Regulation of toll-like receptor signaling (WP1449)

Homo sapiens

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Toll-like receptors (TLRs) are critical pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs), which are conserved and specific molecular “signatures” expressed by pathogens. TLR ligation triggers distinct but shared signaling pathways that lead to effector mechanisms in innate immune responses. TLR specificity and activation are strictly and finely tuned at multiple levels of various signal transduction pathways, resulting in complex signaling platforms. Many molecules, ranging from membrane and cytosol to nuclear, contribute to TLR ligand discrimination or receptor signaling and play different roles in the regulation of TLR responses via different mechanisms, such as cross-regulation, protein modification, helper cofactors, and posttranscriptional and epigenetic regulation. Source: PubMed. Proteins on this pathway have targeted assays available via the CPTAC Assay Portal.

For a description of pathway objects, see the WikiPathways Legend.

Authors

Misbah , Kristina Hanspers , Thomas Kelder , Maiyu , Cloris816 , Alex Pico , Egon Willighagen , Zahra Roudbari , Denise Slenter , Marvin Martens , and Eric Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

CPTAC

Annotations

Pathway Ontology

Toll-like receptor signaling pathway

Participants
Query Drugst.One

Label Type Compact URI Comment
Lipoarabinomannans(Mycobacteria) Metabolite chebi:59524
Zymosan (yeast) Metabolite chebi:37671
Peptidoglycan (G+) Metabolite chebi:8005
Imidazoquinolin Metabolite chebi:38776
(anti-viral compounds) Metabolite chebi:22587
LY96 GeneProduct ncbigene:23643 Original kegg element: gene;71;hsa:23643
MAPK12 GeneProduct ncbigene:6300 Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
RNF31 GeneProduct ensembl:ENSG00000092098
IRAK1 GeneProduct ncbigene:3654 Original kegg element: gene;4;hsa:3654
hsa-mir-105-1 GeneProduct ensembl:ENSG00000207957
hsa-let-7i (gene) GeneProduct ensembl:ENSG00000199179
PELI1 GeneProduct ensembl:ENSG00000197329
NFKB1 GeneProduct ncbigene:4790 Original kegg element: gene;10;hsa:4790 hsa:4791 hsa:5970
RNF41 GeneProduct ensembl:ENSG00000181852
CD80 GeneProduct ncbigene:941 Original kegg element: gene;69;hsa:941
JUN GeneProduct ncbigene:3725 Original kegg element: gene;35;hsa:2353 hsa:3725
IFNA10 GeneProduct ncbigene:3446 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
TLR1 GeneProduct ncbigene:7096 Original kegg element: gene;75;hsa:7096
TIRAP GeneProduct ncbigene:114609 Original kegg element: gene;83;hsa:114609
TLR9 GeneProduct ncbigene:54106 Original kegg element: gene;78;hsa:54106
STAT1 GeneProduct ncbigene:6772 Original kegg element: gene;62;hsa:6772
IRAK4 GeneProduct ncbigene:51135 Original kegg element: gene;5;hsa:51135
TLR5 GeneProduct ncbigene:7100 Original kegg element: gene;72;hsa:7100
PIK3R1 GeneProduct ncbigene:5295 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
NFKB1 GeneProduct ncbigene:4790 Original kegg element: gene;14;hsa:4790
TICAM1 GeneProduct ncbigene:148022 Original kegg element: gene;82;hsa:148022
IFNA8 GeneProduct ncbigene:3445 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
MAPK14 GeneProduct ncbigene:1432 Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
TRAF6 GeneProduct ncbigene:7189 Original kegg element: gene;53;hsa:7189
AKT2 GeneProduct ncbigene:208 Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
CCL5 GeneProduct ncbigene:6352 Original kegg element: gene;58;hsa:6352
PELI2 GeneProduct ensembl:ENSG00000139946
TOLLIP GeneProduct ncbigene:54472 Original kegg element: gene;81;hsa:54472
IL12B GeneProduct ncbigene:3593 Original kegg element: gene;45;hsa:3592 hsa:3593
PIK3CB GeneProduct ncbigene:5291 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
TLR2s GeneProduct ensembl:ENSG00000137462
PIK3CG GeneProduct ncbigene:5294 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
IFNA16 GeneProduct ncbigene:3449 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
TRAF3 GeneProduct ncbigene:7187 Original kegg element: gene;16;hsa:7187
PELI3 GeneProduct ensembl:ENSG00000174516
TLR6 GeneProduct ncbigene:10333 Original kegg element: gene;76;hsa:10333
MAPK10 GeneProduct ncbigene:5602 Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
IRAK2 GeneProduct ensembl:ENSG00000134070
PIK3R5 GeneProduct ncbigene:23533 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
MBL2 GeneProduct ensembl:ENSG00000165471
IFNA2 GeneProduct ncbigene:3440 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
CHUK GeneProduct ncbigene:1147 Original kegg element: gene;2;hsa:1147
CYLD GeneProduct ensembl:ENSG00000083799
TBK1 GeneProduct ncbigene:29110 Original kegg element: gene;52;hsa:29110
AKT3 GeneProduct ncbigene:10000 Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
MAP3K7IP3 GeneProduct ensembl:ENSG00000157625 Original kegg element: gene;61;hsa:23118
NFKBIA GeneProduct ncbigene:4792 Original kegg element: gene;64;hsa:4792
IL12A GeneProduct ncbigene:3592 Original kegg element: gene;45;hsa:3592 hsa:3593
IFNA7 GeneProduct ncbigene:3444 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
SIGIRR GeneProduct ensembl:ENSG00000185187
IFNA21 GeneProduct ncbigene:3452 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
TRAF6 GeneProduct ncbigene:7189 Original kegg element: gene;3;hsa:7189
TNF GeneProduct ncbigene:7124 Original kegg element: gene;66;hsa:7124
CD40 GeneProduct ncbigene:958 Original kegg element: gene;29;hsa:958
IFNA17 GeneProduct ncbigene:3451 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IFNB1 GeneProduct ncbigene:3456 Original kegg element: gene;26;hsa:3456
CD180 GeneProduct ensembl:ENSG00000134061
CUEDC2 GeneProduct ensembl:ENSG00000107874
CASP8 GeneProduct ncbigene:841 Original kegg element: gene;87;hsa:841
TIRAP GeneProduct ncbigene:114609 Original kegg element: gene;46;hsa:114609
SYK GeneProduct ensembl:ENSG00000165025
SPP1 GeneProduct ncbigene:6696 Original kegg element: gene;15;hsa:6696
CCL3 GeneProduct ncbigene:6348 Original kegg element: gene;44;hsa:6348
TLR2 GeneProduct ncbigene:7097 Original kegg element: gene;70;hsa:7097
CXCL10 GeneProduct ncbigene:3627 Original kegg element: gene;25;hsa:3627
OTUD5 GeneProduct ensembl:ENSG00000068308
TLR4 GeneProduct ncbigene:7099 Original kegg element: gene;79;hsa:7099
IRAK3 GeneProduct ensembl:ENSG00000090376
SARM1 GeneProduct ensembl:ENSG00000004139
PLK1 GeneProduct ensembl:ENSG00000166851
IFNA14 GeneProduct ncbigene:3448 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
TLR7 GeneProduct ncbigene:51284 Original kegg element: gene;39;hsa:51284 hsa:51311
IFNA4 GeneProduct ncbigene:3441 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IKBKE GeneProduct ncbigene:9641 Original kegg element: gene;54;hsa:9641
MIR146A GeneProduct ensembl:ENSG00000283733
IFNA1 GeneProduct ncbigene:3439 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
IRF7 GeneProduct ncbigene:3665 Original kegg element: gene;20;hsa:3665
MAP2K4 GeneProduct ncbigene:6416 Original kegg element: gene;63;hsa:5609 hsa:6416
IL1B GeneProduct ncbigene:3553 Original kegg element: gene;51;hsa:3553
hsa-let-7e GeneProduct ensembl:ENSG00000198972
RBCK1 GeneProduct ensembl:ENSG00000125826
MYD88 GeneProduct ncbigene:4615 Original kegg element: gene;6;hsa:4615
IRAK1 GeneProduct ncbigene:3654 Original kegg element: gene;41;hsa:3654
TLR8 GeneProduct ncbigene:51311 Original kegg element: gene;39;hsa:51284 hsa:51311
MAP3K7 GeneProduct ncbigene:6885 Original kegg element: gene;37;hsa:6885
MAP2K6 GeneProduct ncbigene:5608 Original kegg element: gene;65;hsa:5606 hsa:5608
SOCS1 GeneProduct ensembl:ENSG00000185338
CTNNAL1 GeneProduct ensembl:ENSG00000119326
TICAM2 GeneProduct ncbigene:353376 Original kegg element: gene;80;hsa:353376
TRAFD1 GeneProduct ensembl:ENSG00000135148
CISH GeneProduct ensembl:ENSG00000114737
MIR155 GeneProduct ensembl:ENSG00000283904
IRF3 GeneProduct ncbigene:3661 Original kegg element: gene;67;hsa:3661
CHUK GeneProduct ncbigene:1147 Original kegg element: gene;42;hsa:1147
USP7 GeneProduct ensembl:ENSG00000187555
BTK GeneProduct ensembl:ENSG00000010671
IL6 GeneProduct ncbigene:3569 Original kegg element: gene;57;hsa:3569
CD86 GeneProduct ncbigene:942 Original kegg element: gene;28;hsa:942
MAPK3 GeneProduct ncbigene:5595 Original kegg element: gene;11;hsa:5594 hsa:5595
IRAK4 GeneProduct ncbigene:51135 Original kegg element: gene;86;hsa:51135
PIK3CD GeneProduct ncbigene:5293 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
MAPK13 GeneProduct ncbigene:5603 Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
IFNA13 GeneProduct ncbigene:3447 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
CD14 GeneProduct ncbigene:929 Original kegg element: gene;84;hsa:929
TNFAIP3 GeneProduct ensembl:ENSG00000118503
Tifa GeneProduct ensembl:ENSG00000145365
TICAM2 (TAG) GeneProduct ensembl:ENSG00000134970
hsa-mir-98 GeneProduct ncbigene:407054
NEU1 GeneProduct ensembl:ENSG00000184494
IFNB1 GeneProduct ncbigene:3456 Original kegg element: gene;1;hsa:3456
MLST8 GeneProduct ncbigene:64223
RNF216 GeneProduct ensembl:ENSG00000011275
IFNAR1 GeneProduct ncbigene:3454 Original kegg element: gene;49;hsa:3454 hsa:3455
MYD88s GeneProduct ensembl:ENSG00000172936
MYD88 GeneProduct ncbigene:4615 Original kegg element: gene;8;hsa:4615
MAPK8 GeneProduct ncbigene:5599 Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
RIPK1 GeneProduct ncbigene:8737 Original kegg element: gene;17;hsa:8737
SMAD6 GeneProduct ensembl:ENSG00000137834
LBP GeneProduct ncbigene:3929 Original kegg element: gene;77;hsa:3929
MYD88 GeneProduct ncbigene:4615 Original kegg element: gene;7;hsa:4615
IRF5 GeneProduct ncbigene:3663 Original kegg element: gene;21;hsa:3663
MAP3K7IP2 GeneProduct ensembl:ENSG00000055208 Original kegg element: gene;59;hsa:10454
MAP3K7IP1 GeneProduct ncbigene:10454 Original kegg element: gene;59;hsa:10454
IL8 GeneProduct ncbigene:3576 Original kegg element: gene;43;hsa:3576
MAPK1 GeneProduct ncbigene:5594 Original kegg element: gene;11;hsa:5594 hsa:5595
SQSTM1 GeneProduct ensembl:ENSG00000161011
MAP2K1 GeneProduct ncbigene:5604 Original kegg element: gene;12;hsa:5604 hsa:5605
SFTPA1 GeneProduct ensembl:ENSG00000185303
PTPN6 GeneProduct ensembl:ENSG00000111679
FADD GeneProduct ncbigene:8772 Original kegg element: gene;56;hsa:8772
MAP2K2 GeneProduct ncbigene:5605 Original kegg element: gene;12;hsa:5604 hsa:5605
IFNAR2 GeneProduct ncbigene:3455 Original kegg element: gene;49;hsa:3454 hsa:3455
TRAF6 GeneProduct ncbigene:7189 Original kegg element: gene;9;hsa:7189
IFNA5 GeneProduct ncbigene:3442 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
PIK3R3 GeneProduct ncbigene:8503 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
MYD88 GeneProduct ncbigene:4615 Original kegg element: gene;47;hsa:4615
MAP3K8 GeneProduct ncbigene:1326 Original kegg element: gene;13;hsa:1326
RAC1 GeneProduct ncbigene:5879 Original kegg element: gene;48;hsa:5879
TLR2 GeneProduct ncbigene:7097 Original kegg element: gene;74;hsa:7097
PIK3R2 GeneProduct ncbigene:5296 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
MAP2K7 GeneProduct ncbigene:5609 Original kegg element: gene;63;hsa:5609 hsa:6416
CXCL9 GeneProduct ncbigene:4283 Original kegg element: gene;24;hsa:4283
SFTPD GeneProduct ensembl:ENSG00000133661
TLR3 GeneProduct ncbigene:7098 Original kegg element: gene;73;hsa:7098
IFNA6 GeneProduct ncbigene:3443 Original kegg element: gene;27;hsa:3439 hsa:3440 hsa:3441 hsa:3442 hsa:3443 hsa:3444 hsa:3445 hsa:3446 hsa:3447 hsa:3448 hsa:3449 hsa:3451 hsa:3452
AKT1 GeneProduct ncbigene:207 Original kegg element: gene;60;hsa:10000 hsa:207 hsa:208
MAPK11 GeneProduct ncbigene:5600 Original kegg element: gene;40;hsa:1432 hsa:5600 hsa:5603 hsa:6300
MAP2K3 GeneProduct ncbigene:5606 Original kegg element: gene;65;hsa:5606 hsa:5608
TREM1 GeneProduct ensembl:ENSG00000124731
TLR4s GeneProduct ensembl:ENSG00000136869
ZMYND11 GeneProduct ensembl:ENSG00000015171
RELA GeneProduct ncbigene:5970 Original kegg element: gene;10;hsa:4790 hsa:4791 hsa:5970
CCL4 GeneProduct ncbigene:6351 Original kegg element: gene;38;hsa:6351
IKBKG GeneProduct ncbigene:8517 Original kegg element: gene;85;hsa:8517
NFKB2 GeneProduct ncbigene:4791 Original kegg element: gene;10;hsa:4790 hsa:4791 hsa:5970
IKBKB GeneProduct ncbigene:3551 Original kegg element: gene;36;hsa:3551
FOS GeneProduct ncbigene:2353 Original kegg element: gene;35;hsa:2353 hsa:3725
PIK3CA GeneProduct ncbigene:5290 Original kegg element: gene;55;hsa:23533 hsa:5290 hsa:5291 hsa:5293 hsa:5294 hsa:5295 hsa:5296 hsa:8503
CXCL11 GeneProduct ncbigene:6373 Original kegg element: gene;23;hsa:6373
MAPK9 GeneProduct ncbigene:5601 Original kegg element: gene;50;hsa:5599 hsa:5601 hsa:5602
FBXW5 GeneProduct ensembl:ENSG00000159069

References

  1. KEGG Pathway: map04620
  2. Small anti-viral compounds activate immune cells via the TLR7 MyD88-dependent signaling pathway. Hemmi H, Kaisho T, Takeuchi O, Sato S, Sanjo H, Hoshino K, et al. Nat Immunol. 2002 Feb;3(2):196–200. PubMed Europe PMC Scholia
  3. Human TLR7 or TLR8 independently confer responsiveness to the antiviral compound R-848. Jurk M, Heil F, Vollmer J, Schetter C, Krieg AM, Wagner H, et al. Nat Immunol. 2002 Jun;3(6):499. PubMed Europe PMC Scholia
  4. Regulation of Toll-like receptor signaling pathways in innate immune responses. Qian C, Cao X. Ann N Y Acad Sci. 2013 Apr;1283:67–74. PubMed Europe PMC Scholia