA, Flow cytometry, Luciferase reporter assay, QRTPCR, Western blot	23633945
MIRT237424	hsa-miR-6817-3p	PAR-CLIP	22012620
MIRT438020	hsa-miR-149-5p	ELISA, qRT-PCR, Western blot	24375488
MIRT527503	hsa-miR-384	PAR-CLIP	22012620
MIRT527504	hsa-miR-3685	PAR-CLIP	22012620
MIRT527505	hsa-miR-155-3p	PAR-CLIP	22012620
MIRT527506	hsa-miR-6715b-3p	PAR-CLIP	22012620
MIRT527507	hsa-miR-5690	PAR-CLIP	22012620

Transcription factors

Transcription factor	Regulation	Reference
STAT3	Unknown	12244150

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002224	Process	Toll-like receptor signaling pathway	TAS
GO:0002238	Process	Response to molecule of fungal origin	IEA
GO:0002755	Process	MyD88-dependent toll-like receptor signaling pathway	TAS
GO:0005121	Function	Toll binding	IEA
GO:0005123	Function	Death receptor binding	TAS	9374458
GO:0005149	Function	Interleukin-1 receptor binding	IEA
GO:0005515	Function	Protein binding	IPI	10880445, 11544529, 12860405, 15728506, 16189514, 16293622, 16365431, 17126326, 17258210, 17567694, 17583698, 19948740, 20676093, 20696886, 21334391, 21829704, 21988832, 22155231, 22581261, 24316379, 25416956, 25502805, 25910212, 26592460, 26871637, 28514442, 29281743, 29990310, 315
GO:0005634	Component	Nucleus	IDA	22155231
GO:0005737	Component	Cytoplasm	IDA	22155231
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	TAS
GO:0006909	Process	Phagocytosis	IMP	30883606
GO:0006915	Process	Apoptotic process	IMP	22155231
GO:0006954	Process	Inflammatory response	IEA
GO:0007165	Process	Signal transduction	NAS	9013863
GO:0007166	Process	Cell surface receptor signaling pathway	TAS	9374458
GO:0007254	Process	JNK cascade	IEA
GO:0008063	Process	Toll signaling pathway	IBA	21873635
GO:0009615	Process	Response to virus	IEA
GO:0009682	Process	Induced systemic resistance	IEA
GO:0010008	Component	Endosome membrane	TAS
GO:0010628	Process	Positive regulation of gene expression	ISS
GO:0014069	Component	Postsynaptic density	IEA
GO:0016064	Process	Immunoglobulin mediated immune response	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	IEA
GO:0032481	Process	Positive regulation of type I interferon production	IMP	23633945
GO:0032481	Process	Positive regulation of type I interferon production	TAS
GO:0032494	Process	Response to peptidoglycan	IEA
GO:0032722	Process	Positive regulation of chemokine production	IEA
GO:0032740	Process	Positive regulation of interleukin-17 production	ISS
GO:0032747	Process	Positive regulation of interleukin-23 production	ISS
GO:0032755	Process	Positive regulation of interleukin-6 production	ISS
GO:0032757	Process	Positive regulation of interleukin-8 production	IMP	20219467
GO:0032760	Process	Positive regulation of tumor necrosis factor production	IEA
GO:0032991	Component	Protein-containing complex	IEA
GO:0034162	Process	Toll-like receptor 9 signaling pathway	TAS
GO:0035325	Function	Toll-like receptor binding	IBA	21873635
GO:0042742	Process	Defense response to bacterium	IMP	20219467
GO:0042802	Function	Identical protein binding	IPI	11544529, 17258210, 21516116, 21988832, 22155231, 25416956, 25910212, 27107012, 29892012, 32296183
GO:0042832	Process	Defense response to protozoan	ISS
GO:0043066	Process	Negative regulation of apoptotic process	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0043621	Function	Protein self-association	IDA	22155231
GO:0045087	Process	Innate immune response	IBA	21873635
GO:0046330	Process	Positive regulation of JNK cascade	IEA
GO:0048661	Process	Positive regulation of smooth muscle cell proliferation	IEA
GO:0050671	Process	Positive regulation of lymphocyte proliferation	IEA
GO:0050727	Process	Regulation of inflammatory response	ISS
GO:0050830	Process	Defense response to Gram-positive bacterium	IBA	21873635
GO:0050830	Process	Defense response to Gram-positive bacterium	ISS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IMP	22155231
GO:0060337	Process	Type I interferon signaling pathway	IMP	23633945
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0070555	Process	Response to interleukin-1	IMP	19281832
GO:0070935	Process	3'-UTR-mediated mRNA stabilization	IDA	15294994
GO:0070976	Function	TIR domain binding	IPI	19509286
GO:0071222	Process	Cellular response to lipopolysaccharide	ISS
GO:0071260	Process	Cellular response to mechanical stimulus	IEP	19593445
GO:0090557	Process	Establishment of endothelial intestinal barrier	IEA
GO:0140052	Process	Cellular response to oxidised low-density lipoprotein particle stimulus	ISS
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	IMP	20219467
GO:1900017	Process	Positive regulation of cytokine production involved in inflammatory response	ISS
GO:1902622	Process	Regulation of neutrophil migration	IEA
GO:2000338	Process	Regulation of chemokine (C-X-C motif) ligand 1 production	IEA
GO:2000341	Process	Regulation of chemokine (C-X-C motif) ligand 2 production	IEA

Other IDs

• MIM: 602170
• HGNC: 7562
• e!Ensembl: ENSG00000172936

Protein

• UniProt ID: Q99836
• Protein name: Myeloid differentiation primary response protein MyD88
• Protein 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). 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).
• PDB: 2JS7, 2Z5V, 3MOP, 4DOM, 4EO7, 6I3N
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00531	Death	30 → 107	Death domain	Domain
  PF01582	TIR	163 → 295	TIR domain	Family

• Sequence:

  MAAGGPGAGSAAPVSSTSSLPLAALNMRVRRRLSLFLNVRTQVAADWTALAEEMDFEYLE
  IRQLETQADPTGRLLDAWQGRPGASVGRLLELLTKLGRDDVLLELGPSIEEDCQKYILKQ
  QQEEAEKPLQVAAVDSSVPRTAELAGITTLDDPLGHMPERFDAFICYCPSDIQFVQEMIR
  QLEQTNYRLKLCVSDRDVLPGTCVWSIASELIEKRCRRMVVVVSDDYLQSKECDFQTKFA
  LSLSPGAHQKRLIPIKYKAMKKEFPSILRFITVCDYTNPCTKSWFWTRLAKALSLP

• Sequence length: 296