KEGG   PATHWAY: shr04623
Entry
shr04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Sarcophilus harrisii (Tasmanian devil)
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
shr04623  Cytosolic DNA-sensing pathway
shr04623

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100923286  POLR3A; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
100926675  POLR3B; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
100924672  POLR3C; DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
100914519  POLR3D; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
100917311  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X1 [KO:K14721]
100935142  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 isoform X1 [KO:K03027]
100917831  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
100926318  DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
100919182  POLR3H; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
100926499  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
100930488  POLR3G; DNA-directed RNA polymerase III subunit RPC7 [KO:K03024]
100923649  POLR3F; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
100927834  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
100923711  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
100933932  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 isoform X1 [KO:K03016]
100935194  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
116419918  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
100926796  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100932473  RELA; transcription factor p65 [KO:K04735]
105750762  IL6; interleukin-6 [KO:K05405]
100922339  G3BP1; ras GTPase-activating protein-binding protein 1 isoform X2 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
100920386  CGAS; cyclic GMP-AMP synthase isoform X2 [KO:K17834] [EC:2.7.7.86]
100932153  STING1; stimulator of interferon genes protein [KO:K12654]
100934839  probable palmitoyltransferase ZDHHC11 isoform X1 [KO:K20027] [EC:2.3.1.225]
100933971  ZDHHC1; probable palmitoyltransferase ZDHHC1 [KO:K20027] [EC:2.3.1.225]
100920861  DDX41; probable ATP-dependent RNA helicase DDX41 isoform X2 [KO:K13116] [EC:5.6.2.7]
100915362  TBK1; serine/threonine-protein kinase TBK1 isoform X1 [KO:K05410] [EC:2.7.11.10]
100934784  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
100933650  interferon regulatory factor 3 [KO:K05411]
100914965  interferon tau-like [KO:K05414]
100920968  interferon tau-2-like [KO:K05414]
100914703  interferon tau-2-like [KO:K05414]
116420987  interferon omega-1-like [KO:K05414]
116420989  interferon omega-1-like [KO:K05414]
100914443  interferon beta [KO:K05415]
100914177  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
100926701  IKBKG; NF-kappa-B essential modulator isoform X3 [KO:K07210]
100913624  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100917003  C-C motif chemokine 4-like [KO:K12964]
100925102  C-C motif chemokine 4 [KO:K12964]
100915784  C-C motif chemokine 3-like 1 [KO:K12964]
105750580  C-C motif chemokine 4-like [KO:K12964]
100917263  C-C motif chemokine 4-like [KO:K12964]
100916478  C-C motif chemokine 4-like [KO:K12964]
100916737  C-C motif chemokine 4-like [KO:K12964]
100917781  C-C motif chemokine 3 [KO:K12964]
116423442  C-C motif chemokine 4-like [KO:K12964]
100922240  CXCL10; C-X-C motif chemokine 10 [KO:K12671]
105750853  C-X-C motif chemokine 10-like [KO:K12671]
100921789  AIM2; interferon-inducible protein AIM2 [KO:K12966]
100933206  MEFV; pyrin isoform X3 [KO:K12803]
100925732  FADD; FAS-associated death domain protein [KO:K02373]
100931580  CASP8; caspase-8 [KO:K04398] [EC:3.4.22.61]
100925851  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
105749479  PYDC1; pyrin domain-containing protein 1 [KO:K12799]
100935043  caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
100922757  caspase-3-like [KO:K02187] [EC:3.4.22.56]
100922500  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
100927801  CASP7; caspase-7 [KO:K04397] [EC:3.4.22.60]
116419608  GSDME; gasdermin-E [KO:K22146]
100934670  gasdermin-D [KO:K20917]
100922350  IL1B; interleukin-1 beta [KO:K04519]
100919934  interleukin-18-like [KO:K05482]
100920716  IL18; interleukin-18 [KO:K05482]
111719790  interleukin-18-like [KO:K05482]
105749716  IL33; interleukin-33 [KO:K12967]
100925968  ADAR; double-stranded RNA-specific adenosine deaminase isoform X2 [KO:K12968] [EC:3.5.4.37]
100933973  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
105749561  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
100927318  DNASE2; deoxyribonuclease-2-alpha isoform X1 [KO:K01158] [EC:3.1.22.1]
100917174  DNASE2B; deoxyribonuclease-2-beta [KO:K01158] [EC:3.1.22.1]
Compound
C00039  DNA
C20640  Cyclic GMP-AMP
Reference
PMID:19362700
  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
PMID:19497760
  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
PMID:18573338
  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
PMID:19122387
  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
PMID:18280611
  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
PMID:18941233
  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
PMID:19590578
  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
PMID:18375758
  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
PMID:18724932
  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
PMID:19321146
  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
PMID:19567913
  Authors
Krieg AM
  Title
AIMing 2 detect foreign DNA.
  Journal
Sci Signal 2:pe39 (2009)
DOI:10.1126/scisignal.277pe39
Reference
PMID:19665965
  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
PMID:16286919
  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
PMID:19767723
  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
PMID:23258413
  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
PMID:35006429
  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
PMID:34949589
  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
PMID:32829024
  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
PMID:34970269
  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
PMID:34504660
  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
shr04064  NF-kappa B signaling pathway
shr04120  Ubiquitin mediated proteolysis
shr04210  Apoptosis
shr04217  Necroptosis
shr04621  NOD-like receptor signaling pathway
shr04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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