KEGG   PATHWAY: mcc04623
Entry
mcc04623                    Pathway                                
Name
Cytosolic DNA-sensing pathway - Macaca mulatta (rhesus monkey)
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
mcc04623  Cytosolic DNA-sensing pathway
mcc04623

Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100423709  POLR3K; DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
100424410  POLR3A; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
100426388  LOW QUALITY PROTEIN: caspase-1-like [KO:K01370] [EC:3.4.22.36]
100426632  C-C motif chemokine 4 [KO:K12964]
100426798  DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
100429040  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
100429168  TREX1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
100430627  C-C motif chemokine 4 [KO:K12964]
106992322  interferon alpha-17 [KO:K05414]
106995851  IFNA6; interferon alpha-6 [KO:K05414]
114671810  DNA-directed RNA polymerases I, II, and III subunit RPABC4-like [KO:K03009]
114672663  interferon alpha-17-like [KO:K05414]
114672664  interferon alpha-17-like [KO:K05414]
114677647  DNA-directed RNA polymerases I, II, and III subunit RPABC5-like [KO:K03007]
574151  IL18; interleukin-18 [KO:K05482]
574178  CCL5; C-C motif chemokine 5 precursor [KO:K12499]
574217  CCL4L1; C-C motif chemokine 4 precursor [KO:K12964]
574243  CXCL10; C-X-C motif chemokine 10 precursor [KO:K12671]
694353  TMEM173; stimulator of interferon genes protein [KO:K12654]
694473  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
694631  interferon alpha-1/13-like [KO:K05414]
694844  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
695330  POLR3G; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
695335  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
695607  IKBKE; inhibitor of nuclear factor kappa-B kinase subunit epsilon [KO:K07211] [EC:2.7.11.10]
696090  ZBP1; Z-DNA-binding protein 1 [KO:K12965]
696943  POLR3C; DNA-directed RNA polymerase III subunit RPC3 isoform X1 [KO:K03023]
697137  GSDMD; gasdermin-D isoform X1 [KO:K20917]
697633  CASP7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
697901  POLR3E; DNA-directed RNA polymerase III subunit RPC5 isoform X1 [KO:K14721]
697927  POLR3F; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
697969  ZDHHC1; probable palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
698563  POLR3GL; DNA-directed RNA polymerase III subunit RPC7-like [KO:K03024]
699566  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
699578  IRF7; interferon regulatory factor 7 [KO:K09447]
700727  POLR1C; DNA-directed RNA polymerases I and III subunit RPAC1 [KO:K03027]
700742  DDX41; probable ATP-dependent RNA helicase DDX41 isoform X1 [KO:K13116] [EC:5.6.2.7]
701181  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
701237  IKBKG; NF-kappa-B essential modulator isoform X1 [KO:K07210]
701278  NLRP3; NACHT, LRR and PYD domains-containing protein 3 [KO:K12800]
701927  MEFV; pyrin [KO:K12803]
702711  POLR3B; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
702781  CASP8; caspase-8 isoform X1 [KO:K04398] [EC:3.4.22.61]
703441  GSDME; gasdermin-E isoform X1 [KO:K22146]
704638  DDX58; probable ATP-dependent RNA helicase DDX58 [KO:K12646] [EC:5.6.2.6]
704683  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
704701  IL1B; interleukin-1 beta precursor [KO:K04519]
705819  IL6; interleukin-6 precursor [KO:K05405]
706568  caspase-1 [KO:K01370] [EC:3.4.22.36]
707546  POLR3H; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
707923  POLR3D; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
708013  RIPK1; receptor-interacting serine/threonine-protein kinase 1 isoform X2 [KO:K02861] [EC:2.7.11.1]
708464  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 isoform X1 [KO:K03009]
708606  FADD; FAS-associated death domain protein [KO:K02373]
709060  SAMHD1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 [KO:K22544] [EC:3.1.5.-]
709511  CHUK; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X3 [KO:K04467] [EC:2.7.11.10]
709520  PCBP1; poly(rC)-binding protein 1 [KO:K12889]
709559  IFNA13; interferon alpha-1/13 precursor [KO:K05414]
709755  IFNA8; interferon alpha-8 [KO:K05414]
709948  IFNA2; interferon alpha-2 precursor [KO:K05414]
710197  DNASE2B; deoxyribonuclease-2-beta isoform X1 [KO:K01158] [EC:3.1.22.1]
710316  MLKL; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
710324  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
710487  interferon alpha-14 [KO:K05414]
710528  interferon alpha-1/13 [KO:K05414]
710568  interferon alpha-4-like [KO:K05414]
710654  IFNA10; interferon alpha-4 precursor [KO:K05414]
710751  interferon alpha-17-like [KO:K05414]
710848  interferon alpha-17 [KO:K05414]
711088  interferon alpha-17-like [KO:K05414]
711252  IFNA21; interferon alpha-21 [KO:K05414]
711414  IFNB1; interferon beta precursor [KO:K05415]
713563  PYCARD; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
713884  G3BP1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
714477  ZCCHC3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
715919  RELA; transcription factor p65 isoform X1 [KO:K04735]
716138  RIPK3; receptor-interacting serine/threonine-protein kinase 3 [KO:K08847] [EC:2.7.11.1]
716802  DNASE2; deoxyribonuclease-2-alpha [KO:K01158] [EC:3.1.22.1]
717301  IL33; interleukin-33 isoform X1 [KO:K12967]
717427  TBK1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
717616  MAVS; mitochondrial antiviral-signaling protein [KO:K12648]
717665  CGAS; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
718341  POLR1D; DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
718759  ADAR; double-stranded RNA-specific adenosine deaminase isoform X5 [KO:K12968] [EC:3.5.4.37]
718970  IRF3; interferon regulatory factor 3 [KO:K05411]
719253  IFI16; gamma-interferon-inducible protein 16 [KO:K20914]
719260  AIM2; interferon-inducible protein AIM2 isoform X1 [KO:K12966]
721178  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 isoform X2 [KO:K03013]
723056  probable palmitoyltransferase ZDHHC11 isoform X1 [KO:K20027] [EC:2.3.1.225]
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
mcc04064  NF-kappa B signaling pathway
mcc04120  Ubiquitin mediated proteolysis
mcc04210  Apoptosis
mcc04217  Necroptosis
mcc04621  NOD-like receptor signaling pathway
mcc04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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