KEGG   PATHWAY: rno04623
Entry
rno04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Rattus norvegicus (rat)
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 system
Pathway map
rno04623  Cytosolic DNA-sensing pathway
rno04623

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
361102  Polr3a; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
362858  Polr3b; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
310685  Polr3c; DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
306012  Polr3d; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
361640  Polr3e; DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
301246  Polr1c; DNA-directed RNA polymerases I and III subunit RPAC1 [KO:K03027]
366277  Polr3k; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
300088  Polr3h; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
685465  Polr3g; DNA-directed RNA polymerase III subunit RPC7 [KO:K03024]
690254  Polr3gl; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
311487  Polr3f; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
690966  Polr2e; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
83503  Polr2f; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
498109  Polr2h; polymerase (RNA) II (DNA directed) polypeptide H [KO:K03016]
100361574  Polr2k; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
681193  DNA-directed RNA polymerases I, II, and III subunit RPABC5-like [KO:K03007]
502374  Polr2l; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
297989  Ddx58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:3.6.4.13]
311430  Mavs; mitochondrial antiviral-signaling protein [KO:K12648]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
309165  Rela; transcription factor p65 [KO:K04735]
24498  Il6; interleukin-6 precursor [KO:K05405]
682147  Cgas; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
498840  Sting1; stimulator of interferon genes protein [KO:K12654]
299827  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
363984  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
292892  Irf3; interferon regulatory factor 3 [KO:K05411]
293624  Irf7; interferon regulatory factor 7 [KO:K09447]
298205  Ifna4; interferon, alpha 4 precursor [KO:K05414]
298213  Ifna2; interferon alpha family, gene 2 precursor [KO:K05414]
298210  Ifna5; interferon alpha-1 precursor [KO:K05414]
690894  Ifna1; interferon alpha-5 [KO:K05414]
100912314  interferon alpha-1-like [KO:K05414]
502961  RGD1559679; interferon alpha-1-like [KO:K05414]
500491  Ifna16l1; interferon alpha-1-like [KO:K05414]
24481  Ifnb1; interferon beta precursor [KO:K05415]
171091  Zbp1; Z-DNA-binding protein 1 [KO:K12965]
306886  Ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
246240  Ripk3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
309295  Ikbkg; NF-kappa-B essential modulator [KO:K07210]
309361  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
116637  Ccl4; C-C motif chemokine 4 precursor [KO:K12964]
81780  Ccl5; C-C motif chemokine 5 precursor [KO:K12499]
245920  Cxcl10; C-X-C motif chemokine 10 precursor [KO:K12671]
304987  Aim2; interferon-inducible protein AIM2 isoform X1 [KO:K12966]
287362  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
58923  Mefv; pyrin [KO:K12803]
266610  Fadd; FAS-associated death domain protein [KO:K02373]
64044  Casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
282817  Pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
25166  Casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
690743  Mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
25402  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
64026  Casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
353316  Dfna5; deafness, autosomal dominant 5 [KO:K22146]
315084  Gsdmd; gasdermin-D [KO:K20917]
24494  Il1b; interleukin-1 beta [KO:K04519]
29197  Il18; interleukin-18 [KO:K05482]
361749  Il33; interleukin-33 [KO:K12967]
81635  Adar; double-stranded RNA-specific adenosine deaminase [KO:K12968] [EC:3.5.4.37]
311580  Samhd1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
100049583  Trex1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
59296  Dnase2b; deoxyribonuclease-2-beta precursor [KO:K01158] [EC:3.1.22.1]
171575  Dnase2; deoxyribonuclease-2-alpha precursor [KO:K01158] [EC:3.1.22.1]
Compound
C00039  DNA
C20640  Cyclic GMP-AMP
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
Curr Opin Immunol 21:17-22 (2009)
DOI:10.1016/j.coi.2009.01.005
Reference
  Authors
Vilaysane A, Muruve DA
  Title
The innate immune response to DNA.
  Journal
Semin Immunol 21:208-14 (2009)
DOI:10.1016/j.smim.2009.05.006
Reference
  Authors
Takeshita F, Ishii KJ
  Title
Intracellular DNA sensors in immunity.
  Journal
Curr Opin Immunol 20:383-8 (2008)
DOI:10.1016/j.coi.2008.05.009
Reference
  Authors
Takaoka A, Shinohara S
  Title
DNA sensors in innate immune system.
  Journal
Uirusu 58:37-46 (2008)
DOI:10.2222/jsv.58.37
Reference
  Authors
Takaoka A, Taniguchi T
  Title
Cytosolic DNA recognition for triggering innate immune responses.
  Journal
Adv Drug Deliv Rev 60:847-57 (2008)
DOI:10.1016/j.addr.2007.12.002
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
J Immunol 181:6427-34 (2008)
DOI:10.4049/jimmunol.181.9.6427
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
EMBO Rep 10:916-22 (2009)
DOI:10.1038/embor.2009.109
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
Proc Natl Acad Sci U S A 105:5477-82 (2008)
DOI:10.1073/pnas.0801295105
Reference
  Authors
Stetson DB, Ko JS, Heidmann T, Medzhitov R
  Title
Trex1 prevents cell-intrinsic initiation of autoimmunity.
  Journal
Cell 134:587-98 (2008)
DOI:10.1016/j.cell.2008.06.032
Reference
  Authors
Schroder K, Muruve DA, Tschopp J
  Title
Innate immunity: cytoplasmic DNA sensing by the AIM2 inflammasome.
  Journal
Curr Biol 19:R262-5 (2009)
DOI:10.1016/j.cub.2009.02.011
Reference
  Authors
Krieg AM
  Title
AIMing 2 detect foreign DNA.
  Journal
Sci Signal 2:pe39 (2009)
DOI:10.1126/scisignal.277pe39
Reference
  Authors
O'Neill LA
  Title
DNA makes RNA makes innate immunity.
  Journal
Cell 138:428-30 (2009)
DOI:10.1016/j.cell.2009.07.021
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
Nat Immunol 7:40-8 (2006)
DOI:10.1038/ni1282
Reference
  Authors
Cao X
  Title
New DNA-sensing pathway feeds RIG-I with RNA.
  Journal
Nat Immunol 10:1049-51 (2009)
DOI:10.1038/ni1009-1049
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
Science 339:786-91 (2013)
DOI:10.1126/science.1232458
Reference
  Authors
Gao M, He Y, Tang H, Chen X, Liu S, Tao Y
  Title
cGAS/STING: novel perspectives of the classic pathway.
  Journal
Mol Biomed 1:7 (2020)
DOI:10.1186/s43556-020-00006-z
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
AJNR Am J Neuroradiol 43:2-10 (2022)
DOI:10.3174/ajnr.A7362
Reference
  Authors
Place DE, Lee S, Kanneganti TD
  Title
PANoptosis in microbial infection.
  Journal
Curr Opin Microbiol 59:42-49 (2021)
DOI:10.1016/j.mib.2020.07.012
Reference
  Authors
Jiang W, Deng Z, Dai X, Zhao W
  Title
PANoptosis: A New Insight Into Oral Infectious Diseases.
  Journal
Front Immunol 12:789610 (2021)
DOI:10.3389/fimmu.2021.789610
Reference
  Authors
Wang Y, Kanneganti TD
  Title
From pyroptosis, apoptosis and necroptosis to PANoptosis: A mechanistic compendium of programmed cell death pathways.
  Journal
Comput Struct Biotechnol J 19:4641-4657 (2021)
DOI:10.1016/j.csbj.2021.07.038
Related
pathway
rno04064  NF-kappa B signaling pathway
rno04120  Ubiquitin mediated proteolysis
rno04210  Apoptosis
rno04217  Necroptosis
rno04621  NOD-like receptor signaling pathway
rno04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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