Cytosolic DNA-sensing pathway (WP4655)
Homo sapiens
As part of the innate immune system, specific cytosolic pattern recognition receptors recognize DNA from invading viruses and bacteria. These receptors have specificity for certain pathogens. The three receptors that recognize double-stranded cytosolic DNA are CGAS (GMP-AMP Synthase), ZBP1 (DAI) and AIM. CGAS signals via STING (TREM173) and eventually results in expression of type I interferons. ZBP1 activates NFkb and IRF transcription factors which results in expression of interferons and cytokines/chemokines. Activation of AIM leads to the formation of the inflammasome complex, which activates caspase-1 and triggers a form of apoptosis known as pyroptosis. In addition to sensors that directly detect DNA, another mechanism exists where the foreign DNA is first translated into RNA by host polymerase. The RNA is then recognized by the RNA sensor RIG-I, which leads to NFkb and IRF activation.
Authors
Kristina Hanspers and Egon WillighagenActivity
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Cited In
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Organisms
Homo sapiensCommunities
CPTACAnnotations
Disease Ontology
viral infectious disease bacterial infectious diseasePathway Ontology
pattern recognition receptor mediated signaling pathway signaling pathway| Label | Type | Compact URI | Comment |
|---|---|---|---|
| cGAMP | Metabolite | chebi:71580 | |
| dsDNA | Metabolite | chebi:16991 | |
| POLR2E | GeneProduct | ensembl:ENSG00000099817 | |
| POLR3GL | GeneProduct | ensembl:ENSG00000121851 | |
| POLR3F | GeneProduct | ensembl:ENSG00000132664 | |
| POLR3G | GeneProduct | ensembl:ENSG00000113356 | |
| POLR3H | GeneProduct | ensembl:ENSG00000100413 | |
| POLR2K | GeneProduct | ensembl:ENSG00000147669 | |
| POLR2H | GeneProduct | ensembl:ENSG00000163882 | |
| POLR3E | GeneProduct | ensembl:ENSG00000058600 | |
| POLR3K | GeneProduct | ensembl:ENSG00000161980 | |
| POLR2F | GeneProduct | ensembl:ENSG00000100142 | |
| POLR2L | GeneProduct | ensembl:ENSG00000177700 | |
| POLR3A | GeneProduct | ensembl:ENSG00000148606 | |
| TREX1 | GeneProduct | ensembl:ENSG00000213689 | |
| POLR1C | GeneProduct | ensembl:ENSG00000171453 | |
| POLR3C | GeneProduct | ensembl:ENSG00000186141 | |
| POLR3D | GeneProduct | ensembl:ENSG00000168495 | |
| POLR3B | GeneProduct | ensembl:ENSG00000013503 | |
| POLR1D | GeneProduct | ensembl:ENSG00000186184 | |
| ADAR | GeneProduct | ensembl:ENSG00000160710 | |
| ZBP1 | GeneProduct | ensembl:ENSG00000124256 | |
| RIPK1 | GeneProduct | ensembl:ENSG00000137275 | |
| RIPK3 | GeneProduct | ensembl:ENSG00000129465 | |
| IKBKG | GeneProduct | ensembl:ENSG00000269335 | |
| IKBKB | GeneProduct | ensembl:ENSG00000104365 | |
| CHUK | GeneProduct | ensembl:ENSG00000213341 | |
| NFKB1 | GeneProduct | ncbigene:4790 | |
| RELA | GeneProduct | ensembl:ENSG00000173039 | |
| NFKBIA | GeneProduct | ensembl:ENSG00000100906 | |
| NFKBIB | GeneProduct | ensembl:ENSG00000104825 | |
| IL6 | GeneProduct | ensembl:ENSG00000136244 | |
| CCL4L2 | GeneProduct | ensembl:ENSG00000276070 | |
| CCL5 | GeneProduct | ensembl:ENSG00000271503 | |
| CXCL10 | GeneProduct | ensembl:ENSG00000169245 | |
| AIM2 | GeneProduct | ensembl:ENSG00000163568 | |
| CASP1 | GeneProduct | ensembl:ENSG00000137752 | |
| PYCARD | GeneProduct | ensembl:ENSG00000103490 | |
| IL1B | GeneProduct | ensembl:ENSG00000125538 | |
| IL18 | GeneProduct | ensembl:ENSG00000150782 | |
| IL33 | GeneProduct | ensembl:ENSG00000137033 | |
| IRF3 | GeneProduct | ensembl:ENSG00000126456 | |
| IRF7 | GeneProduct | ensembl:ENSG00000185507 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| IFNB1 | GeneProduct | ncbigene:3456 | Original kegg element: gene;1;hsa:3456 |
| TBK1 | GeneProduct | ensembl:ENSG00000183735 | |
| IKBKE | GeneProduct | ensembl:ENSG00000263528 | |
| CGAS | GeneProduct | ensembl:ENSG00000164430 | |
| DDX58 | GeneProduct | ensembl:ENSG00000107201 | |
| TRIM25 | GeneProduct | ensembl:ENSG00000121060 | |
| CYLD | GeneProduct | ensembl:ENSG00000083799 | |
| RNF125 | GeneProduct | ensembl:ENSG00000101695 | |
| ISG15 | GeneProduct | ensembl:ENSG00000187608 | |
| ATG5 | GeneProduct | ensembl:ENSG00000057663 | |
| ATG12 | GeneProduct | ensembl:ENSG00000145782 | |
| NLRX1 | GeneProduct | ensembl:ENSG00000160703 | |
| MAVS | GeneProduct | ensembl:ENSG00000088888 | |
| TMEM173 | GeneProduct | ensembl:ENSG00000184584 | |
| TRADD | GeneProduct | ensembl:ENSG00000102871 | |
| FADD | GeneProduct | ensembl:ENSG00000168040 | |
| CASP8 | GeneProduct | ensembl:ENSG00000064012 | |
| CASP10 | GeneProduct | ensembl:ENSG00000003400 | |
| CCL4 | GeneProduct | ensembl:ENSG00000275302 |
References
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- DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB. Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, et al. EMBO Rep. 2009 Aug;10(8):916–22. PubMed Europe PMC Scholia
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- Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Sun L, Wu J, Du F, Chen X, Chen ZJ. Science. 2013 Feb 15;339(6121):786–91. PubMed Europe PMC Scholia