KEGG   PATHWAY: mni04623
Entry
mni04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Macaca nemestrina (pig-tailed macaque)
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
mni04623  Cytosolic DNA-sensing pathway
mni04623

Organism
Macaca nemestrina (pig-tailed macaque) [GN:mni]
Gene
105466218  POLR3A; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
105497691  POLR3B; DNA-directed RNA polymerase III subunit RPC2 isoform X1 [KO:K03021] [EC:2.7.7.6]
105479034  POLR3C; DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
105482083  POLR3D; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
105485005  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X2 [KO:K14721]
105489564  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 [KO:K03027]
105485935  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
105466659  LOW QUALITY PROTEIN: DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
105490206  DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
105464377  POLR3H; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
105479045  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like isoform X1 [KO:K03024]
105491937  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
105486831  POLR3F; DNA-directed RNA polymerase III subunit RPC6 isoform X1 [KO:K03025]
105486320  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 isoform X1 [KO:K03013]
105464464  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
105480129  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
105477515  DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
105476059  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
105494162  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
105485638  DDX58; probable ATP-dependent RNA helicase DDX58 isoform X1 [KO:K12646] [EC:5.6.2.6]
105481575  MAVS; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
105486337  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
105469585  RELA; transcription factor p65 isoform X1 [KO:K04735]
105475680  IL6; interleukin-6 isoform X1 [KO:K05405]
105465212  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
105466839  G3BP1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
105496140  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
105479453  CGAS; cyclic GMP-AMP synthase isoform X1 [KO:K17834] [EC:2.7.7.86]
105467057  TMEM173; stimulator of interferon genes protein [KO:K12654]
105464584  probable palmitoyltransferase ZDHHC11 [KO:K20027] [EC:2.3.1.225]
105491425  ZDHHC1; probable palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
105484043  DDX41; probable ATP-dependent RNA helicase DDX41 [KO:K13116] [EC:5.6.2.7]
105498135  IFI16; gamma-interferon-inducible protein 16 isoform X1 [KO:K20914]
105473459  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
105484842  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
105497189  IRF3; interferon regulatory factor 3 isoform X1 [KO:K05411]
105494145  IRF7; interferon regulatory factor 7 isoform X1 [KO:K09447]
105465888  IFNA21; LOW QUALITY PROTEIN: interferon alpha-21 [KO:K05414]
105498418  interferon alpha-1/13-like [KO:K05414]
105498422  IFNA8; interferon alpha-8 [KO:K05414]
105498424  interferon alpha-6 [KO:K05414]
105498425  interferon alpha-1/13 [KO:K05414]
105498426  interferon alpha-2 [KO:K05414]
105498430  interferon alpha-4 [KO:K05414]
105465886  IFNB1; interferon beta [KO:K05415]
105470601  ZBP1; Z-DNA-binding protein 1 isoform X1 [KO:K12965]
105487318  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
105477873  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
105471007  LOW QUALITY PROTEIN: NF-kappa-B essential modulator-like [KO:K07210]
105478402  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
105476527  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
105495392  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
105477978  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
105468575  C-C motif chemokine 4 [KO:K12964]
105485102  C-C motif chemokine 4 [KO:K12964]
105485120  CCL5; C-C motif chemokine 5 [KO:K12499]
105477263  CXCL10; C-X-C motif chemokine 10 precursor [KO:K12671]
105498137  AIM2; interferon-inducible protein AIM2 isoform X1 [KO:K12966]
105474735  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
105467877  MEFV; pyrin [KO:K12803]
105469733  FADD; FAS-associated death domain protein [KO:K02373]
105468105  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
105482961  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
105493685  caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
105493689  caspase-1 isoform X1 [KO:K01370] [EC:3.4.22.36]
105491539  MLKL; mixed lineage kinase domain-like protein [KO:K08849] [EC:2.7.11.1]
105466747  CASP3; LOW QUALITY PROTEIN: caspase-3 [KO:K02187] [EC:3.4.22.56]
105492342  caspase-3-like isoform X1 [KO:K02187] [EC:3.4.22.56]
105466939  CASP7; LOW QUALITY PROTEIN: caspase-7 [KO:K04397] [EC:3.4.22.60]
105475708  GSDME; gasdermin-E [KO:K22146]
105488447  GSDMD; gasdermin-D isoform X1 [KO:K20917]
105471787  IL1B; interleukin-1 beta [KO:K04519]
105493609  IL18; interleukin-18 [KO:K05482]
105489145  IL33; interleukin-33 isoform X1 [KO:K12967]
105497976  ADAR; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
105496528  SAMHD1; LOW QUALITY PROTEIN: deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
105480405  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
105465513  DNASE2; deoxyribonuclease-2-alpha [KO:K01158] [EC:3.1.22.1]
105482745  DNASE2B; deoxyribonuclease-2-beta isoform X1 [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
mni04064  NF-kappa B signaling pathway
mni04120  Ubiquitin mediated proteolysis
mni04210  Apoptosis
mni04217  Necroptosis
mni04621  NOD-like receptor signaling pathway
mni04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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