KEGG   PATHWAY: xtr04623
Entry
xtr04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Xenopus tropicalis (tropical clawed frog)
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
xtr04623  Cytosolic DNA-sensing pathway
xtr04623

Organism
Xenopus tropicalis (tropical clawed frog) [GN:xtr]
Gene
100124725  polr3a; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
100127616  polr3gl; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
100127621  sting1; stimulator of interferon genes protein [KO:K12654]
100127742  pycard; PYD and CARD domain containing [KO:K12799]
100145270  ikbkg; NF-kappa-B essential modulator [KO:K07210]
100151728  casp3.2; caspase-3 [KO:K02187] [EC:3.4.22.56]
100158643  polr3b; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
100216212  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
100379789  fadd; FAS-associated death domain protein [KO:K02373]
100379802  polr1c; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X1 [KO:K03027]
100379899  mlkl; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
100380066  polr3c; DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
100485800  polr3g; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
100485829  mavs; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
100486029  gsdme; gasdermin-E isoform X1 [KO:K22146]
100486083  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100486222  casp3.1; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
100487038  il1b; interleukin-1 beta [KO:K04519]
100487744  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100487921  [KO:K27162]
100488048  cgas; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
100490108  cxcl9; C-X-C motif chemokine 11-1 [KO:K12671]
100490202  zdhhc1; probable palmitoyltransferase ZDHHC1 [KO:K20027] [EC:2.3.1.225]
100490277  cxcl10; C-X-C motif chemokine 10 [KO:K12671]
100490493  ripk3.2; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
100490785  cxcl11; C-X-C motif chemokine 11-1 [KO:K12671]
100491169  ripk3.1; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
100491281  ddx41; probable ATP-dependent RNA helicase DDX41 isoform X2 [KO:K13116] [EC:5.6.2.7]
100491605  casp1; caspase-1-A isoform X1 [KO:K01370] [EC:3.4.22.36]
100493195  adar; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
100493927  il6; interleukin-6 [KO:K05405]
100495207  ddx58; probable ATP-dependent RNA helicase DDX58 isoform X2 [KO:K12646] [EC:5.6.2.6]
100495369  polr1d.2; DNA-directed RNA polymerases I and III subunit RPAC2 isoform X2 [KO:K03020]
100495471  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100496395  irf7; interferon regulatory factor 7 [KO:K09447]
100496523  ccl5; C-C motif chemokine 5 isoform X3 [KO:K12499]
100496716  [KO:K05482]
100497163  ccl4; C-C motif chemokine 4 homolog [KO:K12964]
100497374  [KO:K08847] [EC:2.7.11.1]
100497621  [KO:K08849] [EC:2.7.11.1]
100498574  samhd1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
101730829  [KO:K22544] [EC:3.1.5.-]
101732196  [KO:K12799]
101732530  zbp1; Z-DNA-binding protein 1 [KO:K12965]
101734275  irf3; interferon regulatory factor 3 [KO:K05411]
105945198  [KO:K05414]
105945919  [KO:K27162]
105946710  [KO:K12964]
108645259  [KO:K27162]
108648098  il18; interleukin-18 [KO:K05482]
116406494  [KO:K27162]
116406752  [KO:K27162]
116406954  [KO:K27162]
116407924  [KO:K05414]
116407927  [KO:K22544] [EC:3.1.5.-]
116408033  [KO:K05414]
116409443  [KO:K27162]
116409445  [KO:K27162]
116409784  [KO:K04519]
116410477  [KO:K27162]
116410870  [KO:K27162]
394944  polr3f; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
407869  rela; transcription factor p65 [KO:K04735]
448125  ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
448138  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
448728  polr2f; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
493382  polr3e; polr3e protein [KO:K14721]
496759  dnase2b; deoxyribonuclease-2-beta precursor [KO:K01158] [EC:3.1.22.1]
548520  polr3k; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
548867  polr2h; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
549053  casp7; caspase-7 [KO:K04397] [EC:3.4.22.60]
549097  polr2l.1; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
549227  polr2e; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
549263  polr2k; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
549654  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha [KO:K04467] [EC:2.7.11.10]
549724  polr3e; RNA polymerase III polypeptide E [KO:K14721]
549800  g3bp1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
550100  polr3d; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
733553  [KO:K04397] [EC:3.4.22.60]
733868  dnase2; deoxyribonuclease-2-alpha precursor [KO:K01158] [EC:3.1.22.1]
734135  polr2l.2; polymerase (RNA) II (DNA directed) polypeptide L, 7.6kDa, gene 2 [KO:K03007]
779851  polr3h; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
779958  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
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
xtr04120  Ubiquitin mediated proteolysis
xtr04210  Apoptosis
xtr04217  Necroptosis
xtr04621  NOD-like receptor signaling pathway
xtr04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   

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