KEGG   PATHWAY: zca04623
Entry
zca04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Zalophus californianus (California sea lion)
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
zca04623  Cytosolic DNA-sensing pathway
zca04623

Organism
Zalophus californianus (California sea lion) [GN:zca]
Gene
113908218  [KO:K12964]
113908985  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
113909583  [KO:K03025]
113910226  NFKBIA; NF-kappa-B inhibitor alpha isoform X1 [KO:K04734]
113911087  [KO:K03019]
113911210  GSDME; gasdermin-E isoform X1 [KO:K22146]
113911910  IL6; interleukin-6 [KO:K05405]
113912225  [KO:K05414]
113913830  IL18; interleukin-18 [KO:K05482]
113914198  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
113914747  FADD; FAS-associated death domain protein [KO:K02373]
113914873  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
113914948  RELA; transcription factor p65 [KO:K04735]
113916710  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
113916932  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
113916981  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
113917273  DNASE2; deoxyribonuclease-2-alpha [KO:K01158] [EC:3.1.22.1]
113919983  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
113920614  [KO:K03020]
113921986  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
113922533  POLR3H; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
113922582  POLR3B; DNA-directed RNA polymerase III subunit RPC2 isoform X1 [KO:K03021] [EC:2.7.7.6]
113922705  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 isoform X1 [KO:K03014]
113923389  POLR3A; DNA-directed RNA polymerase III subunit RPC1 isoform X1 [KO:K03018] [EC:2.7.7.6]
113923411  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
113923463  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
113923553  [KO:K17265] [EC:5.6.2.3 3.6.4.13]
113924180  IKBKB; LOW QUALITY PROTEIN: inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
113924266  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
113924509  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
113924659  POLR3D; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
113924908  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
113925431  [KO:K03009]
113925513  [KO:K03009]
113926323  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X1 [KO:K03027]
113926618  CGAS; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
113927116  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
113928404  [KO:K20027] [EC:2.3.1.225]
113928695  G3BP1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.3 3.6.4.13]
113928777  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
113928865  DDX41; probable ATP-dependent RNA helicase DDX41 isoform X1 [KO:K13116] [EC:3.6.4.13]
113929903  STING1; stimulator of interferon genes protein isoform X1 [KO:K12654]
113930597  [KO:K07210]
113930605  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
113931151  [KO:K02373]
113931442  POLR3C; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
113932110  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
113932300  IFI16; gamma-interferon-inducible protein 16 [KO:K20914]
113932455  MEFV; pyrin isoform X1 [KO:K12803]
113932682  GSDMD; gasdermin-D isoform X1 [KO:K20917]
113932728  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
113932810  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
113932866  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X1 [KO:K14721]
113933449  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
113933994  DDX58; antiviral innate immune response receptor RIG-I isoform X1 [KO:K12646] [EC:3.6.4.13]
113934419  IFNB1; interferon beta [KO:K05415]
113934655  [KO:K05414]
113934667  [KO:K05414]
113934678  [KO:K05414]
113934682  [KO:K05414]
113934906  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
113934985  [KO:K05414]
113935128  IL33; interleukin-33 isoform X1 [KO:K12967]
113935924  ZDHHC1; palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
113935929  DNASE2B; deoxyribonuclease-2-beta [KO:K01158] [EC:3.1.22.1]
113936110  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
113936398  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
113937052  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
113937234  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
113937259  POLR3F; DNA-directed RNA polymerase III subunit RPC6 isoform X1 [KO:K03025]
113937493  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
113937727  ZBP1; Z-DNA-binding protein 1 isoform X1 [KO:K12965]
113937839  IL1B; interleukin-1 beta [KO:K04519]
113938296  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
113938370  [KO:K03009]
113938749  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
113938902  NLRP3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
113939093  CCL5; C-C motif chemokine 5 [KO:K12499]
118356554  [KO:K07210]
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
zca04064  NF-kappa B signaling pathway
zca04120  Ubiquitin mediated proteolysis
zca04210  Apoptosis
zca04217  Necroptosis
zca04621  NOD-like receptor signaling pathway
zca04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   

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