Entry Name Cytosolic DNA-sensing pathway
Description Specific families of pattern recognition receptors are responsible for detecting foreign DNA from invading microbes or host cells and generating innate immune responses. DAI is the first identified sensor of cytosolic DNA which activates the IRF and NF-{kappa}B transcription factors, leading to production of type I interferon and other cytokines. The second type of cytoplasmic DNA sensor is AIM2. Upon sensing DNA, AIM2 triggers the assembly of the inflammasome, culminating in interleukin maturation. In addition to these receptors, there is a mechanism to sense foreign DNA, with the host RNA polymerase III converting the DNA into RNA for recognition by the RNA sensor RIG-I. These pathways provide various means to alert the cell.
Class Organismal Systems; Immune systemBRITE hierarchy
Pathway map ko04623 Cytosolic DNA-sensing pathway
Drug Orthology K02373 FADD; FAS-associated death domain protein
K02580 NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581 NFKBIB; NF-kappa-B inhibitor beta
K02861 RIPK1, RIP1; receptor-interacting serine/threonine-protein kinase 1 [EC:2.7.11.1 ]
K03007 RPABC5, RPB10, POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5
K03009 RPABC4, RPB12, POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4
K03013 RPABC1, RPB5, POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1
K03014 RPABC2, RPB6, POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2
K03016 RPABC3, RPB8, POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3
K03018 RPC1, POLR3A; DNA-directed RNA polymerase III subunit RPC1 [EC:2.7.7.6 ]
K03019 RPC11, POLR3K; DNA-directed RNA polymerase III subunit RPC11
K03020 RPAC2, RPC19, POLR1D; DNA-directed RNA polymerases I and III subunit RPAC2
K03021 RPC2, POLR3B; DNA-directed RNA polymerase III subunit RPC2 [EC:2.7.7.6 ]
K03022 RPC8, POLR3H; DNA-directed RNA polymerase III subunit RPC8
K03023 RPC3, POLR3C; DNA-directed RNA polymerase III subunit RPC3
K03024 RPC7, POLR3G; DNA-directed RNA polymerase III subunit RPC7
K03025 RPC6, POLR3F; DNA-directed RNA polymerase III subunit RPC6
K03026 RPC4, POLR3D; DNA-directed RNA polymerase III subunit RPC4
K03027 RPAC1, RPC40, POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1
K04467 IKBKA, IKKA, CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha [EC:2.7.11.10 ]
K04519 IL1B; interleukin 1 beta
K04734 NFKBIA; NF-kappa-B inhibitor alpha
K04735 RELA; transcription factor p65
K05411 IRF3; interferon regulatory factor 3
K05482 IL18, IL1F4; interleukin 18
K07209 IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10 ]
K07210 IKBKG, IKKG, NEMO; inhibitor of nuclear factor kappa-B kinase subunit gamma
K07211 IKBKE, IKKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [EC:2.7.11.10 ]
K08847 RIPK3; receptor-interacting serine/threonine-protein kinase 3 [EC:2.7.11.1 ]
K09447 IRF7; interferon regulatory factor 7
K12499 CCL5; C-C motif chemokine 5
K12646 RIGI, DDX58; ATP-dependent RNA helicase DDX58 [EC:5.6.2.6 ]
K12648 MAVS, IPS1; mitochondrial antiviral-signaling protein
K12654 STING1, TMEM173, MITA; stimulator of interferon genes protein
K12671 CXCL10, IP10; C-X-C motif chemokine 10
K12799 PYCARD, ASC; apoptosis-associated speck-like protein containing a CARD
K12800 NLRP3, PYPAF1; NACHT, LRR and PYD domains-containing protein 3
K12889 PCBP1; poly(rC)-binding protein 1
K12964 CCL4; C-C motif chemokine 4
K12965 ZBP1, DAI; Z-DNA binding protein 1
K12966 AIM2; absent in melanoma 2
K12968 ADAR, ADAR1; double-stranded RNA-specific adenosine deaminase [EC:3.5.4.37 ]
K12969 E3L; Poxviridae RNA-binding protein E3
K12970 M45; Murid betaherpesvirus 1 ribonucleoside-diphosphate reductase [EC:1.17.4.1 ]
K12971 IFI202; interferon-activable protein 202
K14721 RPC5, POLR3E; DNA-directed RNA polymerase III subunit RPC5
K20914 IFI16; gamma-interferon-inducible protein 16
K22146 GSDME, DFNA5; gasdermin-E
K22544 SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [EC:3.1.5.-]
K27162 ZCCHC3; zinc finger CCHC domain-containing protein 3
Compound Reference Authors Yanai H, Savitsky D, Tamura T, Taniguchi T
Title Regulation of the cytosolic DNA-sensing system in innate immunity: a current view.
Journal Reference Authors Vilaysane A, Muruve DA
Title The innate immune response to DNA.
Journal Reference Authors Takeshita F, Ishii KJ
Title Intracellular DNA sensors in immunity.
Journal Reference Authors Takaoka A, Shinohara S
Title DNA sensors in innate immune system.
Journal Reference Authors Takaoka A, Taniguchi T
Title Cytosolic DNA recognition for triggering innate immune responses.
Journal Reference Authors Kaiser WJ, Upton JW, Mocarski ES
Title Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors.
Journal Reference Authors Rebsamen M, Heinz LX, Meylan E, Michallet MC, Schroder K, Hofmann K, Vazquez J, Benedict CA, Tschopp J
Title DAI/ZBP1 recruits RIP1 and RIP3 through RIP homotypic interaction motifs to activate NF-kappaB.
Journal Reference Authors Wang Z, Choi MK, Ban T, Yanai H, Negishi H, Lu Y, Tamura T, Takaoka A, Nishikura K, Taniguchi T
Title Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules.
Journal Reference Authors Stetson DB, Ko JS, Heidmann T, Medzhitov R
Title Trex1 prevents cell-intrinsic initiation of autoimmunity.
Journal Reference Authors Schroder K, Muruve DA, Tschopp J
Title Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.
Journal Reference Authors Krieg AM
Title AIMing 2 detect foreign DNA.
Journal Reference Authors O'Neill LA
Title DNA makes RNA makes innate immunity.
Journal Reference Authors Ishii KJ, Coban C, Kato H, Takahashi K, Torii Y, Takeshita F, Ludwig H, Sutter G, Suzuki K, Hemmi H, Sato S, Yamamoto M, Uematsu S, Kawai T, Takeuchi O, Akira S
Title A Toll-like receptor-independent antiviral response induced by double-stranded B-form DNA.
Journal Reference Authors Cao X
Title New DNA-sensing pathway feeds RIG-I with RNA.
Journal Reference Authors Sun L, Wu J, Du F, Chen X, Chen ZJ
Title Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
Journal Reference Authors Gao M, He Y, Tang H, Chen X, Liu S, Tao Y
Title cGAS/STING: novel perspectives of the classic pathway.
Journal Reference Authors Benjamin P, Sudhakar S, D'Arco F, Lobel U, Carney O, Roux CJ, Boddaert N, Hemingway C, Eleftheriou D, Mankad K
Title Spectrum of Neuroradiologic Findings Associated with Monogenic Interferonopathies.
Journal Reference Authors Place DE, Lee S, Kanneganti TD
Title PANoptosis in microbial infection.
Journal Reference Authors Jiang W, Deng Z, Dai X, Zhao W
Title PANoptosis: A New Insight Into Oral Infectious Diseases.
Journal Reference Authors Wang Y, Kanneganti TD
Title From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways.
Journal Related ko04064 NF-kappa B signaling pathway
ko04120 Ubiquitin mediated proteolysis
ko04621 NOD-like receptor signaling pathway
ko04622 RIG-I-like receptor signaling pathway
