KEGG   PATHWAY: loc04623
Entry
loc04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Lepisosteus oculatus (spotted gar)
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
loc04623  Cytosolic DNA-sensing pathway
loc04623

Organism
Lepisosteus oculatus (spotted gar) [GN:loc]
Gene
102696700  polr3a; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
102696058  polr3b; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
102698048  polr3c; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
102689770  polr3d; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
102687012  DNA-directed RNA polymerase III subunit RPC4-like isoform X1 [KO:K03026]
102690088  polr3e; DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
102683546  polr1c; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X2 [KO:K03027]
102691556  polr3k; DNA-directed RNA polymerase III subunit RPC10 isoform X2 [KO:K03019]
102691211  DNA-directed RNA polymerases I and III subunit RPAC2-like [KO:K03020]
102697053  polr3h; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
102688143  polr3g; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
102695428  polr3gl; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
102684479  polr3f; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
102682941  polr2e; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
102682591  polr2f; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
102692910  polr2h; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
102687034  polr2k; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
102684584  probable ATP-dependent RNA helicase DDX58 isoform X1 [KO:K12646] [EC:5.6.2.6]
102686328  ddx58; probable ATP-dependent RNA helicase DDX58 isoform X1 [KO:K12646] [EC:5.6.2.6]
107076971  mitochondrial antiviral-signaling protein-like [KO:K12648]
102693746  nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107078662  il6; interleukin-6 [KO:K05405]
102684601  g3bp1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
107076494  cyclic GMP-AMP synthase-like [KO:K17834] [EC:2.7.7.86]
102683757  mb21d1; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
102691936  tmem173; stimulator of interferon genes protein [KO:K12654]
102694578  zdhhc1; probable palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
102687846  probable palmitoyltransferase ZDHHC11 isoform X1 [KO:K20027] [EC:2.3.1.225]
102688039  ddx41; probable ATP-dependent RNA helicase DDX41 [KO:K13116] [EC:5.6.2.7]
102687024  tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
102692331  ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
107075358  irf3; interferon regulatory factor 3 [KO:K05411]
102698664  irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
107076357  uncharacterized protein LOC107076357 isoform X1 [KO:K05414]
102693774  interferon a3-like [KO:K05414]
107079271  interferon omega-2-like [KO:K05414]
107079272  interferon a3-like [KO:K05414]
102691146  ripk1; receptor-interacting serine/threonine-protein kinase 1 [KO:K02861] [EC:2.7.11.1]
102682818  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
102691336  chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
102690045  ikbkb; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102689470  nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
102690370  fadd; FAS-associated death domain protein [KO:K02373]
102697635  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102697443  casp8; caspase-8 [KO:K04398] [EC:3.4.22.61]
102697829  caspase-8-like [KO:K04398] [EC:3.4.22.61]
102686039  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102686244  apoptosis-associated speck-like protein containing a CARD [KO:K12799]
102696999  casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
102688855  caspase-13-like [KO:K01370] [EC:3.4.22.36]
102687595  mlkl; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
102691196  caspase-3-like [KO:K02187] [EC:3.4.22.56]
102693931  caspase-7-like [KO:K04397] [EC:3.4.22.60]
102691279  casp7; caspase-7 isoform X2 [KO:K04397] [EC:3.4.22.60]
102695170  samhd1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
107075360  deoxynucleoside triphosphate triphosphohydrolase SAMHD1-like [KO:K22544] [EC:3.1.5.-]
102695361  deoxynucleoside triphosphate triphosphohydrolase SAMHD1-like [KO:K22544] [EC:3.1.5.-]
102689536  dnase2b; deoxyribonuclease-2-beta [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
loc04120  Ubiquitin mediated proteolysis
loc04210  Apoptosis
loc04217  Necroptosis
loc04621  NOD-like receptor signaling pathway
loc04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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