ID:MYD88_HUMAN DESCRIPTION: RecName: Full=Myeloid differentiation primary response protein MyD88; FUNCTION: Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response. Acts via IRAK1, IRAK2, IRF7 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Increases IL-8 transcription. 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 (By similarity). SUBUNIT: Homodimer. Also forms heterodimers with TIRAP. Binds to TLR2, TLR4, IRAK1, IRAK2 and IRAK4 via their respective TIR domains. Interacts with IL18R1 (By similarity). Interacts with BMX, IL1RL1 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 (By similarity). INTERACTION: Self; NbExp=3; IntAct=EBI-447677, EBI-447677; Q13158:FADD; NbExp=3; IntAct=EBI-447677, EBI-494804; Q8IUQ4:SIAH1; NbExp=3; IntAct=EBI-447677, EBI-747107; P84022:SMAD3; NbExp=3; IntAct=EBI-447677, EBI-347161; O43791:SPOP; NbExp=6; IntAct=EBI-447677, EBI-743549; Q9UGK3:STAP2; NbExp=3; IntAct=EBI-447677, EBI-1553984; P58753:TIRAP; NbExp=4; IntAct=EBI-447677, EBI-528644; O14836:TNFRSF13B; NbExp=12; IntAct=EBI-447677, EBI-519160; P10599:TXN; NbExp=4; IntAct=EBI-447677, EBI-594644; Q93009:USP7; NbExp=3; IntAct=EBI-447677, EBI-302474; SUBCELLULAR LOCATION: Cytoplasm. TISSUE SPECIFICITY: Ubiquitous. DOMAIN: The intermediate domain (ID) is required for the phosphorylation and activation of IRAK (By similarity). DISEASE: Defects in MYD88 are the cause of MYD88 deficiency (MYD88D) [MIM:612260]; also known as recurrent pyogenic bacterial infections due to MYD88 deficiency. Patients suffer from autosomal recessive, life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease, and die between 1 and 11 months of age. Surviving patients are otherwise healthy, with normal resistance to other microbes, and their clinical status improved with age. SIMILARITY: Contains 1 death domain. SIMILARITY: Contains 1 TIR domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q99836
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0002224 toll-like receptor signaling pathway GO:0002376 immune system process GO:0002755 MyD88-dependent toll-like receptor signaling pathway GO:0006915 apoptotic process GO:0006954 inflammatory response GO:0007165 signal transduction GO:0007166 cell surface receptor signaling pathway GO:0010628 positive regulation of gene expression GO:0032481 positive regulation of type I interferon production GO:0032740 positive regulation of interleukin-17 production GO:0032747 positive regulation of interleukin-23 production GO:0032755 positive regulation of interleukin-6 production GO:0034162 toll-like receptor 9 signaling pathway GO:0043066 negative regulation of apoptotic process GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0045087 innate immune response GO:0050727 regulation of inflammatory response GO:0050830 defense response to Gram-positive bacterium GO:0051092 positive regulation of NF-kappaB transcription factor activity GO:0060337 type I interferon signaling pathway GO:0070498 interleukin-1-mediated signaling pathway GO:0070555 response to interleukin-1 GO:0070935 3'-UTR-mediated mRNA stabilization GO:0071260 cellular response to mechanical stimulus GO:1900017 positive regulation of cytokine production involved in inflammatory response
EU832045 - Synthetic construct Homo sapiens clone HAIB:100067074; DKFZo004E0424 myeloid differentiation primary response gene (88) protein (MYD88) gene, encodes complete protein. EU831951 - Synthetic construct Homo sapiens clone HAIB:100066980; DKFZo008E0423 myeloid differentiation primary response gene (88) protein (MYD88) gene, encodes complete protein. LF208664 - JP 2014500723-A/16167: Polycomb-Associated Non-Coding RNAs. JB181740 - Sequence 5 from Patent WO2012118911. JB181741 - Sequence 6 from Patent WO2012118911. JB181742 - Sequence 7 from Patent WO2012118911. JB181743 - Sequence 8 from Patent WO2012118911. JB181744 - Sequence 9 from Patent WO2012118911. JD590326 - Sequence 4 from Patent WO2015015498. JD590327 - Sequence 5 from Patent WO2015015498. JD590328 - Sequence 6 from Patent WO2015015498. JD590329 - Sequence 7 from Patent WO2015015498. JD590330 - Sequence 8 from Patent WO2015015498. AK296716 - Homo sapiens cDNA FLJ54834 complete cds, highly similar to Myeloid differentiation primary response protein MyD88. U84408 - Human IL-1 receptor related protein MyD88 mRNA, complete cds. BX537602 - Homo sapiens mRNA; cDNA DKFZp686G0185 (from clone DKFZp686G0185). AK300448 - Homo sapiens cDNA FLJ58859 complete cds, highly similar to Myeloid differentiation primary responseprotein MyD88. AK298650 - Homo sapiens cDNA FLJ59950 complete cds, highly similar to Myeloid differentiation primary response protein MyD88. AK298666 - Homo sapiens cDNA FLJ59951 complete cds, highly similar to Myeloid differentiation primary response protein MyD88. AK296570 - Homo sapiens cDNA FLJ54306 complete cds, highly similar to Myeloid differentiation primary response protein MyD88. AB463903 - Synthetic construct DNA, clone: pF1KB6417, Homo sapiens MYD88 gene for myeloid differentiation primary response gene, without stop codon, in Flexi system. AK300051 - Homo sapiens cDNA FLJ54830 complete cds, highly similar to Myeloid differentiation primary response protein MyD88. BC013589 - Homo sapiens myeloid differentiation primary response gene (88), mRNA (cDNA clone MGC:9601 IMAGE:3900951), complete cds. AL832906 - Homo sapiens mRNA; cDNA DKFZp762A0914 (from clone DKFZp762A0914). KJ901587 - Synthetic construct Homo sapiens clone ccsbBroadEn_10981 MYD88 gene, encodes complete protein. KR709327 - Synthetic construct Homo sapiens clone CCSBHm_00000276 MYD88 (MYD88) mRNA, encodes complete protein. KR709328 - Synthetic construct Homo sapiens clone CCSBHm_00000277 MYD88 (MYD88) mRNA, encodes complete protein. U70451 - Human myleoid differentiation primary response protein MyD88 mRNA, complete cds. BT007376 - Homo sapiens myeloid differentiation primary response gene (88) mRNA, complete cds. AB446470 - Homo sapiens MYD88 mRNA for myeloid differentiation primary response gene 88, complete cds. AK304676 - Homo sapiens cDNA FLJ56294 complete cds, highly similar to Myeloid differentiation primary responseprotein MyD88. AK124685 - Homo sapiens cDNA FLJ42695 fis, clone BRAMY3003310, moderately similar to Homo sapiens myeloid differentiation primary response gene (88) (MYD88). AK097983 - Homo sapiens cDNA FLJ40664 fis, clone THYMU2020416. JD519690 - Sequence 500714 from Patent EP1572962. JD251661 - Sequence 232685 from Patent EP1572962. JD164909 - Sequence 145933 from Patent EP1572962. JD260949 - Sequence 241973 from Patent EP1572962. JD162239 - Sequence 143263 from Patent EP1572962. JD470374 - Sequence 451398 from Patent EP1572962. JD414604 - Sequence 395628 from Patent EP1572962. JD532180 - Sequence 513204 from Patent EP1572962. JD277482 - Sequence 258506 from Patent EP1572962. JD441501 - Sequence 422525 from Patent EP1572962. JD173839 - Sequence 154863 from Patent EP1572962. JD052804 - Sequence 33828 from Patent EP1572962. JD468708 - Sequence 449732 from Patent EP1572962. JD354369 - Sequence 335393 from Patent EP1572962. JD545755 - Sequence 526779 from Patent EP1572962. JD360979 - Sequence 342003 from Patent EP1572962. JD282991 - Sequence 264015 from Patent EP1572962. JD473538 - Sequence 454562 from Patent EP1572962. JD110160 - Sequence 91184 from Patent EP1572962. JD412990 - Sequence 394014 from Patent EP1572962. JD098967 - Sequence 79991 from Patent EP1572962. JD097329 - Sequence 78353 from Patent EP1572962. JD280244 - Sequence 261268 from Patent EP1572962. JD089841 - Sequence 70865 from Patent EP1572962. JD069016 - Sequence 50040 from Patent EP1572962. JD224224 - Sequence 205248 from Patent EP1572962. JD083788 - Sequence 64812 from Patent EP1572962. JD240087 - Sequence 221111 from Patent EP1572962. JD399485 - Sequence 380509 from Patent EP1572962. MF281492 - Homo sapiens miAB1_pre miRNA, complete sequence. JD308599 - Sequence 289623 from Patent EP1572962. JD186100 - Sequence 167124 from Patent EP1572962. JD500773 - Sequence 481797 from Patent EP1572962. JD526007 - Sequence 507031 from Patent EP1572962. JD176713 - Sequence 157737 from Patent EP1572962. JD381890 - Sequence 362914 from Patent EP1572962. JD386158 - Sequence 367182 from Patent EP1572962. LF378865 - JP 2014500723-A/186368: Polycomb-Associated Non-Coding RNAs. JD270167 - Sequence 251191 from Patent EP1572962. LF378864 - JP 2014500723-A/186367: Polycomb-Associated Non-Coding RNAs. MA444241 - JP 2018138019-A/16167: Polycomb-Associated Non-Coding RNAs. MA614442 - JP 2018138019-A/186368: Polycomb-Associated Non-Coding RNAs. MA614441 - JP 2018138019-A/186367: Polycomb-Associated Non-Coding RNAs.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_nthiPathway - NFkB activation by Nontypeable Hemophilus influenzae h_tollPathway - Toll-Like Receptor Pathway h_gsk3Pathway - Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages h_il1rPathway - Signal transduction through IL1R h_nfkbPathway - NF-kB Signaling Pathway
Reactome (by CSHL, EBI, and GO)
Protein Q99836 (Reactome details) participates in the following event(s):
R-HSA-166072 MyD88 forms a complex with MAL:activated TLR2/4 R-HSA-937079 MyD88 oligomerization within the complex of activated TLR:Mal:MyD88 R-HSA-975098 MyD88 oligomerization within the complex of activated TLR 7/8 or 9 : MyD88 R-HSA-975175 MyD88 interacts with the activated TLR receptor 7, 8 or 9 R-HSA-975866 MyD88 forms a complex with the activated TLR receptor R-HSA-975880 MyD88 oligomerization within the complex of activated TLR:MyD88 R-HSA-3134953 DHX36 or DHX9 binds MyD88 R-HSA-450133 IL1R1:IL1:IL1RAP binds MYD88 homodimer R-HSA-193665 MYD88 dissociates R-HSA-193686 p75NTR interacts with IRAK:MYD88 R-HSA-193695 IRAK interacts with TRAF6 R-HSA-193647 IRAK is activated R-HSA-446692 IRAK1 binds to MYD88 within the IL1R complex R-HSA-446634 IRAK4 is activated by autophosphorylation R-HSA-446648 IL1R1:IL1:IL1RAP:MYD88 homodimer binds IRAK4 R-HSA-446894 TRAF6 binding leads to IRAK1:TRAF6 release R-HSA-166082 IRAK4 binds to the activated TLR receptor:Mal:MyD88 complex R-HSA-975873 IRAK4 binds to MyD88 bound to the activated TLR5 or 10 receptor R-HSA-975156 IRAK4 binds to the activated TLR7/8 or 9 receptor:MyD88 complex R-HSA-446701 IRAK4-activated IRAK1 autophosphorylates R-HSA-446694 IRAK4 phosphorylates IRAK1 R-HSA-446862 Hyperphosphorylated IRAK1 associates with TRAF6 R-HSA-446868 The Interleukin 1 receptor complex binds Tollip R-HSA-937022 IRAK4 autophosphorylation in the complex with activated TLR:MyD88:Mal R-HSA-166091 IRAK1 or IRAK2 binds to the activated IRAK4 :activated TLR:MyD88:Mal complex R-HSA-166362 Dissociation of hp-IRAK1:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex R-HSA-2262775 Dissociation of p-IRAK2:TRAF6 from the activated TLR:oligo-Myd88:Mal:p-IRAK4 complex R-HSA-975852 IRAK1/or IRAK2 binds to the activated IRAK4 :oligo MyD88:activated TLR5 or 10 complex R-HSA-975865 IRAK4 autophosphorylation within the complex activated TLR:MyD88 R-HSA-975879 Dissociation of hp-IRAK1:TRAF6 or IRAK2:TRAF6-oligomer from the activated TLR5 or 10:oligo-Myd88:p-IRAK4 complex R-HSA-975115 IRAK1/or IRAK2 binds to the activated IRAK4 :MyD88:activated TLR 7/8 or 9. R-HSA-975100 Dissociation of hp-IRAK1/or IRAK2:TRAF6-oligomer from the p-IRAK4 :oligo-Myd88:activated TLR7/8 or 9 complex R-HSA-975170 IRAK4 autophosphorylation in the complex with MyD88:activated TLR 7/8 or 9 R-HSA-166286 Multiple IRAK1 autophosphorylation steps R-HSA-166284 Second phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal R-HSA-166119 First phosphorylation of IRAK1 by IRAK4 bound to activated TLR:MyD88:Mal R-HSA-166363 TRAF6 binds to hp- IRAK1 R-HSA-937059 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:Mal:activated TLR complex R-HSA-2262777 TRAF6 binds to p-IRAK2 R-HSA-975861 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomerl:activated TLR5 or 10 complex R-HSA-975878 First phosphorylation of IRAK1 by IRAK4 bound to MyD88:activated TLR R-HSA-975874 Second phosphorylation of IRAK1 by IRAK4 bound to MyD88:activated TLR complex R-HSA-975853 Multiple IRAK1 autophosphorylation within the complex p-IRAK4:oligo MyD88:activated TLR R-HSA-975857 TRAF6 binds to hp- IRAK1 or p-IRAK2 R-HSA-975125 Multiple IRAK1 autophosphorylation steps within the complex pIRAK4:MyD88:activated TLR7/8 or 9 R-HSA-975134 Second phosphorylation of IRAK1 by IRAK4 bound to MyD88: activated TLR 7/8 or 9 R-HSA-975180 First phosphorylation of IRAK1 by IRAK4 bound to MyD88:activated TLR 7/8 or 9 R-HSA-975160 Phosphorylation of IRAK2 bound to the activated IRAK4:MyD88 oligomer:activated TLR 7/8 or 9 R-HSA-975111 TRAF6 binds to hp- IRAK1/or p-IRAK2:p-IRAK4:MyD88:activated TLR7/8 or 9 R-HSA-975188 TRAF6 interacts with IRF7 upon TLR7/8 or 9 activation R-HSA-975106 Phosphorylation and release of IRF7 upon TLR7/8 or 9 activation R-HSA-975118 TRAF6 ubiquitinqtes IRF7 in a K63-dependent manner following TLR7/8 or 9 stimulation R-HSA-166058 MyD88:Mal cascade initiated on plasma membrane R-HSA-975155 MyD88 dependent cascade initiated on endosome R-HSA-975871 MyD88 cascade initiated on plasma membrane R-HSA-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production R-HSA-5602498 MyD88 deficiency (TLR2/4) R-HSA-166016 Toll Like Receptor 4 (TLR4) Cascade R-HSA-168179 Toll Like Receptor TLR1:TLR2 Cascade R-HSA-168188 Toll Like Receptor TLR6:TLR2 Cascade R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade R-HSA-168181 Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-168142 Toll Like Receptor 10 (TLR10) Cascade R-HSA-168176 Toll Like Receptor 5 (TLR5) Cascade R-HSA-9020702 Interleukin-1 signaling R-HSA-209543 p75NTR recruits signalling complexes R-HSA-1834949 Cytosolic sensors of pathogen-associated DNA R-HSA-5602358 Diseases associated with the TLR signaling cascade R-HSA-5602680 MyD88 deficiency (TLR5) R-HSA-168898 Toll-Like Receptors Cascades R-HSA-181438 Toll Like Receptor 2 (TLR2) Cascade R-HSA-446652 Interleukin-1 family signaling R-HSA-193639 p75NTR signals via NF-kB R-HSA-168249 Innate Immune System R-HSA-5603041 IRAK4 deficiency (TLR2/4) R-HSA-5603037 IRAK4 deficiency (TLR5) R-HSA-5260271 Diseases of Immune System R-HSA-449147 Signaling by Interleukins R-HSA-193704 p75 NTR receptor-mediated signalling R-HSA-168256 Immune System R-HSA-975138 TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-1643685 Disease R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-73887 Death Receptor Signalling R-HSA-162582 Signal Transduction R-HSA-975110 TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
