KEGG   PATHWAY: morg04623
Entry
morg04623                   Pathway                                
Name
Cytosolic DNA-sensing pathway - Microtus oregoni (creeping vole)
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
morg04623  Cytosolic DNA-sensing pathway
morg04623

Organism
Microtus oregoni (creeping vole) [GN:morg]
Gene
121455421  Polr3a; DNA-directed RNA polymerase III subunit RPC1 [KO:K03018] [EC:2.7.7.6]
121462757  Polr3b; DNA-directed RNA polymerase III subunit RPC2 [KO:K03021] [EC:2.7.7.6]
121437893  Polr3c; DNA-directed RNA polymerase III subunit RPC3 [KO:K03023]
121460103  Polr3d; DNA-directed RNA polymerase III subunit RPC4 [KO:K03026]
121457945  Polr3e; DNA-directed RNA polymerase III subunit RPC5 [KO:K14721]
121450451  Polr1c; DNA-directed RNA polymerases I and III subunit RPAC1 [KO:K03027]
121466204  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121466540  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121445445  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121445471  DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
121445494  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121445534  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121440330  DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
121440458  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121440861  DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
121441569  uncharacterized protein LOC121441569 [KO:K03019]
121441623  DNA-directed RNA polymerase III subunit RPC10 [KO:K03019]
121448582  DNA-directed RNA polymerase III subunit RPC10-like [KO:K03019]
121464787  DNA-directed RNA polymerases I and III subunit RPAC2 [KO:K03020]
121461227  Polr3h; DNA-directed RNA polymerase III subunit RPC8 [KO:K03022]
121455868  Polr3g; DNA-directed RNA polymerase III subunit RPC7 isoform X1 [KO:K03024]
121437946  Polr3gl; DNA-directed RNA polymerase III subunit RPC7-like isoform X1 [KO:K03024]
121459986  Polr3f; DNA-directed RNA polymerase III subunit RPC6 [KO:K03025]
121459509  Polr2e; DNA-directed RNA polymerases I, II, and III subunit RPABC1 [KO:K03013]
121461177  Polr2f; DNA-directed RNA polymerases I, II, and III subunit RPABC2 [KO:K03014]
121465166  Polr2h; DNA-directed RNA polymerases I, II, and III subunit RPABC3 [KO:K03016]
121459074  DNA-directed RNA polymerases I, II, and III subunit RPABC4-like [KO:K03009]
121453338  DNA-directed RNA polymerases I, II, and III subunit RPABC4-like [KO:K03009]
121437648  Polr2k; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
121457752  Polr2l; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
121458250  Ddx58; antiviral innate immune response receptor RIG-I [KO:K12646] [EC:5.6.2.6]
121460460  Mavs; mitochondrial antiviral-signaling protein isoform X1 [KO:K12648]
121450269  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
121454688  Rela; transcription factor p65 isoform X1 [KO:K04735]
121439902  Il6; interleukin-6 [KO:K05405]
121438616  Pcbp1; poly(rC)-binding protein 1 [KO:K12889]
121457050  G3bp1; ras GTPase-activating protein-binding protein 1 [KO:K17265] [EC:5.6.2.5 5.6.2.3]
121460287  Zcchc3; zinc finger CCHC domain-containing protein 3 [KO:K27162]
121466160  Cgas; cyclic GMP-AMP synthase [KO:K17834] [EC:2.7.7.86]
121453596  stimulator of interferon genes protein-like [KO:K12654]
121443011  stimulator of interferon genes protein-like [KO:K12654]
121447241  Zdhhc1; palmitoyltransferase ZDHHC1 isoform X1 [KO:K20027] [EC:2.3.1.225]
121433630  palmitoyltransferase ZDHHC11-like [KO:K20027] [EC:2.3.1.225]
121453358  Ddx41; probable ATP-dependent RNA helicase DDX41 [KO:K13116] [EC:5.6.2.7]
121445821  probable ATP-dependent RNA helicase DDX41 [KO:K13116] [EC:5.6.2.7]
121441982  myeloid cell nuclear differentiation antigen-like protein [KO:K20914]
121442001  LOW QUALITY PROTEIN: myeloid cell nuclear differentiation antigen-like protein [KO:K20914]
121461912  Tbk1; serine/threonine-protein kinase TBK1 [KO:K05410] [EC:2.7.11.10]
121446542  Ikbke; inhibitor of nuclear factor kappa-B kinase subunit epsilon isoform X1 [KO:K07211] [EC:2.7.11.10]
121451666  Irf3; interferon regulatory factor 3 [KO:K05411]
121457785  Irf7; interferon regulatory factor 7 isoform X1 [KO:K09447]
121448125  interferon alpha-12-like [KO:K05414]
121448126  interferon alpha-12-like [KO:K05414]
121448127  interferon alpha-1-like [KO:K05414]
121448197  interferon alpha-12-like [KO:K05414]
121448198  interferon alpha-12-like [KO:K05414]
121448492  interferon alpha-12-like [KO:K05414]
121448496  interferon alpha-12-like [KO:K05414]
121448498  interferon alpha-12-like [KO:K05414]
121448501  interferon alpha-12-like [KO:K05414]
121448502  interferon alpha-12-like [KO:K05414]
121448504  interferon alpha-12 [KO:K05414]
121448505  interferon alpha-12-like [KO:K05414]
121448506  interferon alpha-12-like [KO:K05414]
121448508  interferon alpha-12-like [KO:K05414]
121448509  interferon alpha-12-like [KO:K05414]
121448510  interferon alpha-12-like [KO:K05414]
121448511  interferon alpha-12-like [KO:K05414]
121448512  interferon alpha-12-like [KO:K05414]
121448518  interferon alpha-12-like [KO:K05414]
121448524  interferon alpha-12-like [KO:K05414]
121448832  interferon alpha-1-like [KO:K05414]
121447990  Ifnb1; interferon beta [KO:K05415]
121440852  Zbp1; Z-DNA-binding protein 1 isoform X1 [KO:K12965]
121433918  Ripk1; receptor-interacting serine/threonine-protein kinase 1 isoform X1 [KO:K02861] [EC:2.7.11.1]
121435046  Ripk3; receptor-interacting serine/threonine-protein kinase 3 isoform X1 [KO:K08847] [EC:2.7.11.1]
121437198  NF-kappa-B essential modulator-like isoform X1 [KO:K07210]
121440264  NF-kappa-B essential modulator isoform X1 [KO:K07210]
121454691  Chuk; inhibitor of nuclear factor kappa-B kinase subunit alpha isoform X1 [KO:K04467] [EC:2.7.11.10]
121462326  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
121449504  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
121452602  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
121456864  C-C motif chemokine 4-like isoform X1 [KO:K12964]
121456879  C-C motif chemokine 4-like isoform X1 [KO:K12964]
121456922  C-C motif chemokine 4-like isoform X1 [KO:K12964]
121456991  C-C motif chemokine 4-like [KO:K12964]
121457011  Ccl5; C-C motif chemokine 5 [KO:K12499]
121460878  Cxcl10; C-X-C motif chemokine 10 [KO:K12671]
121442006  Aim2; interferon-inducible protein AIM2 [KO:K12966]
121456818  Nlrp3; NACHT, LRR and PYD domains-containing protein 3 isoform X1 [KO:K12800]
121464003  Mefv; pyrin [KO:K12803]
121457709  Fadd; FAS-associated death domain protein [KO:K02373]
121458619  caspase-8-like [KO:K04398] [EC:3.4.22.61]
121444834  caspase-8-like [KO:K04398] [EC:3.4.22.61]
121457950  Pycard; apoptosis-associated speck-like protein containing a CARD [KO:K12799]
121451709  Casp1; caspase-1 [KO:K01370] [EC:3.4.22.36]
121447301  Mlkl; mixed lineage kinase domain-like protein isoform X1 [KO:K08849] [EC:2.7.11.1]
121433874  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
121454121  Casp7; caspase-7 isoform X1 [KO:K04397] [EC:3.4.22.60]
121439917  Gsdme; gasdermin-E isoform X1 [KO:K22146]
121461349  gasdermin-D-like [KO:K20917]
121461372  gasdermin-D-like isoform X1 [KO:K20917]
121460531  Il1b; interleukin-1 beta [KO:K04519]
121438195  interleukin-18-like [KO:K05482]
121438394  interleukin-18-like isoform X1 [KO:K05482]
121454795  Il33; interleukin-33 isoform X1 [KO:K12967]
121450554  Adar; double-stranded RNA-specific adenosine deaminase isoform X1 [KO:K12968] [EC:3.5.4.37]
121460406  Samhd1; deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform X1 [KO:K22544] [EC:3.1.5.-]
121464202  Trex1; three-prime repair exonuclease 1 [KO:K10790] [EC:3.1.11.2]
121450476  Dnase2b; deoxyribonuclease-2-beta isoform X1 [KO:K01158] [EC:3.1.22.1]
121446792  Dnase2; deoxyribonuclease-2-alpha [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
morg04064  NF-kappa B signaling pathway
morg04120  Ubiquitin mediated proteolysis
morg04210  Apoptosis
morg04217  Necroptosis
morg04621  NOD-like receptor signaling pathway
morg04622  RIG-I-like receptor signaling pathway
KO pathway
ko04623   
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